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1

Development of a Simple and Rapid Fluorogenic Procedure for Identification of Vibrionaceae Family Members  

PubMed Central

We describe a simple colony overlay procedure for peptidases (COPP) for the rapid fluorogenic detection and quantification of Vibrionaceae from seawater, shellfish, sewage, and clinical samples. The assay detects phosphoglucose isomerase with a lysyl aminopeptidase activity that is produced by Vibrionaceae family members. Overnight cultures are overlaid for 10 min with membranes containing a synthetic substrate, and the membranes are examined for fluorescent foci under UV illumination. Fluorescent foci were produced by all the Vibrionaceae tested, including Vibrio spp., Aeromonas spp., and Plesiomonas spp. Fluorescence was not produced by non-Vibrionaceae pathogens. Vibrio cholerae strains O1, O139, O22, and O155 were strongly positive. Seawater and oysters were assayed, and 87 of 93 (93.5%) of the positive isolates were identified biochemically as Vibrionaceae, principally Vibrio vulnificus, Vibrio parahaemolyticus, Aeromonas hydrophila, Photobacterium damselae, and Shewanella putrefaciens. None of 50 nonfluorescent isolates were Vibrionaceae. No Vibrionaceae were detected in soil, and only A. hydrophila was detected in sewage. The COPP technique may be particularly valuable in environmental and food-testing laboratories and for monitoring water quality in the aquaculture industry. PMID:16000757

Richards, Gary P.; Watson, Michael A.; Parveen, Salina

2005-01-01

2

Global and phylogenetic distribution of quorum sensing signals, acyl homoserine lactones, in the family of vibrionaceae.  

PubMed

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

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

2014-11-01

3

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

PubMed Central

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

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

2014-01-01

4

Presence of acyl-homoserine lactones in 57 members of the Vibrionaceae family  

PubMed Central

Aims?The aim of this study was to use a sensitive method to screen and quantify 57 Vibrionaceae strains for the production of acyl-homoserine lactones (AHLs) and map the resulting AHL profiles onto a host phylogeny. Methods and Results?We used a high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) protocol to measure AHLs in spent media after bacterial growth. First, the presence/absence of AHLs (qualitative analysis) was measured to choose internal standard for subsequent quantitative AHL measurements. We screened 57 strains from three genera (Aliivibrio,Photobacterium and Vibrio) of the same family (i.e. Vibrionaceae). Our results show that about half of the isolates produced multiple AHLs, typically at 25–5000?nmol?l?1. Conclusions?This work shows that production of AHL quorum sensing signals is found widespread among Vibrionaceae bacteria and that closely related strains typically produce similar AHL profiles. Significance and Impact of the Study?The AHL detection protocol presented in this study can be applied to a broad range of bacterial samples and may contribute to a wider mapping of AHL production in bacteria, for example, in clinically relevant strains. PMID:23725044

Purohit, AA; Johansen, J?A; Hansen, H; Leiros, H-KS; Kashulin, A; Karlsen, C; Smalĺs, A; Haugen, P; Willassen, NP

2013-01-01

5

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

PubMed Central

Nonulosonic acids (NulOs) encompass a large group of structurally diverse nine-carbon backbone ?-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

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

2011-01-01

6

Genomic and systems evolution in Vibrionaceae species  

PubMed Central

Background The steadily increasing number of prokaryotic genomes has accelerated the study of genome evolution; in particular, the availability of sets of genomes from closely related bacteria has facilitated the exploration of the mechanisms underlying genome plasticity. The family Vibrionaceae is found in the Gammaproteobacteria and is abundant in aquatic environments. Taxa from the family Vibrionaceae are diversified in their life styles; some species are free living, others are symbiotic, and others are human pathogens. This diversity makes this family a useful set of model organisms for studying bacterial evolution. This evolution is driven by several forces, among them gene duplication and lateral gene transfer, which are believed to provide raw material for functional redundancy and novelty. The resultant gene copy increase in one genome is then detected as lineage-specific expansion (LSE). Results Here we present the results of a detailed comparison of the genomes of eleven Vibrionaceae strains that have distinct life styles and distinct phenotypes. The core genome shared by all eleven strains is composed of 1,882 genes, which make up about 31%–50% of the genome repertoire. We further investigated the distribution and features of genes that have been specifically expanded in one unique lineage of the eleven strains. Abundant duplicate genes have been identified in the eleven Vibrionaceae strains, with 1–11% of the whole genomes composed lineage specific radiations. These LSEs occurred in two distinct patterns: the first type yields one or more copies of a single gene; we call this a single gene expansion. The second pattern has a high evolutionary impact, as the expansion involves two or more gene copies in a block, with the duplicated block located next to the original block (a contiguous block expansion) or at some distance from the original block (a discontiguous block expansion). We showed that LSEs involve genes that are tied to defense and 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

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

2009-01-01

7

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

PubMed

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

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

1993-01-01

8

Genomic and systems evolution in Vibrionaceae species  

Microsoft Academic Search

BACKGROUND: The steadily increasing number of prokaryotic genomes has accelerated the study of genome evolution; in particular, the availability of sets of genomes from closely related bacteria has facilitated the exploration of the mechanisms underlying genome plasticity. The family Vibrionaceae is found in the Gammaproteobacteria and is abundant in aquatic environments. Taxa from the family Vibrionaceae are diversified in their

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

2009-01-01

9

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

E-print Network

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 ...

Chien, Diana M.

10

Criteria for revealing family secrets  

Microsoft Academic Search

Because revealing family secrets can have substantial influences on individuals and their interpersonal relationships, the criteria people use when they consider whether to divulge a family secret are quite important. The current study was conducted to explore these criteria and to examine the factors that encourage people to employ some criteria as opposed to others. In the first stage of

Anita Vangelisti; John Caughlin; Lindsay Timmerman

2001-01-01

11

Antibacterial compounds from marine Vibrionaceae isolated on a global expedition.  

PubMed

On a global research expedition, over 500 bacterial strains inhibitory towards pathogenic bacteria were isolated. Three hundred of the antibacterial strains were assigned to the Vibrionaceae family. The purpose of the present study was to investigate the phylogeny and bioactivity of five Vibrionaceae strains with pronounced antibacterial activity. These were identified as Vibrio coralliilyticus (two strains), V. neptunius (two strains), and Photobacterium halotolerans (one strain) on the basis of housekeeping gene sequences. The two related V. coralliilyticus and V. neptunius strains were isolated from distant oceanic regions. Chemotyping by LC-UV/MS underlined genetic relationships by showing highly similar metabolite profiles for each of the two V. coralliilyticus and V. neptunius strains, respectively, but a unique profile for P. halotolerans. Bioassay-guided fractionation identified two known antibiotics as being responsible for the antibacterial activity; andrimid (from V. coralliilyticus) and holomycin (from P. halotolerans). Despite the isolation of already known antibiotics, our findings show that marine Vibrionaceae are a resource of antibacterial compounds and may have potential for future natural product discovery. PMID:21339958

Wietz, Matthias; Mansson, Maria; Gotfredsen, Charlotte H; Larsen, Thomas O; Gram, Lone

2010-01-01

12

Antibacterial Compounds from Marine Vibrionaceae Isolated on a Global Expedition  

PubMed Central

On a global research expedition, over 500 bacterial strains inhibitory towards pathogenic bacteria were isolated. Three hundred of the antibacterial strains were assigned to the Vibrionaceae family. The purpose of the present study was to investigate the phylogeny and bioactivity of five Vibrionaceae strains with pronounced antibacterial activity. These were identified as Vibrio coralliilyticus (two strains), V. neptunius (two strains), and Photobacterium halotolerans (one strain) on the basis of housekeeping gene sequences. The two related V. coralliilyticus and V. neptunius strains were isolated from distant oceanic regions. Chemotyping by LC-UV/MS underlined genetic relationships by showing highly similar metabolite profiles for each of the two V. coralliilyticus and V. neptunius strains, respectively, but a unique profile for P. halotolerans. Bioassay-guided fractionation identified two known antibiotics as being responsible for the antibacterial activity; andrimid (from V. coralliilyticus) and holomycin (from P. halotolerans). Despite the isolation of already known antibiotics, our findings show that marine Vibrionaceae are a resource of antibacterial compounds and may have potential for future natural product discovery. PMID:21339958

Wietz, Matthias; Mansson, Maria; Gotfredsen, Charlotte H.; Larsen, Thomas O.; Gram, Lone

2010-01-01

13

The genomic code: inferring Vibrionaceae niche specialization.  

PubMed

The Vibrionaceae show a wide range of niche specialization, from free-living forms to those attached to biotic and abiotic surfaces, from symbionts to pathogens and from estuarine inhabitants to deep-sea piezophiles. The existence of complete genome sequences for closely related species from varied aquatic niches makes this group an excellent case study for genome comparison. PMID:16894340

Reen, F Jerry; Almagro-Moreno, Salvador; Ussery, David; Boyd, E Fidelma

2006-09-01

14

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

PubMed Central

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

Soto, William; Nishiguchi, Michele K.

2014-01-01

15

The fur gene as a new phylogenetic marker for vibrionaceae species identification.  

PubMed

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

Machado, Henrique; Gram, Lone

2015-04-15

16

Small RNAs in the Vibrionaceae: an ocean still to be explored.  

PubMed

In bacteria, the discovery of noncoding small RNAs (sRNAs) as modulators of gene expression in response to environmental signals has brought new insights into bacterial gene regulation, including control of pathogenicity. The Vibrionaceae constitute a family of marine bacteria of which many are responsible for infections affecting not only humans, such as Vibrio cholerae but also fish and marine invertebrates, representing the major cause of mortality in farmed marine species. They are able to colonize many habitats, existing as planktonic forms, in biofilms or associated with various hosts. This high adaptability is linked to their capacity to generate genetic diversity, in part through lateral gene transfer, but also by varying gene expression control. In the recent years, several major studies have illustrated the importance of small regulatory sRNAs in the Vibrionaceae for the control of pathogenicity and adaptation to environment and nutrient sources such as chitin, especially in V. cholerae and Vibrio harveyi. The existence of a complex regulatory network controlled by quorum sensing has been demonstrated in which sRNAs play central roles. This review covers major advances made in the discovery and elucidation of functions of Vibrionaceae sRNAs within the last 10?years. PMID:24458378

Nguyen, An Ngoc; Jacq, Annick

2014-01-01

17

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

PubMed Central

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 ?-glucuronidase and lysyl aminopeptidase activities for E. coli and Vibrionaceae, respectively. Cellulose membranes containing the substrates 4-methylumbeferyl-?-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

Richards, Gary P.; Watson, Michael A.

2010-01-01

18

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

PubMed

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

Richards, Gary P; Watson, Michael A

2010-01-01

19

Production of Bioactive Secondary Metabolites by Marine Vibrionaceae  

PubMed Central

Bacteria belonging to the Vibrionaceae family are widespread in the marine environment. Today, 128 species of vibrios are known. Several of them are infamous for their pathogenicity or symbiotic relationships. Despite their ability to interact with eukaryotes, the vibrios are greatly underexplored for their ability to produce bioactive secondary metabolites and studies have been limited to only a few species. Most of the compounds isolated from vibrios so far are non-ribosomal peptides or hybrids thereof, with examples of N-containing compounds produced independent of nonribosomal peptide synthetases (NRPS). Though covering a limited chemical space, vibrios produce compounds with attractive biological activities, including antibacterial, anticancer, and antivirulence activities. This review highlights some of the most interesting structures from this group of bacteria. Many compounds found in vibrios have also been isolated from other distantly related bacteria. This cosmopolitan occurrence of metabolites indicates a high incidence of horizontal gene transfer, which raises interesting questions concerning the ecological function of some of these molecules. This account underlines the pending potential for exploring new bacterial sources of bioactive compounds and the challenges related to their investigation. PMID:22131950

Mansson, Maria; Gram, Lone; Larsen, Thomas O.

2011-01-01

20

Conservation of the Chitin Utilization Pathway in the Vibrionaceae? †  

PubMed Central

Vibrionaceae are regarded as important marine chitin degraders, and attachment to chitin regulates important biological functions; yet, the degree of chitin pathway conservation in Vibrionaceae is unknown. Here, a core chitin degradation pathway is proposed based on comparison of 19 Vibrio and Photobacterium genomes with a detailed metabolic map assembled for V. cholerae from published biochemical, genomic, and transcriptomic results. Further, to assess whether chitin degradation is a conserved property of Vibrionaceae, a set of 54 strains from 32 taxa were tested for the ability to grow on various forms of chitin. All strains grew on N-acetylglucosamine (GlcNAc), the monomer of chitin. The majority of isolates grew on ? (crab shell) and ? (squid pen) chitin and contained chitinase A (chiA) genes. chiA sequencing and phylogenetic analysis suggest that this gene is a good indicator of chitin metabolism but appears subject to horizontal gene transfer and duplication. Overall, chitin metabolism appears to be a core function of Vibrionaceae, but individual pathway components exhibit dynamic evolutionary histories. PMID:17933912

Hunt, Dana E.; Gevers, Dirk; Vahora, Nisha M.; Polz, Martin F.

2008-01-01

21

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

PubMed Central

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

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

2013-01-01

22

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

PubMed

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 a 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

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

2014-01-01

23

Phylogenetic Analysis of the Incidence of lux Gene Horizontal Transfer in Vibrionaceae  

Microsoft Academic Search

Received 21 January 2008\\/Accepted 11 March 2008 Horizontal gene transfer (HGT) is thought to occur frequently in bacteria in nature and to play an important role in bacterial evolution, contributing to the formation of new species. To gain insight into the frequency of HGT in Vibrionaceae and its possible impact on speciation, we assessed the incidence of interspecies transfer of

Henryk Urbanczyk; Jennifer C. Ast; Allison J. Kaeding; James D. Oliver; Paul V. Dunlap

2008-01-01

24

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...

25

The Complete Genome Sequence of J Virus Reveals a Unique Genome Structure in the Family Paramyxoviridae  

Microsoft Academic Search

J virus (J-V) was isolated from feral mice (Mus musculus) trapped in Queensland, Australia, during the early 1970s. Although studies undertaken at the time revealed that J-V was a new paramyxovirus, it remained unclassified beyond the family level. The complete genome sequence of J-V has now been determined, revealing a genome structure unique within the family Paramyxoviridae. At 18,954 nucleotides

Philippa J. M. Jack; David B. Boyle; Bryan T. Eaton; Lin-Fa Wang

2005-01-01

26

The dynamics of a family’s gut microbiota reveal variations on a theme  

PubMed Central

Background It is clear that the structure and function of the human microbiota has significant impact on maintenance of health and yet the factors that give rise to an adult microbiota are poorly understood. A combination of genetics, diet, environment, and life history are all thought to impact the development of the gut microbiome. Here we study a chronosequence of the gut microbiota found in eight individuals from a family consisting of two parents and six children ranging in age from two months to ten years old. Results Using 16S rRNA gene and metagenomic shotgun sequence data, it was possible to distinguish the family from a cohort of normal individuals living in the same geographic region and to differentiate each family member. Interestingly, there was a significant core membership to the family members’ microbiota where the abundance of this core accounted for the differences between individuals. It was clear that the introduction of solids represents a significant transition in the development of a mature microbiota. This transition was associated with increased diversity, decreased stability, and the colonization of significant abundances of Bacteroidetes and Clostridiales. Although the children and mother shared essentially the identical diet and environment, the children’s microbiotas were not significantly more similar to their mother than they were to their father. Conclusions This analysis underscores the complex interactions that give rise to a personalized microbiota and suggests the value of studying families as a surrogate for longitudinal studies. PMID:25061514

2014-01-01

27

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...

28

Whole Exome Sequencing Reveals Genetic Predisposition in a Large Family with Retinitis Pigmentosa  

PubMed Central

Next-generation sequencing has become more widely used to reveal genetic defect in monogenic disorders. Retinitis pigmentosa (RP), the leading cause of hereditary blindness worldwide, has been attributed to more than 67 disease-causing genes. Due to the extreme genetic heterogeneity, using general molecular screening alone is inadequate for identifying genetic predispositions in susceptible individuals. In order to identify underlying mutation rapidly, we utilized next-generation sequencing in a four-generation Chinese family with RP. Two affected patients and an unaffected sibling were subjected to whole exome sequencing. Through bioinformatics analysis and direct sequencing confirmation, we identified p.R135W transition in the rhodopsin gene. The mutation was subsequently confirmed to cosegregate with the disease in the family. In this study, our results suggest that whole exome sequencing is a robust method in diagnosing familial hereditary disease. PMID:25101269

Wu, Juan; Chen, Lijia; Tam, Oi Sin; Huang, Xiu-Feng; Pang, Chi-Pui; Jin, Zi-Bing

2014-01-01

29

Characterization of the Avian Trojan Gene Family Reveals Contrasting Evolutionary Constraints  

PubMed Central

“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

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

2015-01-01

30

Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.  

PubMed Central

The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcerative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointestinal tract. These conditions have a peak incidence in early adulthood and a combined prevalence of approximately 100-200/100,000. Although the etiology of IBD is multifactorial, a significant genetic contribution to disease susceptibility is implied by epidemiological data revealing a sibling risk of approximately 35-fold for CD and approximately 15-fold for UC. To elucidate the genetic basis for these disorders, we undertook a genomewide scan in 158 Canadian sib-pair families and identified three regions of suggestive linkage (3p, 5q31-33, and 6p) and one region of significant linkage to 19p13 (LOD score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus of genomewide significance (LOD score 3.9) that contributes to CD susceptibility in families with early-onset disease. Both of these genomic regions contain numerous genes that are important to the immune and inflammatory systems and that provide good targets for future candidate-gene studies. PMID:10777714

Rioux, J D; Silverberg, M S; Daly, M J; Steinhart, A H; McLeod, R S; Griffiths, A M; Green, T; Brettin, T S; Stone, V; Bull, S B; Bitton, A; Williams, C N; Greenberg, G R; Cohen, Z; Lander, E S; Hudson, T J; Siminovitch, K A

2000-01-01

31

Structural and functional analysis of amphioxus HIF? reveals ancient features of the HIF? family  

PubMed Central

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 HIF? gene from amphioxus, an invertebrate chordate, and identified several alternatively spliced HIF? isoforms. Whereas HIF? 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 HIF? Ia protein level increased in response to hypoxia or CoCl2 treatment, whereas HIF? Ib, Ic, and Id showed reduced or no hypoxia regulation. Deletion of the ODD sequence in HIF? Ia up-regulated the HIF? Ia levels under normoxia. Gene expression analysis revealed HIF? 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 HIF? isoforms. Functional analyses in mammalian cells showed all 4 HIF? 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. 775KKARL functioned as the primary NLS, but 737KRK and 754KK also contributed to the nuclear localization. All amphioxus HIF? isoforms had 2 functional transactivation domains (TADs). Its C-terminal transactivation (C-TAD) shared high sequence identity with the human HIF-1? and HIF-2? 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 HIF? family and provide novel insights into the evolution of the HIF? family.—Gao, S., Lu, L., Bai, Y., Zhang, P., Song, W., Duan, C. Structural and functional analysis of amphioxus HIF? reveals ancient features of the HIF? family. PMID:24174425

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

2014-01-01

32

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

PubMed Central

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

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

33

Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study  

PubMed Central

Background Rotavirus is the leading cause of acute gastroenteritis (AGE) and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE) is well documented, there are few data on the impact of RVGE on the families of affected children. Methods Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL), conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. Results 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, ? 5 on a 10-point visual analogue scale). Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. Conclusions Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants. PMID:20230601

2010-01-01

34

Phylogenomic analysis reveals dynamic evolutionary history of the Drosophila heterochromatin protein 1 (HP1) gene family.  

PubMed

Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA. To identify new such surrogates for dissecting heterochromatin function and evolution, we conducted a comprehensive phylogenomic analysis of the Heterochromatin Protein 1 gene family across 40 million years of Drosophila evolution. Our study expands this gene family from 5 genes to at least 26 genes, including several uncharacterized genes in Drosophila melanogaster. The 21 newly defined HP1s introduce unprecedented structural diversity, lineage-restriction, and germline-biased expression patterns into the HP1 family. We find little evidence of positive selection at these HP1 genes in both population genetic and molecular evolution analyses. Instead, we find that dynamic evolution occurs via prolific gene gains and losses. Despite this dynamic gene turnover, the number of HP1 genes is relatively constant across species. We propose that karyotype evolution drives at least some HP1 gene turnover. For example, the loss of the male germline-restricted HP1E in the obscura group coincides with one episode of dramatic karyotypic evolution, including the gain of a neo-Y in this lineage. This expanded compendium of ovary- and testis-restricted HP1 genes revealed by our study, together with correlated gain/loss dynamics and chromosome fission/fusion events, will guide functional analyses of novel roles supported by germline chromatin. PMID:22737079

Levine, Mia T; McCoy, Connor; Vermaak, Danielle; Lee, Yuh Chwen G; Hiatt, Mary Alice; Matsen, Frederick A; Malik, Harmit S

2012-01-01

35

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

PubMed Central

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 events seen in both species. PMID:25059596

2014-01-01

36

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

PubMed

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

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

37

Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells.  

PubMed

Dendritic cells (DCs) are heterogeneous, comprising subsets with functional specializations that play distinct roles in immunity as well as immunopathology. We investigated the molecular control of cell survival of two main DC subsets: plasmacytoid DCs (pDCs) and conventional DCs (cDCs) and their dependence on individual antiapoptotic BCL-2 family members. Compared with cDCs, pDCs had higher expression of BCL-2, lower A1, and similar levels of MCL-1 and BCL-XL. Transgenic overexpression of BCL-2 increased the pDC pool size in vivo with only minor impact on cDCs. With a view to immune intervention, we tested BCL-2 inhibitors and found that ABT-199 (the BCL-2 specific inhibitor) selectively killed pDCs but not cDCs. Conversely, genetic knockdown of A1 profoundly reduced the proportion of cDCs but not pDCs. We also found that conditional ablation of MCL-1 significantly reduced the size of both DC populations in mice and impeded DC-mediated immune responses. Thus, we revealed that the two DC types have different cell survival requirements. The molecular basis of survival of different DC subsets thus advocates the antagonism of selective BCL-2 family members for treating diseases pertaining to distinct DC subsets. PMID:25775525

Carrington, Emma M; Zhang, Jian-Guo; Sutherland, Robyn M; Vikstrom, Ingela B; Brady, Jamie L; Soo, Priscilla; Vremec, David; Allison, Cody; Lee, Erinna F; Fairlie, W Douglas; Bouillet, Philippe; Grabow, Stephanie; Ottina, Eleonora; Herold, Marco J; Pellegrini, Marc; Huang, David C S; Tarlinton, David M; Strasser, Andreas; Lew, Andrew M; Zhan, Yifan

2015-03-31

38

RNA profiling reveals familial aggregation of molecular subtypes in non-BRCA1/2 breast cancer families  

PubMed Central

Background In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer patients within the same family. Methods In the current study we analyzed a collection of 70 frozen breast tumor biopsies from a total of 58 families by global RNA profiling and promoter methylation analysis. Results We show that distinct functional subgroupings, similar to the intrinsic molecular breast cancer subtypes, exist among non-BRCA1/2 breast cancers. The distribution of subtypes was markedly different from the distribution found among BRCA1/2 mutation carriers. From 11 breast cancer families, breast tumor biopsies from more than one affected family member were included in the study. Notably, in 8 of these families we found that patients from the same family shared the same tumor subtype, showing a tendency of familial aggregation of tumor subtypes (p-value?=?1.7e-3). Using our previously developed BRCA1/2-signatures, we identified 7 non-BRCA1/2 tumors with a BRCA1-like molecular phenotype and provide evidence for epigenetic inactivation of BRCA1 in three of the tumors. In addition, 7 BRCA2-like tumors were found. Conclusions Our finding indicates involvement of hereditary factors in non-BRCA1/2 breast cancer families in which family members may carry genetic susceptibility not just to breast cancer but to a particular subtype of breast cancer. This is the first study to provide a biological link between breast cancers from family members of high-risk non-BRCA1/2 families in a systematic manner, suggesting that future genetic analysis may benefit from subgrouping families into molecularly homogeneous subtypes in order to search for new high penetrance susceptibility genes. PMID:24479546

2014-01-01

39

New Insights on the Sialidase Protein Family Revealed by a Phylogenetic Analysis in Metazoa  

PubMed Central

Sialidases are glycohydrolytic enzymes present from virus to mammals that remove sialic acid from oligosaccharide chains. Four different sialidase forms are known in vertebrates: the lysosomal NEU1, the cytosolic NEU2 and the membrane-associated NEU3 and NEU4. These enzymes modulate the cell sialic acid content and are involved in several cellular processes and pathological conditions. Molecular defects in NEU1 are responsible for sialidosis, an inherited disease characterized by lysosomal storage disorder and neurodegeneration. The studies on the biology of sialic acids and sialyltransferases, the anabolic counterparts of sialidases, have revealed a complex picture with more than 50 sialic acid variants selectively present in the different branches of the tree of life. The gain/loss of specific sialoconjugates have been proposed as key events in the evolution of deuterostomes and Homo sapiens, as well as in the host-pathogen interactions. To date, less attention has been paid to the evolution of sialidases. Thus we have conducted a survey on the state of the sialidase family in metazoan. Using an in silico approach, we identified and characterized sialidase orthologs from 21 different organisms distributed among the evolutionary tree: Metazoa relative (Monosiga brevicollis), early Deuterostomia, precursor of Chordata and Vertebrata (teleost fishes, amphibians, reptiles, avians and early and recent mammals). We were able to reconstruct the evolution of the sialidase protein family from the ancestral sialidase NEU1 and identify a new form of the enzyme, NEU5, representing an intermediate step in the evolution leading to the modern NEU3, NEU4 and NEU2. Our study provides new insights on the mechanisms that shaped the substrate specificity and other peculiar properties of the modern mammalian sialidases. Moreover, we further confirm findings on the catalytic residues and identified enzyme loop portions that behave as rapidly diverging regions and may be involved in the evolution of specific properties of sialidases. PMID:22952925

Giacopuzzi, Edoardo; Bresciani, Roberto; Schauer, Roland; Monti, Eugenio; Borsani, Giuseppe

2012-01-01

40

Quantitative Phosphoproteomics Reveals SLP-76 Dependent Regulation of PAG and Src Family Kinases in T Cells  

PubMed Central

The SH2-domain-containing leukocyte protein of 76 kDa (SLP-76) plays a critical scaffolding role in T cell receptor (TCR) signaling. As an adaptor protein that contains multiple protein-binding domains, SLP-76 interacts with many signaling molecules and links proximal receptor stimulation to downstream effectors. The function of SLP-76 in TCR signaling has been widely studied using the Jurkat human leukaemic T cell line through protein disruption or site-directed mutagenesis. However, a wide-scale characterization of SLP-76-dependant phosphorylation events is still lacking. Quantitative profiling of over a hundred tyrosine phosphorylation sites revealed new modes of regulation of phosphorylation of PAG, PI3K, and WASP while reconfirming previously established regulation of Itk, PLC?, and Erk phosphorylation by SLP-76. The absence of SLP-76 also perturbed the phosphorylation of Src family kinases (SFKs) Lck and Fyn, and subsequently a large number of SFK-regulated signaling molecules. Altogether our data suggests unique modes of regulation of positive and negative feedback pathways in T cells by SLP-76, reconfirming its central role in the pathway. PMID:23071622

Cao, Lulu; Ding, Yiyuan; Hung, Norris; Yu, Kebing; Ritz, Anna; Raphael, Benjamin J.; Salomon, Arthur R.

2012-01-01

41

Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation  

PubMed Central

Previously, we have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. To gain an overall insight into the entire CCCH zinc finger gene family and to evaluate their potential role in macrophage activation, here we performed a genome-wide survey of CCCH zinc finger genes in mouse and human. Totally 58 CCCH zinc finger genes in mouse and 55 in human were identified and most of them have not been reported previously. Phylogenetic analysis revealed that the mouse CCCH family was divided into 6 groups. Meanwhile, we employed quantitative real-time PCR to profile their tissue expression patterns in adult mice. Clustering analysis showed that most of CCCH genes were broadly expressed in all of tissues examined with various levels. Interestingly, several CCCH genes Mbnl3, Zfp36l2, Zfp36, Zc3h12a, Zc3h12d, Zc3h7a and Leng9 were enriched in macrophage-related organs such as thymus, spleen, lung, intestine and adipose. Consistently, a comprehensive assessment of changes in expression of the 58 members of the mouse CCCH family during macrophage activation also revealed that these CCCH zinc finger genes were associated with the activation of bone marrow-derived macrophages by lipopolysaccharide. Taken together, this study not only identified a functional module of CCCH zinc finger genes in the regulation of macrophage activation but also provided the framework for future studies to dissect the function of this emerging gene family. PMID:18682727

Liang, Jian; Song, Wenjun; Tromp, Gail; Kolattukudy, Pappachan E.; Fu, Mingui

2008-01-01

42

Familial form of hirschsprung disease: nucleotide sequence studies reveal point mutations in the RET proto-oncogene in two of six families but not in other candidate genes.  

PubMed

Hirschsprung disease (HSCR; McKusick 142623) or aganglionic megacolon is a frequent (1 in 5,000 live births) heritable disorder of the enteric nervous system. By haplotyping with a variety of microsatellite markers, by amplifying all 20 exons of the RET proto-oncogene and by applying a direct DNA sequencing protocol, we have analyzed the DNA from HSCR patients in 6 different families. In one family with a joint occurrence of HSCR and FMTC (follicular medullary thyroid carcinoma), we have identified a mutation in codon 609 in one out of 6 cysteine residues encoded in exon 10 of the RET gene. This C609R point mutation has not previously been reported to cause HSCR. In 2 of the HSCR patients described here from different families, we have found a mutation in exon 2 (R77C) and a silent mutation in exon 3 (Y204Y), respectively, in the extracellular part of the RET proto-oncogene. In introns 2 and 17 of the RET proto-oncogene in 2 families, we have detected single nucleotide exchanges that are probably polymorphisms with unknown, if any, relations to HSCR. The DNA sequences of 5 further genes (GDNF, GDNFRalpha, EDN3, EDNRB, and NTN), that may contribute to the development of HSCR, have not shown mutations in the patients analyzed so far. In 2 of the reported families with several affected children and one grandchild, sequence analyses revealed no mutations in the coding regions of any of the candidate genes analyzed. PMID:10982477

Munnes, M; Fanaei, S; Schmitz, B; Muiznieks, I; Holschneider, A M; Doerfler, W

2000-09-01

43

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

PubMed Central

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

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

2014-01-01

44

SH3 Domain–Based Phototrapping in Living Cells Reveals Rho Family GAP Signaling Complexes  

PubMed Central

Rho family GAPs [guanosine triphosphatase (GTPase) activating proteins] negatively regulate Rho family GTPase activity and therefore modulate signaling events that control cytoskeletal dynamics. The spatial distribution of these GAPs and their specificity toward individual GTPases are controlled by their interactions with various proteins within signaling complexes. These interactions are likely mediated through the Src homology 3 (SH3) domain, which is abundant in the Rho family GAP proteome and exhibits a micromolar binding affinity, enabling the Rho family GAPs to participate in transient interactions with multiple binding partners. To capture these elusive GAP signaling complexes in situ, we developed a domain-based proteomics approach, starting with in vivo phototrapping of SH3 domain– binding proteins and the mass spectrometry identification of associated proteins for nine representative Rho family GAPs. After the selection of candidate binding proteins by cluster analysis, we performed peptide array–based high-throughput in vitro binding assays to confirm the direct interactions and map the SH3 domain–binding sequences. We thereby identified 54 SH3-mediated binding interactions (including 51 previously unidentified ones) for nine Rho family GAPs. We constructed Rho family GAP interactomes that provided insight into the functions of these GAPs. We further characterized one of the predicted functions for the Rac-specific GAP WRP and identified a role for WRP in mediating clustering of the postsynaptic scaffolding protein gephyrin and the GABAA (?-aminobutyric acid type A) receptor at inhibitory synapses. PMID:22126966

Okada, Hirokazu; Uezu, Akiyoshi; Mason, Frank M.; Soderblom, Erik J.; Moseley, M. Arthur; Soderling, Scott H.

2012-01-01

45

BCL-2 family genetic profiling reveals microenvironment-specific determinants of chemotherapeutic response  

E-print Network

The Bcl-2 family encompasses a diverse set of apoptotic regulators that are dynamically activated in response to various cell-intrinsic and -extrinsic stimuli. An extensive variety of cell culture experiments have identified ...

Pritchard, Justin Robert

46

Analysis of two Arab families reveals additional support for a DFNB2 nonsyndromic phenotype of MYO7A.  

PubMed

Variants in the head and tail domains of the MYO7A gene, encoding myosin VIIA, cause Usher syndrome type 1B (USH1B) and nonsyndromic deafness (DFNB2, DFNA11). In order to identify the genetic defect(s) underling profound deafness in two consanguineous Arab families living in UAE, we have sequenced a panel of 19 genes involved in Usher syndrome and nonsyndromic deafness in the index cases of the two families. This analysis revealed a novel homozygous insertion of AG (c.1952_1953insAG/p.C652fsX11) in exon 17 of the MYO7A gene in an Iraqi family, and a homozygous point mutation (c.5660C>T/p.P1887L) in exon 41 affecting the same gene in a large Palestinian family. Moreover, some individuals from the Palestinian family also harbored a novel heterozygous truncating variant (c.1267C>T/p.R423X) in the DFNB31 gene, which is involved in autosomal recessive nonsyndromic deafness type DFNB31 and Usher syndrome type II. Assuming an autosomal recessive mode of inheritance in the two inbred families, we conclude that the homozygous variants in the MYO7A gene are the disease-causing mutations in these families. Furthermore, given the absence of retinal disease in all affected patients examined, particularly a 28 year old patient, suggests that at least one family may segregate a DFNB2 presentation rather than USH1B. This finding further supports the premise that the MYO7A gene is responsible for two distinct diseases and gives evidence that the p.P1887L mutation in a homozygous state may be responsible for nonsyndromic hearing loss. PMID:24194196

Ben-Salem, Salma; Rehm, Heidi L; Willems, Patrick J; Tamimi, Zakaria A; Ayadi, Hammadi; Ali, Bassam R; Al-Gazali, Lihadh

2014-01-01

47

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

PubMed

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

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

2012-05-01

48

Analysis of mitochondrial genome revealed a rare 50 bp deletion and substitutions in a family with hypertension.  

PubMed

We have sequenced the complete mtDNA of a family with hypertension (HT), type 2 diabetes (T2D) and coronary artery disease (CAD). Our analysis revealed two novel mutations (C3519T, G13204A); of which G13204A replaces valine to isoleucine. In silico analysis of a rare missense mutation (T8597C) showed a deleterious effect. We also observed a 50bp deletion (m.298_347del50) in the hypervariable region II (HVSII) of all the individuals, who had a common maternal lineage. This (50bp) deletion was not found in 17,785 individuals from different ethnic populations of India or in a variety of different disease phenotypes. We predict that the mtDNA mutations might be responsible for the HT. Analysis of POLG (polymerase gamma) gene revealed 14 variants which might be responsible for some of the mtDNA mutations seen in this family. PMID:21787884

Elango, Santhini; Govindaraj, Periyasamy; Vishwanadha, Vijaya Padma; Reddy, Alla Govardhana; Tamang, Rakesh; Muthusami, Uthiralingam; Kunnoth, Sreejith; Koyilil, Vijaya Kumar; Lakshman, Mohanakrishnan; Shanmugasundharam, N; Singh, Lalji; Thangaraj, Kumarasamy

2011-11-01

49

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 ...

50

Genome-Wide Linkage Analysis Reveals Evidence for Four New Susceptibility Loci for Familial Euthyroid Goiter  

Microsoft Academic Search

Euthyroid goiter is characterized by diffuse or nodular en- largement of the thyroid gland. Iodine deficiency and ciga- rette smoking have been identified as important environmen- tal factors. However, family and twin pair studies suggest a strong genetic predisposition. Therefore, we performed the first extended genome-wide scan to identify susceptibility loci that predispose for euthyroid goiter using 450 microsatellite markers

YVONNE BAYER; SUSANNE NEUMANN; BIRGIT MEYER; FRANZ RUSCHENDORF; ANDREAS RESKE; THOMAS BRIX; LASZLO HEGEDUS; PAVEL LANGER; PETER NURNBERG; RALF PASCHKE

51

Exome sequencing reveals VCP mutations as a cause of familial ALS  

PubMed Central

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

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; Monsurrň, Maria Rosaria; Battistini, Stefania; Salvi, Fabrizio; Spataro, Rossella; Sola, Patrizia; Borghero, Giuseppe; Galassi, Giuliana; Scholz, Sonja W.; Taylor, J. Paul; Restagno, Gabriella; Chiň, Adriano; Traynor, Bryan J.

2010-01-01

52

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

PubMed Central

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

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

2015-01-01

53

Brief Report: An Autistic Spectrum Subtype Revealed through Familial Psychopathology Coupled with Cognition in ASD  

ERIC Educational Resources Information Center

This study identified a possible autistic spectrum subtype expressed through family psychopathology coupled with autistic probands' cognitive functioning (i.e., an endophenotypic profile). Participants included 24 children with Autism Spectrum Disorder (ASD) and 49 children with Learning Disorder (LD). There were significantly higher rates of Mood…

Lajiness-O'Neill, Renee; Menard, Philip

2008-01-01

54

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

PubMed Central

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 literature, we determined that variants occurred in ASD candidate genes 1.65 times more frequently than in random genes captured by exome sequencing (P?=?8.55 × 10-5). Conclusions By studying these unique pedigrees, we have identified novel DNA variations related to ASD, demonstrated that exome sequencing in extended families is a powerful tool for ASD candidate gene discovery, and provided further evidence of an underlying genetic component to a wide range of neurodevelopmental and neuropsychiatric diseases. PMID:24410847

2014-01-01

55

Oxylipin Diversity in the Diatom Family Leptocylindraceae Reveals DHA Derivatives in Marine Diatoms  

PubMed Central

Marine planktonic organisms, such as diatoms, are prospective sources of novel bioactive metabolites. Oxygenated derivatives of fatty acids, generally referred to as oxylipins, in diatoms comprise a highly diverse and complex family of secondary metabolites. These molecules have recently been implicated in several biological processes including intra- and inter-cellular signaling as well as in defense against biotic stressors and grazers. Here, we analyze the production and diversity of C20 and C22 non-volatile oxylipins in five species of the family Leptocylindraceae, which constitute a basal clade in the diatom phylogeny. We report the presence of species-specific lipoxygenase activity and oxylipin patterns, providing the first demonstration of enzymatic production of docosahexaenoic acid derivatives in marine diatoms. The differences observed in lipoxygenase pathways among the species investigated broadly reflected the relationships observed with phylogenetic markers, thus providing functional support to the taxonomic diversity of the individual species. PMID:24445306

Nanjappa, Deepak; d’Ippolito, Giuliana; Gallo, Carmela; Zingone, Adriana; Fontana, Angelo

2014-01-01

56

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

PubMed Central

Background About half of malignant hyperthermia (MH) cases are associated with skeletal muscle ryanodine receptor 1 (RYR1) and calcium channel, voltage-dependent, L type, ?1S 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

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

57

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

Microsoft Academic Search

Extensive expression profiling studies have shown that sporadic breast cancer is composed of five clinically relevant molecular\\u000a subtypes. However, although BRCA1-related tumours are known to be predominantly basal-like, there are few published data on other classes of familial breast\\u000a tumours. We analysed a cohort of 75 BRCA1, BRCA2 and non-BRCA1\\/2 breast tumours by gene expression profiling and found that 74%

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

2010-01-01

58

Evolution of the gastrin-cholecystokinin gene family revealed by synteny analysis.  

PubMed

Gastrin (GAST) and cholecystokinin (CCK) are two structurally and functionally related peptide hormones that exert many functions, including regulation of gastric and pancreatic secretion, feeding behaviour and energy homeostasis. GAST and CCK genes are assumed to have diverged from a common ancestral gene, over 500 million years ago in the vertebrate lineage. However, although a large number of GAST and CCK-related sequences have been identified both in vertebrate and non-vertebrate species, the evolutionary history of the GAST/CCK family remains little understood. To address this issue, we used extensive genome synteny comparisons of vertebrate chromosomes, in particular to evaluate the impact of whole-genome duplications. In the present study, we confirm that the GAST/CCK family in vertebrates is composed of two paralogous genes, namely GAST and CCK, and even three in teleosts, namely GAST, CCK1 and CCK2. We also show that the GAST and CCK genes arose by duplications of a single ancestral gene through the 2R and that the two copies of the CCK gene found in teleosts have probably been generated through the 3R. Finally, our results suggest that the vertebrate ancestor possessed four members of the GAST/CCK family, of which two have likely been lost during evolution. PMID:24231682

Dupré, Délia; Tostivint, Hervé

2014-01-01

59

Vitamin E analyses in seeds reveal a dominant presence of tocotrienols over tocopherols in the Arecaceae family.  

PubMed

Tocopherols are thought to prevent oxidative damage during seed quiescence and dormancy in all angiosperms. However, several monocot species accumulate tocotrienols in seeds and their role remains elusive. Here, we aimed to unravel the distribution of tocopherols and tocotrienols in seeds of the Arecaceae family, to examine possible trends of vitamin E accumulation within different clades of the same family. We examined the tocopherol and tocotrienol content in seeds of 84 species. Furthermore, we evaluated the vitamin E composition of the seed coat, endosperm and embryo of seeds from 6 species, to determine possible tissue-specific functions of particular vitamin E forms. While seeds of 98.8% (83 out of 84) of the species accumulated tocotrienols, only 58.3% (49 out of 84) accumulated tocopherols. The presence of tocopherols did not follow a clear evolutionary trend, and appeared randomly in some clades only. In addition, the tissue-specific location of vitamin E in seeds revealed that the embryo contains mostly ?-tocopherol (in seed tocopherol-accumulating species) or ?-tocotrienol (in seed tocopherol-deficient species). However, some species such as Socratea exorrhiza mostly accumulate ?-tocotrienol, and Parajubaea torallyi accumulates a mixture of tocopherols and tocotrienols in the embryo. This suggests that tocotrienols can play a similar protective role to that exerted by tocopherols in seeds, at least in some species of the Arecaceae family. We conclude that tocotrienol, rather than tocopherol, accumulation is a conserved trait in seeds of the Arecaceae family. PMID:23920227

Siles, Laura; Cela, Jana; Munné-Bosch, Sergi

2013-11-01

60

Exome Sequencing Reveals a Novel PRPS1 Mutation in a Family with CMTX5 without Optic Atrophy  

PubMed Central

Background X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1). There has been only one case report of CMTX5 patients. The aim of this study was to identify the causative gene in a family with CMTX with peripheral neuropathy and deafness. Case Report A Korean family with X-linked recessive CMT was enrolled. The age at the onset of hearing loss of the male proband was 5 months, and that of steppage gait was 6 years; he underwent cochlear surgery at the age of 12 years. In contrast to what was reported for the first patients with CMTX5, this patient did not exhibit optic atrophy. Furthermore, there was no cognitive impairment, respiratory dysfunction, or visual disturbance. Assessment of his family history revealed two male relatives with very similar clinical manifestations. Electrophysiological evaluations disclosed sensorineural hearing loss and peripheral neuropathy. Whole-exome sequencing identified a novel p.Ala121Gly (c.362C>G) PRPS1 mutation as the underlying genetic cause of the clinical phenotype. Conclusions A novel mutation of PRPS1 was identified in a CMTX5 family in which the proband had a phenotype of peripheral neuropathy with early-onset hearing loss, but no optic atrophy. The findings of this study will expand the clinical spectrum of X-linked recessive CMT and will be useful for the molecular diagnosis of clinically heterogeneous peripheral neuropathies. PMID:24285972

Park, Jin; Hyun, Young Se; Kim, Ye Jin; Nam, Soo Hyun; Kim, Sung-hee; Hong, Young Bin; Park, Jin-Mo

2013-01-01

61

Structural basis of the substrate specificity of the FPOD/FAOD family revealed by fructosyl peptide oxidase from Eupenicillium terrenum.  

PubMed

The FAOD/FPOD family of proteins has the potential to be useful for the longterm detection of blood glucose levels in diabetes patients. A bottleneck for this application is to find or engineer a FAOD/FPOD family enzyme that is specifically active towards ?-fructosyl peptides but is inactive towards other types of glycated peptides. Here, the crystal structure of fructosyl peptide oxidase from Eupenicillium terrenum (EtFPOX) is reported at 1.9?Ĺ resolution. In contrast to the previously reported structure of amadoriase II, EtFPOX has an open substrate entrance to accommodate the large peptide substrate. The functions of residues critical for substrate selection are discussed based on structure comparison and sequence alignment. This study reveals the first structural details of group I FPODs that prefer ?-fructosyl substrates and could provide significant useful information for uncovering the mechanism of substrate specificity of FAOD/FPODs and guidance towards future enzyme engineering for diagnostic purposes. PMID:25849495

Gan, Weiqiong; Gao, Feng; Xing, Keke; Jia, Minze; Liu, Haiping; Gong, Weimin

2015-04-01

62

Analysis of Arabidopsis genome sequence reveals a large new gene family in plants  

Microsoft Academic Search

A detailed analysis of the currently available Arabidopsis thaliana genomic sequence has revealed the presence of a large number of open reading frames with homology to the stigmatic self-incompatibility (S) genes of Papaver rhoeas. The products of these potential genes are all predicted to be relatively small, basic, secreted proteins with similar predicted secondary structures. We have named these potential

J. P. Ride; E. M. Davies; F. C. H. Franklin; D. F. Marshall

1999-01-01

63

Engineered kinase activation reveals unique morphodynamic phenotypes and associated trafficking for Src family isoforms  

PubMed Central

The Src kinase family comprises nine homologous members whose distinct expression patterns and cellular distributions indicate that they have unique roles. These roles have not been determined because genetic manipulation has not produced clearly distinct phenotypes, and the kinases’ homology complicates generation of specific inhibitors. Through insertion of a modified FK506 binding protein (insertable FKBP12, iFKBP) into the protein kinase isoforms Fyn, Src, Lyn, and Yes, we engineered kinase analogs that can be activated within minutes in living cells (RapR analogs). Combining our RapR analogs with computational tools for quantifying and characterizing cellular dynamics, we demonstrate that Src family isoforms produce very different phenotypes, encompassing cell spreading, polarized motility, and production of long, thin cell extensions. Activation of Src and Fyn led to patterns of kinase translocation that correlated with morphological changes in temporally distinct stages. Phenotypes were dependent on N-terminal acylation, not on Src homology 3 (SH3) and Src homology 2 (SH2) domains, and correlated with movement between a perinuclear compartment, adhesions, and the plasma membrane. PMID:25118278

Chu, Pei-Hsuan; Tsygankov, Denis; Berginski, Matthew E.; Dagliyan, Onur; Gomez, Shawn M.; Elston, Timothy C.; Karginov, Andrei V.; Hahn, Klaus M.

2014-01-01

64

Next-Generation Sequencing of a 40 Mb Linkage Interval Reveals TSPAN12 Mutations in Patients with Familial Exudative Vitreoretinopathy  

PubMed Central

Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous retinal disorder characterized by abnormal vascularisation of the peripheral retina, often accompanied by retinal detachment. To date, mutations in three genes (FZD4, LRP5, and NDP) have been shown to be causative for FEVR. In two large Dutch pedigrees segregating autosomal-dominant FEVR, genome-wide SNP analysis identified an FEVR locus of ?40 Mb on chromosome 7. Microsatellite marker analysis suggested similar at risk haplotypes in patients of both families. To identify the causative gene, we applied next-generation sequencing in the proband of one of the families, by analyzing all exons and intron-exon boundaries of 338 genes, in addition to microRNAs, noncoding RNAs, and other highly conserved genomic regions in the 40 Mb linkage interval. After detailed bioinformatic analysis of the sequence data, prioritization of all detected sequence variants led to three candidates to be considered as the causative genetic defect in this family. One of these variants was an alanine-to-proline substitution in the transmembrane 4 superfamily member 12 protein, encoded by TSPAN12. This protein has very recently been implicated in regulating the development of retinal vasculature, together with the proteins encoded by FZD4, LRP5, and NDP. Sequence analysis of TSPAN12 revealed two mutations segregating in five of 11 FEVR families, indicating that mutations in TSPAN12 are a relatively frequent cause of FEVR. Furthermore, we demonstrate the power of targeted next-generation sequencing technology to identify disease genes in linkage intervals. PMID:20159111

Nikopoulos, Konstantinos; Gilissen, Christian; Hoischen, Alexander; Erik van Nouhuys, C.; Boonstra, F. Nienke; Blokland, Ellen A.W.; Arts, Peer; Wieskamp, Nienke; Strom, Tim M.; Ayuso, Carmen; Tilanus, Mauk A.D.; Bouwhuis, Sanne; Mukhopadhyay, Arijit; Scheffer, Hans; Hoefsloot, Lies H.; Veltman, Joris A.; Cremers, Frans P.M.; Collin, Rob W.J.

2010-01-01

65

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

PubMed Central

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 importance of this chromosomal region. PMID:24917880

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

66

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

PubMed

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

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

67

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

PubMed Central

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

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

68

Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer's disease  

PubMed Central

Alzheimer's disease (AD) is a genetically complex disorder for which the definite diagnosis is only accomplished post mortem. Mutations in three genes (APP, PSEN1 and PSEN2) are known to cause AD, but a large number of familial cases do not harbor mutations in these genes and several unidentified genes that contain disease-causing mutations are thought to exist. We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family with a complex history of neurological and immunological disorders and identified a mutation in NOTCH3 (p.R1231C), previously described as causing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Complete screening of NOTCH3 in a cohort of 95 early onset AD cases and 95 controls did not reveal any additional pathogenic mutations. Although the complex history of disease in this family precluded us to establish segregation of the mutation found with disease, our results show that exome sequencing is a rapid, cost-effective and comprehensive tool to detect genetic mutations, allowing for the identification of unexpected genetic causes of clinical phenotypes. As etiological based therapeutics become more common, this method will be key in diagnosing and treating disease. PMID:22153900

Guerreiro, Rita Joao; Lohmann, Ebba; Kinsella, Emma; Bras, Jose Miguel; Luu, Nga; Gurulian, Nicole; Dursun, Burcu; Bilgi, Basar; Santana, Isabel; Hanagasi, Hasmet; Gurvit, Hakan; Gibbs, Raphael; Oliveira, Catarina; Emre, Murat; Singleton, Andrew

2011-01-01

69

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

PubMed Central

Summary Dethiobiotin synthetase (DTBS) is involved in the biosynthesis of biotin in bacteria, fungi and plants. As humans lack this pathway, dethiobiotin synthetase is a promising antimicrobial drug target. We determined structures of DBTS from H. pylori (hpDTBS) bound with cofactors and a substrate analog and described its unique characteristics relative to other DTBS proteins. Comparison with bacterial DTBS orthologues revealed considerable structural differences in nucleotide recognition. The C-terminal region of DTBS proteins, which contains two nucleotide-recognition motifs, greatly differs 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, ITC binding studies show that hpDTBS has a strong preference for ATP. The structural determinants of ATP specificity were assessed through 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. PMID:22284390

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

2012-01-01

70

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

PubMed Central

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

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

71

Src family kinase oncogenic potential and pathways in prostate cancer as revealed by AZD0530  

PubMed Central

Prostate cancer is the most frequently diagnosed cancer in American men. We have previously demonstrated that Src mediates androgen-independent proliferation in prostate cancer. We sought to investigate the Src-mediated oncogenic pathways and tumor biology using AZD0530, a novel Src family kinase/Abl dual-kinase inhibitor that is entering phase II clinical trials. We show that while both Src and Abl are expressed in all prostate cancer cell lines, Src but not Abl is activated in the prostate. Furthermore, Src activation is inhibited by AZD0530 in a rapid and dose-dependent manner. We show that Src mediates cell proliferation in DU145 and PC3 cells at the G1 phase of cell cycle. Src inhibition resulted in decreased binding of ?-catenin to the promoters of G1 phase cell cycle regulators cyclin D1 and c-Myc. C-Myc may also be regulated at the protein level by extracellular signal-regulated kinase 1/2 and GSK3?. Cell motility factors focal adhesion kinase, p130CAS and paxillin activation in DU145 and PC3 cells were also inhibited. Administration of AZD0530 in mice reduced orthotopic DU145 xenograft growth by 45%. We have further delineated the Src-mediated oncogenic growth and migration pathways in prostate cancer and established mechanistic rationale for Src inhibition as novel therapy in the treatment of prostate cancer. PMID:18679417

Chang, Y-M; Bai, L; Liu, S; Yang, JC; Kung, H-J; Evans, CP

2009-01-01

72

Plant members of a family of sulfate transporters reveal functional subtypes.  

PubMed Central

Three plant sulfate transporter cDNAs have been isolated by complementation of a yeast mutant with a cDNA library derived from the tropical forage legume Stylosanthes hamata. Two of these cDNAs, shst1 and shst2, encode high-affinity H+/sulfate cotransporters that mediate the uptake of sulfate by plant roots from low concentrations of sulfate in the soil solution. The third, shst3, represents a different subtype encoding a lower affinity H+/sulfate cotransporter, which may be involved in the internal transport of sulfate between cellular or subcellular compartments within the plant. The steady-state level of mRNA corresponding to both subtypes is subject to regulation by signals that ultimately respond to the external sulfate supply. These cDNAs represent the identification of plant members of a family of related sulfate transporter proteins whose sequences exhibit significant amino acid conservation in filamentous fungi, yeast, plants, and mammals. Images Fig. 3 Fig. 4 Fig. 6 PMID:7568135

Smith, F W; Ealing, P M; Hawkesford, M J; Clarkson, D T

1995-01-01

73

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

SciTech Connect

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.

Taneja, Bhupesh; Patel, Asmita; Slesarev, Alexei; Mondragon, Alfonso (NWU); (FSI)

2010-09-02

74

The Genomic Landscape of the Ewing Sarcoma Family of Tumors Reveals Recurrent STAG2 Mutation  

PubMed Central

The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared to population data (OR 7.1, p?=?0.006). Using whole transcriptome sequencing, we find that 11% of tumors pathologically diagnosed as EFT lack a typical EWSR1 fusion oncogene and that these tumors do not have a characteristic Ewing sarcoma gene expression signature. We identify samples harboring novel fusion genes including FUS-NCATc2 and CIC-FOXO4 that may represent distinct small round blue cell tumor variants. In an independent EFT tissue microarray cohort, we show that STAG2 loss as detected by immunohistochemistry may be associated with more advanced disease (p?=?0.15) and a modest decrease in overall survival (p?=?0.10). These results significantly advance our understanding of the genomic and molecular underpinnings of Ewing sarcoma and provide a foundation towards further efforts to improve diagnosis, prognosis, and precision therapeutics testing. PMID:25010205

Brohl, Andrew S.; Solomon, David A.; Chang, Wendy; Wang, Jianjun; Song, Young; Sindiri, Sivasish; Patidar, Rajesh; Hurd, Laura; Chen, Li; Shern, Jack F.; Liao, Hongling; Wen, Xinyu; Gerard, Julia; Kim, Jung-Sik; Lopez Guerrero, Jose Antonio; Machado, Isidro; Wai, Daniel H.; Picci, Piero; Triche, Timothy; Horvai, Andrew E.; Miettinen, Markku; Wei, Jun S.; Catchpool, Daniel; Llombart-Bosch, Antonio; Waldman, Todd; Khan, Javed

2014-01-01

75

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

PubMed Central

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

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

76

Characterization of the PRMT Gene Family in Rice Reveals Conservation of Arginine Methylation  

PubMed Central

Post-translational methylation of arginine residues profoundly affects the structure and functions of protein and, hence, implicated in a myriad of essential cellular processes such as signal transduction, mRNA splicing and transcriptional regulation. Protein arginine methyltransferases (PRMTs), the enzymes catalyzing arginine methylation have been extensively studied in animals, yeast and, to some extent, in model plant Arabidopsis thaliana. Eight genes coding for the PRMTs were identified in Oryza sativa, previously. Here, we report that these genes show distinct expression patterns in various parts of the plant. In vivo targeting experiment demonstrated that GFP-tagged OsPRMT1, OsPRMT5 and OsPRMT10 were localized to both the cytoplasm and nucleus, whereas OsPRMT6a and OsPRMT6b were predominantly localized to the nucleus. OsPRMT1, OsPRMT4, OsPRMT5, OsPRMT6a, OsPRMT6b and OsPRMT10 exhibited in vitro arginine methyltransferase activity against myelin basic protein, glycine-arginine-rich domain of fibrillarin and calf thymus core histones. Furthermore, they depicted specificities for the arginine residues in histones H3 and H4 and were classified into type I and Type II PRMTs, based on the formation of type of dimethylarginine in the substrate proteins. The two homologs of OsPRMT6 showed direct interaction in vitro and further titrating different amounts of these proteins in the methyltransferase assay revealed that OsPRMT6a inhibits the methyltransferase activity of OsPRMT6b, probably, by the formation of heterodimer. The identification and characterization of PRMTs in rice suggests the conservation of arginine methylation in monocots and hold promise for gaining further insight into regulation of plant development. PMID:21853042

Cao, Xiaofeng

2011-01-01

77

Extensive Expansion of A1 Family Aspartic Proteinases in Fungi Revealed by Evolutionary Analyses of 107 Complete Eukaryotic Proteomes  

PubMed Central

The A1 family of eukaryotic aspartic proteinases (APs) forms one of the 16 AP families. Although one of the best characterized families, the recent increase in genome sequence data has revealed many fungal AP homologs with novel sequence characteristics. This study was performed to explore the fungal AP sequence space and to obtain an in-depth understanding of fungal AP evolution. Using a comprehensive phylogeny of approximately 700 AP sequences from the complete proteomes of 87 fungi and 20 nonfungal eukaryotes, 11 major clades of APs were defined of which clade I largely corresponds to the A1A subfamily of pepsin-archetype APs. Clade II largely corresponds to the A1B subfamily of nepenthesin-archetype APs. Remarkably, the nine other clades contain only fungal APs, thus indicating that fungal APs have undergone a large sequence diversification. The topology of the tree indicates that fungal APs have been subject to both “birth and death” evolution and “functional redundancy and diversification.” This is substantiated by coclustering of certain functional sequence characteristics. A meta-analysis toward the identification of Cluster Determining Positions (CDPs) was performed in order to investigate the structural and biochemical basis for diversification. Seven CDPs contribute to the secondary structure of the enzyme. Three other CDPs are found in the vicinity of the substrate binding cleft. Tree topology, the large sequence variation among fungal APs, and the apparent functional diversification suggest that an amendment to update the current A1 AP classification based on a comprehensive phylogenetic clustering might contribute to refinement of the classification in the MEROPS peptidase database. PMID:24869856

Revuelta, María V.; van Kan, Jan A.L.; Kay, John; ten Have, Arjen

2014-01-01

78

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

PubMed Central

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. These findings increase our understanding of the intricate symbiotic relationship between the bacterium and the trypanosomatid host and provide clues to better understand eukaryotic cell evolution. PMID:23560078

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

79

Independent HHsearch, Needleman--Wunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families.  

PubMed

Several families of G protein-coupled receptors (GPCRs) show no significant sequence similarities to each other, and it has been debated which of them share a common origin. We developed and performed integrated and independent HHsearch, Needleman--Wunsch-based and motif analyses on more than 6,600 unique GPCRs from 12 species. Moreover, we mined the evolutionary important Trichoplax adhaerens, Nematostella vectensis, Thalassiosira pseudonana, and Strongylocentrotus purpuratus genomes, revealing remarkably rich vertebrate-like GPCR repertoires already in the early Metazoan species. We found strong evidence that the Adhesion and Frizzled families are children to the cyclic AMP (cAMP) family with HHsearch homology probabilities of 99.8% and 99.4%, respectively, also supported by the Needleman--Wunsch analysis and several motifs. We also found that the large Rhodopsin family is likely a child of the cAMP family with an HHsearch homology probability of 99.4% and conserved motifs. Therefore, we suggest that the Adhesion and Frizzled families originated from the cAMP family in an event close to that which gave rise to the Rhodopsin family. We also found convincing evidence that the Rhodopsin family is parent to the important sensory families; Taste 2 and Vomeronasal type 1 as well as the Nematode chemoreceptor families. The insect odorant, gustatory, and Trehalose receptors, frequently referred to as GPCRs, form a separate cluster without relationship to the other families, and we propose, based on these and others' results, that these families are ligand-gated ion channels rather than GPCRs. Overall, we suggest common descent of at least 97% of the GPCRs sequences found in humans. PMID:21402729

Nordström, Karl J V; Sällman Almén, Markus; Edstam, Monika M; Fredriksson, Robert; Schiöth, Helgi B

2011-09-01

80

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

SciTech Connect

In spite of a rapid growth in the number of sequenced bacteria and significant progress in the annotation of their genomes, current computational technologies are limited in their capability to associate the genotype of a sequenced bacterial organism with its phenotypic traits. We evaluated two novel, complimentary approaches that can facilitate this task. They are based on correlation between the numbers of the trait-specific protein families or Pfam domains and a quantitative characteristic of the phenotypic trait among different bacterial species. Our first, a top-down approach, involves quantification and comparison of a higher-level characteristic, a bacterial phenotype, to reveal genomic characteristics and specific genes related to the phenotype. The second, a bottom-up approach, predicts phenotypes by quantification of molecular functions in the genomes of closely related bacterial species and by following pair-wise correlation of the molecular functions enrichments and their network clustering. The approach is implemented using network analysis tools. The approaches were validated by a comparison of 19 sequenced Shewanella species. Using the first approach, we were able to identify specific domains and gene clusters associated with cold tolerance of these mesophilic species and to predict some novel cellular mechanisms underlying the phenotype. We find that in three tested species both cold and salt tolerance relate to presence in their genome of a specific Na+/H+ antiporter. By using the second approach we identified genomic clusters predicting several environmentally relevant phenotypes in the newly sequenced Shewanella species including degradation of aromatic compounds by an aerobic hybrid pathway, utilization of ethanolamine, and arsenic and copper resistance. Results of the study confirm validity of the approaches and their utility for (i) computational predictions of phenotypic traits in the sequenced organisms, (ii) revealing genomic determinants of known complex phenotypes, (iii) orthologs prediction, and for (iv) discovery of function of unknown domains and hypothetical proteins.

Karpinets, Tatiana V [ORNL; Obraztsova, Anna Y [University of Southern California, Los Angeles; Wang, Yanbin [ORNL; Schmoyer, Denise D [ORNL; Kora, Guruprasad H [ORNL; Kothe, T Brett [ORNL; Serres, Margrethe H. [Woods Hole Oceanographic Institution (WHOI), Woods Hole, MA; Romine, Margaret F [ORNL; Fredrickson, Jim K [Pacific Northwest National Laboratory (PNNL); Nealson, Kenneth H. [University of Southern California; Uberbacher, Edward C [ORNL; Land, Miriam L [ORNL

2009-01-01

81

A DinB variant reveals diverse physiological consequences of incomplete extension by a Y-family DNA polymerase  

E-print Network

The only Y-family DNA polymerase conserved among all domains of life, DinB and its mammalian ortholog pol ?, catalyzes proficient bypass of damaged DNA in translesion synthesis (TLS). Y-family DNA polymerases, including ...

Jarosz, Daniel F.

82

A DinB variant reveals diverse physiological consequences of incomplete TLS extension by a Y-family DNA polymerase  

E-print Network

The only Y-family DNA polymerase conserved among all domains of life, DinB and its mammalian ortholog pol ?, catalyzes proficient bypass of damaged DNA in translesion synthesis (TLS). Y-family DNA polymerases, including ...

Walker, Graham C.

83

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

PubMed Central

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

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

2008-01-01

84

The alternative oxidase family of Vitis vinifera reveals an attractive model to study the importance of genomic design.  

PubMed

'Genomic design' refers to the structural organization of gene sequences. Recently, the role of intron sequences for gene regulation is being better understood. Further, introns possess high rates of polymorphism that are considered as the major source for speciation. In molecular breeding, the length of gene-specific introns is recognized as a tool to discriminate genotypes with diverse traits of agronomic interest. 'Economy selection' and 'time-economy selection' have been proposed as models for explaining why highly expressed genes typically contain small introns. However, in contrast to these theories, plant-specific selection reveals that highly expressed genes contain introns that are large. In the presented research, 'wet'Aox gene identification from grapevine is advanced by a bioinformatics approach to study the species-specific organization of Aox gene structures in relation to available expressed sequence tag (EST) data. Two Aox1 and one Aox2 gene sequences have been identified in Vitis vinifera using grapevine cultivars from Portugal and Germany. Searching the complete genome sequence data of two grapevine cultivars confirmed that V. vinifera alternative oxidase (Aox) is encoded by a small multigene family composed of Aox1a, Aox1b and Aox2. An analysis of EST distribution revealed high expression of the VvAox2 gene. A relationship between the atypical long primary transcript of VvAox2 (in comparison to other plant Aox genes) and its expression level is suggested. V. vinifera Aox genes contain four exons interrupted by three introns except for Aox1a which contains an additional intron in the 3'-UTR. The lengths of primary Aox transcripts were estimated for each gene in two V. vinifera varieties: PN40024 and Pinot Noir. In both varieties, Aox1a and Aox1b contained small introns that corresponded to primary transcript lengths ranging from 1501 to 1810 bp. The Aox2 of PN40024 (12 329 bp) was longer than that from Pinot Noir (7279 bp) because of selection against a transposable-element insertion that is 5028 bp in size. An EST database basic local alignment search tool (BLAST) search of GenBank revealed the following ESTs percentages for each gene: Aox1a (26.2%), Aox1b (11.9%) and Aox2 (61.9%). Aox1a was expressed in fruits and roots, Aox1b expression was confined to flowers and Aox2 was ubiquitously expressed. These data for V. vinifera show that atypically long Aox intron lengths are related to high levels of gene expression. Furthermore, it is shown for the first time that two grapevine cultivars can be distinguished by Aox intron length polymorphism. PMID:19682279

Costa, José Hélio; de Melo, Dirce Fernandes; Gouveia, Zélia; Cardoso, Hélia Guerra; Peixe, Augusto; Arnholdt-Schmitt, Birgit

2009-12-01

85

Multilocus phylogeny of the avian family Alaudidae (larks) reveals complex morphological evolution, non-monophyletic genera and hidden species diversity.  

PubMed

The Alaudidae (larks) is a large family of songbirds in the superfamily Sylvioidea. Larks are cosmopolitan, although species-level diversity is by far largest in Africa, followed by Eurasia, whereas Australasia and the New World have only one species each. The present study is the first comprehensive phylogeny of the Alaudidae. It includes 83.5% of all species and representatives from all recognised genera, and was based on two mitochondrial and three nuclear loci (in total 6.4 kbp, although not all loci were available for all species). In addition, a larger sample, comprising several subspecies of some polytypic species was analysed for one of the mitochondrial loci. There was generally good agreement in trees inferred from different loci, although some strongly supported incongruences were noted. The tree based on the concatenated multilocus data was overall well resolved and well supported by the data. We stress the importance of performing single gene as well as combined data analyses, as the latter may obscure significant incongruence behind strong nodal support values. The multilocus tree revealed many unpredicted relationships, including some non-monophyletic genera (Calandrella, Mirafra, Melanocorypha, Spizocorys). The tree based on the extended mitochondrial data set revealed several unexpected deep divergences between taxa presently treated as conspecific (e.g. within Ammomanes cinctura, Ammomanes deserti, Calandrella brachydactyla, Eremophila alpestris), as well as some shallow splits between currently recognised species (e.g. Certhilauda brevirostris-C. semitorquata-C. curvirostris; Calendulauda barlowi-C. erythrochlamys; Mirafra cantillans-M. javanica). Based on our results, we propose a revised generic classification, and comment on some species limits. We also comment on the extraordinary morphological adaptability in larks, which has resulted in numerous examples of parallel evolution (e.g. in Melanocorypha mongolica and Alauda leucoptera [both usually placed in Melanocorypha]; Ammomanopsis grayi and Ammomanes cinctura/deserti [former traditionally placed in Ammomanes]; Chersophilus duponti and Certhilauda spp.; Eremopterix hova [usually placed in Mirafra] and several Mirafra spp.), as well as both highly conserved plumages (e.g. within Mirafra) and strongly divergent lineages (e.g. Eremopterix hova vs. other Eremopterix spp.; Calandrella cinerea complex vs. Eremophila spp.; Eremalauda dunni vs. Chersophilus duponti; Melanocorypha mongolica and male M. yeltoniensis vs. other Melanocorypha spp. and female M. yeltoniensis). Sexual plumage dimorphism has evolved multiple times. Few groups of birds show the same level of disagreement between taxonomy based on morphology and phylogenetic relationships as inferred from DNA sequences. PMID:23792153

Alström, Per; Barnes, Keith N; Olsson, Urban; Barker, F Keith; Bloomer, Paulette; Khan, Aleem Ahmed; Qureshi, Masood Ahmed; Guillaumet, Alban; Crochet, Pierre-André; Ryan, Peter G

2013-12-01

86

Whole Exome Sequencing Reveals Overlap Between Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis and Familial Hemophagocytic Lymphohistiocytosis  

PubMed Central

Objective Macrophage activation syndrome (MAS), a life-threatening complication of systemic Juvenile Idiopathic Arthritis (SJIA), resembles Familial Hemophagocytic Lymphohistiocytosis (FHLH), a constellation of autosomal recessive immune disorders resulting from deficiency in cytolytic pathway proteins. We hypothesized that MAS predisposition in SJIA could be attributed to rare gene sequence variants affecting the cytotolytic pathway. Methods Whole exome sequencing (WES) was used in 14 SJIA/MAS patients and their parents to identify protein altering SNPs/indels in the known HLH-associated genes. To discover new candidate genes, the entire WES data were filtered to identify protein altering, rare recessive homozygous, compound heterozygous, and de novo variants with the potential to affect the cytolytic pathway. Results Heterozygous protein-altering rare variants in the known genes (LYST, MUNC13-4, and STXBP2) were found in 5 of 14 SJIA/MAS patients (35.7%). This was in contrast to only 4 variants in 4 of 29 (13,7%) SJIA patients without MAS. Homozygosity and compound heterozygosity analysis applied to the entire WES data in SJIAMAS, revealed 3 recessive pairs in 3 genes, and 76 compound heterozygotes in 75 genes. We also identified 22 heterozygous rare protein altering variants that occurred in at least two patients. Many of the identified genes encode proteins with a role in actin and microtubule reorganization and vesicle-mediated transport. “Cellular assembly and organization” was the top cellular function category based on Ingenuity Pathways Analysis (p<3.10E-05). Conclusion WES performed in SJIA/MAS patients identified rare protein altering variants in the known HLH associated genes as well as new candidate genes. PMID:25047945

Kaufman, Kenneth M.; Linghu, Bolan; Szustakowski, Joseph D.; Husami, Ammar; Yang, Fan; Zhang, Kejian; Filipovich, Alexandra; Fall, Ndate; Harley, John B.; Nirmala, N.R.; Grom, Alexei A.

2015-01-01

87

Diverse retrotransposon families and an AT-rich satellite DNA revealed in giant genomes of Fritillaria lilies  

PubMed Central

Background and Aims The genus Fritillaria (Liliaceae) comprises species with extremely large genomes (1C = 30 000–127 000 Mb) and a bicontinental distribution. Most North American species (subgenus Liliorhiza) differ from Eurasian Fritillaria species by their distinct phylogenetic position and increased amounts of heterochromatin. This study examined the contribution of major repetitive elements to the genome obesity found in Fritillaria and identified repeats contributing to the heterochromatin arrays in Liliorhiza species. Methods Two Fritillaria species of similar genome size were selected for detailed analysis, one from each phylogeographical clade: F. affinis (1C = 45·6 pg, North America) and F. imperialis (1C = 43·0 pg, Eurasia). Fosmid libraries were constructed from their genomic DNAs and used for identification, sequence characterization, quantification and chromosome localization of clones containing highly repeated sequences. Key Results and Conclusions Repeats corresponding to 6·7 and 4·7 % of the F. affinis and F. imperialis genome, respectively, were identified. Chromoviruses and the Tat lineage of Ty3/gypsy group long terminal repeat retrotransposons were identified as the predominant components of the highly repeated fractions in the F. affinis and F. imperialis genomes, respectively. In addition, a heterogeneous, extremely AT-rich satellite repeat was isolated from F. affinis. The FriSAT1 repeat localized in heterochromatic bands makes up approx. 26 % of the F. affinis genome and substantial genomic fractions in several other Liliorhiza species. However, no evidence of a relationship between heterochromatin content and genome size variation was observed. Also, this study was unable to reveal any predominant repeats which tracked the increasing/decreasing trends of genome size evolution in Fritillaria. Instead, the giant Fritillaria genomes seem to be composed of many diversified families of transposable elements. We hypothesize that the genome obesity may be partly determined by the failure of removal mechanisms to counterbalance effectively the retrotransposon amplification. PMID:21156758

Ambrožová, Kate?ina; Mandáková, Terezie; Bureš, Petr; Neumann, Pavel; Leitch, Ilia J.; Koblížková, Andrea; Macas, Ji?í; Lysak, Martin A.

2011-01-01

88

SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly  

Microsoft Academic Search

Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family\\u000a sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of\\u000a ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based\\u000a homozygosity mapping and high-resolution microarray-based

Masoud Garshasbi; Mohammad Mahdi Motazacker; Kimia Kahrizi; Farkhondeh Behjati; Seyedeh Sedigheh Abedini; Sahar Esmaeeli Nieh; Saghar Ghasemi Firouzabadi; Christian Becker; Franz Rüschendorf; Peter Nürnberg; Andreas Tzschach; Reza Vazifehmand; Fikret Erdogan; Reinhard Ullmann; Steffen Lenzner; Andreas W. Kuss; H. Hilger Ropers; Hossein Najmabadi

2006-01-01

89

Family Secrets  

Microsoft Academic Search

The purpose of this article is to provide an overview of the literature that reveals extensive classifications of the family secrets. The review includes definitions, comparisons of family secrecy to family privacy, types of family secrets, reasons why families avoid exposing certain activities, and factors contributing to the maintenance of a secret. The disclosing of hidden information is discussed with

NAIMA BROWN-SMITH

1998-01-01

90

A comparative genome analysis of PME and PMEI families reveals the evolution of pectin metabolism in plant cell walls.  

PubMed

Pectins are fundamental polysaccharides in the plant primary cell wall. Pectins are synthesized and secreted to cell walls as highly methyl-esterified polymers and then demethyl-esterified by pectin methylesterases (PMEs), which are spatially regulated by pectin methylesterase inhibitors (PMEIs). Although PME and PMEI genes are pivotal in plant cell wall formation, few studies have focused on the evolutionary patterns of the PME and PMEI gene families. In this study, the gene origin, evolution, and expression diversity of these two families were systematically analyzed using 11 representative species, including algae, bryophytes, lycophytes and flowering land plants. The results show that 1) for the two subfamilies (PME and proPME) of PME, the origin of the PME subfamily is consistent with the appearance of pectins in early charophyte cell walls, 2) Whole genome duplication (WGD) and tandem duplication contribute to the expansion of proPME and PMEI families in land plants, 3) Evidence of selection pressure shows that the proPME and PMEI families have rapidly evolved, particularly the PMEI family in vascular plants, and 4) Comparative expression profile analysis of the two families indicates that the eudicot Arabidopsis and monocot rice have different expression patterns. In addition, the gene structure and sequence analyses show that the origin of the PMEI domain may be derived from the neofunctionalization of the pro domain after WGD. This study will advance the evolutionary understanding of the PME and PMEI families and plant cell wall development. PMID:23951288

Wang, Maojun; Yuan, Daojun; Gao, Wenhui; Li, Yang; Tan, Jiafu; Zhang, Xianlong

2013-01-01

91

A Comparative Genome Analysis of PME and PMEI Families Reveals the Evolution of Pectin Metabolism in Plant Cell Walls  

PubMed Central

Pectins are fundamental polysaccharides in the plant primary cell wall. Pectins are synthesized and secreted to cell walls as highly methyl-esterified polymers and then demethyl-esterified by pectin methylesterases (PMEs), which are spatially regulated by pectin methylesterase inhibitors (PMEIs). Although PME and PMEI genes are pivotal in plant cell wall formation, few studies have focused on the evolutionary patterns of the PME and PMEI gene families. In this study, the gene origin, evolution, and expression diversity of these two families were systematically analyzed using 11 representative species, including algae, bryophytes, lycophytes and flowering land plants. The results show that 1) for the two subfamilies (PME and proPME) of PME, the origin of the PME subfamily is consistent with the appearance of pectins in early charophyte cell walls, 2) Whole genome duplication (WGD) and tandem duplication contribute to the expansion of proPME and PMEI families in land plants, 3) Evidence of selection pressure shows that the proPME and PMEI families have rapidly evolved, particularly the PMEI family in vascular plants, and 4) Comparative expression profile analysis of the two families indicates that the eudicot Arabidopsis and monocot rice have different expression patterns. In addition, the gene structure and sequence analyses show that the origin of the PMEI domain may be derived from the neofunctionalization of the pro domain after WGD. This study will advance the evolutionary understanding of the PME and PMEI families and plant cell wall development. PMID:23951288

Wang, Maojun; Yuan, Daojun; Gao, Wenhui; Li, Yang; Tan, Jiafu; Zhang, Xianlong

2013-01-01

92

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

PubMed

Abstract 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

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

2014-12-01

93

Comparative and Evolutionary Analysis of the HES/HEY Gene Family Reveal Exon/Intron Loss and Teleost Specific Duplication Events  

PubMed Central

Background HES/HEY genes encode a family of basic helix-loop-helix (bHLH) transcription factors with both bHLH and Orange domain. HES/HEY proteins are direct targets of the Notch signaling pathway and play an essential role in developmental decisions, such as the developments of nervous system, somitogenesis, blood vessel and heart. Despite their important functions, the origin and evolution of this HES/HEY gene family has yet to be elucidated. Methods and Findings In this study, we identified genes of the HES/HEY family in representative species and performed evolutionary analysis to elucidate their origin and evolutionary process. Our results showed that the HES/HEY genes only existed in metazoans and may originate from the common ancestor of metazoans. We identified HES/HEY genes in more than 10 species representing the main lineages. Combining the bHLH and Orange domain sequences, we constructed the phylogenetic trees by different methods (Bayesian, ML, NJ and ME) and classified the HES/HEY gene family into four groups. Our results indicated that this gene family had undergone three expansions, which were along with the origins of Eumetazoa, vertebrate, and teleost. Gene structure analysis revealed that the HES/HEY genes were involved in exon and/or intron loss in different species lineages. Genes of this family were duplicated in bony fishes and doubled than other vertebrates. Furthermore, we studied the teleost-specific duplications in zebrafish and investigated the expression pattern of duplicated genes in different tissues by RT-PCR. Finally, we proposed a model to show the evolution of this gene family with processes of expansion, exon/intron loss, and motif loss. Conclusions Our study revealed the evolution of HES/HEY gene family, the expression and function divergence of duplicated genes, which also provide clues for the research of Notch function in development. This study shows a model of gene family analysis with gene structure evolution and duplication. PMID:22808219

Ma, Zhaowu; Zhou, Yang; Abbood, Nibras Najm; Liu, Jianfeng; Su, Li; Jia, Haibo; Guo, An-Yuan

2012-01-01

94

Evolutionary relationship of the members of the sulphur-rich hordein family revealed by common antigenic determinants  

Microsoft Academic Search

Five monoclonal antibodies raised against an enriched C hordein fraction have been characterized in detail and were found to be specific for the members of the sulphur-rich hordein family. Two antibodies specific for B hordein polypeptides were identified, one of which reacted predominantly with CNBr cleavage class III polypeptides. ?1 hordein was recognized by two antibodies, of which one also

K. B. Rechinger; O. V. Bougri; V. Cameron-Mills

1993-01-01

95

Comparative Genomics and Reverse Genetics Analysis Reveal Indispensable Functions of the Serine Acetyltransferase Gene Family in Arabidopsis  

Microsoft Academic Search

Ser acetyltransferase (SERAT), which catalyzes O-acetyl-Ser (OAS) formation, plays a key role in sulfur assimilation and Cys synthesis. Despite several studies on SERATs from various plant species, the in vivo function of multiple SERAT genes in plant cells remains unaddressed. Comparative genomics studies with the five genes of the SERAT gene family in Arabidopsis thaliana indicated that all three Arabidopsis

Mutsumi Watanabe; Keiichi Mochida; Tomohiko Kato; Satoshi Tabata; Naoko Yoshimoto; Masaaki Noji; K. Saito

2008-01-01

96

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

PubMed

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

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

2014-08-01

97

The Barley Genome Sequence Assembly Reveals Three Additional Members of the CslF (1,3;1,4)-?-Glucan Synthase Gene Family  

PubMed Central

An important component of barley cell walls, particularly in the endosperm, is (1,3;1,4)-?- glucan, a polymer that has proven health benefits in humans and that influences processability in the brewing industry. Genes of the cellulose synthase-like (Csl) F gene family have been shown to be involved in (1,3;1,4)-?-glucan synthesis but many aspects of the biosynthesis are still unclear. Examination of the sequence assembly of the barley genome has revealed the presence of an additional three HvCslF genes (HvCslF11, HvCslF12 and HvCslF13) which may be involved in (1,3;1,4)-?-glucan synthesis. Transcripts of HvCslF11 and HvCslF12 mRNA were found in roots and young leaves, respectively. Transient expression of these genes in Nicotiana benthamiana resulted in phenotypic changes in the infiltrated leaves, although no authentic (1,3;1,4)-?-glucan was detected. Comparisons of the CslF gene families in cereals revealed evidence of intergenic recombination, gene duplications and translocation events. This significant divergence within the gene family might be related to multiple functions of (1,3;1,4)-?-glucans in the Poaceae. Emerging genomic and global expression data for barley and other cereals is a powerful resource for characterising the evolution and dynamics of complete gene families. In the case of the CslF gene family, the results will contribute to a more thorough understanding of carbohydrate metabolism in grass cell walls. PMID:24595438

Schreiber, Miriam; Wright, Frank; MacKenzie, Katrin; Hedley, Pete E.; Schwerdt, Julian G.; Little, Alan; Burton, Rachel A.; Fincher, Geoffrey B.; Marshall, David; Waugh, Robbie; Halpin, Claire

2014-01-01

98

Family Secrets and Family Environment  

Microsoft Academic Search

This study explored whether family secrecy might be a potential mediator of later adult psychological functioning in the offspring of the family. Results revealed that family secrecy was related to psychological well-being in adulthood. The number of potentially secretive events, as well as the negativity of the family environment were strongly associated with poorer psychological functioning.

Marianne F. Jahn

1995-01-01

99

Analysis of plant LTR-retrotransposons at the fine-scale family level reveals individual molecular patterns  

PubMed Central

Background Sugarcane is an important crop worldwide for sugar production and increasingly, as a renewable energy source. Modern cultivars have polyploid, large complex genomes, with highly unequal contributions from ancestral genomes. Long Terminal Repeat retrotransposons (LTR-RTs) are the single largest components of most plant genomes and can substantially impact the genome in many ways. It is therefore crucial to understand their contribution to the genome and transcriptome, however a detailed study of LTR-RTs in sugarcane has not been previously carried out. Results Sixty complete LTR-RT elements were classified into 35 families within four Copia and three Gypsy lineages. Structurally, within lineages elements were similar, between lineages there were large size differences. FISH analysis resulted in the expected pattern of Gypsy/heterochromatin, Copia/euchromatin, but in two lineages there was localized clustering on some chromosomes. Analysis of related ESTs and RT-PCR showed transcriptional variation between tissues and families. Four distinct patterns were observed in sRNA mapping, the most unusual of which was that of Ale1, with very large numbers of 24nt sRNAs in the coding region. The results presented support the conclusion that distinct small RNA-regulated pathways in sugarcane target the lineages of LTR-RT elements. Conclusions Individual LTR-RT sugarcane families have distinct structures, and transcriptional and regulatory signatures. Our results indicate that in sugarcane individual LTR-RT families have distinct behaviors and can potentially impact the genome in diverse ways. For instance, these transposable elements may affect nearby genes by generating a diverse set of small RNA's that trigger gene silencing mechanisms. There is also some evidence that ancestral genomes contribute significantly different element numbers from particular LTR-RT lineages to the modern sugarcane cultivar genome. PMID:22507400

2012-01-01

100

Next-Generation Sequencing of a 40 Mb Linkage Interval Reveals TSPAN12 Mutations in Patients with Familial Exudative Vitreoretinopathy  

Microsoft Academic Search

Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous retinal disorder characterized by abnormal vascularisation of the peripheral retina, often accompanied by retinal detachment. To date, mutations in three genes (FZD4, LRP5, and NDP) have been shown to be causative for FEVR. In two large Dutch pedigrees segregating autosomal-dominant FEVR, genome-wide SNP analysis identified an FEVR locus of approximately 40 Mb

Konstantinos Nikopoulos; Christian Gilissen; Alexander Hoischen; C. Erik van Nouhuys; F. Nienke Boonstra; Ellen A. W. Blokland; Peer Arts; Nienke Wieskamp; Tim M. Strom; Carmen Ayuso; Mauk A. D. Tilanus; Sanne Bouwhuis; Arijit Mukhopadhyay; Hans Scheffer; Lies H. Hoefsloot; Joris A. Veltman; Frans P. M. Cremers; Rob W. J. Collin

2010-01-01

101

ST1710DNA complex crystal structure reveals the DNA binding mechanism of the MarR family of regulators  

Microsoft Academic Search

ST1710, a member of the multiple antibiotic resis- tance regulator (MarR) family of regulatory proteins in bacteria and archaea, plays important roles in development of antibiotic resistance, a global health problem. Here, we present the crystal struc- ture of ST1710 from Sulfolobus tokodaii strain 7 complexed with salicylate, a well-known inhibitor of MarR proteins and the ST1710 complex with its

Thirumananseri Kumarevel; Tomoyuki Tanaka; Takashi Umehara; Shigeyuki Yokoyama

2009-01-01

102

Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family  

PubMed Central

Many of the genes that comprise the vertebrate adaptive immune system are conserved across wide evolutionary time scales. Most notably, homologs of the mammalian MHC gene family have been found in virtually all jawed vertebrates, including sharks, bony fishes, reptiles, and birds. The CD1 family of antigen-presenting molecules are related to the MHC class I family but have evolved to bind and present lipid antigens to T cells. Here, we describe two highly divergent nonclassical MHC class I genes found in the chicken (Gallus gallus) that have sequence homology to the mammalian CD1 family of proteins. One of the chicken CD1 genes expresses a full-length transcript, whereas the other has multiple splice variants. Both Southern blot and single nucleotide polymorphism analysis indicates that chicken CD1 is relatively nonpolymorphic. Moreover, cross-hybridizing bands are present in other bird species, suggesting broad conservation in the avian class. Northern analysis of chicken tissue shows a high level of CD1 expression in the bursa and spleen. In addition, molecular modeling predicts that the potential antigen-binding pocket is probably hydrophobic, a universal characteristic of CD1 molecules. Genomic analysis indicates that the CD1 genes are located on chicken chromosome 16 and maps to within 200 kb of the chicken MHC B locus, suggesting that CD1 genes diverged from classical MHC genes while still linked to the major histocompatibility complex locus. The existence of CD1 genes in an avian species suggests that the origin of CD1 extends deep into the evolutionary history of terrestrial vertebrates. PMID:15939884

Miller, Marcia M.; Wang, Carren; Parisini, Emilio; Coletta, Ricardo D.; Goto, Ronald M.; Lee, Stella Y.; Barral, Duarte C.; Townes, Maria; Roura-Mir, Carme; Ford, Heide L.; Brenner, Michael B.; Dascher, Christopher C.

2005-01-01

103

Molecular heterogeneity of familial myeloproliferative neoplasms revealed by analysis of the commonly acquired JAK2, CALR and MPL mutations.  

PubMed

The myeloproliferative neoplasms (MPN) are clonal, hematological malignancies that include polycythemia vera, essential thrombocythemia and primary myelofibrosis. While most cases of MPN are sporadic in nature, a familial pattern of inheritance is well recognised. The phenotype and status of the commonly acquired JAK2 V617F, CALR exon 9 and MPL W515L/K mutations in affected individuals from a consecutive series of ten familial MPN (FMPN) kindred are described. Affected individuals display the classical MPN phenotypes together with one kindred identified suggestive of hereditary thrombocytosis. In affected patients the JAK2 V617F mutation is the most commonly acquired followed by CALR exon nine mutations with no MPL W515L/K mutations detected. The JAK2 V617F and CALR exon 9 mutations appear to occur at approximately the same frequency in FMPN as in the sporadic forms of these diseases. The familial nature of MPN may often be overlooked and accordingly more common than previously considered. Characterisation of these FMPN kindred may allow for the investigation of molecular events that contribute to this inheritance. PMID:25103330

Langabeer, Stephen E; Haslam, Karl; Linders, Jennifer; Percy, Melanie J; Conneally, Eibhlin; Hayat, Amjad; Hennessy, Brian; Leahy, Maeve; Murphy, Karen; Murray, Margaret; Ni Ainle, Fionnuala; Thornton, Patrick; Sargent, Jeremy

2014-12-01

104

Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family  

PubMed Central

The conservation of in vitro DNA-binding properties within families of transcription factors presents a challenge for achieving in vivo specificity. To uncover the mechanisms regulating specificity within the ETS gene family, we have used chromatin immunoprecipitation coupled with genome-wide promoter microarrays to query the occupancy of three ETS proteins in a human T-cell line. Unexpectedly, redundant occupancy was frequently detected, while specific occupancy was less likely. Redundant binding correlated with housekeeping classes of genes, whereas specific binding examples represented more specialized genes. Bioinformatics approaches demonstrated that redundant binding correlated with consensus ETS-binding sequences near transcription start sites. In contrast, specific binding sites diverged dramatically from the consensus and were found further from transcription start sites. One route to specificity was found—a highly divergent binding site that facilitates ETS1 and RUNX1 cooperative DNA binding. The specific and redundant DNA-binding modes suggest two distinct roles for members of the ETS transcription factor family. PMID:17652178

Hollenhorst, Peter C.; Shah, Atul A.; Hopkins, Christopher; Graves, Barbara J.

2007-01-01

105

TcaR–ssDNA complex crystal structure reveals new DNA binding mechanism of the MarR family proteins  

PubMed Central

The teicoplanin-associated locus regulator (TcaR) regulates gene expression of proteins on the intercellular adhesion (ica) locus involved in staphylococci poly-N-acetylglucosamine biosynthesis. The absence of TcaR increases poly-N-acetylglucosamine production and promotes biofilm formation. Until recently, the mechanism of multiple antibiotic resistance regulator family protein members, such as TcaR, was restricted to binding double-stranded DNA. However, we recently found that TcaR strongly interacts with single-stranded DNA, which is a new role for this family of proteins. In this study, we report Staphylococcus epidermidis TcaR–single-stranded DNA complex structures. Our model suggests that TcaR and single-stranded DNA form a 61-symmetry polymer composed of TcaR dimers with single-stranded DNA that wraps outside the polymer and 12 nt per TcaR dimer. Single-stranded DNA binding to TcaR involves a large conformational change at the DNA binding lobe. Several point mutations involving the single-stranded DNA binding surface validate interactions between single-stranded DNA and TcaR. Our results extend the novel role of multiple antibiotic resistance regulator family proteins in staphylococci. PMID:24531929

Chang, Yu-Ming; Ho, Chun-Han; Chen, Cammy K.-M.; Maestre-Reyna, Manuel; Chang-Chien, Masatoshi Weiting; Wang, Andrew H.-J.

2014-01-01

106

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

PubMed Central

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

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

2015-01-01

107

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

PubMed Central

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 Ĺ crystal structure of IE1CORE displays an all ?-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 TRIM5? 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 mutational escape. PMID:25412268

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

2014-01-01

108

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

PubMed Central

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

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

109

Structure-guided functional characterization of DUF1460 reveals a highly specific NlpC/P60 amidase family.  

PubMed

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 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 Ĺ resolution shows that AmiA is related to NlpC/P60 ?-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 subsequently were 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 another amidase family. PMID:25465128

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

2014-12-01

110

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

PubMed Central

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

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

2013-01-01

111

Pyrosequencing of the midgut transcriptome of the poplar leaf beetle Chrysomela tremulae reveals new gene families in Coleoptera.  

PubMed

The insect midgut is the primary target site for Bt-derived insecticides and Bt alternatives. However, despite extensive recent study, the precise role and nature of different Bt receptors remains a subject of considerable debate. This problem is fuelled by a lack of understanding of the genes expressed in the insect midgut and their physiological roles. The poplar leaf beetle, Chrysomela tremulae, is an important model for understanding the mode of action of, and resistance to, coleopteran-specific Bt toxins and currently shows the only known naturally occurring case of resistance to Cry3A toxins. Moreover it belongs to the same family as the corn rootworm, Diabrotica virgifera, an economically important beetle pest and target of hybrid corn expressing Cry3 toxins. Pyrosequencing is a fast and efficient way of defining the transcriptome of specific insect tissues such as the larval midgut. Here we use 454 based pyrosequencing to sample the larval midgut transcriptome of C. tremulae. We identify candidate genes of putative Bt receptors including transcripts encoding cadherin-like proteins, aminopeptidase N and alkaline phosphatase. We also describe a wealth of new transcripts predicting rapidly evolving gene families involved in plant tissue digestion, which have no homologs in the genome of the stored product pest the Red Flour beetle, Tribolium castaneum. PMID:19364528

Pauchet, Yannick; Wilkinson, Paul; van Munster, Manuella; Augustin, Sylvie; Pauron, David; ffrench-Constant, Richard H

2009-01-01

112

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

PubMed

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

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

2013-01-01

113

Proteomic Analyses Reveal an Acidic Prime Side Specificity for the Astacin Metalloprotease Family Reflected by Physiological Substrates*  

PubMed Central

Astacins are secreted and membrane-bound metalloproteases with clear associations to many important pathological and physiological processes. Yet with only a few substrates described their biological roles are enigmatic. Moreover, the lack of knowledge of astacin cleavage site specificities hampers assay and drug development. Using PICS (proteomic identification of protease cleavage site specificity) and TAILS (terminal amine isotopic labeling of substrates) degradomics approaches >3000 cleavage sites were proteomically identified for five different astacins. Such broad coverage enables family-wide determination of specificities N- and C-terminal to the scissile peptide bond. Remarkably, meprin ?, meprin ?, and LAST_MAM proteases exhibit a strong preference for aspartate in the peptide (P)1? position because of a conserved positively charged residue in the active cleft subsite (S)1?. This unparalleled specificity has not been found for other families of extracellular proteases. Interestingly, cleavage specificity is also strongly influenced by proline in P2? or P3? leading to a rare example of subsite cooperativity. This specificity characterizes the astacins as unique contributors to extracellular proteolysis that is corroborated by known cleavage sites in procollagen I+III, VEGF (vascular endothelial growth factor)-A, IL (interleukin)-1?, and pro-kallikrein 7. Indeed, cleavage sites in VEGF-A and pro-kallikrein 7 identified by terminal amine isotopic labeling of substrates matched those reported by Edman degradation. Moreover, the novel substrate FGF-19 was validated biochemically and shown to exhibit altered biological activity after meprin processing. PMID:21693781

Becker-Pauly, Christoph; Barré, Olivier; Schilling, Oliver; auf dem Keller, Ulrich; Ohler, Anke; Broder, Claudia; Schütte, André; Kappelhoff, Reinhild; Stöcker, Walter; Overall, Christopher M.

2011-01-01

114

Snf2 family gene distribution in higher plant genomes reveals DRD1 expansion and diversification in the tomato genome.  

PubMed

As part of large protein complexes, Snf2 family ATPases are responsible for energy supply during chromatin remodeling, but the precise mechanism of action of many of these proteins is largely unknown. They influence many processes in plants, such as the response to environmental stress. This analysis is the first comprehensive study of Snf2 family ATPases in plants. We here present a comparative analysis of 1159 candidate plant Snf2 genes in 33 complete and annotated plant genomes, including two green algae. The number of Snf2 ATPases shows considerable variation across plant genomes (17-63 genes). The DRD1, Rad5/16 and Snf2 subfamily members occur most often. Detailed analysis of the plant-specific DRD1 subfamily in related plant genomes shows the occurrence of a complex series of evolutionary events. Notably tomato carries unexpected gene expansions of DRD1 gene members. Most of these genes are expressed in tomato, although at low levels and with distinct tissue or organ specificity. In contrast, the Snf2 subfamily genes tend to be expressed constitutively in tomato. The results underpin and extend the Snf2 subfamily classification, which could help to determine the various functional roles of Snf2 ATPases and to target environmental stress tolerance and yield in future breeding. PMID:24312269

Bargsten, Joachim W; Folta, Adam; Mlynárová, Ludmila; Nap, Jan-Peter

2013-01-01

115

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

PubMed

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:25117179

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

2014-08-12

116

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

PubMed

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

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

2014-08-01

117

[Intermittent rheumatism revealing a familial syndrome. Arthritis--urticarian eruptions--deafness: Muckle-Wells syndrome without kidney amylosis].  

PubMed

At a consultation with a 31-year-old man, motivated by painful episodes of joint pain that had started considerably earlier, a familial disease entity was discovered that included the three clinical signs of the Muckle and Wells syndrome : urticarial eruption, intermittent pain in the limbs originating in the joints, and bilateral deafness of perception. In spite of the absnece of renal amylosis, the similarity of the characteristics of these three elements, as well as the nature of the biochemical disturbances, and the mode of transmission, led the authors to consider these observations in the contest of this syndrome. The joint manifestations being indicative, the signs of this intermittent rheumatism are described, as well as the characteristics of the other disorders. PMID:1083554

Prost, A; Barričre, H; Legent, F; Cottin, S; Wallez, B

1976-03-01

118

Legumin encoding sequences from the redwood family (Taxodiaceae) reveal precursors lacking the conserved Asn-Gly processing site.  

PubMed

We have cloned and sequenced two different cDNAs encoding legumins from Japanese red cedar (Cryptomeria japonica, Taxodiaceae). The derived amino acid sequences show between 34% and 55% identity when compared with legumins from angiosperms and from Pinaceae, respectively. The predicted precursors are unusual in that they contain potential glycosylation signals, and we have found the corresponding beta-polypeptides actually to be glycosylated. As most outstanding feature one of the precursors is lacking the Asn-Gly processing site which has been assumed to be highly conserved in legumin gene evolution. Legumin encoding sequences amplified from genomic DNA suggest that these unusual precursors are widespread if not ubiquitous in the Taxodiaceae family. From previous reports on legumin precursors with divergent processing sites, on the proteases involved in legumin precursor processing and from the results presented here it is concluded that the Asn-Gly processing site has been acquired rather than conserved during legumin gene evolution. PMID:8612788

Wind, C; Häger, K P

1996-03-25

119

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

PubMed Central

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

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

2012-01-01

120

A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs  

PubMed Central

Background Mounting evidence suggests a major role for epigenetic feedback in Plasmodium falciparum transcriptional regulation. Long non-coding RNAs (lncRNAs) have recently emerged as a new paradigm in epigenetic remodeling. We therefore set out to investigate putative roles for lncRNAs in P. falciparum transcriptional regulation. Results We used a high-resolution DNA tiling microarray to survey transcriptional activity across 22.6% of the P. falciparum strain 3D7 genome. We identified 872 protein-coding genes and 60 putative P. falciparum lncRNAs under developmental regulation during the parasite's pathogenic human blood stage. Further characterization of lncRNA candidates led to the discovery of an intriguing family of lncRNA telomere-associated repetitive element transcripts, termed lncRNA-TARE. We have quantified lncRNA-TARE expression at 15 distinct chromosome ends and mapped putative transcriptional start and termination sites of lncRNA-TARE loci. Remarkably, we observed coordinated and stage-specific expression of lncRNA-TARE on all chromosome ends tested, and two dominant transcripts of approximately 1.5 kb and 3.1 kb transcribed towards the telomere. Conclusions We have characterized a family of 22 telomere-associated lncRNAs in P. falciparum. Homologous lncRNA-TARE loci are coordinately expressed after parasite DNA replication, and are poised to play an important role in P. falciparum telomere maintenance, virulence gene regulation, and potentially other processes of parasite chromosome end biology. Further study of lncRNA-TARE and other promising lncRNA candidates may provide mechanistic insight into P. falciparum transcriptional regulation. PMID:21689454

2011-01-01

121

Mycobacterial Phylogenomics: An Enhanced Method for Gene Turnover Analysis Reveals Uneven Levels of Gene Gain and Loss among Species and Gene Families  

PubMed Central

Species of the genus Mycobacterium differ in several features, from geographic ranges, and degree of pathogenicity, to ecological and host preferences. The recent availability of several fully sequenced genomes for a number of these species enabled the comparative study of the genetic determinants of this wide lifestyle diversity. Here, we applied two complementary phylogenetic-based approaches using information from 19 Mycobacterium genomes to obtain a more comprehensive view of the evolution of this genus. First, we inferred the phylogenetic relationships using two new approaches, one based on a Mycobacterium-specific amino acid substitution matrix and the other on a gene content dissimilarity matrix. Then, we utilized our recently developed gain-and-death stochastic models to study gene turnover dynamics in this genus in a maximum-likelihood framework. We uncovered a scenario that differs markedly from traditional 16S rRNA data and improves upon recent phylogenomic approaches. We also found that the rates of gene gain and death are high and unevenly distributed both across species and across gene families, further supporting the utility of the new models of rate heterogeneity applied in a phylogenetic context. Finally, the functional annotation of the most expanded or contracted gene families revealed that the transposable elements and the fatty acid metabolism-related gene families are the most important drivers of gene content evolution in Mycobacterium. PMID:24904011

Librado, Pablo; Vieira, Filipe G.; Sánchez-Gracia, Alejandro; Kolokotronis, Sergios-Orestis; Rozas, Julio

2014-01-01

122

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

PubMed

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

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

2015-03-01

123

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

PubMed

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

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

124

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

PubMed Central

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 ?/? 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

2014-01-01

125

Conformational Dynamics of a Y-Family DNA Polymerase during Substrate Binding and Catalysis As Revealed by Interdomain Förster Resonance Energy Transfer  

PubMed Central

Numerous kinetic, structural, and theoretical studies have established that DNA polymerases adjust their domain structures to enclose nucleotides in their active sites and then rearrange critical active site residues and substrates for catalysis, with the latter conformational change acting to kinetically limit the correct nucleotide incorporation rate. Additionally, structural studies have revealed a large conformational change between the apoprotein and the DNA–protein binary state for Y-family DNA polymerases. In previous studies [Xu, C., Maxwell, B. A., Brown, J. A., Zhang, L., and Suo, Z. (2009) PLoS Biol.7, e1000225], a real-time Förster resonance energy transfer (FRET) method was developed to monitor the global conformational transitions of DNA polymerase IV from Sulfolobus solfataricus (Dpo4), a prototype Y-family enzyme, during nucleotide binding and incorporation by measuring changes in distance between locations on the enzyme and the DNA substrate. To elucidate further details of the conformational transitions of Dpo4 during substrate binding and catalysis, in this study, the real-time FRET technique was used to monitor changes in distance between various pairs of locations in the protein itself. In addition to providing new insight into the conformational changes as revealed in previous studies, the results here show that the previously described conformational change between the apo and DNA-bound states of Dpo4 occurs in a mechanistic step distinct from initial formation or dissociation of the binary complex of Dpo4 and DNA. PMID:24568554

2015-01-01

126

Structure of the cadherin-related neuronal receptor/protocadherin-alpha first extracellular cadherin domain reveals diversity across cadherin families.  

PubMed

The recent explosion in genome sequencing has revealed the great diversity of the cadherin superfamily. Within the superfamily, protocadherins, which are expressed mainly in the nervous system, constitute the largest subgroup. Nevertheless, the structures of only the classical cadherins are known. Thus, to broaden our understanding of the adhesion repertoire of the cadherin superfamily, we determined the structure of the N-terminal first extracellular cadherin domain of the cadherin-related neuronal receptor/protocadherin-alpha4. The hydrophobic pocket essential for homophilic adhesiveness in the classical cadherins was not found, and the functional significance of this structural domain was supported by exchanging the first extracellular cadherin domains of protocadherin and classical cadherin. Moreover, potentially crucial variations were observed mainly in the loop regions. These included the protocadherin-specific disulfide-bonded Cys-X(5)-Cys motif, which showed Ca(2+)-induced chemical shifts, and the RGD motif, which has been suggested to be involved in heterophilic cell adhesion via the active form of beta1 integrin. Our findings reveal that the adhesion repertoire of the cadherin superfamily is far more divergent than would be predicted by studying the classical cadherins alone. PMID:16916795

Morishita, Hirofumi; Umitsu, Masataka; Murata, Yoji; Shibata, Naoki; Udaka, Keiko; Higuchi, Yoshiki; Akutsu, Hideo; Yamaguchi, Tohru; Yagi, Takeshi; Ikegami, Takahisa

2006-11-01

127

Dynamics of PLC? and Src Family Kinase 1 Interactions during Nuclear Envelope Formation Revealed by FRET-FLIM  

PubMed Central

The nuclear envelope (NE) breaks down and reforms during each mitotic cycle. A similar process happens to the sperm NE following fertilisation. The formation of the NE in both these circumstances involves endoplasmic reticulum membranes enveloping the chromatin, but PLC?-dependent membrane fusion events are also essential. Here we demonstrate the activation of PLC? by a Src family kinase (SFK1) during NE assembly. We show by time-resolved FRET for the first time the direct in vivo interaction and temporal regulation of PLC? and SFK1 in sea urchins. As a prerequisite for protein activation, there is a rapid phosphorylation of PLC? on its Y783 residue in response to GTP in vitro. This phosphorylation is dependent upon SFK activity; thus Y783 phosphorylation and NE assembly are susceptible to SFK inhibition. Y783 phosphorylation is also observed on the surface of the male pronucleus (MPN) in vivo during NE formation. Together the corroborative in vivo and in vitro data demonstrate the phosphorylation and activation of PLC? by SFK1 during NE assembly. We discuss the potential generality of such a mechanism. PMID:22848394

Byrne, Richard D.; Applebee, Christopher; Poccia, Dominic L.; Larijani, Banafshé

2012-01-01

128

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

PubMed

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

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

2015-04-01

129

A systematic, family-wide investigation reveals that ~30% of mammalian PDZ domains engage in PDZ-PDZ interactions  

PubMed Central

Summary PDZ domains are independently folded modules that typically mediate protein-protein interactions by binding to the C-termini of their target proteins. In a few instances, however, PDZ domains have been reported to dimerize with other PDZ domains. To investigate this noncanonical binding mode further, we used protein microarrays comprising virtually every mouse PDZ domain to systematically query all possible PDZ-PDZ pairs. We then used fluorescence polarization to retest and quantify novel interactions and co-affinity purification to test biophysically validated interactions in the context of their full-length proteins. Overall, we discovered 37 PDZ-PDZ interactions involving 46 PDZ domains (~30% of all PDZ domains tested), revealing that dimerization is a more frequently used binding mode than was previously appreciated. This suggests that many PDZ domains evolved to form multiprotein complexes by simultaneously interacting with more than one ligand. PMID:21944753

Chang, Bryan H.; Gujral, Taranjit S.; Karp, Ethan S.; BuKhalid, Raghida; Grantcharova, Viara P.; MacBeath, Gavin

2012-01-01

130

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

PubMed Central

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:24722193

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

2014-01-01

131

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

PubMed

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:24722193

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

2014-01-01

132

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

SciTech Connect

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.

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

133

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

PubMed Central

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

2011-01-01

134

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

PubMed Central

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)-?-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)-?-caryophyllene, the monoterpenes linalool and ?-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

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

2013-01-01

135

Transposon mutagenesis reveals cooperation of ETS family transcription factors with signaling pathways in erythro-megakaryocytic leukemia.  

PubMed

To define genetic lesions driving leukemia, we targeted cre-dependent Sleeping Beauty (SB) transposon mutagenesis to the blood-forming system using a hematopoietic-selective vav 1 oncogene (vav1) promoter. Leukemias of diverse lineages ensued, most commonly lymphoid leukemia and erythroleukemia. The inclusion of a transgenic allele of Janus kinase 2 (JAK2)V617F resulted in acceleration of transposon-driven disease and strong selection for erythroleukemic pathology with transformation of bipotential erythro-megakaryocytic cells. The genes encoding the E-twenty-six (ETS) transcription factors Ets related gene (Erg) and Ets1 were the most common sites for transposon insertion in SB-induced JAK2V617F-positive erythroleukemias, present in 87.5% and 65%, respectively, of independent leukemias examined. The role of activated Erg was validated by reproducing erythroleukemic pathology in mice transplanted with fetal liver cells expressing translocated in liposarcoma (TLS)-ERG, an activated form of ERG found in human leukemia. Via application of SB mutagenesis to TLS-ERG-induced erythroid transformation, we identified multiple loci as likely collaborators with activation of Erg. Jak2 was identified as a common transposon insertion site in TLS-ERG-induced disease, strongly validating the cooperation between JAK2V617F and transposon insertion at the Erg locus in the JAK2V617F-positive leukemias. Moreover, loci expressing other regulators of signal transduction pathways were conspicuous among the common transposon insertion sites in TLS-ERG-driven leukemia, suggesting that a key mechanism in erythroleukemia may be the collaboration of lesions disturbing erythroid maturation, most notably in genes of the ETS family, with mutations that reduce dependence on exogenous signals. PMID:23533276

Tang, Jian Zhong; Carmichael, Catherine L; Shi, Wei; Metcalf, Donald; Ng, Ashley P; Hyland, Craig D; Jenkins, Nancy A; Copeland, Neal G; Howell, Viive M; Zhao, Zhizhuang Joe; Smyth, Gordon K; Kile, Benjamin T; Alexander, Warren S

2013-04-01

136

Transposon mutagenesis reveals cooperation of ETS family transcription factors with signaling pathways in erythro-megakaryocytic leukemia  

PubMed Central

To define genetic lesions driving leukemia, we targeted cre-dependent Sleeping Beauty (SB) transposon mutagenesis to the blood-forming system using a hematopoietic-selective vav 1 oncogene (vav1) promoter. Leukemias of diverse lineages ensued, most commonly lymphoid leukemia and erythroleukemia. The inclusion of a transgenic allele of Janus kinase 2 (JAK2)V617F resulted in acceleration of transposon-driven disease and strong selection for erythroleukemic pathology with transformation of bipotential erythro-megakaryocytic cells. The genes encoding the E-twenty-six (ETS) transcription factors Ets related gene (Erg) and Ets1 were the most common sites for transposon insertion in SB-induced JAK2V617F-positive erythroleukemias, present in 87.5% and 65%, respectively, of independent leukemias examined. The role of activated Erg was validated by reproducing erythroleukemic pathology in mice transplanted with fetal liver cells expressing translocated in liposarcoma (TLS)-ERG, an activated form of ERG found in human leukemia. Via application of SB mutagenesis to TLS-ERG–induced erythroid transformation, we identified multiple loci as likely collaborators with activation of Erg. Jak2 was identified as a common transposon insertion site in TLS-ERG–induced disease, strongly validating the cooperation between JAK2V617F and transposon insertion at the Erg locus in the JAK2V617F-positive leukemias. Moreover, loci expressing other regulators of signal transduction pathways were conspicuous among the common transposon insertion sites in TLS-ERG–driven leukemia, suggesting that a key mechanism in erythroleukemia may be the collaboration of lesions disturbing erythroid maturation, most notably in genes of the ETS family, with mutations that reduce dependence on exogenous signals. PMID:23533276

Tang, Jian Zhong; Carmichael, Catherine L.; Shi, Wei; Metcalf, Donald; Ng, Ashley P.; Hyland, Craig D.; Jenkins, Nancy A.; Copeland, Neal G.; Howell, Viive M.; Zhao, Zhizhuang Joe; Smyth, Gordon K.; Kile, Benjamin T.; Alexander, Warren S.

2013-01-01

137

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

SciTech Connect

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.

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

138

Comparative venom gland transcriptome surveys of the saw-scaled vipers (Viperidae: Echis) reveal substantial intra-family gene diversity and novel venom transcripts  

PubMed Central

Background Venom variation occurs at all taxonomical levels and can impact significantly upon the clinical manifestations and efficacy of antivenom therapy following snakebite. Variation in snake venom composition is thought to be subject to strong natural selection as a result of adaptation towards specific diets. Members of the medically important genus Echis exhibit considerable variation in venom composition, which has been demonstrated to co-evolve with evolutionary shifts in diet. We adopt a venom gland transcriptome approach in order to investigate the diversity of toxins in the genus and elucidate the mechanisms which result in prey-specific adaptations of venom composition. Results Venom gland transcriptomes were created for E. pyramidum leakeyi, E. coloratus and E. carinatus sochureki by sequencing ~1000 expressed sequence tags from venom gland cDNA libraries. A standardised methodology allowed a comprehensive intra-genus comparison of the venom gland profiles to be undertaken, including the previously described E. ocellatus transcriptome. Blast annotation revealed the presence of snake venom metalloproteinases, C-type lectins, group II phopholipases A2, serine proteases, L-amino oxidases and growth factors in all transcriptomes throughout the genus. Transcripts encoding disintegrins, cysteine-rich secretory proteins and hyaluronidases were obtained from at least one, but not all, species. A representative group of novel venom transcripts exhibiting similarity to lysosomal acid lipase were identified from the E. coloratus transcriptome, whilst novel metallopeptidases exhibiting similarity to neprilysin and dipeptidyl peptidase III were identified from E. p. leakeyi and E. coloratus respectively. Conclusion The comparison of Echis venom gland transcriptomes revealed substantial intrageneric venom variation in representations and cluster numbers of the most abundant venom toxin families. The expression profiles of established toxin groups exhibit little obvious association with venom-related adaptations to diet described from this genus. We suggest therefore that alterations in isoform diversity or transcript expression levels within the major venom protein families are likely to be responsible for prey specificity, rather than differences in the representation of entire toxin families or the recruitment of novel toxin families, although the recruitment of lysosomal acid lipase as a response to vertebrate feeding cannot be excluded. Evidence of marked intrageneric venom variation within the medically important genus Echis strongly advocates further investigations into the medical significance of venom variation in this genus and its impact upon antivenom therapy. PMID:19948012

2009-01-01

139

Crystal Structure of a Conserved Hypothetical Protein MJ0927 from Methanocaldococcus jannaschii Reveals a Novel Quaternary Assembly in the Nif3 Family  

PubMed Central

A Nif3 family protein of Methanocaldococcus jannaschii, MJ0927, is highly conserved from bacteria to humans. Although several structures of bacterial Nif3 proteins are known, no structure representing archaeal Nif3 has yet been reported. The crystal structure of Methanocaldococcus jannaschii MJ0927 was determined at 2.47?Ĺ resolution to understand the structural differences between the bacterial and archaeal Nif3 proteins. Intriguingly, MJ0927 is found to adopt an unusual assembly comprising a trimer of dimers that forms a cage-like architecture. Electrophoretic mobility-shift assays indicate that MJ0927 binds to both single-stranded and double-stranded DNA. Structural analysis of MJ0927 reveals a positively charged region that can potentially explain its DNA-binding capability. Taken together, these data suggest that MJ0927 adopts a novel quartenary architecture that could play various DNA-binding roles in Methanocaldococcus jannaschii. PMID:25243119

Chen, Sheng-Chia; Yang, Chia Shin; Kuan, Shu-Min; Lin, Ching-Ting; Chou, Shan-Ho

2014-01-01

140

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

PubMed Central

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 Fucus suggest that climatic factors promoted differentiation between the two major clades, while the recent and rapid species radiation in the temperate clade during Pleistocene glacial cycles coincided with several potential speciation drivers. PMID:22188734

2011-01-01

141

The structure of RdDddP from Roseobacter denitrificans reveals that DMSP lyases in the DddP-family are metalloenzymes.  

PubMed

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 Ĺ resolution, shows that RdDddP is a homodimeric metalloprotein with a binuclear center of two metal ions located 2.7 Ĺ 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

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

2014-01-01

142

Genetic testing in Tunisian families with heritable retinoblastoma using a low cost approach permits accurate risk prediction in relatives and reveals incomplete penetrance in adults.  

PubMed

Heritable retinoblastoma is caused by oncogenic mutations in the RB1 tumor suppressor gene. Identification of these mutations in patients is important for genetic counseling and clinical management of relatives at risk. In order to lower analytical efforts, we designed a stepwise mutation detection strategy that was adapted to the spectrum of oncogenic RB1 gene mutations. We applied this strategy on 20 unrelated patients with familial and/or de novo bilateral retinoblastoma from Tunisia. In 19 (95%) patients, we detected oncogenic mutations including base substitutions, small length mutations, and large deletions. Further analyses on the origin of the mutations showed mutational mosaicism in one unilaterally affected father of a bilateral proband and incomplete penetrance in two mothers. In a large family with several retinoblastoma patients, the mutation identified in the index patient was also detected in several non-penetrant relatives. RNA analyses showed that this mutation results in an in-frame loss of exon 9. In summary, our strategy can serve as a model for RB1 mutation identification with high analytical sensitivity. Our results point out that genetic testing is needed to reveal or exclude incomplete penetrance specifically in parents of patients with sporadic disease. PMID:24810223

Ayari Jeridi, Hajer; Bouguila, Hédi; Ansperger-Rescher, Birgit; Baroudi, Olfa; Mdimegh, Imen; Omran, Ines; Charradi, Khaoula; Bouzayene, Hssan; Benammar-Elgaaďed, Amel; Lohmann, Dietmar R

2014-07-01

143

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

PubMed Central

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 Ĺ resolution, shows that RdDddP is a homodimeric metalloprotein with a binuclear center of two metal ions located 2.7 Ĺ 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

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

2014-01-01

144

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

PubMed Central

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

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

2015-01-01

145

Cloning of three human tyrosine phosphatases reveals a multigene family of receptor-linked protein-tyrosine-phosphatases expressed in brain  

SciTech Connect

A human brainstem cDNA library in bacteriophage {lambda}gt11 was screened under conditions of reduced bybridization stringency with a leukocyte common antigen (LCA) probe that spanned both conserved cytoplasmic domains. cDNA encoding a receptor-linked protein-tyrosinephosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48), RPTPase {alpha}, has been cloned and sequenced. Human RPTPase {alpha} consists of 802 amino acids. The extracellular domain of 150 residues includes a hydrophobic signal peptide and eight potential N-glycosylation sites. This is followed by a transmembrane region and two tandemly repeated conserved domains characteristic of all RPTPases identified thus far. The gene for RPTPase {alpha} has been localized to human chromosome region 20pter-20q12 by analysis of its segregation pattern in rodent-human somatic cell hybrids. Northern blot analysis revealed the presence of two major transcripts of 4.3 and 6.3 kilobases. In addition to PRTPase {alpha}, two other RPTPases ({beta} and {gamma}), identified in the same screen, have been partially cloned and sequenced. Analysis of sequence comparisons among LCA, the LCA-related protein LAR, and RPTP-ases {alpha}, {beta}, and {gamma} reveals the existence of a multigene family encoding different RPTPases, each containing a distinct extracellular domain, a single hydrophobic transmembrane region, and two tandemly repeated conserved cytoplasmic domains.

Kaplan, R.; Morse, B.; Howk, R.; Ravera, M.; Ricca, G.; Jaye, M. (Rorer Biotechnology, Inc., King of Prussia, PA (USA)); Huebner, K.; Croce, C. (Temple Univ., Philadephia, PA (USA)); Schlessinger, J. (New York Univ., NY (USA))

1990-09-01

146

Spitzer Reveals Stellar 'Family Tree'  

NASA Technical Reports Server (NTRS)

[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.

2008-01-01

147

Spitzer Reveals Stellar 'Family Tree'  

NASA Technical Reports Server (NTRS)

[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.

2008-01-01

148

Non-monophyly and intricate morphological evolution within the avian family Cettiidae revealed by multilocus analysis of a taxonomically densely sampled dataset  

PubMed Central

Background The avian family Cettiidae, including the genera Cettia, Urosphena, Tesia, Abroscopus and Tickellia and Orthotomus cucullatus, has recently been proposed based on analysis of a small number of loci and species. The close relationship of most of these taxa was unexpected, and called for a comprehensive study based on multiple loci and dense taxon sampling. In the present study, we infer the relationships of all except one of the species in this family using one mitochondrial and three nuclear loci. We use traditional gene tree methods (Bayesian inference, maximum likelihood bootstrapping, parsimony bootstrapping), as well as a recently developed Bayesian species tree approach (*BEAST) that accounts for lineage sorting processes that might produce discordance between gene trees. We also analyse mitochondrial DNA for a larger sample, comprising multiple individuals and a large number of subspecies of polytypic species. Results There are many topological incongruences among the single-locus trees, although none of these is strongly supported. The multi-locus tree inferred using concatenated sequences and the species tree agree well with each other, and are overall well resolved and well supported by the data. The main discrepancy between these trees concerns the most basal split. Both methods infer the genus Cettia to be highly non-monophyletic, as it is scattered across the entire family tree. Deep intraspecific divergences are revealed, and one or two species and one subspecies are inferred to be non-monophyletic (differences between methods). Conclusions The molecular phylogeny presented here is strongly inconsistent with the traditional, morphology-based classification. The remarkably high degree of non-monophyly in the genus Cettia is likely to be one of the most extraordinary examples of misconceived relationships in an avian genus. The phylogeny suggests instances of parallel evolution, as well as highly unequal rates of morphological divergence in different lineages. This complex morphological evolution apparently misled earlier taxonomists. These results underscore the well-known but still often neglected problem of basing classifications on overall morphological similarity. Based on the molecular data, a revised taxonomy is proposed. Although the traditional and species tree methods inferred much the same tree in the present study, the assumption by species tree methods that all species are monophyletic is a limitation in these methods, as some currently recognized species might have more complex histories. PMID:22142197

2011-01-01

149

Families with Gifted Adolescents  

ERIC Educational Resources Information Center

Studies of families with gifted adolescents have revealed conflicting results. Adolescents, mothers, and fathers of 84 families with a gifted adolescent and of 95 families with a non-gifted adolescent evaluated their family system independently. Dependent variables were cohesion, democratic family style (adaptability), organisation, achievement…

Schilling, Susanne R.; Sparfeldt, Jorn; Rost, Detlef H.

2006-01-01

150

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

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 Ĺ, revealing a monomeric structure mainly folded into ?-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

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

2014-12-01

151

Functional Complementation Analyses Reveal that the Single PRAT Family Protein of Trypanosoma brucei Is a Divergent Homolog of Tim17 in Saccharomyces cerevisiae.  

PubMed

Trypanosoma brucei, a parasitic protozoan that causes African trypanosomiasis, possesses a single member of the presequence and amino acid transporter (PRAT) protein family, which is referred to as TbTim17. In contrast, three homologous proteins, ScTim23, ScTim17, and ScTim22, are found in Saccharomyces cerevisiae and higher eukaryotes. Here, we show that TbTim17 cannot rescue Tim17, Tim23, or Tim22 mutants of S. cerevisiae. We expressed S. cerevisiae Tim23, Tim17, and Tim22 in T. brucei. These heterologous proteins were properly imported into mitochondria in the parasite. Further analysis revealed that although ScTim23 and ScTim17 were integrated into the mitochondrial inner membrane and assembled into a protein complex similar in size to TbTim17, only ScTim17 was stably associated with TbTim17. In contrast, ScTim22 existed as a protease-sensitive soluble protein in the T. brucei mitochondrion. In addition, the growth defect caused by TbTim17 knockdown in T. brucei was partially restored by the expression of ScTim17 but not by the expression of either ScTim23 or ScTim22, whereas the expression of TbTim17 fully complemented the growth defect caused by TbTim17 knockdown, as anticipated. Similar to the findings for cell growth, the defect in the import of mitochondrial proteins due to depletion of TbTim17 was in part restored by the expression of ScTim17 but was not complemented by the expression of either ScTim23 or ScTim22. Together, these results suggest that TbTim17 is divergent compared to ScTim23 but that its function is closer to that of ScTim17. In addition, ScTim22 could not be sorted properly in the T. brucei mitochondrion and thus failed to complement the function of TbTim17. PMID:25576485

Weems, Ebony; Singha, Ujjal K; Hamilton, VaNae; Smith, Joseph T; Waegemann, Karin; Mokranjac, Dejana; Chaudhuri, Minu

2015-03-01

152

Global Mapping of Cell Type–Specific Open Chromatin by FAIRE-seq Reveals the Regulatory Role of the NFI Family in Adipocyte Differentiation  

PubMed Central

Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type–specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation) and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq). FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPAR? and C/EBP?, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI) transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPAR? binding sites near PPAR?, C/EBP?, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA–mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our study demonstrates the utility of FAIRE-seq in providing a global view of cell type–specific regulatory elements in the genome and in identifying transcriptional regulators of adipocyte differentiation. PMID:22028663

Yu, Jing; Hirose-Yotsuya, Lisa; Take, Kazumi; Sun, Wei; Iwabu, Masato; Okada-Iwabu, Miki; Fujita, Takanori; Aoyama, Tomohisa; Tsutsumi, Shuichi; Ueki, Kohjiro; Kodama, Tatsuhiko; Sakai, Juro; Aburatani, Hiroyuki; Kadowaki, Takashi

2011-01-01

153

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

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.

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. (SLAC); (Michigan); (U. Muchen)

2011-08-17

154

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

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

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

155

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

PubMed Central

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 cellular processes. PMID:21085602

Desvignes, Thomas; Pontarotti, Pierre; Bobe, Julien

2010-01-01

156

A novel ?-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

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 ?-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 ?-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 Ĺ) crystal structure has been determined, resulting in the first reported structure of a GH52 family member. A lower resolution (2.6 Ĺ) 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 ?-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

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

2014-05-01

157

Small Molecule Inhibitor of Formin Homology 2 Domains (SMIFH2) Reveals the Roles of the Formin Family of Proteins in Spindle Assembly and Asymmetric Division in Mouse Oocytes  

PubMed Central

Dynamic actin reorganization is the main driving force for spindle migration and asymmetric cell division in mammalian oocytes. It has been reported that various actin nucleators including Formin-2 are involved in the polarization of the spindle and in asymmetric cell division. In mammals, the formin family is comprised of 15 proteins. However, their individual roles in spindle migration and/or asymmetric division have not been elucidated yet. In this study, we employed a newly developed inhibitor for formin family proteins, small molecule inhibitor of formin homology 2 domains (SMIFH2), to assess the functions of the formin family in mouse oocyte maturation. Treatment with SMIFH2 during in vitro maturation of mouse oocytes inhibited maturation by decreasing cytoplasmic and cortical actin levels. In addition, treatment with SMIFH2, especially at higher concentrations (500 ?M), impaired the proper formation of meiotic spindles, indicating that formins play a role in meiotic spindle formation. Knockdown of the mDia2 formins caused a similar decrease in oocyte maturation and abnormal spindle morphology, mimicking the phenotype of SMIFH2-treated cells. Collectively, these results suggested that besides Formin-2, the other proteins of the formin, including mDia family play a role in asymmetric division and meiotic spindle formation in mammalian oocytes. PMID:25837661

Kim, Hak-Cheol; Jo, Yu-Jin; Kim, Nam-Hyung; Namgoong, Suk

2015-01-01

158

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

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

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

2015-02-15

159

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

Microsoft Academic Search

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

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

2010-01-01

160

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

Microsoft Academic Search

Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction.\\u000a Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR)\\u000a has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest\\u000a that in the Iranian population NS-ARMR is

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

2007-01-01

161

Evolutionarily conserved and divergent expression of members of the FGF receptor family among vertebrate embryos, as revealed by FGFR expression patterns in Xenopus  

Microsoft Academic Search

Fibroblast growth factors (FGFs) mediate many cell-cell signaling events during early development. While the actions of FGFs\\u000a have been well-studied, the roles played by specific members of the FGF receptor (FGFR) family are poorly understood. To characterize\\u000a the roles played by individual FGFRs we compared the regulation and expression of the three Xenopus FGFRs described to date (XFGFR-1, XFGFR-2, and

Richard Golub; Zach Adelman; Jennifer Clementi; Rebecca Weiss; Jean Bonasera; Marc Servetnick

2000-01-01

162

Genome-wide transcription profiles reveal genotype-dependent responses of biological pathways and gene-families in Daphnia exposed to single and mixed stressors.  

PubMed

The present study investigated the possibilities and limitations of implementing a genome-wide transcription-based approach that takes into account genetic and environmental variation to better understand the response of natural populations to stressors. When exposing two different Daphnia pulex genotypes (a cadmium-sensitive and a cadmium-tolerant one) to cadmium, the toxic cyanobacteria Microcystis aeruginosa, and their mixture, we found that observations at the transcriptomic level do not always explain observations at a higher level (growth, reproduction). For example, although cadmium elicited an adverse effect at the organismal level, almost no genes were differentially expressed after cadmium exposure. In addition, we identified oxidative stress and polyunsaturated fatty acid metabolism-related pathways, as well as trypsin and neurexin IV gene-families as candidates for the underlying causes of genotypic differences in tolerance to Microcystis. Furthermore, the whole-genome transcriptomic data of a stressor mixture allowed a better understanding of mixture responses by evaluating interactions between two stressors at the gene-expression level against the independent action baseline model. This approach has indicated that ubiquinone pathway and the MAPK serine-threonine protein kinase and collagens gene-families were enriched with genes showing an interactive effect in expression response to exposure to the mixture of the stressors, while transcription and translation-related pathways and gene-families were mostly related with genotypic differences in interactive responses to this mixture. Collectively, our results indicate that the methods we employed may improve further characterization of the possibilities and limitations of transcriptomics approaches in the adverse outcome pathway framework and in predictions of multistressor effects on natural populations. PMID:24552364

De Coninck, Dieter I M; Asselman, Jana; Glaholt, Stephen; Janssen, Colin R; Colbourne, John K; Shaw, Joseph R; De Schamphelaere, Karel A C

2014-03-18

163

The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations  

PubMed Central

Background Parkinson's disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson's disease in sibships from North America. Objective To make a thorough assessment of the SPR gene region in sporadic Parkinson's disease. Methods A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson's disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non?parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. Results Significant LOD scores between 2 and 3 were obtained at the two SPR?flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p?value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter?correlated SNPs were significantly associated with Parkinson's disease affection status (p?value 0.004). Conclusions DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson's disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson's disease. PMID:16443856

Sharma, M; Mueller, J C; Zimprich, A; Lichtner, P; Hofer, A; Leitner, P; Maass, S; Berg, D; Dürr, A; Bonifati, V; De Michele, G; Oostra, B; Brice, A; Wood, N W; Muller?Myhsok, B; Gasser, T

2006-01-01

164

Genome-Wide Transcription Profiles Reveal Genotype-Dependent Responses of Biological Pathways and Gene-Families in Daphnia Exposed to Single and Mixed Stressors  

PubMed Central

The present study investigated the possibilities and limitations of implementing a genome-wide transcription-based approach that takes into account genetic and environmental variation to better understand the response of natural populations to stressors. When exposing two different Daphnia pulex genotypes (a cadmium-sensitive and a cadmium-tolerant one) to cadmium, the toxic cyanobacteria Microcystis aeruginosa, and their mixture, we found that observations at the transcriptomic level do not always explain observations at a higher level (growth, reproduction). For example, although cadmium elicited an adverse effect at the organismal level, almost no genes were differentially expressed after cadmium exposure. In addition, we identified oxidative stress and polyunsaturated fatty acid metabolism-related pathways, as well as trypsin and neurexin IV gene-families as candidates for the underlying causes of genotypic differences in tolerance to Microcystis. Furthermore, the whole-genome transcriptomic data of a stressor mixture allowed a better understanding of mixture responses by evaluating interactions between two stressors at the gene-expression level against the independent action baseline model. This approach has indicated that ubiquinone pathway and the MAPK serine-threonine protein kinase and collagens gene-families were enriched with genes showing an interactive effect in expression response to exposure to the mixture of the stressors, while transcription and translation-related pathways and gene-families were mostly related with genotypic differences in interactive responses to this mixture. Collectively, our results indicate that the methods we employed may improve further characterization of the possibilities and limitations of transcriptomics approaches in the adverse outcome pathway framework and in predictions of multistressor effects on natural populations. PMID:24552364

2015-01-01

165

Targeted Deletion Reveals Essential and Overlapping Functions of the miR17?92 Family of miRNA Clusters  

Microsoft Academic Search

miR-17?92, miR-106b?25, and miR-106a?363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-17?92 is observed in human cancers, and its oncogenic properties have been confirmed in a mouse model of B cell lymphoma. Here we show that mice deficient for miR-17?92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17?92

Andrea Ventura; Amanda G. Young; Monte M. Winslow; Laura Lintault; Alex Meissner; Stefan J. Erkeland; Jamie Newman; Roderick T. Bronson; Denise Crowley; James R. Stone; Rudolf Jaenisch; Phillip A. Sharp; Tyler Jacks

2008-01-01

166

Unlocking the family secret in family play therapy  

Microsoft Academic Search

Family play therapy combines play therapy with family systems therapy. When family secrets are revealed in a family setting, with play to cushion the family's anxiety, families have the opportunity to resolve long-standing intrapsychic and interpersonal difficulties that impede the psychological well-being of both children and parents. Family play therapy effectively reduces symptomatic behavior in children in an age-appropriate manner—an

Bonnie Eaker

1986-01-01

167

Familial malignant retroperitoneal paraganglioma.  

PubMed Central

Paragangliomas are neuroendocrine tumours and those occurring in the head and neck have well recognized familial association. Retroperitoneal paragangliomas are uncommon and we present two cases of familial malignant retroperitoneal paraganglioma. Review of the literature revealed marked differences in the incidence and malignant potential of familial and non-familial paraganglioma. In contrast to the cases reported here, familial tumours are generally benign, though they may occur at multiple sites. Familial and non-familial paragangliomas may indeed be different disease entities. Images Figure 1 Figure 2 Figure 3 PMID:2559401

Sebastian, J. P.; Williams, S. E.; Wells, M.; Peake, M. D.

1989-01-01

168

Characterization of five subgroups of the sieve element occlusion gene family in Glycine max reveals genes encoding non-forisome P-proteins, forisomes and forisome tails.  

PubMed

P-proteins are structural phloem proteins discussed to be involved in the rapid sealing of injured sieve elements. P-proteins are found in all dicotyledonous and some monocotyledonous plants, but additional crystalloid P-proteins, known as forisomes, have evolved solely in the Fabaceae. Both types are encoded by members of the sieve element occlusion (SEO) gene family, which comprises seven phylogenetic subgroups. The Fabaceae-specific subgroup 1 contains genes encoding forisome subunits in e.g. Medicago truncatula, Vicia faba, Dipteryx panamensis and Canavalia gladiata whereas basal subgroup 5 encodes P-proteins in Nicotiana tabacum (tobacco) and Arabidopsis thaliana. The function of remaining subgroups is still unknown. We chose Glycine max (soybean) as a model to investigate SEO proteins representing different subgroups in one species. We isolated native P-proteins to determine the SEO protein composition and analyzed the expression pattern, localization and structure of the G. max SEO proteins representing five of the subgroups. We found that subgroup 1 GmSEO genes encode forisome subunits, a member of subgroup 5 encodes a non-forisome P-protein and subgroup 2 GmSEO genes encode the components of forisome tails, which are present in a restricted selection of Fabaceaen species. We therefore present the first molecular characterization of a Fabaceae non-forisome P-protein and the first evidence that forisome tails are encoded by a phylogenetically-distinct branch of the SEO gene family. PMID:24928491

Zielonka, Sascia; Ernst, Antonia M; Hawat, Susan; Twyman, Richard M; Prüfer, Dirk; Noll, Gundula A

2014-09-01

169

Genetic Analysis of Loop Sequences in the Let-7 Gene Family Reveal a Relationship between Loop Evolution and Multiple IsomiRs  

PubMed Central

While mature miRNAs have been widely studied, the terminal loop sequences are rarely examined despite regulating both primary and mature miRNA functions. Herein, we attempted to understand the evolutionary pattern of loop sequences by analyzing loops in the let-7 gene family. Compared to the stable miRNA length distributions seen in most metazoans, higher metazoan species exhibit a longer length distribution. Examination of these loop sequence length distributions, in addition to phylogenetic tree construction, implicated loop sequences as the main evolutionary drivers in miRNA genes. Moreover, loops from relevant clustered miRNA gene families showed varying length distributions and higher levels of nucleotide divergence, even between homologous pre-miRNA loops. Furthermore, we found that specific nucleotides were dominantly distributed in the 5? and 3? terminal loop ends, which may contribute to the relatively precise cleavage that leads to a stable isomiR expression profile. Overall, this study provides further insight into miRNA processing and maturation and further enriches our understanding of miRNA biogenesis. PMID:25397967

Liang, Tingming; Yang, Chen; Li, Ping; Liu, Chang; Guo, Li

2014-01-01

170

Importance of Gene Duplication in the Evolution of Genomic Imprinting Revealed by Molecular Evolutionary Analysis of the Type I MADS-Box Gene Family in Arabidopsis Species  

PubMed Central

The pattern of molecular evolution of imprinted genes is controversial and the entire picture is still to be unveiled. Recently, a relationship between the formation of imprinted genes and gene duplication was reported in genome-wide survey of imprinted genes in Arabidopsis thaliana. Because gene duplications influence the molecular evolution of the duplicated gene family, it is necessary to investigate both the pattern of molecular evolution and the possible relationship between gene duplication and genomic imprinting for a better understanding of evolutionary aspects of imprinted genes. In this study, we investigated the evolutionary changes of type I MADS-box genes that include imprinted genes by using relative species of Arabidopsis thaliana (two subspecies of A. lyrata and three subspecies of A. halleri). A duplicated gene family enables us to compare DNA sequences between imprinted genes and its homologs. We found an increased number of gene duplications within species in clades containing the imprinted genes, further supporting the hypothesis that local gene duplication is one of the driving forces for the formation of imprinted genes. Moreover, data obtained by phylogenetic analysis suggested “rapid evolution” of not only imprinted genes but also its closely related orthologous genes, which implies the effect of gene duplication on molecular evolution of imprinted genes. PMID:24039992

Yoshida, Takanori; Kawabe, Akira

2013-01-01

171

Importance of gene duplication in the evolution of genomic imprinting revealed by molecular evolutionary analysis of the type I MADS-box gene family in Arabidopsis species.  

PubMed

The pattern of molecular evolution of imprinted genes is controversial and the entire picture is still to be unveiled. Recently, a relationship between the formation of imprinted genes and gene duplication was reported in genome-wide survey of imprinted genes in Arabidopsis thaliana. Because gene duplications influence the molecular evolution of the duplicated gene family, it is necessary to investigate both the pattern of molecular evolution and the possible relationship between gene duplication and genomic imprinting for a better understanding of evolutionary aspects of imprinted genes. In this study, we investigated the evolutionary changes of type I MADS-box genes that include imprinted genes by using relative species of Arabidopsis thaliana (two subspecies of A. lyrata and three subspecies of A. halleri). A duplicated gene family enables us to compare DNA sequences between imprinted genes and its homologs. We found an increased number of gene duplications within species in clades containing the imprinted genes, further supporting the hypothesis that local gene duplication is one of the driving forces for the formation of imprinted genes. Moreover, data obtained by phylogenetic analysis suggested "rapid evolution" of not only imprinted genes but also its closely related orthologous genes, which implies the effect of gene duplication on molecular evolution of imprinted genes. PMID:24039992

Yoshida, Takanori; Kawabe, Akira

2013-01-01

172

Phylogenic analysis revealed an expanded C2H2-homeobox subfamily and expression profiles of C2H2 zinc finger gene family in Verticillium dahliae.  

PubMed

C2H2 zinc finger (CZF) proteins are a major class of transcription factors that play crucial roles in fungal growth, development, various stress responses, and virulence. Little genome-wide data is available regarding the roles of CZF proteins in Verticillium dahliae, a destructive pathogen that causes vascular wilt disease in more than 200 plant species. We identified a total of 79 typical CZF genes in V. dahliae. Comparative analysis revealed that four plant pathogenic fungi, V. dahliae, Fusarium oxysporum, Magnaporthe oryzae, and Botrytis cinerea, have comparable numbers of predicted CZF genes with similar characteristics. Phylogenetic analysis identified a C2H2-homeobox subfamily in V. dahliae containing seven genes with similar gene structures. V. dahliae and F. oxysporum (Hypocreomycetidae) have more genes of this subfamily than M. oryzae (Sordariomycetidae) and B. cinerea (Leotiomycetes). Furthermore, gene-expression analysis of the smoke tree wilt fungus V. dahliae strain XS11 using digital gene-expression profiling and RT-qPCR revealed that a number of CZF genes were differentially expressed during microsclerotia formation, nutritional starvation, and simulated in planta conditions. Furthermore, the expression profiles revealed that some CZF genes were overrepresented during multiple stages, indicating that they might play diverse roles. Our results provide useful information concerning the functions of CZF genes in microsclerotia formation, nutritional stress responses, and pathogenicity in V. dahliae, and form a basis for future functional studies of these genes. PMID:25725127

Xiong, Dianguang; Wang, Yonglin; Deng, Chenglin; Hu, Ruowen; Tian, Chengming

2015-05-15

173

Analysis of the complete genome of a virus associated with twisted leaf disease of cherry reveals evidence of a close relationship to unassigned viruses in the family Betaflexiviridae.  

PubMed

The genome of a virus associated with cherry twisted leaf disease (CTLaV, isolate ZH) was sequenced and consists of 8431 nucleotides, excluding a poly(A) tail at the 3' end. Genome analysis shows that CTLaV-ZH represents a new and distinct species and has a genome organization similar to those of unassigned viruses in the family Betaflexiviridae. The CTLaV-ZH genome has five open reading frames (ORFs), with putative ORFs within ORF2 and ORF5, identified as ORF2a and ORF5a, respectively. The AUG start codons of ORF2a and ORF5a are in contexts suitable for efficient translation, with appropriate stop codons in frame. PMID:24737006

James, Delano; Varga, Aniko; Lye, David

2014-09-01

174

Secondary structure analysis of swine pasivirus (family Picornaviridae) RNA reveals a type-IV IRES and a parechovirus-like 3' UTR organization.  

PubMed

The potential RNA structures of the 5' and 3' untranslated regions (UTRs) and cis-acting replication elements (CREs) of a novel pasivirus (PaV) genotype (family Picornaviridae) were analysed. PaV-A3 (KM259923) was identified in a faecal sample from a domestic pig in Hungary with posterior paraplegia of unknown etiology. Based on likely structural features of the 5' UTR, the pasiviruses were inferred to possess Hepacivirus/Pestivirus-like type-IV IRES. The pasivirus CRE was mapped to the 2B genome region, similar to Ljungan virus. The secondary RNA structure of the pasivirus 3' UTR was structurally similar to that of human parechoviruses. The genome, CRE, and 3' UTR of pasiviruses provide further evidence of the common origin of the members of the genera Parechovirus and Pasivirus, although their different 5' UTR IRES types suggest that a recombination event occurred during the divergence these viruses. PMID:25716922

Boros, Ákos; Fenyvesi, Hajnalka; Pankovics, Péter; Biró, Hunor; Phan, Tung Gia; Delwart, Eric; Reuter, Gábor

2015-05-01

175

Structural Analysis and Detection of Biological Inositol Pyrophosphates Reveal That the Family of VIP/Diphosphoinositol Pentakisphosphate Kinases Are 1/3-Kinases*S?  

PubMed Central

We have characterized the positional specificity of the mammalian and yeast VIP/diphosphoinositol pentakisphosphate kinase (PPIP5K) family of inositol phosphate kinases. We deployed a microscale metal dye detection protocol coupled to a high performance liquid chromatography system that was calibrated with synthetic and biologically synthesized standards of inositol pyrophosphates. In addition, we have directly analyzed the structures of biological inositol pyrophosphates using two-dimensional 1H-1H and 1H-31P nuclear magnetic resonance spectroscopy. Using these tools, we have determined that the mammalian and yeast VIP/PPIP5K family phosphorylates the 1/3-position of the inositol ring in vitro and in vivo. For example, the VIP/PPIP5K enzymes convert inositol hexakisphosphate to 1/3-diphosphoinositol pentakisphosphate. The latter compound has not previously been identified in any organism. We have also unequivocally determined that 1/3,5-(PP)2-IP4 is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate that is synthesized by yeasts and mammals, through a collaboration between the inositol hexakisphosphate kinase and VIP/PPIP5K enzymes. These data uncover phylogenetic variability within the crown taxa in the structures of inositol pyrophosphates. For example, in the Dictyostelids, the major bis-diphosphoinositol tetrakisphosphate is 5,6-(PP)2-IP4 (Laussmann, T., Eujen, R., Weisshuhn, C. M., Thiel, U., Falck, J. R., and Vogel, G. (1996) Biochem. J. 315,715 -7258645148). Our study brings us closer to the goal of understanding the structure/function relationships that control specificity in the synthesis and biological actions of inositol pyrophosphates. PMID:18981179

Lin, Hongying; Fridy, Peter C.; Ribeiro, Anthony A.; Choi, Jae H.; Barma, Deb K.; Vogel, Günter; Falck, J. R.; Shears, Stephen B.; York, John D.; Mayr, Georg W.

2009-01-01

176

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

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

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

177

Crystal structures of the Erp protein family members ErpP and ErpC from Borrelia burgdorferi reveal the reason for different affinities for complement regulator factor H.  

PubMed

Borrelia burgdorferi is the causative agent of Lyme disease, which can be acquired after the bite of an infected Ixodes tick. As a strategy to resist the innate immunity and to successfully spread and proliferate, B. burgdorferi expresses a set of outer membrane proteins that are capable of binding complement regulator factor H (CFH), factor H-like protein 1 (CFHL-1) and factor H-related proteins (CFHR) to avoid complement-mediated killing. B. burgdorferi B31 contains three proteins that belong to the Erp (OspE/F-related) protein family and are capable of binding CFH and some CFHRs, namely ErpA, ErpC and ErpP. We have determined the crystal structure of ErpP at 2.53Ĺ resolution and the crystal structure of ErpC at 2.15Ĺ resolution. Recently, the crystal structure of the Erp family member OspE from B. burgdorferi N40 was determined in complex with CFH domains 19-20, revealing the residues involved in the complex formation. Despite the high sequence conservation between ErpA, ErpC, ErpP and the homologous protein OspE (78-80%), the affinity for CFH and CFHRs differs markedly among the Erp family members, suggesting that ErpC may bind only CFHRs but not CFH. A comparison of the binding site in OspE with those of ErpC and ErpP revealed that the extended loop region, which is only observed in the potential binding site of ErpC, plays an important role by preventing the binding of CFH. These results can explain the inability of ErpC to bind CFH, whereas ErpP and ErpA still possess the ability to bind CFH. PMID:25582082

Brangulis, Kalvis; Petrovskis, Ivars; Kazaks, Andris; Akopjana, Inara; Tars, Kaspars

2015-05-01

178

Phylogenetic and transcriptomic analyses reveal the evolution of bioluminescence and light detection in marine deep-sea shrimps of the family Oplophoridae (Crustacea: Decapoda).  

PubMed

Bioluminescence is essential to the survival of many organisms, particularly in the deep sea where light is limited. Shrimp of the family Oplophoridae exhibit a remarkable mechanism of bioluminescence in the form of a secretion used for predatory defense. Three of the ten genera possess an additional mode of bioluminescence in the form of light-emitting organs called photophores. Phylogenetic analyses can be useful for tracing the evolution of bioluminescence, however, the few studies that have attempted to reconcile the relationships within Oplophoridae have generated trees with low-resolution. We present the most comprehensive phylogeny of Oplophoridae to date, with 90% genera coverage using seven genes (mitochondrial and nuclear) across 30 oplophorid species. We use our resulting topology to trace the evolution of bioluminescence within Oplophoridae. Previous studies have suggested that oplophorid visual systems may be tuned to differentiate the separate modes of bioluminescence. While all oplophorid shrimp possess a visual pigment sensitive to blue-green light, only those bearing photophores have an additional pigment sensitive to near-ultraviolet light. We attempt to characterize opsins, visual pigment proteins essential to light detection, in two photophore-bearing species (Systellaspis debilis and Oplophorus gracilirostris) and make inferences regarding their function and evolutionary significance. PMID:25482362

Wong, Juliet M; Pérez-Moreno, Jorge L; Chan, Tin-Yam; Frank, Tamara M; Bracken-Grissom, Heather D

2015-02-01

179

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

PubMed

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

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

2015-03-01

180

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

PubMed

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

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

2013-10-10

181

Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGF? as potential targets.  

PubMed

The mesenchymal, clear cell, and dedifferentiated chondrosarcoma subtypes are extremely rare, together constituting 10% to 15% of all chondrosarcomas. Their poor prognosis and lack of efficacious treatment emphasizes the need to elucidate the pathways playing a pivotal role in these tumors. We constructed tissue microarrays containing 42 dedifferentiated, 23 clear cell, and 23 mesenchymal chondrosarcomas and performed immunohistochemistry to study the expression of growth plate-signaling molecules and molecules shown to be involved in conventional chondrosarcoma. We observed high expression of SOX-9 and FGFR-3, as well as aberrant cellular localization of heparan sulfate proteoglycans, in all subtypes. TGF? signaling through p-SMAD2 and PAI-1 was highly active in all chondrosarcoma subtypes, which suggests that TGF? inhibitors as a possible therapeutic strategy in rare chondrosarcoma subtypes. As in conventional chondrosarcoma, antiapoptotic proteins (Bcl-2, and/or Bcl-xl) were highly expressed in all subtypes. Inhibition with the BH-3 mimetic ABT-737 rendered dedifferentiated chondrosarcoma cell lines sensitive to doxorubicin or cisplatin. Our data indicate that antiapoptotic proteins may play an important role in chemoresistance, suggesting a promising role for targeting Bcl-2 family members in chondrosarcoma treatment, irrespective of the subtype. PMID:23415961

van Oosterwijk, Jolieke G; Meijer, Danielle; van Ruler, Maayke A J H; van den Akker, Brendy E W M; Oosting, Jan; Krenács, Tibor; Picci, Piero; Flanagan, Adrienne M; Liegl-Atzwanger, Bernadette; Leithner, Andreas; Athanasou, Nick; Daugaard, Sřren; Hogendoorn, Pancras C W; Bovée, Judith V M G

2013-04-01

182

Analysis of Familial Hemophagocytic Lymphohistiocytosis Type 4 (FHL-4) Mutant Proteins Reveals that S-Acylation Is Required for the Function of Syntaxin 11 in Natural Killer Cells  

PubMed Central

Natural killer (NK) cell secretory lysosome exocytosis and cytotoxicity are impaired in familial hemophagocytic lymphohistiocytosis type 4 (FHL-4), a disorder caused by mutations in the gene encoding the SNARE protein syntaxin 11. We show that syntaxin 11 binds to SNAP23 in NK cells and that this interaction is reduced by FHL-4 truncation and frameshift mutation proteins that delete all or part of the SNARE domain of syntaxin 11. In contrast the FHL-4 mutant proteins bound to the Sec-1/Munc18-like (SM) protein Munc18-2. We demonstrate that the C-terminal cysteine rich region of syntaxin 11, which is deleted in the FHL-4 mutants, is S-acylated. This posttranslational modification is required for the membrane association of syntaxin 11 and for its polarization to the immunological synapse in NK cells conjugated to target cells. Moreover, we show that Munc18-2 is recruited by syntaxin 11 to intracellular membranes in resting NK cells and to the immunological synapse in activated NK cells. This recruitment of Munc18-2 is abolished by deletion of the C-terminal cysteine rich region of syntaxin 11. These results suggest a pivotal role for S-acylation in the function of syntaxin 11 in NK cells. PMID:24910990

Hellewell, Andrew L.; Foresti, Ombretta; Gover, Nicola; Porter, Morwenna Y.; Hewitt, Eric W.

2014-01-01

183

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

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

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

2015-02-01

184

Visualization of a substrate-induced productive conformation of the catalytic triad of the Neisseria meningitidis peptidoglycan O-acetylesterase reveals mechanistic conservation in SGNH esterase family members.  

PubMed

Peptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily. PMID:25286847

Williams, Allison H; Veyrier, Frédéric J; Bonis, Mathilde; Michaud, Yann; Raynal, Bertrand; Taha, Muhamed Kheir; White, Stephen W; Haouz, Ahmed; Boneca, Ivo G

2014-10-01

185

Visualization of a substrate-induced productive conformation of the catalytic triad of the Neisseria meningitidis peptidoglycan O-acetylesterase reveals mechanistic conservation in SGNH esterase family members  

PubMed Central

Peptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily. PMID:25286847

Williams, Allison H.; Veyrier, Frédéric J.; Bonis, Mathilde; Michaud, Yann; Raynal, Bertrand; Taha, Muhamed-Kheir; White, Stephen W.; Haouz, Ahmed; Boneca, Ivo G.

2014-01-01

186

Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability  

PubMed Central

Background De novo mutations are emerging as an important cause of neurocognitive impairment, and whole exome sequencing of case-parent trios is a powerful way of detecting them. Here, we report the findings in four such trios. Methods The Deciphering Developmental Disorders study is using whole exome sequencing in family trios to investigate children with severe, sporadic, undiagnosed developmental delay. Three of our patients were ascertained from the first 1133 children to have been investigated through this large-scale study. Case 4 was a phenotypically isolated case recruited into an undiagnosed rare disorders sequencing study. Results Protein-altering de novo mutations in PURA were identified in four subjects. They include two different frameshifts, one inframe deletion and one missense mutation. PURA encodes Pur-?, a highly conserved multifunctional protein that has an important role in normal postnatal brain development in animal models. The associated human phenotype of de novo heterozygous mutations in this gene is variable, but moderate to severe neurodevelopmental delay and learning disability are common to all. Neonatal hypotonia, early feeding difficulties and seizures, or ‘seizure-like’ movements, were also common. Additionally, it is suspected that anterior pituitary dysregulation may be within the spectrum of this disorder. Psychomotor developmental outcomes appear variable between patients, and we propose a possible genotype–phenotype correlation, with disruption of Pur repeat III resulting in a more severe phenotype. Conclusions These findings provide definitive evidence for the role of PURA in causing a variable syndrome of neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements and epilepsy in humans, and help clarify the role of PURA in the previously described 5q31.3 microdeletion phenotype. PMID:25342064

Hunt, David; Leventer, Richard J; Simons, Cas; Taft, Ryan; Swoboda, Kathryn J; Gawne-Cain, Mary; Magee, Alex C; Turnpenny, Peter D; Baralle, Diana

2014-01-01

187

Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish  

PubMed Central

Background The high degree of sequence conservation between coding regions in fish and mammals can be exploited to identify genes in mammalian genomes by comparison with the sequence of similar genes in fish. Conversely, experimentally characterized mammalian genes may be used to annotate fish genomes. However, gene families that escape this principle include the rapidly diverging cytokines that regulate the immune system, and their receptors. A classic example is the class II helical cytokines (HCII) including type I, type II and lambda interferons, IL10 related cytokines (IL10, IL19, IL20, IL22, IL24 and IL26) and their receptors (HCRII). Despite the report of a near complete pufferfish (Takifugu rubripes) genome sequence, these genes remain undescribed in fish. Results We have used an original strategy based both on conserved amino acid sequence and gene structure to identify HCII and HCRII in the genome of another pufferfish, Tetraodon nigroviridis that is amenable to laboratory experiments. The 15 genes that were identified are highly divergent and include a single interferon molecule, three IL10 related cytokines and their potential receptors together with two Tissue Factor (TF). Some of these genes form tandem clusters on the Tetraodon genome. Their expression pattern was determined in different tissues. Most importantly, Tetraodon interferon was identified and we show that the recombinant protein can induce antiviral MX gene expression in Tetraodon primary kidney cells. Similar results were obtained in Zebrafish which has 7 MX genes. Conclusion We propose a scheme for the evolution of HCII and their receptors during the radiation of bony vertebrates and suggest that the diversification that played an important role in the fine-tuning of the ancestral mechanism for host defense against infections probably followed different pathways in amniotes and fish. PMID:12869211

Lutfalla, Georges; Crollius, Hugues Roest; Stange-thomann, Nicole; Jaillon, Olivier; Mogensen, Knud; Monneron, Daničle

2003-01-01

188

Activity-based profiling of a physiologic aglycone library reveals sugar acceptor promiscuity of family 1 UDP-glucosyltransferases from grape.  

PubMed

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 ?-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 ?-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

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

2014-09-01

189

Domain Analyses Reveal That Chlamydia trachomatis CT694 Protein Belongs to the Membrane-localized Family of Type III Effector Proteins*  

PubMed Central

The Chlamydia trachomatis type three-secreted effector protein CT694 is expressed during late-cycle development yet is secreted by infectious particles during the invasion process. We have previously described the presence of at least two functional domains within CT694. CT694 was found to interact with the human protein Ahnak through a C-terminal domain and affect formation of host-cell actin stress fibers. Immunolocalization analyses of ectopically expressed pEGFP-CT694 also revealed plasma membrane localization for CT694 that was independent of Ahnak binding. Here we provide evidence that CT694 contains multiple functional domains. Plasma membrane localization and CT694-induced alterations in host cell morphology are dependent on an N-terminal domain. We demonstrate that membrane association of CT694 is dependent on a domain resembling a membrane localization domain (MLD) found in anti-host proteins from Yersinia, Pseudomonas, and Salmonella spp. This domain is necessary and sufficient for localization and morphology changes but is not required for Ahnak binding. Further, the CT694 MLD is able to complement ExoS ?MLD when ectopically expressed. Taken together, our data indicate that CT694 is a multidomain protein with the potential to modulate multiple host cell processes. PMID:22711538

Bullock, Holly D.; Hower, Suzanne; Fields, Kenneth A.

2012-01-01

190

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

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-?-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-?-tyrosine and the 2-naphthonate moieties in KED biosynthesis. PMID:23360970

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

2013-01-01

191

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

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

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

192

Complete proteomic-based enzyme reaction and inhibition kinetics reveal how monolignol biosynthetic enzyme families affect metabolic flux and lignin in Populus trichocarpa.  

PubMed

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

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

2014-03-01

193

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

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

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

2012-01-01

194

Genetic analysis of the Replication Protein A large subunit family in Arabidopsis reveals unique and overlapping roles in DNA repair, meiosis and DNA replication  

PubMed Central

Replication Protein A (RPA) is a heterotrimeric protein complex that binds single-stranded DNA. In plants, multiple genes encode the three RPA subunits (RPA1, RPA2 and RPA3), including five RPA1-like genes in Arabidopsis. Phylogenetic analysis suggests two distinct groups composed of RPA1A, RPA1C, RPA1E (ACE group) and RPA1B, RPA1D (BD group). ACE-group members are transcriptionally induced by ionizing radiation, while BD-group members show higher basal transcription and are not induced by ionizing radiation. Analysis of rpa1 T-DNA insertion mutants demonstrates that although each mutant line is likely null, all mutant lines are viable and display normal vegetative growth. The rpa1c and rpa1e single mutants however display hypersensitivity to ionizing radiation, and combination of rpa1c and rpa1e results in additive hypersensitivity to a variety of DNA damaging agents. Combination of the partially sterile rpa1a with rpa1c results in complete sterility, incomplete synapsis and meiotic chromosome fragmentation, suggesting an early role for RPA1C in promoting homologous recombination. Combination of either rpa1c and/or rpa1e with atr revealed additive hypersensitivity phenotypes consistent with each functioning in unique repair pathways. In contrast, rpa1b rpa1d double mutant plants display slow growth and developmental defects under non-damaging conditions. We show these defects in the rpa1b rpa1d mutant are likely the result of defective DNA replication leading to reduction in cell division. PMID:24335281

Aklilu, Behailu B.; Soderquist, Ryan S.; Culligan, Kevin M.

2014-01-01

195

Families with Daughters, Families with Sons: Different Challenges for Family Relationships and Marital Satisfaction?  

Microsoft Academic Search

In a longitudinal study, the links between family relations and marital relations were examined in families with early adolescent children. Over the course of 4 years, 128 mother–father–adolescent triads were investigated annually. They completed questionnaires assessing family climate and marital relationships. Longitudinal analyses revealed that the initially large discrepancies between adolescents' and their parents' perceptions of family cohesion, support, and

Inge Seiffge-Krenke

1999-01-01

196

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

ERIC Educational Resources Information Center

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…

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

2012-01-01

197

Poly(perfluoroalkylation) of metallic nitride fullerenes reveals addition-pattern guidelines: synthesis and characterization of a family of Sc3N@C80(CF3)n (n = 2-16) and their radical anions.  

PubMed

A family of highly stable (poly)perfluoroalkylated metallic nitride cluster fullerenes was prepared in high-temperature reactions and characterized by spectroscopic (MS, (19)F NMR, UV-vis/NIR, ESR), structural and electrochemical methods. For two new compounds, Sc(3)N@C(80)(CF(3))(10) and Sc(3)N@C(80)(CF(3))(12,) single crystal X-ray structures are determined. Addition pattern guidelines for endohedral fullerene derivatives with bulky functional groups are formulated as a result of experimental ((19)F NMR spectroscopy and single crystal X-ray diffraction) studies and exhaustive quantum chemical calculations of the structures of Sc(3)N@C(80)(CF(3))(n) (n = 2-16). Electrochemical studies revealed that Sc(3)N@C(80)(CF(3))(n) derivatives are easier to reduce than Sc(3)N@C(80), the shift of E(1/2) potentials ranging from +0.11 V (n = 2) to +0.42 V (n = 10). Stable radical anions of Sc(3)N@C(80)(CF(3))(n) were generated in solution and characterized by ESR spectroscopy, revealing their (45)Sc hyperfine structure. Facile further functionalizations via cycloadditions or radical additions were achieved for trifluoromethylated Sc(3)N@C(80) making them attractive versatile platforms for the design of molecular and supramolecular materials of fundamental and practical importance. PMID:21294511

Shustova, Natalia B; Peryshkov, Dmitry V; Kuvychko, Igor V; Chen, Yu-Sheng; Mackey, Mary A; Coumbe, Curtis E; Heaps, David T; Confait, Bridget S; Heine, Thomas; Phillips, J Paige; Stevenson, Steven; Dunsch, Lothar; Popov, Alexey A; Strauss, Steven H; Boltalina, Olga V

2011-03-01

198

HOST FAMILY PROGRAM Host family: ____________________________________ Family No. _________  

E-print Network

HOST FAMILY PROGRAM Host family: ____________________________________ Family No. _________ Student: 13 January ­ 28 May 2003 THE FAMILY PROVIDES THE STUDENT WITH: 1. Three meals daily all week long. (If a student should arrive home too late for a meal, the family should leave the prepared meal

199

Cloning, functional identification and sequence analysis of flavonoid 3'-hydroxylase and flavonoid 3',5'-hydroxylase cDNAs reveals independent evolution of flavonoid 3',5'-hydroxylase in the Asteraceae family.  

PubMed

Flavonoids are ubiquitous secondary plant metabolites which function as protectants against UV light and pathogens and are involved in the attraction of pollinators as well as seed and fruit dispersers. The hydroxylation pattern of the B-ring of flavonoids is determined by the activity of two members of the vast and versatile cytochrome P450 protein (P450) family, the flavonoid 3'-hydroxylase (F3'H) and flavonoid 3',5'-hydroxylase (F3'5'H). Phylogenetic analysis of known sequences of F3'H and F3'5'H indicated that F3'5'H was recruited from F3'H before the divergence of angiosperms and gymnosperms. Seven cDNAs were isolated from species of the Asteraceae family, all of which were predicted to code for F3'Hs based on their sequences. The recombinant proteins of four of the heterologously in yeast expressed cDNAs exhibited the expected F3'H activity but surprisingly, three recombinant proteins showed F3'5'H activity. Phylogenetic analyses indicated the independent evolution of an Asteraceae-specific F3'5'H. Furthermore, sequence analysis of these unusual F3'5'H cDNAs revealed an elevated rate of nonsynonymous substitutions as typically found for duplicated genes acquiring new functions. Since F3'5'H is necessary for the synthesis of 3',4',5'-hydroxylated delphinidin-derivatives, which normally provide the basis for purple to blue flower colours, the evolution of an Asteraceae-specific F3'5'H probably reflects the adaptive value of efficient attraction of insect pollinators. PMID:16830174

Seitz, Christian; Eder, Christian; Deiml, Bettina; Kellner, Sandra; Martens, Stefan; Forkmann, Gert

2006-06-01

200

Families under Economic Pressure.  

ERIC Educational Resources Information Center

Data from two-parent families in midwestern rural county revealed that adverse economic change increased economic pressures and hardship adaptations in ways that matched effect of income level and exceeded influence of unstable work. Pressures and adaptations mediated negative effects of economic adversity on emotional health and family

Elder, Glen H., Jr.; And Others

1992-01-01

201

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

ERIC Educational Resources Information Center

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…

Holt, Elizabeth S.; Kaiser, Donna H.

2001-01-01

202

Revealed Preference  

Microsoft Academic Search

This is a survey of revealed preference analysis focusing on the period since Samuelson's seminal development of the topic with emphasis on empirical applications. It was prepared for Samuelsonian Economics and the 21st Century, edited by Michael Szenberg.

Hal R. Varian

203

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 ...

204

Family Privilege  

ERIC Educational Resources Information Center

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…

Seita, John R.

2014-01-01

205

Georgia Revealed  

NSDL National Science Digital Library

OneWorld Journeys.com and Washingtonpost.com present Georgia Revealed: Searching for the Soul of the Caucasus. The site showcases a Georgia expedition that occurred April 16-29, the first of three explorations OneWorldJourneys.com have planned this year. Wilderness and nature photographers, journalists, and technicians collaborate here to bring users on their journey through the Caucasus Mountains Region of the Country of Georgia. Georgia Revealed not only features daily journal entries (text, streaming video and audio, and photographs) of the expedition, but also has sections providing background on history, travel, culture, and more. Altogether, this is a very well organized, educational site. We look forward to the next expedition to the Sonoran Desert.

206

America Revealed  

NSDL National Science Digital Library

The tagline on the America Revealed website says it all: "America Revealed explores the hidden patterns and rhythms that make America work." A remarkable series from PBS, the show talks about everything from how fresh seafood is sourced to how farmers combat crop pests. The Stories section includes a collage of images that, when scrolled over, provide accounts from a variety of people and industries. First-time visitors might want to watch the "Introduction to Manufacturing" series, which explores items that are made in the United States. Visitors can also use the Map section to look for stories of note from around the country, from Long Island to Southern California. The Teachers area includes ten lesson plans and links to additional resources. Finally, visitors can click on the Episodes area to watch complete episodes of the program.

2013-04-22

207

Hereditary nonpolyposis colon cancer: Analysis of linkage to 2p 15-16 places the COCA1 locus telomeric to D2S123 and reveals genetic heterogeneity in seven Canadian families  

SciTech Connect

Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant trait responsible for approximately 6% of colorectal cancers. Linkage of the HNPCC trait to the D2S123 locus on 2p 15-16 has previously been reported in two families. This HNPCC locus is now designated [open quotes]COCA1[close quotes]. The authors have tested seven Canadian HNPCC families, who have a variety of clinical presentations, for linkage to a panel of microsatellite polymorphisms in the vicinity of D2S123. One family was clearly linked to the COCA1 locus (LOD = 4.21), and a second family is likely to be linked (LOD = 0.92). In three families linkage was excluded. In the remaining two families the data were inconclusive. In the linked family, individuals with cancer of the endometrium or ureter share a common haplotype with 12 family members with colorectal cancer. This supports the suspected association between these extracolonic neoplasms and the HNPCC syndrome. In addition, five of the six individuals with adenomatous polyps (but no colorectal cancer) have the same haplotype as the affected individuals, while the sixth carries a recombination. One individual with colorectal cancer carries a recombination that places the COCA1 locus telomeric to D2S123. This study localizes the COCA1 gene to an 8-cM region that is consistent with the location of the hMSH2 gene. The authors also confirm that families presently classified as HNPCC are genetically heterogeneous. 36 refs., 4 figs., 2 tabs.

Green, R.C.; Young, T.L. (Memorial Univ. of Newfoundland, St. John's (Canada)); Narod, S.A.; Tonin, P.; Ginsburg, O.; Miller, S. (Montreal General Hospital, Montreal (Canada) Royal Victoria Hospital, Montreal (Canada)); Morasse, J. (Hopital St-Francois d'Assise, Quebec City (Canada)); Cox, J.; Fitzgerald, G.W.N. (Grenfell Regional Health Services, St. Anthony, Newfoundland (Canada)); Jothy, S. (Royal Victoria Hospital, Montreal (Canada)) (and others)

1994-06-01

208

Family Member Involvement in Hastened Death  

Microsoft Academic Search

When patients pursue a hastened death, how is the labor of family caregiving affected? The authors examined this question in a qualitative study of 35 families. Four cases reveal the main themes: “taking care” included mutual protection between patients and family members; “midwifing the death” without professional support left families unprepared for adverse events; “tying up loose ends” included dealing

Helene Starks; Anthony L. Back; Robert A. Pearlman; Barbara A. Koenig; Clarissa Hsu; Judith R. Gordon; Ashok J. Bharucha

2007-01-01

209

Georgians Revealed  

NSDL National Science Digital Library

What was life like during the Georgian era in Britain? During the period between 1714 and 1830, cities and towns were transformed, conspicuous consumption became the pastime of the emerging middle classes, and gardening and shopping for leisure became commonplace. This digital companion to the British Library's "Georgians Revealed" exhibit brings together some of the key books and newspapers from the period, along with details about guided tours through the physical exhibitions, a Georgian London walking tour, and more. For those unable to view the exhibit in person, this companion site provides brief but detailed narratives on interesting facets of the exhibit, including dancing with the Georgians and celebrity culture. The site is rounded out by an excellent timeline of key events from the time of George I (1714-1727) to George IV (1820-1830) accompanied by vivid illustrations and portraiture.

210

Family History  

MedlinePLUS

... Home CDC 24/7: Saving Lives. Protecting People.™ Genomics All CDC Topics Search The CDC Note: Javascript ... visit this page: About CDC.gov . Public Health Genomics Genomics Family Health History Share Compartir Family History ...

211

Family Arguments  

MedlinePLUS

... Pediatric First Aid for Caregivers and Teachers (PedFACTs) Teaching Package HealthyChildren.org Post-it Notes Family Life Health Management - Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types ...

212

Family Meals  

MedlinePLUS

... Sports: Keeping Kids Safe Concussions: What to Know Family Meals KidsHealth > Parents > Nutrition & Fitness Center > Healthy Eating & ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

213

Foster Families  

MedlinePLUS

... child in another home. Continue Why Do Kids Live With Foster Families? Most often, a kid goes ... this stressful and emotional time. Why Do Kids Live With Foster Families? Most often, a kid goes ...

214

Family Support.  

ERIC Educational Resources Information Center

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);…

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

1990-01-01

215

Family therapy.  

PubMed

Another major force not letting us succeed in the treatment of diabetes remains right inside the patients home, their family members. Hence, it is important to know the perception of the close family members about this simple and strong tool in diabetes, 'insulin'. The drug is nearing its century, it has not fully being accepted gracefully even in todays electronic savvy society. So, we need to strongly discover the reason for its non-acceptance, while trials are out inventing new drugs. One vital thing that can change this attitude is increasing the understanding of this drug, insulin in depth to close people around the patient, the 'family'. Underestimating family's perception about disease and treatment for diabetes is detrimental to both diseased and the doctor. This consists of a biopsychosocial model; biological, psychological and social factors. Family forms the most important part of it. The strategies in family therapy include psychodynamic, structural, strategic, and cognitive-behavioral component. Diabetes has and will continue to rise, so will be the treatment options. From the clinicians side its to fix fasting first but from patients its fix family first. Family therapy demonstrates the importance of insulin initiation and maintenance in insulin naive patients, and continuation for others. The specific needs of such patients and their impact on family life are met with family therapy. Who needs family therapy? Benefits of family therapy and a case based approach is covered. PMID:24251191

Altamash, Shaikh

2013-10-01

216

Family grief  

Microsoft Academic Search

Grief traditionally has been described from the individual perspective. In contrast, this article presents a family systems perspective on death and grieving. A group of interconnected individuals forming a system, defined as a “family,” reciprocally affect one another in response to internal or external events. Minuchin's structural theory emphasizes the importance of subsystems within a family; boundaries between subsystems are

Carol Michler Detmer; Joseph W. Lamberti

1991-01-01

217

Chemoprevention of Familial Melanoma  

Microsoft Academic Search

Bleaching agents 4-tertiary butyl phenol (4-TBP) and monobenzyl ether of hydroquinone (MBEH) have been known to cause occupational vitiligo This project answers whether agents 4-TBP and MBEH can be used for prophylactic treatment of familial melanoma by being specifically toxic to melanocytes and activating an immune response against distant pigment cells. Cytotoxic experiments reveal that similar to 4-TBP, MBEH induces

Vidhya Hariharan

2011-01-01

218

Parent Education and Family Relations.  

ERIC Educational Resources Information Center

Examined effects of parenting courses (Parent Effectiveness Training or Systematic Training for Effective Parenting) on family relationships in 31 married couples. Found courses were generally seen as beneficial; revealed no perceived differences in the two courses. (Author/ABL)

Noller, Patricia; Taylor, Robert

1989-01-01

219

Revealing Rembrandt  

PubMed Central

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

Parker, Andrew J.

2014-01-01

220

The Revealer  

NSDL National Science Digital Library

For those interested in insightful and critical analysis of issues regarding religion and its portrayal in the media, it can be difficult to sift and winnow through the myriad of material offered on the web. Jointly sponsored by the New York University Department of Journalism and New York Universityâ??s Center for Religion and Media, The Revealer is a well-thought out review of just such matters, and one that will be of great interest to persons with a penchant for the subject. The review is divided into three playful headings: Today, Timely, and Timeless. As might be expected, the Today section culls media coverage from that particular day. The Timely section offers links to media coverage of particularly germane issues and events, while the Timeless area offers some exclusive commentaries on photography and the occult and the relationship between science and religion. Finally, visitors can zero in on the religion of their choice by looking through the material as organized by faith, such as Hinduism, Paganism, and Christianity.

2005-01-01

221

Revealing Mercury  

NASA Astrophysics Data System (ADS)

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-frequency distribution suggest that smooth plains on Mercury's surface range in age from the end of the period of heavy impact bombardment to as young as perhaps 1 billion years; these ongoing measurements are helping to elucidate the volcanic history of the planet. Mercury's global tectonic history is also revealed by the MESSENGER image and laser altimeter data. Significant evidence for global contraction was seen in Mariner 10 images in the form of widespread lobate scarps. The MESSENGER images show that contractional features are the dominant tectonic landform globally, and the inferred average contractional strain is at least one third greater than previously inferred from Mariner 10 observations. Only three exceptions to the dominance of contractional deformation have been found to date: extensional troughs that include prominent basin-radial systems documented in two basins, the Pantheon Fossae within the 1500-km-diameter Caloris basin and a similar set of features within a newly-imaged 700-km-diameter basin, and a circumferential trough system within the smaller, younger Raditladi basin. That these extensional tectonic features are rare on Mercury, and that they are not seen within basins elsewhere in the Solar System, pose important constraints on the thermal and mechanical evolution of Mercury's interior.

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

222

Revealing Things  

NSDL National Science Digital Library

Revealing Things is the Smithsonian Institution's first specifically web based exhibit; both the content and design of the site are fascinating. This work in progress is a prototype of a future, more fully-developed exhibit. It concentrates on "common, everyday objects to tell stories about people, their cultures, and the meanings they associate with their possessions." Items discussed include a 1937 chemistry set, a Vietnam memorial offering, a duckpin bowling ball, an early TV, and a celery vase, among many others. Organized according to theme, era, and object, the exhibit is presented in a new pop-up browser window. Within that window, navigation takes place via "maplets," a connected series of moving colored labels representing the three ways that the exhibit is organized. Users can move slider bars to effect the placement of the labels, and search on terms to create their own thematic or object-based exhibit. When the cursor is placed over an object label, scrolling text introduces it. Alternatively, the site can be navigated via a series of icons that run down the middle of the exhibition page. When an icon is clicked, the series of icons may rearrange. Each exhibit contains a photo of the object, along with written commentary on it. In addition, sound is sometimes available to play period music, or render out loud the exhibition text. The most fully-developed object at this time is "Patched Bellbottoms." Users are advised to read the help files on both the main page and the exhibit page for navigation tips. The exhibit is a fascinating precursor of what could be a new way to interactively view museum exhibits, allowing the user to cast off the restraints of a linear orientation. Note that the exhibit is extremely browser and bandwidth intensive.

223

Cloning, Functional Identification and Sequence Analysis of Flavonoid 3?-hydroxylase and Flavonoid 3?,5?-hydroxylase cDNAs Reveals Independent Evolution of Flavonoid 3?,5?-hydroxylase in the Asteraceae Family  

Microsoft Academic Search

Flavonoids are ubiquitous secondary plant metabolites which function as protectants against UV light and pathogens and are\\u000a involved in the attraction of pollinators as well as seed and fruit dispersers. The hydroxylation pattern of the B-ring of\\u000a flavonoids is determined by the activity of two members of the vast and versatile cytochrome P450 protein (P450) family, the\\u000a flavonoid 3?-hydroxylase (F3?H)

Christian Seitz; Christian Eder; Bettina Deiml; Sandra Kellner; Stefan Martens; Gert Forkmann

2006-01-01

224

Veritas Asteroid Family Still Holds Secrets?  

NASA Astrophysics Data System (ADS)

Veritas asteroid family has been studied for about two decades. These studies have revealed many secrets, and a respectable knowledge about this family had been collected. Here I will present many of these results and review the current knowledge about the family. However, despite being extensively studied, Veritas family is still a mystery. This will be illustrated through the presentation of the most interesting open problems. Was there a secondary collision within this family? Does asteroid (490) Veritas belong to the family named after it? How large was the parent body of the family? Finally, some possible directions for future studies that aims to address these questions are discussed as well.

Novakovic, B.

2012-12-01

225

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

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

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

2015-01-01

226

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 Geminiviridae for inclusion in the ICTV 8th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of vira...

227

FAMILY GEMINIVIRIDAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The International Committee on the Taxonomy of Viruses geminivirus study group has revised the description of the family Geminiviridae for inclusion in the ICTV 8th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of vi...

228

Family, Extended  

ERIC Educational Resources Information Center

Parents are a child's first and most influential teacher. People hear this truism often, yet nowhere has the author seen it more taken to heart than at Tower Street Elementary School. The school's efforts to form a true partnership with students' families--from involving families in the first day of school, to the principal making home visits, to…

Patton, Jessica Rae

2006-01-01

229

Family Theory and Family Health Research  

PubMed Central

Different family theories can be applied to different aspects of how families experience health and illness. The family health and illness cycle describes the phases of a family's experience, beginning with health promotion and risk reduction, then family vulnerability and disease onset or relapse, family illness appraisal, family acute response, and finally family adaptation to illness and recovery. For each phase, specific family theories that are most appropriate for guiding family and health research are discussed. PMID:21229056

Doherty, William J.

1991-01-01

230

Parental Nonverbal Behavior within the Family Context.  

ERIC Educational Resources Information Center

Examines how parents use nonverbal behaviors in family situations. Results revealed that nonverbal behaviors which parents model for their children vary with the number of family members interacting, the gender of the offspring, and the gender of the parent. Results were discussed in terms of family dynamics. (Author)

Brody, Gene H.; Stoneman, Zolinda

1981-01-01

231

Phylogenetic relationships of Acheilognathidae (Cypriniformes: Cyprinoidea) as revealed from evidence of both nuclear and mitochondrial gene sequence variation: evidence for necessary taxonomic revision in the family and the identification of cryptic species.  

PubMed

Bitterlings are relatively small cypriniform species and extremely interesting evolutionarily due to their unusual reproductive behaviors and their coevolutionary relationships with freshwater mussels. As a group, they have attracted a great deal of attention in biological studies. Understanding the origin and evolution of their mating system demands a well-corroborated hypothesis of their evolutionary relationships. In this study, we provide the most comprehensive phylogenetic reconstruction of species relationships of the group based on partitioned maximum likelihood and Bayesian methods using DNA sequence variation of nuclear and mitochondrial genes on 41 species, several subspecies and three undescribed species. Our findings support the monophyly of the Acheilognathidae. Two of the three currently recognized genera are not monophyletic and the family can be subdivided into six clades. These clades are further regarded as genera based on both their phylogenetic relationships and a reappraisal of morphological characters. We present a revised classification for the Acheilognathidae with five genera/lineages: Rhodeus, Acheilognathus (new constitution), Tanakia (new constitution), Paratanakia gen. nov., and Pseudorhodeus gen. nov. and an unnamed clade containing five species currently referred to as "Acheilognathus". Gene trees of several bitterling species indicate that the taxa are not monophyletic. This result highlights a potentially dramatic underestimation of species diversity in this family. Using our new phylogenetic framework, we discuss the evolution of the Acheilognathidae relative to classification, taxonomy and biogeography. PMID:25238947

Chang, Chia-Hao; Li, Fan; Shao, Kwang-Tsao; Lin, Yeong-Shin; Morosawa, Takahiro; Kim, Sungmin; Koo, Hyeyoung; Kim, Won; Lee, Jae-Seong; He, Shunping; Smith, Carl; Reichard, Martin; Miya, Masaki; Sado, Tetsuya; Uehara, Kazuhiko; Lavoué, Sébastien; Chen, Wei-Jen; Mayden, Richard L

2014-12-01

232

Expression profiling reveals Spot 42 small RNA as a key regulator in the central metabolism of Aliivibrio salmonicida  

PubMed Central

Background Spot 42 was discovered in Escherichia coli nearly 40 years ago as an abundant, small and unstable RNA. Its biological role has remained obscure until recently, and is today implicated in having broader roles in the central and secondary metabolism. Spot 42 is encoded by the spf gene. The gene is ubiquitous in the Vibrionaceae family of gamma-proteobacteria. One member of this family, Aliivibrio salmonicida, causes cold-water vibriosis in farmed Atlantic salmon. Its genome encodes Spot 42 with 84% identity to E. coli Spot 42. Results We generated a A. salmonicida spf deletion mutant. We then used microarray and Northern blot analyses to monitor global effects on the transcriptome in order to provide insights into the biological roles of Spot 42 in this bacterium. In the presence of glucose, we found a surprisingly large number of ? 2X differentially expressed genes, and several major cellular processes were affected. A gene encoding a pirin-like protein showed an on/off expression pattern in the presence/absence of Spot 42, which suggests that Spot 42 plays a key regulatory role in the central metabolism by regulating the switch between fermentation and respiration. Interestingly, we discovered an sRNA named VSsrna24, which is encoded immediately downstream of spf. This new sRNA has an expression pattern opposite to that of Spot 42, and its expression is repressed by glucose. Conclusions We hypothesize that Spot 42 plays a key role in the central metabolism, in part by regulating the pyruvat dehydrogenase enzyme complex via pirin. PMID:22272603

2012-01-01

233

Family History  

MedlinePLUS

... Brain Aneurysm Statistics and Facts Seeking Medical Attention Pediatric Aneurysms Brain Aneurysm Causes and Risk Factors Family History Early Detection and Screening Unruptured Brain Aneurysms Subarachnoid Hemorrhage Treatment Options Aneurysm Complications Post ...

234

Tomorrow's Family  

ERIC Educational Resources Information Center

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)

Pickett, Robert S.

1977-01-01

235

Family Issues  

MedlinePLUS

... Bullying Prevention Preparedness Tips for Families Tips for First Responders Serving Victims of Crime Take Me Home Emergency Preparedness Related Links Safe and Sound Task Force Voices Blog DONATE BECOME A MEMBER ...

236

FAMILIES FIRST: Keys to Successful Family Functioning Family Roles  

E-print Network

FAMILIES FIRST: Keys to Successful Family Functioning Family Roles Rick Peterson, Extension or family status. An equal opportunity/affirmative action employer. Issued in furtherance of Cooperative. publication 350-093 Types of family Roles Family roles are the recurrent patterns of behavior by which

Liskiewicz, Maciej

237

Family Limitation  

PubMed Central

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

Smith, Robert

1966-01-01

238

Crystal Structures of the Catalytic Domain of a Novel Glycohydrolase Family 23 Chitinase from Ralstonia sp. A-471 Reveals a Unique Arrangement of the Catalytic Residues for Inverting Chitin Hydrolysis  

PubMed Central

Chitinase C from Ralstonia sp. A-471 (Ra-ChiC) has a catalytic domain sequence similar to goose-type (G-type) lysozymes and, unlike other chitinases, belongs to glycohydrolase (GH) family 23. Using NMR spectroscopy, however, Ra-ChiC was found to interact only with the chitin dimer but not with the peptidoglycan fragment. Here we report the crystal structures of wild-type, E141Q, and E162Q of the catalytic domain of Ra-ChiC with or without chitin oligosaccharides. Ra-ChiC has a substrate-binding site including a tunnel-shaped cavity, which determines the substrate specificity. Mutation analyses based on this structural information indicated that a highly conserved Glu-141 acts as a catalytic acid, and that Asp-226 located at the roof of the tunnel activates a water molecule as a catalytic base. The unique arrangement of the catalytic residues makes a clear contrast to the other GH23 members and also to inverting GH19 chitinases. PMID:23658014

Arimori, Takao; Kawamoto, Noriko; Shinya, Shoko; Okazaki, Nobuo; Nakazawa, Masami; Miyatake, Kazutaka; Fukamizo, Tamo; Ueda, Mitsuhiro; Tamada, Taro

2013-01-01

239

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

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

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

240

Families Speak to Early Childhood Teachers: Impressions and Expectations  

ERIC Educational Resources Information Center

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…

Thomas, Suzanne B.; Dykes, Frank

2013-01-01

241

Family Hypnotherapy.  

ERIC Educational Resources Information Center

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)

Araoz, Daniel L.; Negley-Parker, Esther

1985-01-01

242

Family matters.  

PubMed

'Why do you want to know?' a nurse friend was recently asked when she phoned the ward to ask how her father was. He was very ill in his local hospital and she and the rest of the family were on tenterhooks, anxious for news. PMID:25827999

Bates, Jane

2015-04-01

243

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...

244

Family Grouping.  

ERIC Educational Resources Information Center

This report describes an observational study of one family-grouped classroom, a system in which elementary school children remain with the same teacher for two or more years. The class was composed of junior kindergarten, senior kindergarten, and grade 1 pupils. Each child was observed over a period of one year. A detailed observation schedule,…

Young, Vivienne; Reich, Carol

245

Serving Families.  

ERIC Educational Resources Information Center

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…

Link, Geoffrey; Beggs, Marjorie; Seiderman, Ethel

246

Community Support in Israeli Kibbutz and City Families of Children with Disabilities: Family Climate and Parental Coherence.  

ERIC Educational Resources Information Center

The study compared families with disabled children (43 families living in an Israeli kibbutz and 48 families living in an Israeli city) and similar families with nonhandicapped children. Findings revealed more dissatisfaction in parents of disabled children, greater differences between mothers and fathers of disabled children, and no mediating…

Margalit, Malka; And Others

1991-01-01

247

The CIA's Family Jewels  

NSDL National Science Digital Library

The National Security Archive at George Washington University has been bringing important documents to the general public's attention for years, and they recently finally received a copy of the CIA's "family jewels" report from the 1970s. They had originally filed a request for the document in 1992, and on June 26th, 2007 CIA officers finally brought the document to their headquarters. James Schlesinger, director of the CIA at the time, started the actual "family jewels" operation in 1973. Noted journalist Seymour Hersh reported on the story of this illegal domestic operation in 1974, and his investigation also revealed that the CIA had been involved in wiretapping and various break-ins since the 1950s. The document can be viewed in its entirety here, and interested parties can also search the entire document by keywords.

248

Family Therapy and Disturbed Families.  

ERIC Educational Resources Information Center

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…

Zuk, Gerald H., Ed.; Boszormenyi-Nagy, Ivan, Ed.

249

Family Therapy with Families Having Delinquent Offspring  

ERIC Educational Resources Information Center

Family therapy with families of delinquent children provokes a number of defensive maneuvers to avoid family involvement in solving their problems. Many families view delinquent behavior as others view psychopathology. The problem is to help the family deal with one another and work together. (Author)

Johnson, Thomas F.

1975-01-01

250

Family Caregivers  

Microsoft Academic Search

Caregiving an elder with cancer has the potential to be rewarding and meaningful but is often described as burdensome and\\u000a overwhelming because caregiver needs are frequently unmet. As the provision of care has transitioned from the hospital to\\u000a outpatient settings, family caregivers have take responsibility for the day-to-day care of their ill loved ones at home [1–4].\\u000a Despite the fact

Betty R. Ferrell; Polly Mazanec

251

Trematodes of the family Opisthorchiidae: a minireview  

PubMed Central

Examination of the original descriptions of genera placed within the family Opisthorchiidae has revealed that only 33 of the original 43 genera are valid members of this family. Further study of these descriptions should also reveal that many of the subfamilies are also invalid. With reference to the original descriptions of these genera, and subsequent literature, a brief survey of the family has been compiled. Information on the spectrum of definitive hosts that these helminths parasitize is provided, as well as information on the life cycles, geographic distribution, and socioeconomic impacts of the family. More in-depth information is given on those species that are of particular medical importance; namely, Clonorchis sinensis, Opisthorchis viverrini, and O. felineus. The final aims of this review are to provide information on the entire genera of the family Opisthorchiidae, which will aid understanding of the phylogenetic relationships not only within the family, but also within the Class Trematoda. PMID:11590910

King, Sandie

2001-01-01

252

Parents FamiliesGuide PARENT & FAMILY RESOURCES  

E-print Network

Parents FamiliesGuide #12;11 Contents: PARENT & FAMILY RESOURCES Welcome from Vice Presidents ---------- 2 Parents Program Welcome --------------- 3 Parents & Families Weekend Information ---------------------- 5 Partnering with Penn State ------------- 6 The Role of the Student ------------------- 6 Penn

Thompson, Anne

253

Family Patterns of Gender Role Attitudes  

Microsoft Academic Search

Study goals were to identify family patterns of gender role attitudes, to examine the conditions under which these patterns\\u000a emerged, and to assess the implications of gender attitude patterns for family conflict. Participants were mothers, fathers,\\u000a and first- and second-born adolescents from 358 White, working and middle-class US families. Results of cluster analysis revealed\\u000a three gender role attitude patterns: egalitarian

Jaime L. Marks; Chun Bun Lam; Susan M. McHale

2009-01-01

254

The Art of Archaeology: A Family Adventure  

E-print Network

The Art of Archaeology: A Family Adventure Saturday, March 10, 2012 1:00­4:00 p.m. children of all's mouth, wall panels from an Assyrian palace, and more! Decode ancient writing to reveal a secret password's larger- than-life Assyrian relief sculptures. STORYTIME IN THE GALLERIES First Fridays for Families

Aalberts, Daniel P.

255

Roles within the Family  

MedlinePLUS

... family unit, and which rights, privileges, obligations, and roles are assigned to each family member. In most families parents are expected to be the leaders or executives of the family; children are expected to follow the ...

256

Single Parent Families  

MedlinePLUS

... Families > Single Parent Families Family Life Listen Single Parent Families Article Body Single parenthood can be one ... in the United States live with only one parent. Most single-parent situations result from divorce, but ...

257

DEPLOYMENT & THE MILITARY FAMILY  

E-print Network

1 DEPLOYMENT & THE MILITARY FAMILY NEW ORLEANS, LOUISIANA ACTIVE DUTY MILITARY FAMILY MEMBERS: THE FLEET AND FAMILY SUPPORT CENTER ................. 3 II. POINTS OF CONTACT (POC).............................................................................................. 3 III. HEALTH & MENTAL HEALTH RESOURCES FOR IMMEDIATE FAMILY MEMBERS OF ACTIVE DUTY MILITARY

258

Families Experiencing Homelessness  

MedlinePLUS

... which may compound the stress the family feels. Families experiencing homelessness: Are typically comprised of a mother ... of other women. The Relationship Between Homelessness and Family Separation: Families who have experienced homelessness have much ...

259

Psychoanalysis: a dysfunctional family?  

PubMed

The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve. PMID:9531859

Grosskurth, P

1998-01-01

260

Temporal and spatial expression of polygalacturonase gene family members reveals  

E-print Network

regulation during fleshy fruit ripening and abscission in the monocot species oil palm Roongsattham et al divergent regulation during fleshy fruit ripening and abscission in the monocot species oil palm Peerapat in the abscission zone (AZ) during fruit shedding of the tropical monocot oil palm, and to analyze PG gene

Paris-Sud XI, Université de

261

Positive Family Functioning.  

ERIC Educational Resources Information Center

The persistence of the nuclear family as the primary social unit in the United States and most all other societies, especially complex ones, is a fact. Values shape the definition of family, especially the "good family," and the "great debate" of this period on family failure, family corruption and the family's near demise originates in…

Sussman, Marvin B.

262

Reclaiming Family Privilege  

ERIC Educational Resources Information Center

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…

Seita, John

2012-01-01

263

FMLA: Family & Medical FLA: Family Leave Act  

E-print Network

FMLA: Family & Medical Leave Act FLA: Family Leave Act DVL: Domestic Violence Leave Faculty Sick Leave FCAL: Family Care Act Leave Parental Leave & Leave Without Salary Who is · Faculty (9 month calendar weeks during one academic year (26 calendar weeks if eligible for "Service Member Family Leave

Borenstein, Elhanan

264

The Impact of Family Life Events and Changes on the Health of a Chronically Ill Child.  

ERIC Educational Resources Information Center

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.…

Patterson, Joan M.; McCubbin, Hamilton I.

1983-01-01

265

Sacred disease secrets revealed: the genetics of human epilepsy  

E-print Network

Sacred disease secrets revealed: the genetics of human epilepsy Julie Turnbull1,{ , Hannes Lohi1 channel mutations cause benign familial neonatal convulsions. Sodium channel mutations cause generalized and calcium channel mutations are found in rare families with the common syndromes childhood absence epilepsy

Sandini, Giulio

266

Familial Hypercholesterolaemia  

PubMed Central

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

Marais, A David

2004-01-01

267

Family Support and Conflict: Prospective Relations to Adolescent Depression  

Microsoft Academic Search

The relations between family support, family conflict, and adolescent depressive symptomatology were examined longitudinally in a sample of 231 female and 189 male adolescents and their mothers. Structural equation models revealed that less supportive and more con-flictual family environments were associated with greater depressive symptomatology both concurrently and prospectively over a 1-year period. Conversely, adolescent depressive symptomatology did not predict

Lisa Sheeber; Hyraan Hops; Anthony Alpert; Betsy Davis; Judy Andrews

1997-01-01

268

Father Influences on Employed Mothers' Work-Family Balance  

ERIC Educational Resources Information Center

This study employed the ecological systems perspective and gender ideology theory to examine the influence of fathers' paid work-family crossover and family involvement on self-reports of work-family balance by employed mothers with children under the age of 13 (N = 179). Multiple regression analyses revealed that fathers' crossover factors had a…

Fagan, Jay; Press, Julie

2008-01-01

269

Pathological Conflict Avoidance in Anorexia Nervosa: Family Perspectives  

Microsoft Academic Search

Conflict avoidance is a common pattern in families of patients with anorexia nervosa (AN), but little systematic controlled research has been conducted to elucidate the formal mechanics of such interaction. Forty family triads with daughters suffering from AN were compared to 40 matched control (CON) triads, on five measures of conflictual family situations. Results revealed that the AN group had

Yael Latzer; Lee B. Gaber

1998-01-01

270

Familism, Family Environment, and Suicide Attempts among Latina Youth  

ERIC Educational Resources Information Center

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

Pena, Juan B.; Kuhlberg, Jill A.; Zayas, Luis H.; Baumann, Ana A.; Gulbas, Lauren; Hausmann-Stabile, Carolina; Nolle, Allyson P.

2011-01-01

271

Scholastic Achievement and Family Marital Structure: Bedouin-Arab Adolescents from Monogamous and Polygamous Families in Israel.  

ERIC Educational Resources Information Center

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…

Elbedour, Salman; Bart, William M.; Hektner, Joel M.

2000-01-01

272

Family and family therapy in Russia.  

PubMed

This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized. PMID:22515460

Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

2012-04-01

273

The Changing Family Structure.  

ERIC Educational Resources Information Center

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";…

Bernard van Leer Foundation Newsletter, 1993

1993-01-01

274

Family Treatment Unit.  

ERIC Educational Resources Information Center

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…

Sawicki, Donna

275

Boston University Family Medicine  

E-print Network

Boston University Family Medicine Global Health CollaborativeFamily Medicine As part of the Department of Family Medicine at Boston University, the Collaborative is committed to introducing and improving Family Medicine programs around the world. Family Medicine is a holistic specialty that attends

Spence, Harlan Ernest

276

Family Reading Night  

ERIC Educational Resources Information Center

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…

Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

2007-01-01

277

The truncated nuclear family  

Microsoft Academic Search

The truncated nuclear family is defined: it is the garden-variety family “pathology” found. The critical role of polarized continuity and discontinuity values in producing the truncated nuclear family is discussed. There is a brief review of factors in American society which, over the decades since the Second World War, have evolved the nuclear family as a dominant family unit, and

Gerald H. Zuk

1985-01-01

278

Living My Family's Story  

PubMed Central

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

Underhill, Meghan L.; Lally, Robin M.; Kiviniemi, Marc T.; Murekeyisoni, Christine; Dickerson, Suzanne S.

2013-01-01

279

Anticipation in familial leukemia  

SciTech Connect

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. 55 refs., 4 figs.

Horwitz, M.; Jarvik, G.P.; Goode, E.L. [Univ. of Washington, Seattle, WA (United States)

1996-11-01

280

[Familial transthyretin amyloidosis].  

PubMed

A case of familial transthyretin amyloidosis with TTR Cys 114 gene polymorphism is described (first in Russia and third in the world). The clinical picture of the proband was dominated by symptoms of autonomous polyneuropathy (orthostatic hypotension, erectile dysfunction, diarrhea, tachycardia, foot dyshydrosis) and of somatic nerve lesions (dumbness, impaired surface and deep sensitivity in the limbs). The patient presented with vitreous body opacity, disturbed eye movements, lateralized sensory symptoms, and difficulty of speech (baryphonia). Electromyographic quantitative autonomous testing and measurement of evoked sympathetic skin potentials confirmed affection of peripheral nerves. Heart ultrasound revealed restrictive amyloid cardiopathy. Histological analysis showed amyloid deposition in the intestines and sural nerve. The proband, his daughter, brother (monozygous twin), and brother's daughter had mutant TTR Cys 114 gene. The brother also had amyloid deposits in the absence of clinical signs of the disease. Analysis of familial medical history demonstrated autosomal dominant inheritance of this mutation in 4 generations. Its possible origin and clinical features of the disease are discussed. PMID:20143571

Pogromov, A P; Diukova, G M; Koval'chuk, M O; Strokov, I A; Akhmedzhanova, L T; Generozov, E V; Markin, S S

2009-01-01

281

Family Research and Family Therapy: A Reunion?  

ERIC Educational Resources Information Center

Identifies several of the most important forms of recent and current family research and family therapy that are important to clinicians. Suggests that the reunion of clinical and research interests signifies a new growth of the family therapy field. (Author/JAC)

Wynne, Lyman C.

1983-01-01

282

Family Capital: Implications for Interventions with Families  

ERIC Educational Resources Information Center

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…

Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

2011-01-01

283

Importance of Family Routines  

MedlinePLUS

... Pediatric First Aid for Caregivers and Teachers (PedFACTs) Teaching Package First Aid for Families (PedFACTs) Allergies and Asthma Family Life Health Management - Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types ...

284

Family Reunion Health Guide  

MedlinePLUS

... HEALTH GUIDE 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. ...

285

Graduate School INTERNATIONAL FAMILY  

E-print Network

Graduate School Graduate School INTERNATIONAL FAMILY AND COMMUNITY STUDIES Doctor of Philosophy Certificate the doctoral program in International Family and community Studies educates professionals to generate, diffuse, and apply knowledge needed to strengthen communities' capacity for family support

Stuart, Steven J.

286

Choosing a Family Doctor  

MedlinePLUS

... do? Family doctors take care of the physical, mental and emotional health of both their patients and their patients' families. They know your family's health history and how it can affect you. They are ...

287

Media Time Family Pledge  

MedlinePLUS

... Media Time Family Pledge Family Life Listen Media Time Family Pledge Article Body At the beginning and ... them. Kids learn best with small lessons over time as opposed to one big lecture or sit- ...

288

About Familial Pulmonary Fibrosis  

MedlinePLUS

About Familial Pulmonary Fibrosis An estimated 10-15 percent of patients with idiopathic pulmonary fibrosis (IPF) have a form of the pulmonary fibrosis that runs in families. This is called Familial ...

289

A missense (Asp*5O-+Asn) mutation in the lipoprotein lipase gene in two unrelated families with familial lipoprotein lipase deficiency  

Microsoft Academic Search

We have identified the molecular basis for familial lipoprotein lipase (LPL) deficiency in two unrelated families with the syndrome of familial hyperchylomicronemia. All 10 exons of the LPL gene were amplified from the two probands' genomic DNA by polymerase chain reaction. In family 1 of French descent, direct sequencing of the amplification products revealed that the patient was heterozygous for

Kazumi Ishimura-Oka; Clay F. Semenkovich; Fabrizia Faustinella; Ira J. Goldberg; Neil Shachter; Louis C. Smith; Trey Coleman; Winston A. Hide; W. Virgil Brown; Kazuhiro Oka; Lawrence Chan

290

Changing Family, Changing Education  

Microsoft Academic Search

\\u000a Sociologists of education increasingly have recognized the crucial role that families assume in children’s educational development.\\u000a Meanwhile, sociologists have identified major changes in family structure and contemporary family life—among these, increases\\u000a in the number of single-parent and step-parent families, families with older parents, and same-sex families, adoptive families,\\u000a and multiracial families. These changes have compelled sociologists of education to redirect

Laura Hamilton; Regina Werum; Lala Carr Steelman; Brian Powell

291

Systematic review of family functioning in families of children and adolescents with chronic pain  

PubMed Central

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

Lewandowski, Amy S.; Palermo, Tonya M.; Stinson, Jennifer; Handley, Susannah; Chambers, Christine T.

2010-01-01

292

How Are Preferences Revealed?  

PubMed Central

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

Beshears, John; Choi, James J.; Laibson, David; Madrian, Brigitte C.

2009-01-01

293

Ecology and population structure of vibrionaceae in the coastal ocean  

E-print Network

Extensive genetic diversity has been discovered in the microbial world, yet mechanisms that shape and maintain this diversity remain poorly understood. This thesis investigates to what extent populations of the ...

Preheim, Sarah Pacocha

2010-01-01

294

Family Court counselling with separating families.  

PubMed

Family Court counsellors, attached to the Family Court, see married couples who are separating, particularly those already involved, or likely to be, in Court disputes concerning their children. Children seen by the counsellors are from families in crises, and are usually detrimentally affected by family separation, and more so by any accompanying conflict. The impact on them depends on their developmental stage and position in the family system, and may be manifested in aggressive behaviour, general anxiety, psychosomatic symptoms, or manipulation and 'acting out'. The examination of the whole family system is essential to defuse the situation and thereby move the focus from the children; the close cooperation of all professionals working with the family is necessary to achieve this. PMID:7225212

Scambler, D

1980-08-01

295

Stress on the Job: How Family Literacy Program Directors Perceive Occupational Stress  

ERIC Educational Resources Information Center

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…

Sandlin, Jennifer A.; Chen, Chia-Yin

2007-01-01

296

Changing Family Forms.  

ERIC Educational Resources Information Center

Explores the definition of family. Considers three facets of the contemporary family measured by U.S. Census statistics: (1) marriage and divorce trends; (2) declining fertility; and (3) the rise in single-headed families. Addresses the societal changes (economic, cultural, legal, and technological) that have influenced the changes in family

Seibert, M. Therese; Willetts, Marion C.

2000-01-01

297

Families in Transition .  

ERIC Educational Resources Information Center

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…

Bundy, Michael L., Ed.; Gumaer, James, Ed.

1984-01-01

298

THE FAMILY FLAVIVIRIDAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The family Flaviviridae, commonly referred to as the flavivirus family, contains viruses important to both human and veterinary medicine. The term flavivirus can be confusing because it is used both to refer to the family and one of the three genera within that family. The proper name of the viral...

299

Black Families. Third Edition.  

ERIC Educational Resources Information Center

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…

McAdoo, Harriette Pipes, Ed.

300

Familial aggregation analysis of gene expressions  

PubMed Central

Traditional studies of familial aggregation are aimed at defining the genetic (and non-genetic) causes of a disease from physiological or clinical traits. However, there has been little attempt to use genome-wide gene expressions, the direct phenotypic measures of genes, as the traits to investigate several extended issues regarding the distributions of familially aggregated genes on chromosomes or in functions. In this study we conducted a genome-wide familial aggregation analysis by using the in vitro cell gene expressions of 3300 human autosome genes (Problem 1 data provided to Genetic Analysis Workshop 15) in order to answer three basic genetics questions. First, we investigated how gene expressions aggregate among different types (degrees) of relative pairs. Second, we conducted a bioinformatics analysis of highly familially aggregated genes to see how they are distributed on chromosomes. Third, we performed a gene ontology enrichment test of familially aggregated genes to find evidence to support their functional consensus. The results indicated that 1) gene expressions did aggregate in families, especially between sibs. Of 3300 human genes analyzed, there were a total of 1105 genes with one or more significant (empirical p < 0.05) familial correlation; 2) there were several genomic hot spots where highly familially aggregated genes (e.g., the chromosome 6 HLA genes cluster) were clustered; 3) as we expected, gene ontology enrichment tests revealed that the 1105 genes were aggregating not only in families but also in functional categories. PMID:18466548

Rao, Shao-Qi; Xu, Liang-De; Zhang, Guang-Mei; Li, Xia; Li, Lin; Shen, Gong-Qing; Jiang, Yang; Yang, Yue-Ying; Gong, Bin-Sheng; Jiang, Wei; Zhang, Fan; Xiao, Yun; Wang, Qing K

2007-01-01

301

Supervisor referrals to work-family programs.  

PubMed

Supervisors play an important role in determining whether employees use work-family programs. Yet little research has examined the factors that relate to supervisor perceptions of and behaviors surrounding work-family programs. This study builds on past research, the theory of reasoned action, and expectancy theory to explore factors that contribute to supervisors' decisions to refer subordinates to work-family programs. Usable surveys assessing perceptions of work-family programs were completed and returned by 1972 managers in a large government agency. Results revealed that program awareness and instrumentality perceptions both contributed uniquely to predicting the frequency of supervisors' referrals to work-family programs. Supportive attitudes also predicted referrals, but only through their shared relationship with instrumentality perceptions. PMID:15053713

Casper, Wendy J; Fox, Kevin E; Sitzmann, Traci M; Landy, Ann L

2004-04-01

302

Ibsen's truth, family secrets, and family therapy.  

PubMed

In certain Ibsen plays a character (would-be family therapist) enters during a crisis revolving around family secrets. Taking two such plays as models, this paper examines family processes and clinical issues surrounding secrets and myths. In Ghosts, Ibsen demonstrates the tragic foreclosure visited upon the Alvings' lives by a generation of secrecy. For contrast, in The Wild Duck the would-be reformer Gregers brings out the truth, to expose and correct consequences of his father's past machinations. The biographical roots of Ibsen's obsession with truth and illusion are explored. Lastly, the notion that Ibsen and early family therapist were reformers is viewed in historical perspective. PMID:6628642

Grolnick, L

1983-09-01

303

Boundary-Spanning Demands, Personal Mastery, and Family Satisfaction: Individual and Crossover Effects Among Dual-Earner Parents  

Microsoft Academic Search

Grounded in ecological systems theory, this study modeled family satisfaction as a function of family-unfriendly work culture, work–family blurring, and personal mastery, examining both individual crossover effects. Analysis of data from 273 married dual-earner parents revealed that family-unfriendly work culture was negatively related to family satisfaction, whereas personal mastery was positively related to family satisfaction. Mothers' family-unfriendly work culture and

Stephan Desrochers; Leisa D. Sargent; Andrew J. Hostetler

2012-01-01

304

Improving Youth Mental Health through Family-Based Prevention In Family Homeless Shelters.  

PubMed

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

Lynn, Cynthia J; Acri, Mary C; Goldstein, Leah; Bannon, William; Beharie, Nisha; McKay, Mary M

2014-09-01

305

Family assessment: Centripetal and centrifugal family systems  

Microsoft Academic Search

A consideration of interactional style is useful to both researchers and clinicians interested in family assessment. This paper offers data and process evaluation scales designed to determine family interactional style, conceptualized as a continuum ranging from centripetal (CP) to centrifugal (CF), and containing at the midpoint a mixed area in which facets of both the CP and the CF styles

Martha Kelsey-smith; W. Robert Beavers M. D

1981-01-01

306

The Family Relationships Grid: Measuring Family Structure.  

ERIC Educational Resources Information Center

This study examined the Family Relationships Grid (FRG), a new measure of family structure that evaluates alliances, identification, isolation, and the relative strength of sibling and marital relationships. Subjects were 52 female and 35 male adolescents who were recruited through a university course and who each had at least one sibling.…

Copeland, Anne P.; And Others

307

Karyotype analysis and achiasmatic meiosis in pseudoscorpions of the family Chthoniidae (Arachnida: Pseudoscorpiones)  

E-print Network

Karyotype analysis and achiasmatic meiosis in pseudoscorpions of the family Chthoniidae (Arachnida. 2004. Karyotype analysis and achiasmatic meiosis in pseudoscorpions of the family Chthoniidae of prophase I chromosomes in males revealed an achiasmatic mode of meiosis. Findings of the achiasmatic

Stahlavsky, Frantisek

308

Invest in Family*  

PubMed Central

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.

Shah, Nilesh; De Sousa, Avinash

2015-01-01

309

Schizophrenia Genetics Revealed | The Scientist http://the-scientist.com/2011/08/08/schizophrenia-genetics-revealed/[8/9/2011 10:03:33 AM  

E-print Network

Schizophrenia Genetics Revealed | The Scientist http://the-scientist.com/2011/08/08/schizophrenia-genetics-revealed/[8/9/2011 10:03:33 AM] FLICKR, MARCO CASTELLANI The Nutshell Schizophrenia Genetics Revealed Researchers identify new mutations in schizophrenia patients without a family history of the disease. By Jef

310

US weapons secrets revealed  

SciTech Connect

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.

Norris, R.S.; Arkin, W.M.

1993-03-01

311

Shipwrecks Reveal Ocean Currents  

NSDL National Science Digital Library

In this video segment adapted from NOVA, a detailed map showing the trajectories of abandoned ships from the late 1800's is used to reveal the routes of surface currents in the Atlantic Ocean. Animations illustrate the role played by ocean currents in the colonization of North America.

2005-12-17

312

Efficient haplotyping for families  

E-print Network

Hapi is a novel dynamic programming algorithm for haplotyping nuclear families that outperforms contemporary family-based haplotyping algorithms. Haplotypes are useful for mapping and identifying genes which cause and ...

Williams, Amy Lynne, Ph.D. Massachusetts Institute of Technology

2010-01-01

313

EATING DISORDERS FAMILY PROBLEMS  

E-print Network

ANXIETY DEPRESSION EATING DISORDERS FAMILY PROBLEMS GENERAL CONCERNS INTERPERSONAL DIFFICULTIES.946.5117 Counselling and Cyber Counselling Services to Help With: · Anxiety · Depression · Eating disorders · Family

Toronto, University of

314

Improving Family Communications  

MedlinePLUS

... Pediatric First Aid for Caregivers and Teachers (PedFACTs) Teaching Package Infant CPR Anytime® (English/Spanish) Nutrition: What Every Parent Needs to Know Family Life Health Management - Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types ...

315

Helping Friends and Family  

MedlinePLUS

... chapter Join our online community Helping Friends and Family Part of living well with Alzheimerâ??s is adjusting to your â??new normalâ?ť and helping family and friends do the same. Knowing what to ...

316

Family Policy in Scotland   

E-print Network

This briefing looks at the development of family policy in Scotland, considers the interplay between devolved and reserved matters, outlines the Departments of the Scottish Executive responsible for family policy, and considers the relationship...

Wasoff, Fran; Hill, Malcolm

317

Familial Periodic Paralyses  

MedlinePLUS

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 prognosis? What research is ...

318

Heat stroke in familial dysautonomia.  

PubMed

A 14-month-old female with familial dysautonomia was referred to the pediatric department with high fever (41.6 degrees C), watery diarrhea, and vomiting. A few hours later, signs of encephalopathy appeared. Laboratory tests revealed elevated levels of lactate dehydrogenase (3500 U/L), aspartate aminotransferase (640 U/L), alanine aminotransferase (320 U/L), and creatine kinase (28,420 U/L). The diagnosis was heat stroke. Impaired autonomic nervous system function may be another risk factor for the development of heat stroke in young children. PMID:14580663

Tirosh, Irit; Hoffer, Vered; Finkelstein, Yaron; Garty, Ben Zion

2003-08-01

319

Family Relationships From Adolescence to Early Adulthood: Changes in the Family System Following Firstborns’ Leaving Home  

PubMed Central

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

Whiteman, Shawn D.; McHale, Susan M.; Crouter, Ann C.

2010-01-01

320

Fatherhood and Family Support.  

ERIC Educational Resources Information Center

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…

Goetz, Kathy, Ed.

1996-01-01

321

Year of the Family.  

ERIC Educational Resources Information Center

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…

California Agriculture, 1994

1994-01-01

322

The Family Leukemia Association  

ERIC Educational Resources Information Center

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…

Pollitt, Eleanor

1976-01-01

323

Families for All Children.  

ERIC Educational Resources Information Center

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…

Shoultz, Bonnie, Ed.; Kalyanpur, Maya, Ed.

324

Doing Better for Families  

ERIC Educational Resources Information Center

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…

OECD Publishing (NJ3), 2011

2011-01-01

325

Establishing Family Math.  

ERIC Educational Resources Information Center

The Family Math Program is an outgrowth of the Equals Program at the Lawrence Hall of Science at UC Berkeley. Piloted in 1982 in Richmond, California, this widespread program boasts a simple philosophy: Families "doing math" will get the same result as families who read--improved skills and enjoyment. The program also confronts parental math…

Bobango, Janet, Milgram, Joel

1993-01-01

326

The Family Farm Project  

NSDL National Science Digital Library

Kenyon College's Family Farm Project, "a three-year study exploring family farming and community life in Knox County, Ohio," presents an intimate multimedia view of the daily life of the family farm, which some consider a vanishing institution in America.

1996-01-01

327

Treatment of violent families.  

PubMed Central

Family violence is responsible for a significant proportion of homicides, a major cause of premature deaths in African-Americans. This article reviews the prevalence of family violence and explores associated risk factors. Principles and tips of treatment, along with a cognitive framework to guide the actual therapy, are outlined. Finally, issues of preventing family violence are discussed. PMID:2038079

Bell, C. C.; Chance-Hill, G.

1991-01-01

328

FAMILY MEDICINE* Definition Of  

E-print Network

healthcare in family medicine is the achievement of optimal physical and mental health through accessible the patient's total health needs, and provides personal care within one or more fields of medicine. The family in the context of the family and the community. This care emphasizes disease prevention and health promotion

Finley Jr., Russell L.

329

Family Life Cycle Stages  

Microsoft Academic Search

Individual life stages happen within the context of family life. This article describes Betty Carter's and Monica McGoldrick's Family Life Cycle stages as a context for Eric Erikson's stages of psychosocial development, Daniel Levinson's Stages of a Man's Life, and Jean Piaget's stages of cognitive development. The author juxtaposes the tasks of each family life stage with the individual life

M. A. Armour

1995-01-01

330

Religion and the Family.  

ERIC Educational Resources Information Center

Examines religion's place in the social sciences, reciprocal influences of family and religion, cohesion/polarization in American Catholic families, religion in Middletown, USA, gender and religion in Canadian and American students, domestic/religious individualism and suicide, and the New Christian Right's view of the family. (BH)

Thomas, Darwin L., Ed.

1985-01-01

331

Family Member Casualty Assistance  

E-print Network

Family Member Casualty Assistance Handbook Taking Care of Our Own #12;2 TABLE OF CONTENTS 1: Important Documents and Information p 22 Appendix 2: Developing Family Plans in Case Your.S. Army Corps of Engineer (USACE*) Family Members whose Soldier or Department of the Army (DA) Civilian

US Army Corps of Engineers

332

Family Housing Wysocki House  

E-print Network

Family Housing Wysocki House 911 North Pleasant Street University of Massachusetts Amherst, MA):________________________________________ STUDENT ENROLLMENT: Undergrad Graduate Are you a current Family Housing Tenant?_________ UMASS STAFF WOULD LIKE US TO KNOW? LIST REMARKS BELOW: SEE REVERSE SIDE FOR APARTMENT PREFERENCE SELECTION FAMILY

Massachusetts at Amherst, University of

333

Family Member Casualty Assistance  

E-print Network

Family Member Casualty Assistance Handbook Taking Care of Our Own #12;2 TABLE OF CONTENTS 1: Important Documents and Information p 18 Appendix 2: Developing a Family Plan in Case Your.S. Army Corps of Engineer (USACE*) Family Members whose Soldier or Department of the Army (DA) Civilian

US Army Corps of Engineers

334

Family Employability Development Plan.  

ERIC Educational Resources Information Center

In the Family Employability Development Plan (FEDP) process, a facilitator works with the family to help its members acquire the skills to develop their own plan for economic independence. The facilitator helps coordinate the interagency effort and helps the family become empowered to carry out its own plan. Carried out as a pilot project in 13…

Michigan State Dept. of Education, Lansing. Adult Extended Learning Services.

335

Employment Characteristics of Families  

NSDL National Science Digital Library

The Bureau of Labor Statistics site offers data on the employment characteristics of American families. The statistics include data on employment and unemployment in families by race, relationship, sex, marital status, presence of children in the family, and presence of children under three, among others. The data can be accessed from a table of contents or reviewed in an extensive news release.

336

Strengthening America's Families.  

ERIC Educational Resources Information Center

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…

Alvarado, Rose; Kumpfer, Karol

2000-01-01

337

Socialization and Family Violence.  

ERIC Educational Resources Information Center

Community professionals are dealing increasingly with family conflict and violence but typically have little training in this area. Family dynamics in the causation and consequences of intra-family aggression were studied in a project involving seven groups of community professionals, including lawyers, ministers, physicians, police, nurses,…

Hutchison, Ira W.

338

Family Customs and Traditions.  

ERIC Educational Resources Information Center

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…

MacGregor, Cynthia

339

Familial hyperuricemic nephropathy  

Microsoft Academic Search

This report describes a Polynesian family that had the rare combination of hyperuricemia, precocious gout, hypertension, and renal failure at an early age, with an autosomal dominant inheritance. One family member had renal biopsy evidence of interstitial urate crystal deposition, a surprisingly uncommon observation in such families, and most had decreased fractional excretion of urate, reflecting either decreased secretion or

Reiter Loretta; A. Mark Brown

1995-01-01

340

Families and Assisted Living  

ERIC Educational Resources Information Center

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…

Gaugler, Joseph E.; Kane, Robert L.

2007-01-01

341

Fields of Toil: A Migrant Family's Journey.  

ERIC Educational Resources Information Center

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…

Valle, Isabel

342

Gene Family Evolution across 12 Drosophila Genomes  

Microsoft Academic Search

Comparison of whole genomes has revealed large and frequent changes in the size of gene families. These changes occur because of high rates of both gene gain (via duplication) and loss (via deletion or pseudogenization), as well as the evolution of entirely new genes. Here we use the genomes of 12 fully sequenced Drosophila species to study the gain and

Matthew W. Hahn; Mira V. Han; Sang-Gook Han

2007-01-01

343

Some Family Antecedents of Severe Shyness.  

ERIC Educational Resources Information Center

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)

Gilmartin, Brian G.

1985-01-01

344

Methadone Maintenance: The Addict's Family Recreated.  

ERIC Educational Resources Information Center

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)

Schwartzman, John; Bokos, Peter

1979-01-01

345

Family Emergency Preparedness Plan 1 Family Emergency Preparedness Plan  

E-print Network

#12;#12;Family Emergency Preparedness Plan 1 Family Emergency Preparedness Plan Why Plan Emergency Telephone Numbers.....................................................26 Credits The Family Military Department, Emergency Management Division. #12;2 Family Emergency Preparedness Plan Why plan

Noble, James S.

346

Family Environment and Social Development in Gifted Students  

ERIC Educational Resources Information Center

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…

Olszewski-Kubilius, Paula; Lee, Seon-Young; Thomson, Dana

2014-01-01

347

Grandparents' Involvement and Support in Families with Children with Disabilities  

Microsoft Academic Search

This study reviews recent literature related to grandparents' involvement and support for grandchildren with disabilities and their grandchildrens' family. The literature reveals that grandparents' initial reactions are similar to parents' reactions of shock, anger, and grief when they learn a grandchild has a disability. Over time, grandparents become involved in their grandchild's family system, providing practical and emotional support. Factors

Misuk Lee; J. Emmett Gardner

2010-01-01

348

Results Not Typical: One Latino Family's Experiences in Higher Education  

ERIC Educational Resources Information Center

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…

Jimenez-Silva, Margarita; Jimenez Hernandez, Norma V.; Luevanos, Ruth; Jimenez, Dulcemonica; Jimenez, Abel, Jr.

2009-01-01

349

AIDS family caregiving: transitions through uncertainty.  

PubMed

The purpose of this study was to describe the experience of AIDS family caregiving. Grounded theory provided the methodological basis for qualitative data generation and analysis. Extensive interviews were conducted with 53 individuals (lovers, spouses, parents of either adults or children with AIDS, siblings, and friends) who were taking care of a person with AIDS at home. Relevant features of the social context of AIDS family caregiving were explored. Findings revealed the basic social psychological problem of Uncertainty, a core category of Transitions Through Uncertainty, and five subcategories: Managing and Being Managed by the Illness; Living With Loss and Dying; Renegotiating the Relationship; Going Public; and Containing the Spread of HIV. Stages and strategies of each subcategory detailed individuals' responses to the challenges of AIDS family caregiving and elaborated the day-to-day experiences. Uncertainty as a critical challenge for individuals and families facing life-threatening illness is discussed in light of recent research. PMID:1956812

Brown, M A; Powell-Cope, G M

1991-01-01

350

Revealing power in truth  

PubMed Central

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

Lee, Kelley

2015-01-01

351

[Cervicobrachial neuralgia revealing neurosarcoma].  

PubMed

Malignant peripheral nerve sheath tumor (MPNST) or neurofibrosarcoma, previously described as malignant Schwannoma or neurosarcoma, is an extremely rare cause of malignancy localized in the neck. Half of reported cases occurred in patients with neurofibromatosis in Von Recklinghausen disease type I. Typical features include high grade malignancy and a tendency to recurrence and distant metastases. We report the case of a 56-year-old woman with neurosarcoma of the neck, which was revealed by a cervicobrachial neuralgia. The physical examination found a mass on the left side of the neck. Plain radiographs showed osteoarthritis. MRI showed a well-defined paravertebral mass. Pathologic diagnosis was neurosarcoma. Radiotherapy was delivered. PMID:18342062

Tekaya, R; Hamdi, W; Azzouz, D; Bouaziz, M; Jaafoura, M H; Ladeb, M F; Kchir, M Montacer

2008-01-01

352

Family Ties: Communicating Identity Through Jointly Told Family Stories  

Microsoft Academic Search

Family stories work to construct family identity. Little research, however, has examined storytelling in families. This study examined storytelling content and process to assess the extent to which families jointly integrated or fragmented a shared sense of identity and how these discursive practices relate to family qualities. Results of a study involving 58 family triads indicate relationships between story theme

Jody Koenig Kellas

2005-01-01

353

Family dynamics and family psychotherapy of psychosomatic.  

PubMed

Family therapy of psychosomatic disorders is oftern difficult and comparable to the therapy of psychotic patients. Nonetheless, the results published today by authors such as Minuchin and Selvini and our own experiences are promising indeed. We have found that what seemed to be a deep-rooted psychic structure changed rapidly and enduringly if the relationship field changed. Amelioration of symptoms is in many cases easily attained if they are understood in their function within a relational system. Also, we regard the system or family approach as a chance for medical practice. The general practioner who usually deals with family systems has, in our view, an ideal position to bring about change if he uses his authority and trust properly. He has to obtain a positive, not pathology-oriented view and should use family and social resources in spite of engaging in an often fruitless and endless contact with the designated patient, which only serves to maintain and even to increase the homeostatic lock of the family system. PMID:550166

Wirsching, M; Stierlin, H

1979-01-01

354

Incest Family Dynamics  

Microsoft Academic Search

A self-administered questionnaire study in a self-help group for incest families focused on individual family members'perceptions of their interrelationships before and after participation in therapy. The results show that perceptions of the same relationships varied greatly among family members. Before therapy, the father-daughter relationship received the most divergent ratings,with fathers rating it as extremely good and daughters as extremely bad.

Inger J. Sagatun; Louise Prince

1989-01-01

355

Neighborhoods and Families  

Microsoft Academic Search

\\u000a Neighborhoods have a profound impact on children and their families, including health and safety, educational attainment,\\u000a child maltreatment risk, and many others. Yet, surprisingly little is known about the specific mechanisms through which neighborhood\\u000a physical and social characteristics features influence child and family outcomes. This chapter looks at current definitions\\u000a for community and family and reviews research for community effects

James R. McDonell

356

The family and HIV.  

PubMed Central

The impact of HIV and AIDS on the family is described, with particular focus on the situation where the child is the first member of the family to be diagnosed. The results of the social stigma, the effect on relationships together with the global, economic and cultural aspects of the disease make it unique. These issues are discussed and an integrated approach to confidentiality, the provision of services for families and involvement of the community is described. PMID:1743706

Gibb, D M; Duggan, C; Lwin, R

1991-01-01

357

Households and Families  

NSDL National Science Digital Library

The US Census Bureau has released a report which demonstrates that "traditional families" (married couples with children) have begun to stabilize as a percentage of all families in the 1990s, and the growth of single-parent families has slowed. Most of the information in the report comes from the March 1997 Current Population Survey. Users may download the full report as well as detailed tables in .pdf format.

Bryson, Ken.

1998-01-01

358

Favorite Family Traditions  

NSDL National Science Digital Library

Students use the text The Relatives Came by Cynthia Rylant as a springboard for discussion about family traditions. After identifying the traditions observed by the relatives, students meet in small groups to brainstorm new traditions that could arise from the families gathering together during the winter. The lesson is concluded by having each student write about their own favorite family tradition and share it with a small group.

2012-12-08

359

Families Without Fathers  

ERIC Educational Resources Information Center

Common generalizations about children growing up in fatherless families are reexamined. Topics include school achievement, delinquency, masculine identity, role of the mother, and societal attitudes. (NH)

Herzog, Elizabeth; Sudia, Cecelia E.

1972-01-01

360

Understanding Fragile Families  

MedlinePLUS

... school performance. The research showed similar effects of relationship transitions on aggressive, depressive, and withdrawal behaviors. Contrary to expectations that access to college promotes family stability and ...

361

The Family Collider  

E-print Network

Granting that the $SU_c(3) \\times SU_L(2) \\times U(1) \\times SU_f(3)$ Standard Model is valid (or, partially valid), for the real world, we propose the $\\mu^+ e^-$ collider in the $10^2\\, GeV$ range as the family collider. This family collider may work efficiently in producing the family Higgs particles and detecting the effects of family gauge bosons, with the range of sub-sub-fermi's (a few $10^{-2} \\, fermi$'s).

W-Y. Pauchy Hwang

2014-09-22

362

Familial Transient Global Amnesia  

PubMed Central

Following an episode of typical transient global amnesia (TGA), a female patient reported similar clinical attacks in 2 maternal aunts. Prior reports of familial TGA are few, and no previous account of affected relatives more distant than siblings or parents was discovered in a literature survey. The aetiology of familial TGA is unknown. A pathophysiological mechanism akin to that in migraine attacks, comorbidity reported in a number of the examples of familial TGA, is one possibility. The study of familial TGA cases might facilitate the understanding of TGA aetiology. PMID:23275787

Davies, R. Rhys; Larner, A.J.

2012-01-01

363

Familial transient global amnesia.  

PubMed

Following an episode of typical transient global amnesia (TGA), a female patient reported similar clinical attacks in 2 maternal aunts. Prior reports of familial TGA are few, and no previous account of affected relatives more distant than siblings or parents was discovered in a literature survey. The aetiology of familial TGA is unknown. A pathophysiological mechanism akin to that in migraine attacks, comorbidity reported in a number of the examples of familial TGA, is one possibility. The study of familial TGA cases might facilitate the understanding of TGA aetiology. PMID:23275787

Davies, R Rhys; Larner, A J

2012-09-01

364

Asteroid Family Physical Properties  

E-print Network

An asteroid family is typically formed when a larger parent body undergoes a catastrophic collisional disruption, and as such family members are expected to show physical properties that closely trace the composition and mineralogical evolution of the parent. Recently a number of new datasets have been released that probe the physical properties of a large number of asteroids, many of which are members of identified families. We review these data sets and the composite properties of asteroid families derived from this plethora of new data. We also discuss the limitations of the current data, and the open questions in the field.

Masiero, Joseph; Kasuga, Toshihiro; Parker, Alex H

2015-01-01

365

Social Structure of Pilot Whales Revealed by Analytical DNA Profiling  

Microsoft Academic Search

Long-finned pilot whales swim in large, extremely cohesive social groups known as pods. Molecular typing revealed that pod members form a single extended family. Mature males neither disperse from nor mate within their natal pods, a situation unusual for mammals. Such behavior could be explained in terms of inclusive fitness benefits gained by adult males helping the large number of

Bill Amos; Christian Schlotterer; Diethard Tautz

1993-01-01

366

Lineage-Specific Expansion of IFIT Gene Family: An Insight into Coevolution with IFN Gene Family  

PubMed Central

In mammals, IFIT (Interferon [IFN]-induced proteins with Tetratricopeptide Repeat [TPR] motifs) family genes are involved in many cellular and viral processes, which are tightly related to mammalian IFN response. However, little is known about non-mammalian IFIT genes. In the present study, IFIT genes are identified in the genome databases from the jawed vertebrates including the cartilaginous elephant shark but not from non-vertebrates such as lancelet, sea squirt and acorn worm, suggesting that IFIT gene family originates from a vertebrate ancestor about 450 million years ago. IFIT family genes show conserved gene structure and gene arrangements. Phylogenetic analyses reveal that this gene family has expanded through lineage-specific and species-specific gene duplication. Interestingly, IFN gene family seem to share a common ancestor and a similar evolutionary mechanism; the function link of IFIT genes to IFN response is present early since the origin of both gene families, as evidenced by the finding that zebrafish IFIT genes are upregulated by fish IFNs, poly(I:C) and two transcription factors IRF3/IRF7, likely via the IFN-stimulated response elements (ISRE) within the promoters of vertebrate IFIT family genes. These coevolution features creates functional association of both family genes to fulfill a common biological process, which is likely selected by viral infection during evolution of vertebrates. Our results are helpful for understanding of evolution of vertebrate IFN system. PMID:23818968

Liu, Ying; Zhang, Yi-Bing; Liu, Ting-Kai; Gui, Jian-Fang

2013-01-01

367

Fractured families: parental perspectives of the effects of adolescent drug abuse on family life.  

PubMed

Drug use in young people has serious ramifications for health and well-being of young people and their families and continues to be an area of major concern for health workers. Though the task of dealing with drug-related problems falls on families, particularly parents, very little literature has explored parental experiences of managing drug use within the context of family life. Eighteen parents of drug-abusing young people were recruited into this qualitative study that aimed to develop understandings into the effects of adolescent drug use on family life. Findings revealed that the experience of having a drug-abusing adolescent family member had a profound effect on other members of the immediate family. Family relationships were fractured and split as a result of the on-going destructive and damaging behaviour of the drug-abusing young person. Five themes were identified that captured the concept of fractured families. These are: betrayal and loss of trust: 'You had to have the doors locked'; abuse, threats and violence: 'there were holes in the wall'; sibling anger and resentment: 'Better off now with him gone'; isolated, disgraced and humiliated: 'You are on your own with it'; and, feeling blamed: 'You are not a good parent'. Implications for practice and further research are drawn from the findings of this paper. PMID:17343535

Jackson, Debra; Usher, Kim; O'Brien, Louise

368

Metabolic Regulation by p53 Family Members  

PubMed Central

The function of p53 is best understood in response to genotoxic stress, but increasing evidence suggests that p53 also plays a key role in the regulation of metabolic homeostasis. p53 and its family members directly influence various metabolic pathways, enabling cells to respond to metabolic stress. These functions are likely to be important for restraining the development of cancer but could also have a profound effect on the development of metabolic diseases, including diabetes. A better understanding of the metabolic functions of p53 family members may aid in the identification of therapeutic targets and reveal novel uses for p53-modulating drugs. PMID:23954639

Berkers, Celia R.; Maddocks, Oliver D.K.; Cheung, Eric C.; Mor, Inbal; Vousden, Karen H.

2013-01-01

369

Ancient Writings Revealed!  

NSDL National Science Digital Library

Sometime in the 3rd century BCE, the noted scholar and scientist Archimedes composed a series of diagrams and passages of text on a manuscript that was subsequently written over in the Middle Ages by a monk. Long thought to be lost forever, the document was given new life in 1906 when a Danish professor identified this item. Eventually the document found its way to The Walters Art Museum in Baltimore, and it now appears that scientists and researchers will be able to uncover Archimedesâ?? original writings. This delightful saga will unfold courtesy of this website, created by the Exploratorium Museum in San Francisco. Working in tandem with researchers at the Stanford Synchrotron Radiation Laboratory, they will use an intense X-Ray to reveal the original letters and diagrams. Visitors will be able to watch all of this happen in real time on a webcast (or take a look on the archived webcast after the event is over), and learn about the original document, and how researchers read such ancient texts.

2006-01-01

370

Ten Adaptive Strategies for Family and Work Balance: Advice from Successful Families.  

ERIC Educational Resources Information Center

Investigated adaptive strategies of middle class, dual earner couples (N=47) with children that are successfully managing family and work. Guided by grounded-theory methodology, analysis of interview data revealed these successful couples structured their lives around 10 major strategies. Each strategy is defined and illustrated through the…

Haddock, Shelley A.; Zimmerman, Toni Schindler; Ziemba, Scott J.; Current, Lisa R.

2001-01-01

371

Population- and Family-Based Studies Associate the "MTHFR" Gene with Idiopathic Autism in Simplex Families  

ERIC Educational Resources Information Center

Two methylenetetrahydrofolate reductase gene ("MTHFR") functional polymorphisms were studied in 205 North American simplex (SPX) and 307 multiplex (MPX) families having one or more children with an autism spectrum disorder. Case-control comparisons revealed a significantly higher frequency of the low-activity 677T allele, higher prevalence of the…

Liu, Xudong; Solehdin, Fatima; Cohen, Ira L.; Gonzalez, Maripaz G.; Jenkins, Edmund C.; Lewis, M. E. Suzanne; Holden, Jeanette J. A.

2011-01-01

372

Family Group Conferencing.  

ERIC Educational Resources Information Center

A suburban Pennsylvania school district is increasingly using family group conferences to address incidents of misconduct and violence. Through a reintegrative shaming process, family group conferences allow offenders to face their victims, move past their inappropriate behavior, discard the offender label, make amends, and return to the community…

Taylor, Bruce R.; Kummery, Glenn

1996-01-01

373

Changing Families, Changing Workplaces  

ERIC Educational Resources Information Center

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…

Bianchi, Suzanne M.

2011-01-01

374

Education and the Family.  

ERIC Educational Resources Information Center

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…

Kaplan, Leonard, Ed.

375

Black Families. Interdisciplinary Perspectives.  

ERIC Educational Resources Information Center

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…

Cheatham, Harold E., Ed.; Stewart, James B., Ed.

376

Balancing Family and Work.  

ERIC Educational Resources Information Center

The purpose of this monograph is to present a series of activities designed to teach strategies needed for effectively managing the multiple responsibilities of family and work. The guide contains 11 lesson plans dealing with balancing family and work that can be used in any home economics class, from middle school through college. The lesson…

Yahnke, Sally; And Others

377

Phases of Family Treatment  

ERIC Educational Resources Information Center

This article describes the three major phases of family treatment. Each phase is defined and compared to phases of individual therapy. The position developed in this paper is that the processes and stages of therapy with family systems are significantly different from those of therapy with individuals. (Author)

Freeman, David S.

1976-01-01

378

Teaching Feminist Family Therapy  

Microsoft Academic Search

This paper describes a specialized course on Feminist Family Therapy. Special emphasis is given to the process and content of the course, drawing from the literature on feminist family therapy, feminist pedagogy, and experience from teaching the class. The author describes the isomorphic nature of feminist teaching and feminist practice. Educators are encouraged to define their own gender politics; integrate

Elizabeth Ann Sirles

1994-01-01

379

[Focus: Family Communication].  

ERIC Educational Resources Information Center

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…

Barnes, Richard E., Ed.

1977-01-01

380

Families under Economic Pressure.  

ERIC Educational Resources Information Center

The economic decline of rural America has widespread consequences for families, children, and education. Broad changes in farming and in the rural nonfarm sector have pushed the poverty rate for rural areas in the 1980s higher than the central cities rate. Projections indicate that by the mid-1990s, one-half of all farm families in the midwest may…

Elder, Glen H., Jr.; And Others

381

Families Falling Apart.  

ERIC Educational Resources Information Center

Reviews trends in Black male unemployment, out-of-wedlock births, and the number of Aid to Families with Dependent Children cases over the past 25 years. Argues that family breakdown is creating a state of urban social chaos that could lead to martial law. (FMW)

Moynihan, Daniel Patrick

1990-01-01

382

National Military Family Association  

MedlinePLUS

... quick fact sheet about this program. Military Spouse Scholarships The mission of this scholarship program is to help prepare military spouses for ... better contribute to their family’s financial security. Our scholarships are awarded to spouses of all Uniformed Services ...

383

Busy families' awareness needs  

Microsoft Academic Search

This work examines how awareness systems, a class of technologies that support sustained and effortless communication between individuals and groups, can support family communication. Going beyond the evaluation of specific design concepts, this paper reports on three studies that aimed to answer the following research questions: (a) Do families want to be aware of each other through the day? Or,

Vassilis-javed Khan; Panos Markopoulos

2009-01-01

384

Family Bonding with Universities  

ERIC Educational Resources Information Center

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…

Meer, Jonathan; Rosen, Harvey S.

2010-01-01

385

Asthma and family interaction.  

PubMed Central

Patterns of family interaction were compared in the families of 22 children with chronic asthma, 30 children with diabetes mellitus, and six healthy children. The groups were similar in terms of age (range 4-14 years and mean 10.2 years). Peak expiratory flow and signs of allergy were correlated with family interaction in the subjects with asthma. The following significant findings were made. Family interaction was more disturbed in asthma compared with both the diabetic and the healthy groups. In most of the disturbed families interaction patterns were rigid and enmeshed, but a few showed chaotic and disengaged patterns. There was a negative correlation between peak expiratory flow and disturbed cohesion in non-steroid dependent cases. The severely ill children with asthma living in families with a normal cohesion score had higher IgE concentrations than children living in disturbed families. It is concluded that family interaction should be considered to be an important dimension in the investigation of severe childhood asthma. PMID:3566317

Gustafsson, P A; Kjellman, N I; Ludvigsson, J; Cederblad, M

1987-01-01

386

Home and Family Life.  

ERIC Educational Resources Information Center

The "Goldfinch" is a magazine that introduces children to different aspects of Iowa History. Each issue contains articles to provide in-depth knowledge of a topic about Iowa. The focus of this issue is homes and family life in Iowa history. Selections address what has been important to Iowa's families over time and what homes were like before…

Frese, Millie K., Ed.

1996-01-01

387

The traveling family.  

PubMed

Traveling as a family can be an extraordinarily rewarding experience. Providing good pretravel counsel--and travelers' adherence to it--can decrease the likelihood that illness or injury of the more vulnerable family members will disrupt the adventure! PMID:12687904

Huntington, Mark K

2002-12-01

388

Family-Friendly Art  

ERIC Educational Resources Information Center

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…

Williams, Patterson; Garcia, Maria

2004-01-01

389

Relationships within the aldehyde dehydrogenase extended family.  

PubMed Central

One hundred-forty-five full-length aldehyde dehydrogenase-related sequences were aligned to determine relationships within the aldehyde dehydrogenase (ALDH) extended family. The alignment reveals only four invariant residues: two glycines, a phenylalanine involved in NAD binding, and a glutamic acid that coordinates the nicotinamide ribose in certain E-NAD binary complex crystal structures, but which may also serve as a general base for the catalytic reaction. The cysteine that provides the catalytic thiol and its closest neighbor in space, an asparagine residue, are conserved in all ALDHs with demonstrated dehydrogenase activity. Sixteen residues are conserved in at least 95% of the sequences; 12 of these cluster into seven sequence motifs conserved in almost all ALDHs. These motifs cluster around the active site of the enzyme. Phylogenetic analysis of these ALDHs indicates at least 13 ALDH families, most of which have previously been identified but not grouped separately by alignment. ALDHs cluster into two main trunks of the phylogenetic tree. The largest, the "Class 3" trunk, contains mostly substrate-specific ALDH families, as well as the class 3 ALDH family itself. The other trunk, the "Class 1/2" trunk, contains mostly variable substrate ALDH families, including the class 1 and 2 ALDH families. Divergence of the substrate-specific ALDHs occurred earlier than the division between ALDHs with broad substrate specificities. A site on the World Wide Web has also been devoted to this alignment project. PMID:10210192

Perozich, J.; Nicholas, H.; Wang, B. C.; Lindahl, R.; Hempel, J.

1999-01-01

390

Alcohol Consumption Patterns among Adolescents are Related to Family Structure and Exposure to Drunkenness within the Family: Results from the SEYLE Project  

PubMed Central

There is expedient evidence showing that differences in adolescent alcohol consumption and other risk-behaviour depend on both family structure and family member drunkenness exposure. Data were obtained among adolescents (N = 12,115, mean age 14.9 ± 0.89) in Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain within the European Union’s 7th Framework Programme funded project, ‘Saving and Empowering Young Lives in Europe (SEYLE)’. The current study reveals how adolescents’ alcohol consumption patterns are related to their family structure and having seen their family member drunk. The results revealed statistically significant differences in adolescent alcohol consumption depending on whether the adolescent lives in a family with both birth parents, in a single-parent family or in a family with one birth parent and one step-parent. The study also revealed that the abstaining from alcohol percentage among adolescents was greater in families with both birth parents compared to other family types. The study also showed that the more often adolescents see their family member drunk the more they drink themselves. There is no difference in adolescent drinking patterns whether they see their family member drunk once a month or once a week. This study gives an insight on which subgroups of adolescents are at heightened risk of alcohol abuse and that decrease of family member drunkenness may have positive effects on the drinking habits of their children. PMID:25493392

Rüütel, Erik; Sisask, Merike; Värnik, Airi; Värnik, Peeter; Carli, Vladimir; Wasserman, Camilla; Hoven, Christina W.; Sarchiapone, Marco; Apter, Alan; Balazs, Judit; Bobes, Julio; Brunner, Romuald; Corcoran, Paul; Cosman, Doina; Haring, Christian; Iosue, Miriam; Kaess, Michael; Kahn, Jean-Pierre; Poštuvan, Vita; Sáiz, Pilar A.; Wasserman, Danuta

2014-01-01

391

What Is a Family?: Accepting Various Styles of Japanese Families  

ERIC Educational Resources Information Center

In this article, the authors talk about the family and how students think of a family. They discuss a family defined in a law and various styles of families in reality. A lesson plan about "What is a Family?" is presented. (Contains 1 note.)

Sugiyama, Takashi; Ofuji, Keiko

2003-01-01

392

Family Relations and the Internet: Exploring a Family Boundaries Approach  

Microsoft Academic Search

The introduction of new technologies such as the Internet into the household can po- tentially change the quality of family relationships. We developed and tested a family boundaries approach, suggesting that frequency and type of Internet use are nega- tively related to family time and positively related to family conflicts, yielding a low overall perception of family cohesion. We also

Gustavo S. Mesch

2006-01-01

393

Engaging Families in In-Home Family Intervention  

ERIC Educational Resources Information Center

Boys Town has created a program called In-Home Family Services to deliver help to families in stress. In-home family intervention programs have become widely used to help more families who are at risk and experiencing difficulties with a wide range of problems including domestic violence, child behavior problems, parent-child and family

Thompson, Ronald W.; Koley, Sarah

2014-01-01

394

Oury Family Papers  

NSDL National Science Digital Library

The Oury Family was an Arizona pioneer family, prominent in territorial political and military affairs. Their number included William S. Oury, who served as the first mayor of Tucson in 1864. He later purchased the "Arizonian" newspaper in Tubac and moved it to Tucson. Other family members contributed to the spirit and culture of the Arizona territory during the late 19th century as well. This site provides interested parties with access to their family papers, which are part of the University of Arizona Libraries Special Collections. First-time visitors should check out the Finding Aid area, as it will help them get acclimated to the breadth of the materials. The documents include family correspondence, diaries, photographs, deeds, articles, and speeches related to the Ourys' involvement in Arizona territorial military experience. It's quite a collection and one that anyone with an interest in American history will find most edifying.

395

Children's Loneliness, Sense of Coherence, Family Climate, and Hope: Developmental Risk and Protective Factors  

Microsoft Academic Search

The study examined the contributions of individual and familial variables for the prediction of loneliness as a developmental risk and the sense of coherence as a protective factor. The sample consisted of 287 children from grades 5–6. Their loneliness, sense of coherence, hope, effort, and family climate were assessed. Separate hierarchical multiple regression analyses revealed that family cohesion and children's

Adi Sharabi; Uzi Levi; Malka Margalit

2012-01-01

396

Understanding Adoptive Families: An Integrative Review of Empirical Research and Future Directions for Counseling Psychology  

ERIC Educational Resources Information Center

Contrary to societal stereotypes about adoption, this integrative review of published empirical research on adoptive families noted several positive and few negative out-comes with regard to satisfaction with the adoption, familial functioning, and parent-child communication. The critical analysis of 38 studies on adoptive families revealed a…

O'Brien, Karen M.; Zamostny, Kathy P.

2003-01-01

397

Family Functioning and the Development of Trust and Intimacy among Adolescents in Residential Treatment  

ERIC Educational Resources Information Center

This study examined relations between family cohesion and adaptability (as measured by the Family Adaptability and Cohesion Scales-III) and the formation of trust and intimacy (assessed with the Measure of Psychosocial Development) among adolescents in residential treatment. Bivariate correlation revealed a significant association between family

Coll, Kenneth M.; Powell, Stephanie; Thobro, Patti; Haas, Robin

2010-01-01

398

Support Services for Victims of Political Violence and Their Families: A Comparison between Israelis and Palestinians  

ERIC Educational Resources Information Center

This report summarizes interviews with five social workers who helped families that experienced political violence, and with 16 families that lost a family member due to terrorist activity in Israel and Palestine from 2000 to 2005. Results revealed a great disparity between the Israelis and the Palestinians on the types of and extent of benefits…

Abbott, Douglas A.

2010-01-01

399

Families of Children with Disabilities: Findings from a National Sample of Eighth-Grade Students.  

ERIC Educational Resources Information Center

Family demographics of 8th-grade students with visual impairments (n=89), hearing impairments (n=105), deafness (n=29), and orthopedic impairments (n=60) were compared to those of 22,368 additional U.S. 8th-grade students. Analysis revealed that families of children with disabilities showed higher percentages of divorce or separation, lower family

Hodapp, Robert M.; Krasner, Diane V.

1995-01-01

400

Mothers' Differential Treatment of Their Adolescent Childbearing and Nonchildbearing Children: Contrasts Between and Within Families  

Microsoft Academic Search

This study examined mothers' differential treatment of adolescent sibling pairs in 2 family contexts: families with and without an adolescent childbearing daughter. Results based on mothers' ratings and children's ratings revealed that the mothers of childbearing daughters treated all of their children less affectionately than did the mothers of nonchildbearing adolescents. In families with a childbearing daughter, mothers expected a

Patricia L. East; Leanne J. Jacobson

2003-01-01

401

Diverse Family Types and Out-of-School Learning Time of Young School-Age Children  

ERIC Educational Resources Information Center

Sources of differentials in out-of-school learning time between children in first marriage biological parent families and children in six nontraditional family types are identified. Analyses of time diaries reveal that children in four of the six nontraditional family types spend fewer minutes learning than do children in first marriage biological…

Ono, Hiromi; Sanders, James

2010-01-01

402

Children's Literacy: Children's Books for Healthy Families/Libros de Ninos Para Familias Saludables.  

ERIC Educational Resources Information Center

A 2-year project taught reading methods and provided culturally appropriate books for Spanish-speaking and English-speaking families (year 1, 1,013 families; year 2, 1,408 families). Data from home visits and follow-up surveys (n=207) revealed that positive parent/child interaction and time spent reading to children increased and the number of…

Kock, Jo Anne

2003-01-01

403

Family Factors in Migration Plans of Youth, High School Seniors in St. Lawrence County, New York.  

ERIC Educational Resources Information Center

Analyses of data obtained from 790 questionnaires collected from a sample of public high school seniors in a relatively low income, sparsely settled county in northern New York State in May, 1962, revealed some of the effects of 2 family systems--the immediate family and the extended family--on the migration planning of high school seniors.…

Crawford, Charles O.

404

Distribution of Candida albicans genotypes among family members  

NASA Technical Reports Server (NTRS)

Thirty-three families (71 subjects) were screened for the presence of Candida albicans in mouthwash or stool specimens; 12 families (28 subjects) were culture-positive for this yeast. An enrichment procedure provided a twofold increase in the recovery of C. albicans from mouthwash specimens. Nine of the twelve culture-positive families had two positive members each, two families had three positive members each, and one family had four positive members. Genetic profiles were obtained by three methods: pulsed-field gel electrophoresis; restriction endonuclease analysis, and random amplification of polymorphic DNA analysis. DNA fingerprinting of C. albicans isolated from one body site three consecutive times revealed that each of the 12 families carried a distinct genotype. No two families shared the same strain, and two or more members of a family commonly shared the same strain. Intrafamily genotypic identity (i.e., each member within the family harbored the same strain) was demonstrated in six families. Genotypes of isolates from husband and wife differed from one another in five families. All three methods were satisfactory in determining genotypes; however, we concluded that restriction endonuclease analysis provided adequate resolving power.

Mehta, S. K.; Stevens, D. A.; Mishra, S. K.; Feroze, F.; Pierson, D. L.

1999-01-01

405

Multiple etiologies for Alzheimer disease are revealed by segregation analysis  

SciTech Connect

We have evaluated several transmission models for Alzheimer disease (AD), using the logistic regressive approach in 401 nuclear families of consecutively ascertained and rigorously diagnosed probands. Models postulating no major gene effect, random environmental transmission, recessive inheritance, and sporadic occurrence were rejected under varied assumptions regarding the associations among sex, age, and major gene susceptibility. Transmission of the disorder was not fully explained by a single Mendelian model for all families. Stratification of families as early- and late-onset by using the median of family mean onset ages showed that, regardless of the model studied, two groups of families fit better than a single group. AD in early-onset families is transmitted as an autosomal dominant trait with full penetrance in both sexes and has a gene frequency of 1.5%. Dominant inheritance also gave the best fit of the data in late-onset families, but this hypothesis was rejected, suggesting the presence of heterogeneity within this subset. Our study also revealed that genetically nonsusceptible males and females develop AD, indicating the presence of phenocopies within early-onset and late-onset groups. Moreover, our results suggest that the higher risk to females is not solely due to their increased longevity. 50 refs., 5 tabs.

Rao, V.S.; Connor-Lacke, L.; Cupplies, L.A.; Growdon, J.H.; Farrer, L.A. [Harvard Medical School, Boston, MA (United States); Duijn, C.M. van [Erasmus Univ., Rotterdam (Netherlands)

1994-11-01

406

Family planning education.  

PubMed

17 days were spent devoted to the effort of learning about China's educational approach to family planning in the hope of discovering how they are achieving their remarkable success in reducing population growth. As a member of the 1981 New York University/SIECUS Colloquim in China, it was necessary to rely on the translation provided by the excellent guides. Discussions were focused on questions prepared in advance about the topics that concerned the group. These observations, based on a short and limited exposure, cover the following areas: marriage and family planning policies; the family planning program; school programs; adult education; family planning workers; and unique aspects of the program. China has an official position on marriage and family planning that continues to undergo revisions. The new marriage law sets the minimum ages of marriage at 22 for men and 20 for women. Almost everyone marries, and an unmarried person over age 28 is a rarity. The family planning program in China is carried out by an extensive organizational network at national, provincial, and local government levels. Officials termed it a "propaganda campaign." Hospitals, clinics, and factories invariably displayed posters; a popular set of four presents the advantages of the 1 child family as follows: late marriage is best, for it allows more time to work and study; 1 child is best for the health of the mother; one gets free medical care for his/her child if a family has only 1 child; and there is more time to teach 1 child. The state operated television regularly explains the 1 child policy utilizing special films. According to 1 family planning official, "before marriage there is little sex." There are few abortions for unmarried women. Education about sex is for adults, for those persons who are about to be married. There is little if any sex education in schools. Sexual teaching is not generally acceptable, especially in the rural areas. By contrast, in Shanghai the physiology teaching in the middle school does include sex education and reproduction. Sex information for adults is offered at the time of marriage. Married or about to be married adults are the major target of the state's family planning education effort. The key educators are an extensive network of family planning workers. All hospitals have a family planning office, and there are also family planning workers in the factories. What is unique about the Chinese approach is its use of reward and punishment. PMID:6550674

Hamburg, M V

1983-02-01

407

Family intervention for schizophrenia  

PubMed Central

Background People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. Objectives To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. Search strategy We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). Selection criteria We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. Data collection and analysis We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). Main results This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Authors’ conclusions Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings. PMID:21154340

Pharoah, Fiona; Mari, Jair; Rathbone, John; Wong, Winson

2014-01-01

408

Does Addiction Run in Families?  

MedlinePLUS

Listen to this page Does Addiction Run in Families? Addiction can run in families. If people in your family have addictions, you are more likely to become ... En espańol "Heart disease runs in some families. Addiction runs in ours." Matt's family has a history ...

409

Familial thyroid cancer: a review  

Microsoft Academic Search

Thyroid carcinomas can be sporadic or familial. Familial syndromes are classified into familial medullary thyroid carcinoma (FMTC), derived from calcitonin-producing C cells, and familial non-medullary thyroid carcinoma, derived from follicular cells. The familial form of medullary thyroid carcinoma (MTC) is usually a component of multiple endocrine neoplasia (MEN) IIA or IIB, or presents as pure FMTC syndrome. The histopathological features

Vânia Nosé

2011-01-01

410

75 FR 9247 - Single Family Mortgage Insurance Premium, Single Family  

Federal Register 2010, 2011, 2012, 2013, 2014

...DEVELOPMENT [Docket No. FR-5376-N-13] Single Family Mortgage Insurance Premium, Single Family AGENCY: Office of the Chief Information Officer...the subject proposal. Lenders use the Single Family Premium Collection Subsystem-Upfront...

2010-03-01

411

The Centrality of Values in Families and Family Therapy.  

ERIC Educational Resources Information Center

Values are discussed in terms of development, nature, and implications for family therapy. Clinical examples are used to demonstrate concepts and a model is presented which depicts how the various leverages utilized in family therapy related to family values. (Author)

Trotzer, James P.

1981-01-01

412

The family planning service.  

PubMed

In 1978, 1,521,400 women in Great Britain obtained contraceptives through the National Health Service (NHS) family planning clinics, in 1980 the number was 1,468,000; likewise in 1978 2,118,313 women obtained them through general practitioners who offer a contraceptive service and in 1980 the number was also down, to 2,033,810. There has been little expansion in the provision of family planning clinics or the organization of extra sessions, contrasting with the expansion program of the Family Planning Association (FPA) when they largely had the responsibility of providing services, before 1974. Clinic sessions should be available for people of all ages but young people might respond better to separate, less formal arrangements. For children under age 16 the professional should persuade the child to involve the parents as soon as possible. Health visitors must be well trained in family planning to provide advice and support to patients. With the recent restructuring of Health Authorities, family planning services must not be cut in order to save money. The FPA must ask the government to reissue the May 1974 family planning service Memorandum of Guidance, and must write to those responsible for the supervision of family planning services in this regard. PMID:6550171

Arger, K

1983-01-01

413

Family policy in Germany: appraisal and assessment.  

PubMed

The German government spends about euro 185 billion on measures to support families. This amount is above European Union average, but still, families have become smaller and the number of childless couples has increased. This article outlines some of the 145 German policy measures to support families and their purpose. An assessment that takes into account economic theory and empirical studies shows that an increase of monetary incentives could influence the decision to bear a child only moderately. This implies that policy measures alone cannot be held responsible for the entire difference in fertility rates between countries. Cited studies based on surveys among the German and French populations reveal how different attitudes of the population may also play their role in determining the fertility rate of a country. PMID:19244718

Honekamp, Ivonne

2008-10-01

414

Interrelations between siblings and parents in families living with children with cancer.  

PubMed

Having a child diagnosed with cancer is a stressful event for the family. This exploratory multimethod study utilized both quantitative and qualitative multiinformant methodologies to investigate the relationships between parental family functioning and siblings' health-related quality of life (HRQOL) and to describe interrelations between the experiences of parents and siblings of children with childhood cancer. A total of 14 Japanese families participated in the quantitative study, and 4 families of the 14 participated in the qualitative study. In-depth, semistructured interviews revealed three family-unit stages during the time course of the ill child's treatment that included particular parent-sibling interrelations. We also found strong correlation between parental family functioning and siblings' HRQOL in the quantitative study. The results suggest the importance of family nursing interventions directed to individual family members and the family unit that focus on strengthening the parent-sibling relationship and supporting families who are experiencing childhood cancer. PMID:25538049

Kobayashi, Kyoko; Hayakawa, Akira; Hohashi, Naohiro

2015-02-01

415

Needs of Military Families: Family and Educator Perspectives  

E-print Network

that can cause the family to be more cohesive or pulled apart. Recovering from physical injuries or post-traumatic stress disorder NEEDS OF MILITARY FAMILIES 4 (PTSD) compounds the unique challenges families are already facing with relocations... and deployments. The stress that a family experiences when a family member is recovering from an injury or PTSD may have a significant impact on the functioning of the family. We know there is a sharp rise of PTSD incidences as the number of deployments...

Classen, Audra I.

2014-08-31

416

Predictors of Family Structure  

NSDL National Science Digital Library

This activity is used in an sociology class class for undergraduate students. This activity explores topics of households/families, income and race to understand how family structure and demographic information predict trends in family structure. This activity uses a customized data set made from combining census information from 1950-1990 and guides students through data manipulation using WebCHIP software found at DataCounts!. To open WebCHIP with the dataset for the activity, please see instructions and links in the exercise documents under teaching materials. For more information on how to use WebCHIP, see the How To section on DataCounts!

Maxine Atkinson

417

Managing a Family Budget  

E-print Network

of living you have established. Example Jack and Jane Farmer are not happy with their current financial situation and have decided to take a closer look at their family expenditures. They have been using some of their equity to pay for family... and loan payments are paid, $18,000 is available for family living expenses. Jane works off the farm and has annual take home ? pay of $36,000. The Farmers also earn a small amount of interest income each year. They are satisfied with their current...

McCorkle, Dean; Klinefelter, Danny A.

2008-09-16

418

Salmonella pathogenesis reveals that BMP signaling regulates blood cell homeostasis and immune  

E-print Network

Salmonella pathogenesis reveals that BMP signaling regulates blood cell homeostasis and immune that Decapentaplegic (Dpp; a Drosophila BMP family mem- ber) plays a role in blood cell homeostasis and immune and adult homeostasis in many species. In this family Drosophila Dpp shows greatest amino acid similarity

Newfeld, Stuart J.

419

Choosing television programs by family vote  

Microsoft Academic Search

This study investigated the nature of verbal interaction and interpersonal influence operating within middle?class Midwestern families as they selected television programs for group viewing in their homes. A task?specific Bales?type coding scheme was used to analyze the talk generated by fathers, mothers, older and younger children. Interaction structure, ability to express a preference, preference consensus, and perceptions of influence reveal

James Lull

1978-01-01

420

Family Demands, Social Support and Family Functioning in Taiwanese Families Rearing Children with Down Syndrome  

ERIC Educational Resources Information Center

Background: Down syndrome (DS) affects not only children but also their families. Much remains to be learned about factors that influence how families of children with DS function, especially families in non-Western populations. The purpose of this cross-sectional, correlational study was to examine how family demographics, family demands and…

Hsiao, C-Y.

2014-01-01

421

Family in transition: parents, children and grandparents in lesbian families give meaning to 'doing family'  

Microsoft Academic Search

Lesbian parents, their children and grandparents 'do family' in rich and diverse ways. This article draws on innovative grounded theory research using qualitative, multi-generational family interviews with twenty les- bian-parented families living in Victoria, Australia. The intersection between the public and the private in lesbian family life has been seriously neglected by family researchers, and in particular the perspectives of

Amaryll Perlesz; Rhonda Brown; Jo Lindsay; Ruth McNair; David de Vaus; Marian Pitts

2006-01-01

422

The Family Map: Structured Family Interview to Identify Risks and Strengths in Head Start Families  

Microsoft Academic Search

The Family Map is a semistructured interview developed to assess important aspects of the family and home environment associated with well-being in 3- to 5-year old children. The measure is designed so that it can be used during home visits with Head Start families. Accordingly, it was developed in collaboration with Head Start providers and families. The Family Map systematically

Leanne Whiteside-Mansell; Robert Bradley; Nicola Conners; Patti Bokony

2007-01-01

423

Family Health History and Diabetes  

MedlinePLUS

... Diabetes > Know Your Family Health History Family Health History and Diabetes En espańol Haywood, a physical education ... story > 1 2 3 4 5 Family health history is an important risk factor for developing type ...

424

Welfare Policies and Black Families.  

ERIC Educational Resources Information Center

The family is an important resource for minority persons, and many minority families depend on public welfare for their survival. This article offers a compact analysis of how welfare policies often work to the disadvantage of poor Black families. (Author)

Trader, Harriet Peat

1979-01-01

425

Laetiporus sulphureus lectin and aerolysin protein family.  

PubMed

The parasitic mushroom Laetiporus sulphureus produces a family of lectins (LSL's) sharing 80-90% sequence identity that possesses a low but significant sequence similarity to the bacterial pore-forming toxins mosquitocidal toxin Mtx-2 from Bacillus sphaericus and a toxin from Clostridium septicum. The crystal structure of one member of the L. sulphureus lectins family (LSLa) reveals unexpected structural similarities to the 1-pore-forming toxins from the aerolysin family, namely, aerolysin from the Gram-negative bacterium Aeromonas hydrophila, epsilon-toxin from Clostridium perfringens and parasporin from B. thuringiensis. This similarity presumably indicates that the hemolytic activity of LSLa proceeds through a molecular mechanism that involves the formation of oligomeric transmembrane beta-barrels. Comparison of the crystal structures of the above mentioned proteins reveals common pore-forming modules, which are then distributed both in bacteria and fungi. Currently, it can be stated that the above three dimensional structures have been key in revealing structural similarities that were elusive at the sequence level. A potential corollary from this is that structural studies aimed at determining high resolution structures of aerolysin-like pore-forming toxins, whose biological activity involves large conformational changes, are mandatory to define protein domains or structural motifs with membrane-binding properties. PMID:20687481

Mancheńo, José Miguel; Tateno, Hiroaki; Sher, Daniel; Goldstein, Irwin J

2010-01-01

426

[Familial hypokalemic periodic paralysis].  

PubMed

Recent genetic studies have identified mutations in the genes causative for familial hypokalemic periodic paralysis (F-HypoPP) . The major locus for F-HypoPP is the skeletal muscle calcium channel alpha(1S) subunit (CACNA1S), and two predominant missense mutations were found in the same gene. A small part of other F-HypoPP families has been identified to result from the missense mutations found in the skeletal muscle sodium channel alpha subunit (SCN4A) gene. We analyzed Japanese hypokalemic periodic paralysis patients (familial, sporadic and thyrotoxic), and detected the Arg 528His mutation in two F-HypoPP families. Thus F-HypoPP is related to the functional deficiency of the skeletal muscle ion-channels. PMID:15775665

Ikeda, Y; Okamoto, K

2001-11-01

427

Learning about Familial Hypercholesterolemia  

MedlinePLUS

... mutation) that causes familial hypercholesterolemia is located on chromosome number 19. It contains the information for a protein called ... on only one of the person's two number 19 chromosomes. A person who inherits one copy of the ...

428

Families of Riemann Surfaces  

E-print Network

of Riemann Surfaces and Weil-Petersson Geometry held at Central Connecticut State University, New Britain, CT Cataloging-in-Publication Data Wolpert, Scott A. Families of Riemann surfaces and Weil-Petersson geometry

Wolpert, Scott A.

429

Veterans and their families   

E-print Network

This briefing paper reports on the outcomes of a range of activities undertaken with a number of veterans, veterans’ families, and third and public sector organisations located in Scotland. Our aim was to explore the resettlement experiences...

McKie, Linda; Morrison, Zoe; Thomson, Fionagh; Alstead, Allan

430

My Fact Family  

NSDL National Science Digital Library

Students will use cut out people shapes and number cards to create two addition problems and two subtraction problems using the same three numbers of a fact family to explore the commutative property.

Elizabeth Gehron

2012-08-15

431

Familial Mediterranean fever  

MedlinePLUS

... Recurrent polyserositis; Benign paroxysmal peritonitis; Periodic disease; Periodic fever; FMF ... Familial Mediterranean fever is most often caused by a mutation in the MEFV gene. This gene creates proteins involved in inflammation. ...

432

Titan Casts Revealing Shadow  

NASA Astrophysics Data System (ADS)

A rare celestial event was captured by NASA's Chandra X-ray Observatory as Titan -- Saturn's largest moon and the only moon in the Solar System with a thick atmosphere -- crossed in front of the X-ray bright Crab Nebula. The X-ray shadow cast by Titan allowed astronomers to make the first X-ray measurement of the extent of its atmosphere. On January 5, 2003, Titan transited the Crab Nebula, the remnant of a supernova explosion that was observed to occur in the year 1054. Although Saturn and Titan pass within a few degrees of the Crab Nebula every 30 years, they rarely pass directly in front of it. "This may have been the first transit of the Crab Nebula by Titan since the birth of the Crab Nebula," said Koji Mori of Pennsylvania State University in University Park, and lead author on an Astrophysical Journal paper describing these results. "The next similar conjunction will take place in the year 2267, so this was truly a once in a lifetime event." Animation of Titan's Shadow on Crab Nebula Animation of Titan's Shadow on Crab Nebula Chandra's observation revealed that the diameter of the X-ray shadow cast by Titan was larger than the diameter of its solid surface. The difference in diameters gives a measurement of about 550 miles (880 kilometers) for the height of the X-ray absorbing region of Titan's atmosphere. The extent of the upper atmosphere is consistent with, or slightly (10-15%) larger, than that implied by Voyager I observations made at radio, infrared, and ultraviolet wavelengths in 1980. "Saturn was about 5% closer to the Sun in 2003, so increased solar heating of Titan may account for some of this atmospheric expansion," said Hiroshi Tsunemi of Osaka University in Japan, one of the coauthors on the paper. The X-ray brightness and extent of the Crab Nebula made it possible to study the tiny X-ray shadow cast by Titan during its transit. By using Chandra to precisely track Titan's position, astronomers were able to measure a shadow one arcsecond in diameter, which corresponds to the size of a dime as viewed from about two and a half miles. Illustration of Crab, Titan's Shadow and Chandra Illustration of Crab, Titan's Shadow and Chandra Unlike almost all of Chandra's images which are made by focusing X-ray emission from cosmic sources, Titan's X-ray shadow image was produced in a manner similar to a medical X-ray. That is, an X-ray source (the Crab Nebula) is used to make a shadow image (Titan and its atmosphere) that is recorded on film (Chandra's ACIS detector). Titan's atmosphere, which is about 95% nitrogen and 5% methane, has a pressure near the surface that is one and a half times the Earth's sea level pressure. Voyager I spacecraft measured the structure of Titan's atmosphere at heights below about 300 miles (500 kilometers), and above 600 miles (1000 kilometers). Until the Chandra observations, however, no measurements existed at heights in the range between 300 and 600 miles. Understanding the extent of Titan's atmosphere is important for the planners of the Cassini-Huygens mission. The Cassini-Huygens spacecraft will reach Saturn in July of this year to begin a four-year tour of Saturn, its rings and its moons. The tour will include close flybys of Titan that will take Cassini as close as 600 miles, and the launching of the Huygens probe that will land on Titan's surface. Chandra's X-ray Shadow of Titan Chandra's X-ray Shadow of Titan "If Titan's atmosphere has really expanded, the trajectory may have to be changed." said Tsunemi. The paper on these results has been accepted and is expected to appear in a June 2004 issue of The Astrophysical Journal. Other members of the research team were Haroyoski Katayama (Osaka University), David Burrows and Gordon Garmine (Penn State University), and Albert Metzger (JPL). Chandra observed Titan from 9:04 to 18:46 UT on January 5, 2003, using its Advanced CCD Imaging Spectrometer instrument. NASA's Marshall Space Flight Center, Huntsville, Ala., manages the Chandra program for the Office of Space Science, NASA Headquarters,

2004-05-01

433

Revealing the Beast Within  

NASA Astrophysics Data System (ADS)

Deeply Embedded Massive Stellar Clusters Discovered in Milky Way Powerhouse Summary Peering into a giant molecular cloud in the Milky Way galaxy - known as W49 - astronomers from the European Southern Observatory (ESO) have discovered a whole new population of very massive newborn stars . This research is being presented today at the International Astronomical Union's 25th General Assembly held in Sydney, Australia, by ESO-scientist Joăo Alves. With the help of infrared images obtained during a period of excellent observing conditions with the ESO 3.5-m New Technology Telescope (NTT) at the La Silla Observatory (Chile), the astronomers looked deep into this molecular cloud and discovered four massive stellar clusters, with hot and energetic stars as massive as 120 solar masses. The exceedingly strong radiation from the stars in the largest of these clusters is "powering" a 20 light-year diameter region of mostly ionized hydrogen gas (a "giant HII region"). W49 is one of the most energetic regions of star formation in the Milky Way. With the present discovery, the true sources of the enormous energy have now been revealed for the first time, finally bringing to an end some decades of astronomical speculations and hypotheses. PR Photo 21a/03 : Colour Composite of W49A (NTT+SOFI). PR Photo 21b/03 : Radio and Near-Infrared Composite of W49A Giant molecular clouds Stars form predominantly inside Giant Molecular Clouds which populate our Galaxy, the Milky Way. One of the most prominent of these is W49 , which has a mass of a million solar masses. It is located some 37,000 light-years away and is the most luminous star-forming region known in our home galaxy: its luminosity is several million times the luminosity of our Sun. A smaller region within this cloud is denoted W49A - this is one of the strongest radio-emitting areas known in the Galaxy . Massive stars are excessive in all ways. Compared to their smaller and ligther brethren, they form at an Olympic speed and have a frantic and relatively short life. Formation sites of massive stars are quite rare and, accordingly, most are many thousands of light-years away. For that reason alone, it is in general much more difficult to observe details of massive-star formation. Moreover, as massive stars are generally formed in the main plane of the Galaxy, in the disc where a lot of dust is present, the first stages of such stars are normally hidden behind very thick curtains. In the case of W49A , less than one millionth of the visible light emitted by a star in this region will find its way through the heavy intervening layers of galactic dust and reach the telescopes on Earth. And finally, because massive stars just formed are still very deeply embedded in their natal clouds, they are anyway not detectable at optical wavelengths. Observations of this early phase of the lives of heavy stars must therefore be done at longer wavelengths (where the dust is more transparent), but even so, such natal dusty clouds still absorb a large proportion of the light emitted by the young stars. Infrared observations of W49 ESO PR Photo 21a/03 ESO PR Photo 21a/03 [Preview - JPEG: 464 x 400 pix - 88k [Normal - JPEG: 928 x 800 pix - 972k] ESO PR Photo 21b/03 ESO PR Photo 21b/03 [Preview - JPEG: 400 x 461 pix - 104k [Normal - JPEG: 800 x 922 pix - 1.1M] Captions : PR Photo 21a/03 presents a composite near-infrared colour image from NTT/SofI. It covers a sky area of 5 x 5 arcmin 2 and the red, green and blue colours correspond to the Ks- (wavelength 2.2 µm), H- (1.65 µm) and J-band (1.2 µm), respectively. North is up and East is to the left. The labels identify known radio sources. The main cluster is seen north-east of the region labelled "O3". The colour of a star in this image is mostly a measure of the amount of dust absorption towards this star. Hence, all blue stars in this image are located in front of the star-forming region. PR Photo 21b/03 shows a three-colour composite of the central region of the star-forming region W49A , based on a radio emission map (w

2003-07-01

434

Families-at-risk and home-based intervention: A therapist training model  

Microsoft Academic Search

Home-based family therapy programs are designed to provide intensive family intervention for at-risk children and adolescents. However, examination of the literature reveals limited publications about training therapists for this difficult task. The purpose of this paper is to describe a therapist training model based upon a family-as-context approach to crisis intervention. Specific units covered during the course include: family-as-a-system, structural

John J. Zarski; Carol A. Pastore; Richard N. Shepler

1988-01-01

435

Observed and Perceived Dyadic and Systemic Functioning in Families of Preadolescents With Spina Bifida  

Microsoft Academic Search

Objective: To examine dyadic and systemic family functioning across several domains (conflict, cohesion, and stress) in families of preadolescents with spina bifida in comparison to families of able-bodied preado- lescents (8- and 9-year olds; n 68 in each sample). Methods: Mother-, father-, and child-reported questionnaire data and observational ratings of family behav- ior were employed. Results: Findings revealed significant group

Grayson N. Holmbeck; Rachael Millstein Coakley; Jennifer S. Hommeyer; Wendy E. Shapera; Venette C. Westhoven

2002-01-01

436

Containing Family Clutter  

Microsoft Academic Search

In this paper, we present material from an ongoing ethnographic investigation of family life. Drawing on selected fieldwork\\u000a materials, we look at the ways families deal with household clutter, and in particular how clutter can be contained in bowls\\u000a and drawers. Based on this research, a case is made for rethinking digital media management in domestic settings. We argue\\u000a that

Laurel Swan; Alex S. Taylor; Shahram Izadi; Richard Harper

2007-01-01

437

Swedish Family Policy.  

ERIC Educational Resources Information Center

Family policy remains one of the leading issues of Swedish domestic politics. All parties are agreed that families with children must be given a better deal in the wake of the economic crisis. But how is this to be done and how quickly can it be achieved? Is the expansion of day nursery facilities to be speeded up, or are parents to be given a…

Herrstrom, Staffan

1986-01-01

438

All in the family?  

Microsoft Academic Search

Numerous studies have analyzed the effects of family structure, composition, and resources on socioeconomic status attainment. Fewer studies have explored how these family-based factors affect the variation—or the correlation—between siblings in socioeconomic status. The current study draws on data from the Panel Study of Income Dynamics and provides a descriptive account of the correlations between siblings along a number of

Dalton Conley; Rebecca Glauber

2008-01-01

439

Changing Families, Changing Workplaces  

Microsoft Academic Search

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 distribution. Between 1975 and 2009, the labor force rate of mothers

Suzanne M. Bianchi

2011-01-01

440

Changing Families, Changing Workplaces  

Microsoft Academic Search

Summary: 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 distribution. Between 1975 and 2009, the labor force rate of

Suzanne M. Bianchi

2011-01-01

441

Familial Nasopharyngeal Carcinoma  

Microsoft Academic Search

\\u000a Familial nasopharyngeal carcinoma (NPC) is defined as NPC occurring in two or more first-degree relatives. The rate of familial\\u000a NPC is likely to be about 8% in any cohort of NPC patients in a high-risk region. The risk of a first-degree relative of an\\u000a NPC patient being diagnosed with NPC is 2–15 times that of the general population in the

Kwok Seng Loh

442

Mandolin Family Instruments  

NASA Astrophysics Data System (ADS)

The mandolin family of instruments consists of plucked chordophones, each having eight strings in four double courses. With the exception of the mandobass, the courses are tuned in intervals of fifths, as are the strings in violin family instruments. The soprano member of the family is the mandolin, tuned G3-D4-A4-E5. The alto member of the family is the mandola, tuned C3-G3-D4-A4. The mandola is usually referred to simply as the mandola in the USA, but is called the tenor mandola in Europe. The tenor member of the family is the octave mandolin, tuned G2-D3-A3-E4. It is referred to as the octave mandolin in the USA, and as the octave mandola in Europe. The baritone member of the family is the mandocello, or mandoloncello, tuned C2-G2-D3-A3. A variant of the mandocello not common in the USA is the five-course liuto moderno, or simply liuto, designed for solo repertoire. Its courses are tuned C2-G2-D3-A3-E4. A mandobass was also made by more than one manufacturer during the early twentieth century, though none are manufactured today. They were fretted instruments with single string courses tuned E1-A1-D2-G2. There are currently a few luthiers making piccolo mandolins, tuned C4-G4-D5-A5.

Cohen, David J.; Rossing, Thomas D.

443

The Peale Family Papers  

NSDL National Science Digital Library

Housed at the Smithsonian Institution's National Portrait Gallery, The Charles Willson Peale Family Papers is a boon to researchers in the history and culture of America from the 1730s to the 1880s. Comprised of copies of more than 6,000 documents, spanning three generations of the Peale family, "the archive traces the family's history from the arrival of Charles Peale, a transported felon, through the career of Charles Willson Peale -- artist, Revolutionary soldier, naturalist and museum keeper, and Enlightenment polymath -- down through the nineteenth-century careers and lives of his many children." Unfortunately, the papers themselves are not accessible online, but the site features essays discussing the papers, the history of the Peale family, and the editorial philosophy behind the publication of the first four volumes of the Peale Family Papers. (The entire collection is currently available in microfiche, and bibliographic information about this resource and the print publications of the papers are provided on-site.) The Website also features a photo gallery of paintings either by or of Peale family members.

444

Families and brain death.  

PubMed

It is necessary to support the family of a patient with a progressively worsening severe acute brain injury, and to do this with the utmost understanding of their ultimate hopelessness. Any conversation starts with an explanation of the catastrophic nature of the illness, but also with establishing the point of no return. When brainstem reflexes are lost and the patient has become apneic, family members should be appropriately informed. In contrast to circulatory death, the relatives of such a patient do not see a deceased person in the traditional sense, and even the neurologic progression may not have been obvious to family members. The conversation about brain death with the close relatives is therefore different, and is more detailed than a conversation about cardiopulmonary death. In this review, a six-phase approach of communication with the relatives is proposed. Insightful snippets of personal conversations with family members are included. Communicating with family members also necessarily involves a discussion on the potential suitability for organ donation. Some suggestions on how to approach reluctant family members to accept death of their loved one are included. PMID:25839726

Kompanje, Erwin J O

2015-04-01

445

Chitinase family GH18: evolutionary insights from the genomic history of a diverse protein family  

PubMed Central

Background Chitinases (EC.3.2.1.14) hydrolyze the ?-1,4-linkages in chitin, an abundant N-acetyl-?-D-glucosamine polysaccharide that is a structural component of protective biological matrices such as insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 (GH18) family of chitinases is an ancient gene family widely expressed in archea, prokaryotes and eukaryotes. Mammals are not known to synthesize chitin or metabolize it as a nutrient, yet the human genome encodes eight GH18 family members. Some GH18 proteins lack an essential catalytic glutamic acid and are likely to act as lectins rather than as enzymes. This study used comparative genomic analysis to address the evolutionary history of the GH18 multiprotein family, from early eukaryotes to mammals, in an effort to understand the forces that shaped the human genome content of chitinase related proteins. Results Gene duplication and loss according to a birth-and-death model of evolution is a feature of the evolutionary history of the GH18 family. The current human family likely originated from ancient genes present at the time of the bilaterian expansion (approx. 550 mya). The family expanded in the chitinous protostomes C. elegans and D. melanogaster, declined in early deuterostomes as chitin synthesis disappeared, and expanded again in late deuterostomes with a significant increase in gene number after the avian/mammalian split. Conclusion This comprehensive genomic study of animal GH18 proteins reveals three major phylogenetic groups in the family: chitobiases, chitinases/chitolectins, and stabilin-1 interacting chitolectins. Only the chitinase/chitolectin group is associated with expansion in late deuterostomes. Finding that the human GH18 gene family is closely linked to the human major histocompatibility complex paralogon on chromosome 1, together with the recent association of GH18 chitinase activity with Th2 cell inflammation, suggests that its late expansion could be related to an emerging interface of innate and adaptive immunity during early vertebrate history. PMID:17594485

Funkhouser, Jane D; Aronson, Nathan N

2007-01-01

446

Changing families, changing workplaces.  

PubMed

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 distribution. Between 1975 and 2009, the labor force rate of mothers with children under age eighteen increased from 47.4 percent to 71.6 percent. Mothers today also return to work much sooner after the birth of a child than did mothers half a century ago. High divorce rates and a sharp rise in the share of births to unmarried mothers mean that more children are being raised by a single parent, usually their mother. Workplaces too have changed, observes Bianchi. Today's employees increasingly work nonstandard hours. The well-being of highly skilled workers and less-skilled workers has been diverging. For the former, work hours may be long, but income has s