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Sample records for vps10 domain family

  1. (WO/2009/140972) MODULATION OF THE VPS10P-DOMAIN RECEPTORS FOR THE TREATMENT OF CARDIOVASCULAR DISEASE

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to methods for modulating the activity of one or more Vps10p-domain receptors selected from the group consisting of Sortilin, SorLA, SorCS1, SorCS2 and SorCS3, in an animal and methods for preparation of a medicament for the treatment of abnormal plasma lipid...... concentrations and associated diseases and/or disorders.The modulation is carried out by inhibiting or promoting the binding of ligands to the Vps10p-domain receptor. In vitro and in vivo methods for screening for agents capable of modulation of said Vps10p-domain receptor activity are also provided...

  2. Ligand recognition and domain structure of Vps10p, a vacuolar protein sorting receptor in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Jørgensen, M U; Emr, S D; Winther, Jakob R.

    1999-01-01

    Vp10p is a receptor that sorts several different vacuolar proteins by cycling between a late Golgi compartment and the endosome. The cytoplasmic tail of Vps10p is necessary for the recycling, whereas the lumenal domain is predicted to interact with the soluble ligands. We have studied ligand bind...

  3. Sequence and structural analysis of the Asp-box motif and Asp-box beta-propellers; a widespread propeller-type characteristic of the Vps10 domain family and several glycoside hydrolase families

    Directory of Open Access Journals (Sweden)

    Quistgaard Esben M

    2009-07-01

    Full Text Available Abstract Background The Asp-box is a short sequence and structure motif that folds as a well-defined β-hairpin. It is present in different folds, but occurs most prominently as repeats in β-propellers. Asp-box β-propellers are known to be characteristically irregular and to occur in many medically important proteins, most of which are glycosidase enzymes, but they are otherwise not well characterized and are only rarely treated as a distinct β-propeller family. We have analyzed the sequence, structure, function and occurrence of the Asp-box and s-Asp-box -a related shorter variant, and provide a comprehensive classification and computational analysis of the Asp-box β-propeller family. Results We find that all conserved residues of the Asp-box support its structure, whereas the residues in variable positions are generally used for other purposes. The Asp-box clearly has a structural role in β-propellers and is highly unlikely to be involved in ligand binding. Sequence analysis of the Asp-box β-propeller family reveals it to be very widespread especially in bacteria and suggests a wide functional range. Disregarding the Asp-boxes, sequence conservation of the propeller blades is very low, but a distinct pattern of residues with specific properties have been identified. Interestingly, Asp-boxes are occasionally found very close to other propeller-associated repeats in extensive mixed-motif stretches, which strongly suggests the existence of a novel class of hybrid β-propellers. Structural analysis reveals that the top and bottom faces of Asp-box β-propellers have striking and consistently different loop properties; the bottom is structurally conserved whereas the top shows great structural variation. Interestingly, only the top face is used for functional purposes in known structures. A structural analysis of the 10-bladed β-propeller fold, which has so far only been observed in the Asp-box family, reveals that the inner strands of the

  4. Protein kinase C and rho activated coiled coil protein kinase 2 (ROCK2 modulate Alzheimer's APP metabolism and phosphorylation of the Vps10-domain protein, SorL1

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    Ehrlich Michelle E

    2010-12-01

    Full Text Available Abstract Background Generation of the amyloid β (Aβ peptide of Alzheimer's disease (AD is differentially regulated through the intracellular trafficking of the amyloid β precursor protein (APP within the secretory and endocytic pathways. Protein kinase C (PKC and rho-activated coiled-coil kinases (ROCKs are two "third messenger" signaling molecules that control the relative utilization of these two pathways. Several members of the Vps family of receptors (Vps35, SorL1, SorCS1 play important roles in post-trans-Golgi network (TGN sorting and generation of APP derivatives, including Aβ at the TGN, endosome and the plasma membrane. We now report that Vps10-domain proteins are candidate substrates for PKC and/or ROCK2 and act as phospho-state-sensitive physiological effectors for post-TGN sorting of APP and its derivatives. Results Analysis of the SorL1 cytoplasmic tail revealed multiple consensus sites for phosphorylation by protein kinases. SorL1 was subsequently identified as a phosphoprotein, based on sensitivity of its electrophoretic migration pattern to calf intestine alkaline phosphatase and on its reaction with anti-phospho-serine antibodies. Activation of PKC resulted in increased shedding of the ectodomains of both APP and SorL1, and this was paralleled by an apparent increase in the level of the phosphorylated form of SorL1. ROCK2, the neuronal isoform of another protein kinase, was found to form complexes with SorL1, and both ROCK2 inhibition and ROCK2 knockdown enhanced generation of both soluble APP and Aβ. Conclusion These results highlight the potential importance of SorL1 in elucidating phospho-state sensitive mechanisms in the regulation of metabolism of APP and Aβ by PKC and ROCK2.

  5. The Popeye domain-containing gene family.

    Science.gov (United States)

    Brand, Thomas

    2005-01-01

    The Popeye domain-containing gene family has been isolated on the basis of a subtractive screen aiming at the identification of novel genes with a heart-restricted gene expression pattern. The gene family codes for membrane proteins containing three transmembrane domains. The carboxy-terminal part of the protein is localized to the cytoplasm and contains a protein domain with high sequence conservation named the Popeye domain. This domain is involved in protein homo dimerization. The gene family is expressed in heart and skeletal muscle cells as well as smooth muscle cells. In addition, Popdc genes are expressed in other cell types such as neuronal cells in restricted areas of the brain, spinal cord, and dorsal root ganglia, and in various epithelial cells. Recently, it has been proposed that Popdc proteins may function as a novel family of adhesion proteins. That the expression pattern has been conserved during evolution and is very similar in all vertebrate classes and also in basal chordates suggests that Popdc proteins play an important role in cardiac and skeletal muscle.

  6. Integral UBL domain proteins: a family of proteasome interacting proteins

    DEFF Research Database (Denmark)

    Hartmann-Petersen, Rasmus; Gordon, Colin

    2004-01-01

    The family of ubiquitin-like (UBL) domain proteins (UDPs) comprises a conserved group of proteins involved in a multitude of different cellular activities. However, recent studies on UBL-domain proteins indicate that these proteins appear to share a common property in their ability to interact wi...

  7. A multi-domain approach to asteroid families identification

    CERN Document Server

    Carruba, V; Nesvorný, D; Roig, F; Huaman, M E; Souami, D

    2013-01-01

    Previous works have identified families halos by an analysis in proper elements domains, or by using Sloan Digital Sky Survey-Moving Object Catalog data, fourth release (SDSS-MOC4) multi-band photometry to infer the asteroid taxonomy, or by a combination of the two methods. The limited number of asteroids for which geometric albedo was known until recently discouraged in the past the extensive use of this additional parameter, which is however of great importance in identifying an asteroid taxonomy. The new availability of geometric albedo data from the Wide-field Infrared Survey Explorer (WISE) mission for about 100,000 asteroids significantly increased the sample of objects for which such information, with some errors, is now known. In this work we proposed a new method to identify families halos in a multi-domain space composed by proper elements, SDSS-MOC4 (a*,i-z) colors, and WISE geometric albedo for the whole main belt (and the Hungaria and Cybele orbital regions). Assuming that most families were crea...

  8. Reconceptualizing the Domain and Boundaries of Family Life Education

    Science.gov (United States)

    Myers-Walls, Judith A.; Ballard, Sharon M.; Darling, Carol Anderson; Myers-Bowman, Karen S.

    2011-01-01

    Many scholars have defined family life education (FLE), and some have differentiated it from other family-related fields. For example, Doherty (1995) provided a definition of the boundaries between FLE and family therapy; however, we believe those criteria can be improved. We explore the professions of family life education, family therapy, and…

  9. Syntaxin 7 complexes with mouse Vps10p tail interactor 1b, syntaxin 6, vesicle-associated membrane protein (VAMP)8, and VAMP7 in b16 melanoma cells.

    Science.gov (United States)

    Wade, N; Bryant, N J; Connolly, L M; Simpson, R J; Luzio, J P; Piper, R C; James, D E

    2001-06-01

    Syntaxin 7 is a mammalian target soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) involved in membrane transport between late endosomes and lysosomes. The aim of the present study was to use immunoaffinity techniques to identify proteins that interact with Syntaxin 7. We reasoned that this would be facilitated by the use of cells producing high levels of Syntaxin 7. Screening of a large number of tissues and cell lines revealed that Syntaxin 7 is expressed at very high levels in B16 melanoma cells. Moreover, the expression of Syntaxin 7 increased in these cells as they underwent melanogenesis. From a large scale Syntaxin 7 immunoprecipitation, we have identified six polypeptides using a combination of electrospray mass spectrometry and immunoblotting. These polypeptides corresponded to Syntaxin 7, Syntaxin 6, mouse Vps10p tail interactor 1b (mVti1b), alpha-synaptosome-associated protein (SNAP), vesicle-associated membrane protein (VAMP)8, VAMP7, and the protein phosphatase 1M regulatory subunit. We also observed partial colocalization between Syntaxin 6 and Syntaxin 7, between Syntaxin 6 and mVti1b, but not between Syntaxin 6 and the early endosomal t-SNARE Syntaxin 13. Based on these and data reported previously, we propose that Syntaxin 7/mVti1b/Syntaxin 6 may form discrete SNARE complexes with either VAMP7 or VAMP8 to regulate fusion events within the late endosomal pathway and that these events may play a critical role in melanogenesis.

  10. Longins: a new evolutionary conserved VAMP family sharing a novel SNARE domain.

    Science.gov (United States)

    Filippini, F; Rossi, V; Galli, T; Budillon, A; D'Urso, M; D'Esposito, M

    2001-07-01

    This article describes the discovery of a novel SNARE domain that might be involved in the regulation of membrane fusion. This domain is shared by a novel family of VAMPs called long VAMPs or longins. Members of this family are more conserved among eukaryotes than are classical VAMPs, possibly because of their underlying basic SNARE function.

  11. Satisfaction Domains Differ between the Patient and Their Family in Adult Intensive Care Units

    Science.gov (United States)

    Song, Ge; Sim, Pei Zhen; Ting, Kit Cheng; Yoo, Jeffrey Kwang Sui; Wang, Qing Li; Mascuri, Raudhah Binte Haji Mohamad; Ong, Venetia Hui Ling; Phua, Jason; Kowitlawakul, Yanika

    2016-01-01

    Background. Patients' and family's satisfaction data from the Asian intensive care units (ICUs) is lacking. Objective. Domains between patient and family satisfaction and contribution of each domain to the general satisfaction were studied. Method. Over 3 months, adult patients across 4 ICUs staying for more than 48 hours with abbreviated mental test score of 7 or above and able to understand English and immediate family members were surveyed by separate validated satisfaction questionnaires. Results. Two hundred patients and 194 families were included in the final analysis. Significant difference in the satisfaction scores was observed between the ICUs. Patients were most and least satisfied in the communication (4.2 out of 5) and decision-making (2.9 out of 5) domains, respectively. Families were most and least satisfied in the relationship with doctors (3.9 out of 5) and family's involvement domains (3.3 out of 5), respectively. Domains contributing most to the general satisfaction were the illness management domain for patients (β coefficient = 0.44) and characteristics of doctors and nurses domain for family (β coefficient = 0.45). Discussion. In an Asian ICU community, patients and families differ in their expectations and valuations of health care processes. Health care providers have difficult tasks in attending to these different domains. PMID:28044138

  12. Satisfaction Domains Differ between the Patient and Their Family in Adult Intensive Care Units.

    Science.gov (United States)

    Mukhopadhyay, Amartya; Song, Ge; Sim, Pei Zhen; Ting, Kit Cheng; Yoo, Jeffrey Kwang Sui; Wang, Qing Li; Mascuri, Raudhah Binte Haji Mohamad; Ong, Venetia Hui Ling; Phua, Jason; Kowitlawakul, Yanika

    2016-01-01

    Background. Patients' and family's satisfaction data from the Asian intensive care units (ICUs) is lacking. Objective. Domains between patient and family satisfaction and contribution of each domain to the general satisfaction were studied. Method. Over 3 months, adult patients across 4 ICUs staying for more than 48 hours with abbreviated mental test score of 7 or above and able to understand English and immediate family members were surveyed by separate validated satisfaction questionnaires. Results. Two hundred patients and 194 families were included in the final analysis. Significant difference in the satisfaction scores was observed between the ICUs. Patients were most and least satisfied in the communication (4.2 out of 5) and decision-making (2.9 out of 5) domains, respectively. Families were most and least satisfied in the relationship with doctors (3.9 out of 5) and family's involvement domains (3.3 out of 5), respectively. Domains contributing most to the general satisfaction were the illness management domain for patients (β coefficient = 0.44) and characteristics of doctors and nurses domain for family (β coefficient = 0.45). Discussion. In an Asian ICU community, patients and families differ in their expectations and valuations of health care processes. Health care providers have difficult tasks in attending to these different domains.

  13. A specificity map for the PDZ domain family.

    Directory of Open Access Journals (Sweden)

    Raffi Tonikian

    2008-09-01

    Full Text Available PDZ domains are protein-protein interaction modules that recognize specific C-terminal sequences to assemble protein complexes in multicellular organisms. By scanning billions of random peptides, we accurately map binding specificity for approximately half of the over 330 PDZ domains in the human and Caenorhabditis elegans proteomes. The domains recognize features of the last seven ligand positions, and we find 16 distinct specificity classes conserved from worm to human, significantly extending the canonical two-class system based on position -2. Thus, most PDZ domains are not promiscuous, but rather are fine-tuned for specific interactions. Specificity profiling of 91 point mutants of a model PDZ domain reveals that the binding site is highly robust, as all mutants were able to recognize C-terminal peptides. However, many mutations altered specificity for ligand positions both close and far from the mutated position, suggesting that binding specificity can evolve rapidly under mutational pressure. Our specificity map enables the prediction and prioritization of natural protein interactions, which can be used to guide PDZ domain cell biology experiments. Using this approach, we predicted and validated several viral ligands for the PDZ domains of the SCRIB polarity protein. These findings indicate that many viruses produce PDZ ligands that disrupt host protein complexes for their own benefit, and that highly pathogenic strains target PDZ domains involved in cell polarity and growth.

  14. Dynamics of the Tec-family tyrosine kinase SH3 domains.

    Science.gov (United States)

    Roberts, Justin M; Tarafdar, Sreya; Joseph, Raji E; Andreotti, Amy H; Smithgall, Thomas E; Engen, John R; Wales, Thomas E

    2016-04-01

    The Src Homology 3 (SH3) domain is an important regulatory domain found in many signaling proteins. X-ray crystallography and NMR structures of SH3 domains are generally conserved but other studies indicate that protein flexibility and dynamics are not. We previously reported that based on hydrogen exchange mass spectrometry (HX MS) studies, there is variable flexibility and dynamics among the SH3 domains of the Src-family tyrosine kinases and related proteins. Here we have extended our studies to the SH3 domains of the Tec family tyrosine kinases (Itk, Btk, Tec, Txk, Bmx). The SH3 domains of members of this family augment the variety in dynamics observed in previous SH3 domains. Txk and Bmx SH3 were found to be highly dynamic in solution by HX MS and Bmx was unstructured by NMR. Itk and Btk SH3 underwent a clear EX1 cooperative unfolding event, which was localized using pepsin digestion and mass spectrometry after hydrogen exchange labeling. The unfolding was localized to peptide regions that had been previously identified in the Src-family and related protein SH3 domains, yet the kinetics of unfolding were not. Sequence alignment does not provide an easy explanation for the observed dynamics behavior, yet the similarity of location of EX1 unfolding suggests that higher-order structural properties may play a role. While the exact reason for such dynamics is not clear, such motions can be exploited in intra- and intermolecular binding assays of proteins containing the domains.

  15. Domain structures and inter-domain interactions defining the holoenzyme architecture of archaeal d-family DNA polymerase.

    Science.gov (United States)

    Matsui, Ikuo; Matsui, Eriko; Yamasaki, Kazuhiko; Yokoyama, Hideshi

    2013-07-05

    Archaea-specific D-family DNA polymerase (PolD) forms a dimeric heterodimer consisting of two large polymerase subunits and two small exonuclease subunits. According to the protein-protein interactions identified among the domains of large and small subunits of PolD, a symmetrical model for the domain topology of the PolD holoenzyme is proposed. The experimental evidence supports various aspects of the model. The conserved amphipathic nature of the N-terminal putative α-helix of the large subunit plays a key role in the homodimeric assembly and the self-cyclization of the large subunit and is deeply involved in the archaeal PolD stability and activity. We also discuss the evolutional transformation from archaeal D-family to eukaryotic B-family polymerase on the basis of the structural information.

  16. Domain Structures and Inter-Domain Interactions Defining the Holoenzyme Architecture of Archaeal D-Family DNA Polymerase

    Directory of Open Access Journals (Sweden)

    Hideshi Yokoyama

    2013-07-01

    Full Text Available Archaea-specific D-family DNA polymerase (PolD forms a dimeric heterodimer consisting of two large polymerase subunits and two small exonuclease subunits. According to the protein-protein interactions identified among the domains of large and small subunits of PolD, a symmetrical model for the domain topology of the PolD holoenzyme is proposed. The experimental evidence supports various aspects of the model. The conserved amphipathic nature of the N-terminal putative α-helix of the large subunit plays a key role in the homodimeric assembly and the self-cyclization of the large subunit and is deeply involved in the archaeal PolD stability and activity. We also discuss the evolutional transformation from archaeal D-family to eukaryotic B-family polymerase on the basis of the structural information.

  17. Identification and Analysis of the SET-Domain Family in Silkworm, Bombyx mori

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    Hailong Zhao

    2015-01-01

    Full Text Available As an important economic insect, Bombyx mori is also a useful model organism for lepidopteran insect. SET-domain-containing proteins belong to a group of enzymes named after a common domain that utilizes the cofactor S-adenosyl-L-methionine (SAM to achieve methylation of its substrates. Many SET-domain-containing proteins have been shown to display catalytic activity towards particular lysine residues on histones, but emerging evidence also indicates that various nonhistone proteins are specifically targeted by this clade of enzymes. To explore their diverse functions of SET-domain superfamily in insect, we identified, cloned, and analyzed the SET-domains proteins in silkworm, Bombyx mori. Firstly, 24 genes containing SET domain from silkworm genome were characterized and 17 of them belonged to six subfamilies of SUV39, SET1, SET2, SUV4-20, EZ, and SMYD. Secondly, SET domains of silkworm SET-domain family were intraspecifically and interspecifically conserved, especially for the catalytic core “NHSC” motif, substrate binding site, and catalytic site in the SET domain. Lastly, further analyses indicated that silkworm SET-domain gene BmSu(var3-9 owned different characterization and expression profiles compared to other invertebrates. Overall, our results provide a new insight into the functional and evolutionary features of SET-domain family.

  18. Identification and Analysis of the SET-Domain Family in Silkworm, Bombyx mori.

    Science.gov (United States)

    Zhao, Hailong; Zheng, Chunqin; Cui, Hongjuan

    2015-01-01

    As an important economic insect, Bombyx mori is also a useful model organism for lepidopteran insect. SET-domain-containing proteins belong to a group of enzymes named after a common domain that utilizes the cofactor S-adenosyl-L-methionine (SAM) to achieve methylation of its substrates. Many SET-domain-containing proteins have been shown to display catalytic activity towards particular lysine residues on histones, but emerging evidence also indicates that various nonhistone proteins are specifically targeted by this clade of enzymes. To explore their diverse functions of SET-domain superfamily in insect, we identified, cloned, and analyzed the SET-domains proteins in silkworm, Bombyx mori. Firstly, 24 genes containing SET domain from silkworm genome were characterized and 17 of them belonged to six subfamilies of SUV39, SET1, SET2, SUV4-20, EZ, and SMYD. Secondly, SET domains of silkworm SET-domain family were intraspecifically and interspecifically conserved, especially for the catalytic core "NHSC" motif, substrate binding site, and catalytic site in the SET domain. Lastly, further analyses indicated that silkworm SET-domain gene BmSu(var)3-9 owned different characterization and expression profiles compared to other invertebrates. Overall, our results provide a new insight into the functional and evolutionary features of SET-domain family.

  19. Domain Structures and Inter-Domain Interactions Defining the Holoenzyme Architecture of Archaeal D-Family DNA Polymerase

    OpenAIRE

    Hideshi Yokoyama; Kazuhiko Yamasaki; Ikuo Matsui; Eriko Matsui

    2013-01-01

    Archaea-specific D-family DNA polymerase (PolD) forms a dimeric heterodimer consisting of two large polymerase subunits and two small exonuclease subunits. According to the protein-protein interactions identified among the domains of large and small subunits of PolD, a symmetrical model for the domain topology of the PolD holoenzyme is proposed. The experimental evidence supports various aspects of the model. The conserved amphipathic nature of the N-terminal putative α-helix of the large sub...

  20. Gender, Ethnicity, Ethnic Identity, and Language Choices of Malaysian Youths: the Case of the Family Domain

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    Mehdi Granhemat

    2017-04-01

    Full Text Available This study examined the relationships between gender, ethnicity, ethnic identity, and language choices of Malaysian multilingual youths in the family domain of language use. Five hundred undergraduate students who belonged to different Malaysian ethnic groups were selected as participants of the study. The participant aged between 17 to 25 years old. To select the participants, a random proportional stratified sampling strategy was developed. A self administered questionnaire survey comprising three sections was used for gathering information about participants’ demographic profiles, their language choices in the family domain, and the concepts of their ethnic identity. To make analyses about the most used languages of the participants and the relationships between variables, SPSS software was run. Descriptive statistics was used to describe the participants’ profiles as well as participants’ used languages in the family domain of language use. Inferential statistics was used to examine relationships between variables. According to results of the study, in the family domain five codes were mostly used by the participants. These five codes were respectively, the Malay language, mixed use of Malay and English, Chinese, Mixed use of Chinese and English, and English. Furthermore, in the family domain, gender did not exert any influence on the choice of language of the multilingual participants, but ethnicity was found to be a determinant of language choice. Ethnic identity was found to influence the language choices of the Malays as well, but it did not affect the Chinese and Indian participants’ language choices in this domain of language use.

  1. Evolution of SET-domain protein families in the unicellular and multicellular Ascomycota fungi

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    Moriyama Etsuko N

    2008-07-01

    Full Text Available Abstract Background The evolution of multicellularity is accompanied by the occurrence of differentiated tissues, of organismal developmental programs, and of mechanisms keeping the balance between proliferation and differentiation. Initially, the SET-domain proteins were associated exclusively with regulation of developmental genes in metazoa. However, finding of SET-domain genes in the unicellular yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe suggested that SET-domain proteins regulate a much broader variety of biological programs. Intuitively, it is expected that the numbers, types, and biochemical specificity of SET-domain proteins of multicellular versus unicellular forms would reflect the differences in their biology. However, comparisons across the unicellular and multicellular domains of life are complicated by the lack of knowledge of the ancestral SET-domain genes. Even within the crown group, different biological systems might use the epigenetic 'code' differently, adapting it to organism-specific needs. Simplifying the model, we undertook a systematic phylogenetic analysis of one monophyletic fungal group (Ascomycetes containing unicellular yeasts, Saccharomycotina (hemiascomycetes, and a filamentous fungal group, Pezizomycotina (euascomycetes. Results Systematic analysis of the SET-domain genes across an entire eukaryotic phylum has outlined clear distinctions in the SET-domain gene collections in the unicellular and in the multicellular (filamentous relatives; diversification of SET-domain gene families has increased further with the expansion and elaboration of multicellularity in animal and plant systems. We found several ascomycota-specific SET-domain gene groups; each was unique to either Saccharomycotina or Pezizomycotina fungi. Our analysis revealed that the numbers and types of SET-domain genes in the Saccharomycotina did not reflect the habitats, pathogenicity, mechanisms of sexuality, or the ability to

  2. Genome dynamics explain the evolution of flowering time CCT domain gene families in the Poaceae.

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    James Cockram

    Full Text Available Numerous CCT domain genes are known to control flowering in plants. They belong to the CONSTANS-like (COL and PREUDORESPONSE REGULATOR (PRR gene families, which in addition to a CCT domain possess B-box or response-regulator domains, respectively. Ghd7 is the most recently identified COL gene to have a proven role in the control of flowering time in the Poaceae. However, as it lacks B-box domains, its inclusion within the COL gene family, technically, is incorrect. Here, we show Ghd7 belongs to a larger family of previously uncharacterized Poaceae genes which possess just a single CCT domain, termed here CCT MOTIF FAMILY (CMF genes. We molecularly describe the CMF (and related COL and PRR gene families in four sequenced Poaceae species, as well as in the draft genome assembly of barley (Hordeum vulgare. Genetic mapping of the ten barley CMF genes identified, as well as twelve previously unmapped HvCOL and HvPRR genes, finds the majority map to colinear positions relative to their Poaceae orthologues. Combined inter-/intra-species comparative and phylogenetic analysis of CMF, COL and PRR gene families indicates they evolved prior to the monocot/dicot divergence ∼200 mya, with Poaceae CMF evolution described as the interplay between whole genome duplication in the ancestral cereal, and subsequent clade-specific mutation, deletion and duplication events. Given the proven role of CMF genes in the modulation of cereals flowering, the molecular, phylogenetic and comparative analysis of the Poaceae CMF, COL and PRR gene families presented here provides the foundation from which functional investigation can be undertaken.

  3. Genome dynamics explain the evolution of flowering time CCT domain gene families in the Poaceae.

    Science.gov (United States)

    Cockram, James; Thiel, Thomas; Steuernagel, Burkhard; Stein, Nils; Taudien, Stefan; Bailey, Paul C; O'Sullivan, Donal M

    2012-01-01

    Numerous CCT domain genes are known to control flowering in plants. They belong to the CONSTANS-like (COL) and PREUDORESPONSE REGULATOR (PRR) gene families, which in addition to a CCT domain possess B-box or response-regulator domains, respectively. Ghd7 is the most recently identified COL gene to have a proven role in the control of flowering time in the Poaceae. However, as it lacks B-box domains, its inclusion within the COL gene family, technically, is incorrect. Here, we show Ghd7 belongs to a larger family of previously uncharacterized Poaceae genes which possess just a single CCT domain, termed here CCT MOTIF FAMILY (CMF) genes. We molecularly describe the CMF (and related COL and PRR) gene families in four sequenced Poaceae species, as well as in the draft genome assembly of barley (Hordeum vulgare). Genetic mapping of the ten barley CMF genes identified, as well as twelve previously unmapped HvCOL and HvPRR genes, finds the majority map to colinear positions relative to their Poaceae orthologues. Combined inter-/intra-species comparative and phylogenetic analysis of CMF, COL and PRR gene families indicates they evolved prior to the monocot/dicot divergence ∼200 mya, with Poaceae CMF evolution described as the interplay between whole genome duplication in the ancestral cereal, and subsequent clade-specific mutation, deletion and duplication events. Given the proven role of CMF genes in the modulation of cereals flowering, the molecular, phylogenetic and comparative analysis of the Poaceae CMF, COL and PRR gene families presented here provides the foundation from which functional investigation can be undertaken.

  4. The starch-binding domain family CBM41 - an in silico analysis of evolutionary relationships

    DEFF Research Database (Denmark)

    Janeček, Štefan; Majzlová, Katarína; Svensson, Birte

    2017-01-01

    residues (Phe, Tyr, His) other than tryptophan, resulting in the existence of six different carbohydrate-binding CBM41 groups, that reflect mostly differences in taxonomy, but which should retain the ability to bind an α-glucan. In addition, three more groups have been proposed that, although lacking......Within the CAZy database, there are 81 carbohydrate-binding module (CBM) families. A CBM represents a non-catalytic domain in a modular arrangement of glycoside hydrolases (GHs). The present in silico study has been focused on starch-binding domains from the family CBM41 that are usually part...... of pullulanases from the α-amylase family GH13. Currently there are more than 1,600 sequences classified in the family CBM41, almost exclusively from Bacteria, and so a study was undertaken in an effort to divide the members into relevant groups (subfamilies) and also to contribute to the evolutionary picture...

  5. Molecular evolution of Cide family proteins: Novel domain formation in early vertebrates and the subsequent divergence

    OpenAIRE

    2008-01-01

    Abstract Background Cide family proteins including Cidea, Cideb and Cidec/Fsp27, contain an N-terminal CIDE-N domain that shares sequence similarity to the N-terminal CAD domain (NCD) of DNA fragmentation factors Dffa/Dff45/ICAD and Dffb/Dff40/CAD, and a unique C-terminal CIDE-C domain. We have previously shown that Cide proteins are newly emerged regulators closely associated with the development of metabolic diseases such as obesity, diabetes and liver steatosis. They modulate many metaboli...

  6. A Protein Domain and Family Based Approach to Rare Variant Association Analysis

    Science.gov (United States)

    Richardson, Tom G.; Shihab, Hashem A.; Rivas, Manuel A.; McCarthy, Mark I.; Campbell, Colin; Timpson, Nicholas J.; Gaunt, Tom R.

    2016-01-01

    Background It has become common practice to analyse large scale sequencing data with statistical approaches based around the aggregation of rare variants within the same gene. We applied a novel approach to rare variant analysis by collapsing variants together using protein domain and family coordinates, regarded to be a more discrete definition of a biologically functional unit. Methods Using Pfam definitions, we collapsed rare variants (Minor Allele Frequency ≤ 1%) together in three different ways 1) variants within single genomic regions which map to individual protein domains 2) variants within two individual protein domain regions which are predicted to be responsible for a protein-protein interaction 3) all variants within combined regions from multiple genes responsible for coding the same protein domain (i.e. protein families). A conventional collapsing analysis using gene coordinates was also undertaken for comparison. We used UK10K sequence data and investigated associations between regions of variants and lipid traits using the sequence kernel association test (SKAT). Results We observed no strong evidence of association between regions of variants based on Pfam domain definitions and lipid traits. Quantile-Quantile plots illustrated that the overall distributions of p-values from the protein domain analyses were comparable to that of a conventional gene-based approach. Deviations from this distribution suggested that collapsing by either protein domain or gene definitions may be favourable depending on the trait analysed. Conclusion We have collapsed rare variants together using protein domain and family coordinates to present an alternative approach over collapsing across conventionally used gene-based regions. Although no strong evidence of association was detected in these analyses, future studies may still find value in adopting these approaches to detect previously unidentified association signals. PMID:27128313

  7. A Protein Domain and Family Based Approach to Rare Variant Association Analysis.

    Directory of Open Access Journals (Sweden)

    Tom G Richardson

    Full Text Available It has become common practice to analyse large scale sequencing data with statistical approaches based around the aggregation of rare variants within the same gene. We applied a novel approach to rare variant analysis by collapsing variants together using protein domain and family coordinates, regarded to be a more discrete definition of a biologically functional unit.Using Pfam definitions, we collapsed rare variants (Minor Allele Frequency ≤ 1% together in three different ways 1 variants within single genomic regions which map to individual protein domains 2 variants within two individual protein domain regions which are predicted to be responsible for a protein-protein interaction 3 all variants within combined regions from multiple genes responsible for coding the same protein domain (i.e. protein families. A conventional collapsing analysis using gene coordinates was also undertaken for comparison. We used UK10K sequence data and investigated associations between regions of variants and lipid traits using the sequence kernel association test (SKAT.We observed no strong evidence of association between regions of variants based on Pfam domain definitions and lipid traits. Quantile-Quantile plots illustrated that the overall distributions of p-values from the protein domain analyses were comparable to that of a conventional gene-based approach. Deviations from this distribution suggested that collapsing by either protein domain or gene definitions may be favourable depending on the trait analysed.We have collapsed rare variants together using protein domain and family coordinates to present an alternative approach over collapsing across conventionally used gene-based regions. Although no strong evidence of association was detected in these analyses, future studies may still find value in adopting these approaches to detect previously unidentified association signals.

  8. Coverage of protein domain families with structural protein-protein interactions: current progress and future trends.

    Science.gov (United States)

    Goncearenco, Alexander; Shoemaker, Benjamin A; Zhang, Dachuan; Sarychev, Alexey; Panchenko, Anna R

    2014-01-01

    Protein interactions have evolved into highly precise and regulated networks adding an immense layer of complexity to cellular systems. The most accurate atomistic description of protein binding sites can be obtained directly from structures of protein complexes. The availability of structurally characterized protein interfaces significantly improves our understanding of interactomes, and the progress in structural characterization of protein-protein interactions (PPIs) can be measured by calculating the structural coverage of protein domain families. We analyze the coverage of protein domain families (defined according to CDD and Pfam databases) by structures, structural protein-protein complexes and unique protein binding sites. Structural PPI coverage of currently available protein families is about 30% without any signs of saturation in coverage growth dynamics. Given the current growth rates of domain databases and structural PPI deposition, complete domain coverage with PPIs is not expected in the near future. As a result of this study we identify families without any protein-protein interaction evidence (listed on a supporting website http://www.ncbi.nlm.nih.gov/Structure/ibis/coverage/) and propose them as potential targets for structural studies with a focus on protein interactions. Published by Elsevier Ltd.

  9. Status of Tamil Language in Singapore: An Analysis of Family Domain

    Science.gov (United States)

    Kadakara, Shanmugam

    2015-01-01

    This paper addresses the phenomenon of Language Maintenance and Language Shift through a qualitative study of Tamil language in the family domain in Singapore. The influence of Singapore's bilingual policy and the institutional support offered for maintenance of Tamil language provide the context in which the central research problem of the status…

  10. Gender, Ethnicity, Ethnic Identity, and Language Choices of Malaysian Youths: The Case of the Family Domain

    Science.gov (United States)

    Granhemat, Mehdi; Abdullah, Ain Nadzimah

    2017-01-01

    This study examined the relationships between gender, ethnicity, ethnic identity, and language choices of Malaysian multilingual youths in the family domain of language use. Five hundred undergraduate students who belonged to different Malaysian ethnic groups were selected as participants of the study. The participant aged between 17 to 25 years…

  11. Molecular evolution of Cide family proteins: Novel domain formation in early vertebrates and the subsequent divergence

    Directory of Open Access Journals (Sweden)

    Sun Zhirong

    2008-05-01

    Full Text Available Abstract Background Cide family proteins including Cidea, Cideb and Cidec/Fsp27, contain an N-terminal CIDE-N domain that shares sequence similarity to the N-terminal CAD domain (NCD of DNA fragmentation factors Dffa/Dff45/ICAD and Dffb/Dff40/CAD, and a unique C-terminal CIDE-C domain. We have previously shown that Cide proteins are newly emerged regulators closely associated with the development of metabolic diseases such as obesity, diabetes and liver steatosis. They modulate many metabolic processes such as lipolysis, thermogenesis and TAG storage in brown adipose tissue (BAT and white adipose tissue (WAT, as well as fatty acid oxidation and lipogenesis in the liver. Results To understand the evolutionary process of Cide proteins and provide insight into the role of Cide proteins as potential metabolic regulators in various species, we searched various databases and performed comparative genomic analysis to study the sequence conservation, genomic structure, and phylogenetic tree of the CIDE-N and CIDE-C domains of Cide proteins. As a result, we identified signature sequences for the N-terminal region of Dffa, Dffb and Cide proteins and CIDE-C domain of Cide proteins, and observed that sequences homologous to CIDE-N domain displays a wide phylogenetic distribution in species ranging from lower organisms such as hydra (Hydra vulgaris and sea anemone (Nematostella vectensis to mammals, whereas the CIDE-C domain exists only in vertebrates. Further analysis of their genomic structures showed that although evolution of the ancestral CIDE-N domain had undergone different intron insertions to various positions in the domain among invertebrates, the genomic structure of Cide family in vertebrates is stable with conserved intron phase. Conclusion Based on our analysis, we speculate that in early vertebrates CIDE-N domain was evolved from the duplication of NCD of Dffa. The CIDE-N domain somehow acquired the CIDE-C domain that was formed around the

  12. The macro domain protein family: structure, functions, and their potential therapeutic implications.

    Science.gov (United States)

    Han, Weidong; Li, Xiaolei; Fu, Xiaobing

    2011-01-01

    Macro domains are ancient, highly evolutionarily conserved domains that are widely distributed throughout all kingdoms of life. The 'macro fold' is roughly 25kDa in size and is composed of a mixed α-β fold with similarity to the P loop-containing nucleotide triphosphate hydrolases. They function as binding modules for metabolites of NAD(+), including poly(ADP-ribose) (PAR), which is synthesized by PAR polymerases (PARPs). Although there is a high degree of sequence similarity within this family, particularly for residues that might be involved in catalysis or substrates binding, it is likely that the sequence variation that does exist among macro domains is responsible for the specificity of function of individual proteins. Recent findings have indicated that macro domain proteins are functionally promiscuous and are implicated in the regulation of diverse biological functions, such as DNA repair, chromatin remodeling and transcriptional regulation. Significant advances in the field of macro domain have occurred in the past few years, including biological insights and the discovery of novel signaling pathways. To provide a framework for understanding these recent findings, this review will provide a comprehensive overview of the known and proposed biochemical, cellular and physiological roles of the macro domain family. Recent data that indicate a critical role of macro domain regulation for the proper progression of cellular differentiation programs will be discussed. In addition, the effect of dysregulated expression of macro domain proteins will be considered in the processes of tumorigenesis and bacterial pathogenesis. Finally, a series of observations will be highlighted that should be addressed in future efforts to develop macro domains as effective therapeutic targets.

  13. The Role of Nuclear Receptor-Binding SET Domain Family Histone Lysine Methyltransferases in Cancer.

    Science.gov (United States)

    Bennett, Richard L; Swaroop, Alok; Troche, Catalina; Licht, Jonathan D

    2017-06-01

    The nuclear receptor-binding SET Domain (NSD) family of histone H3 lysine 36 methyltransferases is comprised of NSD1, NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1). These enzymes recognize and catalyze methylation of histone lysine marks to regulate chromatin integrity and gene expression. The growing number of reports demonstrating that alterations or translocations of these genes fundamentally affect cell growth and differentiation leading to developmental defects illustrates the importance of this family. In addition, overexpression, gain of function somatic mutations, and translocations of NSDs are associated with human cancer and can trigger cellular transformation in model systems. Here we review the functions of NSD family members and the accumulating evidence that these proteins play key roles in tumorigenesis. Because epigenetic therapy is an important emerging anticancer strategy, understanding the function of NSD family members may lead to the development of novel therapies. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  14. Cancer Research Advance in CKLF-like MARVEL Transmembrane Domain Containing Member Family (Review).

    Science.gov (United States)

    Lu, Jia; Wu, Qian-Qian; Zhou, Ya-Bo; Zhang, Kai-Hua; Pang, Bing-Xin; Li, Liang; Sun, Nan; Wang, Heng-Shu; Zhang, Song; Li, Wen-Jian; Zheng, Wei; Liu, Wei

    2016-01-01

    CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of genes first reported at international level by Peking University Human Disease Gene Research Center. The gene products are between chemokines and the transmembrane-4 superfamily. Loaceted in several human chromosomes, CMTMs, which are unregulated in kinds of tumors, are potential tumor suppressor genes consisting of CKLF and CMTM1 to CMTM8. CMTMs play important roles in immune, male reproductive and hematopoietic systems. Also, it has been approved that CMTM family has strong connection with diseases of autoimmunity, haematopoietic system and haematopoietic system. The in-depth study in recent years found the close relation between CMTMs and umorigenesis, tumor development and metastasis. CMTM family has a significant clinical value in diagnosis and treatment to the diseases linking to tumor and immune system.

  15. Rhamnogalacturonan lyase reveals a unique three-domain modular structure for polysaccharide lyase family 4

    DEFF Research Database (Denmark)

    McDonough, Michael A.; Kadirvelraj, Renuka; Harris, Pernille

    2004-01-01

    Rhamnogalacturonan lyase (RG-lyase) specifically recognizes and cleaves alpha-1,4 glycosidic bonds between L-rhamnose and D-galacturonic acids in the backbone of rhamno galacturonan-I, a major component of the plant cell wall polysaccharide, pectin. The three-dimensional structure of RG-lyase fro...... structural homology to non-catalytic domains from other carbohydrate active enzymes.......Rhamnogalacturonan lyase (RG-lyase) specifically recognizes and cleaves alpha-1,4 glycosidic bonds between L-rhamnose and D-galacturonic acids in the backbone of rhamno galacturonan-I, a major component of the plant cell wall polysaccharide, pectin. The three-dimensional structure of RG-lyase from...... Aspergillus aculeatus has been determined to 1.5 Angstrom resolution representing the first known structure from polysaccharide lyase family 4 and of an enzyme with this catalytic specificity. The 508-amino acid polypeptide displays a unique arrangement of three distinct modular domains. Each domain shows...

  16. Structural, evolutionary and functional analysis of the NAC domain protein family in Eucalyptus.

    Science.gov (United States)

    Hussey, Steven G; Saïdi, Mohammed N; Hefer, Charles A; Myburg, Alexander A; Grima-Pettenati, Jacqueline

    2015-06-01

    NAC domain transcription factors regulate many developmental processes and stress responses in plants and vary widely in number and family structure. We analysed the characteristics and evolution of the NAC gene family of Eucalyptus grandis, a fast-growing forest tree in the rosid order Myrtales. NAC domain genes identified in the E. grandis genome were subjected to amino acid sequence, phylogenetic and motif analyses. Transcript abundance in developing tissues and abiotic stress conditions in E. grandis and E. globulus was quantified using RNA-seq and reverse transcription quantitative PCR (RT-qPCR). One hundred and eighty-nine E. grandis NAC (EgrNAC) proteins, arranged into 22 subfamilies, are extensively duplicated in subfamilies associated with stress response. Most EgrNAC genes form tandem duplicate arrays that frequently carry signatures of purifying selection. Sixteen amino acid motifs were identified in EgrNAC proteins, eight of which are enriched in, or unique to, Eucalyptus. New candidates for the regulation of normal and tension wood development and cold responses were identified. This first description of a Myrtales NAC domain family reveals an unique history of tandem duplication in stress-related subfamilies that has likely contributed to the adaptation of eucalypts to the challenging Australian environment. Several new candidates for the regulation of stress, wood formation and tree-specific development are reported.

  17. Genomewide analysis of LATERAL ORGAN BOUNDARIES Domain gene family in Zea mays

    Indian Academy of Sciences (India)

    Yue-Min Zhang; Shi-Zhong Zhang; Cheng-Chao Zheng

    2014-04-01

    The investigation of transcription factor (TF) families is a major focus of postgenomic research. The plant-specific ASYMMETRIC LEAVES2-LIKE (ASL) / LATERAL ORGAN BOUNDARIES Domain (LBD) proteins constitute a major zincfinger-like-domain transcription factor family, and regulate diverse biological processes in plants. However, little is known about LBD genes in maize (Zea mays). In this study, a total of 44 LBD genes were identified in maize genome and were phylogenetically clustered into two groups (I and II), together with LBDs from Arabidopsis. The predicted maize LBDs were distributed across all the 10 chromosomes with different densities. In addition, the gene structures of maize LBDs were analysed. The expression profiles of the maize LBD genes under normal growth conditions were analysed by microarray data and qRT-PCR. The results indicated that LBDs might be involved in various aspects of physiological and developmental processes in maize. To our knowledge, this is the first report of a genomewide analysis of the maize LBD gene family, which would provide valuable information for understanding the classification and putative functions of the gene family.

  18. Systematic analysis of public domain compound potency data identifies selective molecular scaffolds across druggable target families.

    Science.gov (United States)

    Hu, Ye; Wassermann, Anne Mai; Lounkine, Eugen; Bajorath, Jürgen

    2010-01-28

    Molecular scaffolds that yield target family-selective compounds are of high interest in pharmaceutical research. There continues to be considerable debate in the field as to whether chemotypes with a priori selectivity for given target families and/or targets exist and how they might be identified. What do currently available data tell us? We present a systematic and comprehensive selectivity-centric analysis of public domain target-ligand interactions. More than 200 molecular scaffolds are identified in currently available active compounds that are selective for established target families. A subset of these scaffolds is found to produce compounds with high selectivity for individual targets among closely related ones. These scaffolds are currently underrepresented in approved drugs.

  19. Functional Pathways of Social Support for Mental Health in Work and Family Domains Among Chinese Scientific and Technological Professionals.

    Science.gov (United States)

    Gan, Yiqun; Gan, Tingting; Chen, Zhiyan; Miao, Miao; Zhang, Kan

    2015-10-01

    This study investigated the role of social support in the complex pattern of associations among stressors, work-family interferences and depression in the domains of work and family. A questionnaire was administered to a nationwide sample of 11,419 Chinese science and technology professionals. Several structural equation models were specified to determine whether social support functioned as a predictor or a mediator. Using Mplus 5.0, we compared the moderation model, the independence model, the antecedent model and the mediation model. The results revealed that the relationship between work-family interference and social support was domain specific. The independence model fit the data best in the work domain. Both the moderation model and the antecedent model fit the family domain data equally well. The current study was conducted to answer the need for comprehensive investigations of cultural uniqueness in the antecedents of work-family interference. The domain specificity, i.e. the multiple channels of the functions of support in the family domain and not in the work domain, ensures that this study is unique and culturally specific.

  20. Genomewide analysis of the lateral organ boundaries domain gene family in Vitis vinifera.

    Science.gov (United States)

    Cao, Hui; Liu, Cai-Yun; Liu, Chun-Xiang; Zhao, Yue-Ling; Xu, Rui-Rui

    2016-09-01

    In plants, the transcription factor families have been implicated in many important biological processes. These processes include morphogenesis, signal transduction and environmental stress responses. Proteins containing the lateral organ boundaries domain (LBD), which encodes a zinc finger-like domain are only found in plants. This finding indicates that this unique gene family regulates only plant-specific biological processes. LBD genes play crucial roles in the growth and development of plants such as Arabidopsis, Oryza sativa, Zea mays, poplar, apple and tomato. However, relatively little is known about the LBD genes in grape (Vitis vinifera). In this study, we identified 40 LBD genes in the grape genome. A complete overview of the chromosomal locations, phylogenetic relationships, structures and expression profiles of this gene family during development in grape is presented here. Phylogenetic analysis showed that the LBD genes could be divided into classes I and II, together with LBDs from Arabidopsis. We mapped the 40 LBD genes on the grape chromosomes (chr1-chr19) and found that 37 of the predicted grape LBD genes were distributed in different densities across 12 chromosomes. Grape LBDs were found to share a similar intron/exon structure and gene length within the same class. The expression profiles of grape LBD genes at different developmental stages were analysed using microarray data. Results showed that 21 grape LBD genes may be involved in grape developmental processes, including preveraison, veraison and ripening. Finally, we analysed the expression patterns of six LBD genes through quantitative real-time polymerase chain reation analysis. The six LBD genes showed differential expression patterns among the three representative grape tissues, and five of these genes were found to be involved in responses to mannitol, sodium chloride, heat stress and low temperature treatments. To our knowledge, this is the first study to analyse the LBD gene family in

  1. Genomewide analysis of the lateral organ boundaries domain gene family in Vitis vinifera

    Indian Academy of Sciences (India)

    HUI CAO; CAI-YUN LIU; HUN-XIANG LIU; YUE-LING ZHAO; RUI-RUI XU

    2016-09-01

    In plants, the transcription factor families have been implicated in many important biological processes. These processes include morphogenesis, signal transduction and environmental stress responses. Proteins containing the lateral organ bound-aries domain (LBD), which encodes a zinc finger-like domain are only found in plants. This finding indicates that this unique gene family regulates only plant-specific biological processes. LBD genes play crucial roles in the growth and development of plants such as Arabidopsis, Oryza sativa, Zea mays , poplar, apple and tomato. However, relatively little is known about the LBD genes in grape ( Vitis vinifera). In this study, we identified 40 LBD genes in the grape genome. A complete overview of the chromosomal locations, phylogenetic relationships, structures and expression profiles of this gene family during development in grape is presented here. Phylogenetic analysis showed that the LBD genes could be divided into classes I and II, together with LBDs from Arabidopsis. We mapped the 40 LBD genes on the grape chromosomes (chr1–chr19) and found that 37 of the predicted grape LBD genes were distributed in different densities across 12 chromosomes. Grape LBDs were found to share a similar intron/exon structure and gene length within the same class. The expression profiles of grape LBD genes at different developmental stages were analysed using microarray data. Results showed that 21 grape LBD genes may be involved in grape developmental processes, including preveraison, veraison and ripening. Finally, we analysed the expres-sion patterns of six LBD genes through quantitative real-time polymerase chain reation analysis. The six LBD genes showed differential expression patterns among the three representative grape tissues, and five of these genes were found to be involved in responses to mannitol, sodium chloride, heat stress and low temperature treatments. To our knowledge, this is the first study to analyse the LBD gene

  2. Relationship of work-family conflict with burnout and marital satisfaction: cross-domain or source attribution relations?

    Directory of Open Access Journals (Sweden)

    Razieh Bagherzadeh

    2016-03-01

    Conclusion: In terms of practical implication, to avoid creating disadvantages of WIF and FIW,facilitation in two domains of improving work and family conditions can be a useful means to prevent WFC and its consequences.

  3. Analysis of Domain Architecture and Phylogenetics of Family 2 Glycoside Hydrolases (GH2).

    Science.gov (United States)

    Talens-Perales, David; Górska, Anna; Huson, Daniel H; Polaina, Julio; Marín-Navarro, Julia

    2016-01-01

    In this work we report a detailed analysis of the topology and phylogenetics of family 2 glycoside hydrolases (GH2). We distinguish five topologies or domain architectures based on the presence and distribution of protein domains defined in Pfam and Interpro databases. All of them share a central TIM barrel (catalytic module) with two β-sandwich domains (non-catalytic) at the N-terminal end, but differ in the occurrence and nature of additional non-catalytic modules at the C-terminal region. Phylogenetic analysis was based on the sequence of the Pfam Glyco_hydro_2_C catalytic module present in most GH2 proteins. Our results led us to propose a model in which evolutionary diversity of GH2 enzymes is driven by the addition of different non-catalytic domains at the C-terminal region. This model accounts for the divergence of β-galactosidases from β-glucuronidases, the diversification of β-galactosidases with different transglycosylation specificities, and the emergence of bicistronic β-galactosidases. This study also allows the identification of groups of functionally uncharacterized protein sequences with potential biotechnological interest.

  4. Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants

    Directory of Open Access Journals (Sweden)

    Fraser Paul E

    2008-01-01

    Full Text Available Abstract Background Amyloid precursor protein (APP is enzymatically cleaved by γ-secretase to form two peptide products, either Aβ40 or the more neurotoxic Aβ42. The Aβ42/40 ratio is increased in many cases of familial Alzheimer's disease (FAD. The transmembrane domain (TM of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains. Results Using synthetic peptides derived from the APP-TM domain, we show that this segment is capable of forming stable transmembrane dimers. A model of a dimeric APP-TM domain reveals a putative dimerization interface, and interestingly, majority of FAD mutations in APP are localized to this interface region. We find that FAD-APP mutations destabilize the APP-TM dimer and increase the population of APP peptide monomers. Conclusion The dissociation constants are correlated to both the Aβ42/Aβ40 ratio and the mean age of disease onset in AD patients. We also show that these TM-peptides reduce Aβ production and Aβ42/Aβ40 ratios when added to HEK293 cells overexpressing the Swedish FAD mutation and γ-secretase components, potentially revealing a new class of γ-secretase inhibitors.

  5. Mutational analysis of the PRYSPRY domain of pyrin and implications for familial mediterranean fever (FMF).

    Science.gov (United States)

    Goulielmos, G N; Fragouli, E; Aksentijevich, I; Sidiropoulos, P; Boumpas, D T; Eliopoulos, E

    2006-07-14

    Familial Mediterranean fever (FMF) is an autosomal, recessively inherited disease, characterized by recurrent fever and serositis that affects mainly patients of the Mediterranean basin. The gene responsible for FMF, named MEFV, was cloned and several missense mutations were found to be responsible for the disease. Based on a recent molecular analysis of MEFV gene mutations in 43 patients from Crete aiming to correlate specific genotypes and clinical manifestations of FMF, we were prompted to construct a three-dimensional model (3-D model) of the PRYSPRY domain of pyrin. The majority of the known MEFV mutations located on this domain have been classified, according to disease severity, and localized on this 3-D model. The functional consequences of these mutations and their implications on disease severity are discussed. Moreover, we report a putative novel missense mutation, S702C, which we identified in exon 10 of the MEFV gene and localized on the constructed 3-D model.

  6. Comparison and correlation of binding mode of ATP in the kinase domains of Hexokinase family

    Science.gov (United States)

    Kumar, Yellapu Nanda; Kumar, Pasupuleti Santhosh; Sowjenya, Gopal; Rao, Valasani Koteswara; Yeswanth, Sthanikam; Prasad, Uppu Venkateswara; Pradeepkiran, Jangampalli Adi; Sarma, PVGK; Bhaskar, Matcha

    2012-01-01

    Hexokinases (HKs) are the enzymes that catalyses the ATP dependent phosphorylation of Hexose sugars to Hexose-6-Phosphate (Hex-6-P). There exist four different forms of HKs namely HK-I, HK-II, HK-III and HK-IV and all of them share a common ATP binding site core surrounded by more variable sequence that determine substrate affinities. Although they share a common binding site but they differ in their kinetic functions, hence the present study is aimed to analyze the binding mode of ATP. The analysis revealed that the four ATP binding domains are showing 13 identical, 7 similar and 6 dissimilar residues with similar structural conformation. Molecular docking of ATP into the kinase domains using Molecular Operating Environment (MOE) soft ware tool clearly showed the variation in the binding mode of ATP with variable docking scores. This probably explains the variable phosphorylation rates among hexokinases family. PMID:22829728

  7. Mapping C-terminal transactivation domains of the nuclear HER family receptor tyrosine kinase HER3.

    Science.gov (United States)

    Brand, Toni M; Iida, Mari; Luthar, Neha; Wleklinski, Matthew J; Starr, Megan M; Wheeler, Deric L

    2013-01-01

    Nuclear localized HER family receptor tyrosine kinases (RTKs) have been observed in primary tumor specimens and cancer cell lines for nearly two decades. Inside the nucleus, HER family members (EGFR, HER2, and HER3) have been shown to function as co-transcriptional activators for various cancer-promoting genes. However, the regions of each receptor that confer transcriptional potential remain poorly defined. The current study aimed to map the putative transactivation domains (TADs) of the HER3 receptor. To accomplish this goal, various intracellular regions of HER3 were fused to the DNA binding domain of the yeast transcription factor Gal4 (Gal4DBD) and tested for their ability to transactivate Gal4 UAS-luciferase. Results from these analyses demonstrated that the C-terminal domain of HER3 (CTD, amino acids distal to the tyrosine kinase domain) contained potent transactivation potential. Next, nine HER3-CTD truncation mutants were constructed to map minimal regions of transactivation potential using the Gal4 UAS-luciferase based system. These analyses identified a bipartite region of 34 (B₁) and 27 (B₂) amino acids in length that conferred the majority of HER3's transactivation potential. Next, we identified full-length nuclear HER3 association and regulation of a 122 bp region of the cyclin D1 promoter. To understand how the B₁ and B₂ regions influenced the transcriptional functions of nuclear HER3, we performed cyclin D1 promoter-luciferase assays in which HER3 deleted of the B₁ and B₂ regions was severely hindered in regulating this promoter. Further, the overexpression of HER3 enhanced cyclin D1 mRNA expression, while HER3 deleted of its identified TADs was hindered at doing so. Thus, the ability for HER3 to function as a transcriptional co-activator may be dependent on specific C-terminal TADs.

  8. Clostridium thermocellum cellulase CelT, a family 9 endoglucanase without an Ig-like domain or family 3c carbohydrate-binding module.

    Science.gov (United States)

    Kurokawa, J; Hemjinda, E; Arai, T; Kimura, T; Sakka, K; Ohmiya, K

    2002-08-01

    The celT gene of Clostridium thermocellum strain F1 was found downstream of the mannanase gene man26B [Kurokawa J et al. (2001) Biosci Biotechnol Biochem 65:548-554] in pKS305. The open reading frame of celT consists of 1,833 nucleotides encoding a protein of 611 amino acids with a predicted molecular weight of 68,510. The mature form of CelT consists of a family 9 cellulase domain and a dockerin domain responsible for cellulosome assembly, but lacks a family 3c carbohydrate-binding module (CBM) and an immunoglobulin (Ig)-like domain, which are often found with family 9 catalytic domains. CelT devoid of the dockerin domain (CelTDeltadoc) was constructed and purified from a recombinant Escherichia coli, and its enzyme properties were examined. CelTDeltadoc showed strong activity toward carboxymethylcellulose (CMC) and barley beta-glucan, and low activity toward xylan. The V(max) and K(m) values were 137 micro mol min(-1) mg(-1) and 16.7 mg/ml, respectively, for CMC. Immunological analysis indicated that CelT is a catalytic component of the C. thermocellum F1 cellulosome. This is the first report describing the characterization of a family 9 cellulase without an Ig-like domain or family 3c CBM.

  9. Starch‐binding domains in the CBM45 family – low‐affinity domains from glucan, water dikinase and α‐amylase involved in plastidial starch metabolism

    DEFF Research Database (Denmark)

    Glaring, Mikkel Andreas; Baumann, Martin; Abou Hachem, Maher

    2011-01-01

    Starch‐binding domains are noncatalytic carbohydrate‐binding modules that mediate binding to granular starch. The starch‐binding domains from the carbohydrate‐binding module family 45 (CBM45, ) are found as N‐terminal tandem repeats in a small number of enzymes, primarily from photosynthesizing...... amylolytic enzymes. This suggests that low‐affinity starch‐binding domains are a recurring feature in plastidial starch metabolism, and supports the hypothesis that reversible binding, effectuated through low‐affinity interaction with starch granules, facilitates dynamic regulation of enzyme activities and...

  10. The Bromodomain and Extra-Terminal Domain (BET Family: Functional Anatomy of BET Paralogous Proteins

    Directory of Open Access Journals (Sweden)

    Yasushi Taniguchi

    2016-11-01

    Full Text Available The Bromodomain and Extra-Terminal Domain (BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises BRD2, BRD3, BRD4, and BRDT, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-MYC These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

  11. Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family

    Energy Technology Data Exchange (ETDEWEB)

    Liban, Tyler J.; Medina, Edgar M.; Tripathi, Sarvind; Sengupta, Satyaki; Henry, R. William; Buchler, Nicolas E.; Rubin, Seth M. (UCSC); (Duke); (MSU)

    2017-04-24

    The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs. We find that although CTD–CM binding is conserved across protein families, Rb and p107 CTDs show clear preferences for different E2Fs. A crystal structure of the p107 CTD bound to E2F5 and its dimer partner DP1 reveals the molecular basis for pocket protein–E2F binding specificity and how cyclin-dependent kinases differentially regulate pocket proteins through CTD phosphorylation. Our structural and biochemical data together with phylogenetic analyses of Rb and E2F proteins support the conclusion that Rb evolved specific structural motifs that confer its unique capacity to bind with high affinity those E2Fs that are the most potent activators of the cell cycle.

  12. Guanylate kinase domains of the MAGUK family scaffold proteins as specific phospho-protein-binding modules

    Science.gov (United States)

    Zhu, Jinwei; Shang, Yuan; Xia, Caihao; Wang, Wenning; Wen, Wenyu; Zhang, Mingjie

    2011-01-01

    Membrane-associated guanylate kinases (MAGUKs) are a large family of scaffold proteins that play essential roles in tissue developments, cell–cell communications, cell polarity control, and cellular signal transductions. Despite extensive studies over the past two decades, the functions of the signature guanylate kinase domain (GK) of MAGUKs are poorly understood. Here we show that the GK domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner. The structure of the DLG1 SH3-GK tandem in complex with a phospho-LGN peptide reveals that the GMP-binding site of GK has evolved into a specific pSer/pThr-binding pocket. Residues both N- and C-terminal to the pSer are also critical for the specific binding of the phospho-LGN peptide to GK. We further demonstrate that the previously reported GK domain-mediated interactions of DLGs with other targets, such as GKAP/DLGAP1/SAPAP1 and SPAR, are also phosphorylation dependent. Finally, we provide evidence that other MAGUK GKs also function as phospho-peptide-binding modules. The discovery of the phosphorylation-dependent MAGUK GK/target interactions indicates that MAGUK scaffold-mediated signalling complex organizations are dynamically regulated. PMID:22117215

  13. Interrole conflict and self-efficacy to manage work and family demands mediate the relationships of job and family demands with stress in the job and family domains.

    Science.gov (United States)

    Smoktunowicz, Ewelina; Cieslak, Roman; Demerouti, Evangelia

    2017-09-01

    This study derives from Work-Home Resources model (ten Brummelhuis, L. L., & Bakker, A. B. (2012). A resource perspective on the work-home interface: The work-home resources model. American Psychologist, 67(7), 545-556. doi: 10.1037/a0027974 ) and Social Cognitive Theory (Bandura, A. (1986). Social foundations of thought and action: A social cognitive theory. Englewood Cliffs, NJ, US: Prentice-Hall, Inc.) to investigate mechanisms responsible for the effect of job and family demands on work- and family-related perceived stress. We hypothesized that interrole conflict and self-efficacy to manage work and family demands operate either independently or sequentially transmitting the effects of demands on perceived stress. A sample of 100 employees of various occupations participated in the study conducted online in two waves: Time 1 (T1) and Time 2 (T2) with a three-month interval. Regression analysis with bootstrapping was applied. Interrole conflict (T1) did not mediate the relationships between demands (T1) and perceived stress (T2), whereas self-efficacy (T1) mediated only those between family demands (T1) and stress (T2). However, data supported the sequential mediation hypotheses: Demands (T1) were associated with increased interrole conflict (T1) which in turn decreased self-efficacy (T1) and ultimately resulted in the elevated perceived stress at work and in the family (T2). Demands originating in one domain can impact stress both in the same and other life areas through the sequence of interrole conflict and context-specific self-efficacy.

  14. Starch-binding domains in the CBM45 family--low-affinity domains from glucan, water dikinase and α-amylase involved in plastidial starch metabolism.

    Science.gov (United States)

    Glaring, Mikkel A; Baumann, Martin J; Abou Hachem, Maher; Nakai, Hiroyuki; Nakai, Natsuko; Santelia, Diana; Sigurskjold, Bent W; Zeeman, Samuel C; Blennow, Andreas; Svensson, Birte

    2011-04-01

    Starch-binding domains are noncatalytic carbohydrate-binding modules that mediate binding to granular starch. The starch-binding domains from the carbohydrate-binding module family 45 (CBM45, http://www.cazy.org) are found as N-terminal tandem repeats in a small number of enzymes, primarily from photosynthesizing organisms. Isolated domains from representatives of each of the two classes of enzyme carrying CBM45-type domains, the Solanum tuberosumα-glucan, water dikinase and the Arabidopsis thaliana plastidial α-amylase 3, were expressed as recombinant proteins and characterized. Differential scanning calorimetry was used to verify the conformational integrity of an isolated CBM45 domain, revealing a surprisingly high thermal stability (T(m) of 84.8 °C). The functionality of CBM45 was demonstrated in planta by yellow/green fluorescent protein fusions and transient expression in tobacco leaves. Affinities for starch and soluble cyclodextrin starch mimics were measured by adsorption assays, surface plasmon resonance and isothermal titration calorimetry analyses. The data indicate that CBM45 binds with an affinity of about two orders of magnitude lower than the classical starch-binding domains from extracellular microbial amylolytic enzymes. This suggests that low-affinity starch-binding domains are a recurring feature in plastidial starch metabolism, and supports the hypothesis that reversible binding, effectuated through low-affinity interaction with starch granules, facilitates dynamic regulation of enzyme activities and, hence, of starch metabolism.

  15. InterPro in 2017—beyond protein family and domain annotations

    Science.gov (United States)

    Finn, Robert D.; Attwood, Teresa K.; Babbitt, Patricia C.; Bateman, Alex; Bork, Peer; Bridge, Alan J.; Chang, Hsin-Yu; Dosztányi, Zsuzsanna; El-Gebali, Sara; Fraser, Matthew; Gough, Julian; Haft, David; Holliday, Gemma L.; Huang, Hongzhan; Huang, Xiaosong; Letunic, Ivica; Lopez, Rodrigo; Lu, Shennan; Marchler-Bauer, Aron; Mi, Huaiyu; Mistry, Jaina; Natale, Darren A.; Necci, Marco; Nuka, Gift; Orengo, Christine A.; Park, Youngmi; Pesseat, Sebastien; Piovesan, Damiano; Potter, Simon C.; Rawlings, Neil D.; Redaschi, Nicole; Richardson, Lorna; Rivoire, Catherine; Sangrador-Vegas, Amaia; Sigrist, Christian; Sillitoe, Ian; Smithers, Ben; Squizzato, Silvano; Sutton, Granger; Thanki, Narmada; Thomas, Paul D; Tosatto, Silvio C. E.; Wu, Cathy H.; Xenarios, Ioannis; Yeh, Lai-Su; Young, Siew-Yit; Mitchell, Alex L.

    2017-01-01

    InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences. PMID:27899635

  16. Cellulose affinity purification of fusion proteins tagged with fungal family 1 cellulose-binding domain.

    Science.gov (United States)

    Sugimoto, Naohisa; Igarashi, Kiyohiko; Samejima, Masahiro

    2012-04-01

    N- or C-terminal fusions of red-fluorescent protein (RFP) with various fungal cellulose-binding domains (CBDs) belonging to carbohydrate binding module (CBM) family 1 were expressed in a Pichia pastoris expression system, and the resulting fusion proteins were used to examine the feasibility of large-scale affinity purification of CBD-tagged proteins on cellulose columns. We found that RFP fused with CBD from Trichoderma reesei CBHI (CBD(Tr)(CBHI)) was expressed at up to 1.2g/l in the culture filtrate, which could be directly injected into the cellulose column. The fusion protein was tightly adsorbed on the cellulose column in the presence of a sufficient amount of ammonium sulfate and was efficiently eluted with pure water. Bovine serum albumin (BSA) was not captured under these conditions, whereas both BSA and the fusion protein were adsorbed on a phenyl column, indicating that the cellulose column can be used for the purification of not only hydrophilic proteins but also for hydrophobic proteins. Recovery of various fusion proteins exceeded 80%. Our results indicate that protein purification by expression of a target protein as a fusion with a fungal family 1 CBD tag in a yeast expression system, followed by affinity purification on a cellulose column, is simple, effective and easily scalable.

  17. Isolation and characterization of a conserved domain in the eremophyte H+-PPase family.

    Directory of Open Access Journals (Sweden)

    Yanqin Wang

    Full Text Available H(+-translocating inorganic pyrophosphatases (H(+-PPase were recognized as the original energy donors in the development of plants. A large number of researchers have shown that H(+-PPase could be an early-originated protein that participated in many important biochemical and physiological processes. In this study we cloned 14 novel sequences from 7 eremophytes: Sophora alopecuroid (Sa, Glycyrrhiza uralensis (Gu, Glycyrrhiza inflata (Gi, Suaeda salsa (Ss, Suaeda rigida (Sr, Halostachys caspica (Hc, and Karelinia caspia (Kc. These novel sequences included 6 ORFs and 8 fragments, and they were identified as H(+-PPases based on the typical conserved domains. Besides the identified domains, sequence alignment showed that there still were two novel conserved motifs. A phylogenetic tree was constructed, including the 14 novel H(+-PPase amino acid sequences and the other 34 identified H(+-PPase protein sequences representing plants, algae, protozoans and bacteria. It was shown that these 48 H(+-PPases were classified into two groups: type I and type II H(+-PPase. The novel 14 eremophyte H(+-PPases were classified into the type I H(+-PPase. The 3D structures of these H(+-PPase proteins were predicted, which suggested that all type I H(+-PPases from higher plants and algae were homodimers, while other type I H(+-PPases from bacteria and protozoans and all type II H(+-PPases were monomers. The 3D structures of these novel H(+-PPases were homodimers except for SaVP3, which was a monomer. This regular structure could provide important evidence for the evolutionary origin and study of the relationship between the structure and function among members of the H(+-PPase family.

  18. A conserved gene family encodes transmembrane proteins with fibronectin, immunoglobulin and leucine-rich repeat domains (FIGLER

    Directory of Open Access Journals (Sweden)

    Haga Christopher L

    2007-09-01

    Full Text Available Abstract Background In mouse the cytokine interleukin-7 (IL-7 is required for generation of B lymphocytes, but human IL-7 does not appear to have this function. A bioinformatics approach was therefore used to identify IL-7 receptor related genes in the hope of identifying the elusive human cytokine. Results Our database search identified a family of nine gene candidates, which we have provisionally named fibronectin immunoglobulin leucine-rich repeat (FIGLER. The FIGLER 1–9 genes are predicted to encode type I transmembrane glycoproteins with 6–12 leucine-rich repeats (LRR, a C2 type Ig domain, a fibronectin type III domain, a hydrophobic transmembrane domain, and a cytoplasmic domain containing one to four tyrosine residues. Members of this multichromosomal gene family possess 20–47% overall amino acid identity and are differentially expressed in cell lines and primary hematopoietic lineage cells. Genes for FIGLER homologs were identified in macaque, orangutan, chimpanzee, mouse, rat, dog, chicken, toad, and puffer fish databases. The non-human FIGLER homologs share 38–99% overall amino acid identity with their human counterpart. Conclusion The extracellular domain structure and absence of recognizable cytoplasmic signaling motifs in members of the highly conserved FIGLER gene family suggest a trophic or cell adhesion function for these molecules.

  19. Do Workers Who Experience Conflict between the Work and Family Domains Hit a "Glass Ceiling?": A Meta-Analytic Examination

    Science.gov (United States)

    Hoobler, Jenny M.; Hu, Jia; Wilson, Morgan

    2010-01-01

    Based in Conservation of Resources (COR; Hobfoll, 1989) and self-verification (Swann, 1987) theories, we argue that when workers experience conflict between the work and family domains, this should have implications for evaluations of their work performance and ultimately affect more "objective" career outcomes such as salary and hierarchical…

  20. Role of the Sec14-like domain of Dbl family exchange factors in the regulation of Rho family GTPases in different subcellular sites.

    Science.gov (United States)

    Ueda, Shuji; Kataoka, Tohru; Satoh, Takaya

    2004-08-01

    Mechanisms underlying subcellular region-specific regulation of Rho family GTPases through Dbl family guanine nucleotide exchange factors (GEFs) remain totally unknown. Here we show that the Sec14-like domain, which lies in the N-terminus of the Dbl family GEFs Dbl and Ost, directs the subcellular localization of these GEFs and also their substrate Cdc42. When coexpressed with Cdc42 in human adenocarcinoma HeLa cells, Dbl-I and Ost-I, which lack the Sec14-like domain, translocated Cdc42 to the plasma membrane, where Dbl-I or Ost-I was colocalized. In marked contrast, Dbl-II and Ost-II, which contain the Sec14-like domain, were colocalized with Cdc42 in endomembrane compartments. Furthermore, ruffle membrane formation upon epidermal growth factor treatment was mediated by Dbl-I or Ost-I, but neither Dbl-II nor Ost-II, supporting a notion that GEFs with or without the Sec14-like domain are linked to different upstream signals. By employing a novel method to detect the active GTP-bound form of Cdc42 in situ, we demonstrate that Dbl-I and Ost-I, but neither Dbl-II nor Ost-II, indeed activate colocalized Cdc42.

  1. The MB2 gene family of Plasmodium species has a unique combination of S1 and GTP-binding domains

    Directory of Open Access Journals (Sweden)

    Ogunjumo Oluwasanmi

    2004-06-01

    Full Text Available Abstract Background Identification and characterization of novel Plasmodium gene families is necessary for developing new anti-malarial therapeutics. The products of the Plasmodium falciparum gene, MB2, were shown previously to have a stage-specific pattern of subcellular localization and proteolytic processing. Results Genes homologous to MB2 were identified in five additional parasite species, P. knowlesi, P. gallinaceum, P. berghei, P. yoelii, and P. chabaudi. Sequence comparisons among the MB2 gene products reveal amino acid conservation of structural features, including putative S1 and GTP-binding domains, and putative signal peptides and nuclear localization signals. Conclusions The combination of domains is unique to this gene family and indicates that MB2 genes comprise a novel family and therefore may be a good target for drug development.

  2. A novel firmicute protein family related to the actinobacterial resuscitation-promoting factors by non-orthologous domain displacement

    Directory of Open Access Journals (Sweden)

    Finan Christopher L

    2005-03-01

    Full Text Available Abstract Background In Micrococcus luteus growth and resuscitation from starvation-induced dormancy is controlled by the production of a secreted growth factor. This autocrine resuscitation-promoting factor (Rpf is the founder member of a family of proteins found throughout and confined to the actinobacteria (high G + C Gram-positive bacteria. The aim of this work was to search for and characterise a cognate gene family in the firmicutes (low G + C Gram-positive bacteria and obtain information about how they may control bacterial growth and resuscitation. Results In silico analysis of the accessory domains of the Rpf proteins permitted their classification into several subfamilies. The RpfB subfamily is related to a group of firmicute proteins of unknown function, represented by YabE of Bacillus subtilis. The actinobacterial RpfB and firmicute YabE proteins have very similar domain structures and genomic contexts, except that in YabE, the actinobacterial Rpf domain is replaced by another domain, which we have called Sps. Although totally unrelated in both sequence and secondary structure, the Rpf and Sps domains fulfil the same function. We propose that these proteins have undergone "non-orthologous domain displacement", a phenomenon akin to "non-orthologous gene displacement" that has been described previously. Proteins containing the Sps domain are widely distributed throughout the firmicutes and they too fall into a number of distinct subfamilies. Comparative analysis of the accessory domains in the Rpf and Sps proteins, together with their weak similarity to lytic transglycosylases, provide clear evidence that they are muralytic enzymes. Conclusions The results indicate that the firmicute Sps proteins and the actinobacterial Rpf proteins are cognate and that they control bacterial culturability via enzymatic modification of the bacterial cell envelope.

  3. Social Support from Work and Family Domains as an Antecedent or Moderator of Work-Family Conflicts?

    Science.gov (United States)

    Seiger, Christine P.; Wiese, Bettina S.

    2009-01-01

    On the basis of Conservation of Resources theory, we investigated how social support from supervisor, co-workers, life partner, and family members is associated with work-family conflicts in N=107 working mothers. We used data from a cross-sectional questionnaire and a standardized diary to examine two possible forms of interplay: (a) Social…

  4. Statistical analysis of genomic protein family and domain controlled annotations for functional investigation of classified gene lists

    Directory of Open Access Journals (Sweden)

    Masseroli Marco

    2007-03-01

    Full Text Available Abstract Background The increasing protein family and domain based annotations constitute important information to understand protein functions and gain insight into relations among their codifying genes. To allow analyzing of gene proteomic annotations, we implemented novel modules within GFINDer, a Web system we previously developed that dynamically aggregates functional and phenotypic annotations of user-uploaded gene lists and allows performing their statistical analysis and mining. Results Exploiting protein information in Pfam and InterPro databanks, we developed and added in GFINDer original modules specifically devoted to the exploration and analysis of functional signatures of gene protein products. They allow annotating numerous user-classified nucleotide sequence identifiers with controlled information on related protein families, domains and functional sites, classifying them according to such protein annotation categories, and statistically analyzing the obtained classifications. In particular, when uploaded nucleotide sequence identifiers are subdivided in classes, the Statistics Protein Families&Domains module allows estimating relevance of Pfam or InterPro controlled annotations for the uploaded genes by highlighting protein signatures significantly more represented within user-defined classes of genes. In addition, the Logistic Regression module allows identifying protein functional signatures that better explain the considered gene classification. Conclusion Novel GFINDer modules provide genomic protein family and domain analyses supporting better functional interpretation of gene classes, for instance defined through statistical and clustering analyses of gene expression results from microarray experiments. They can hence help understanding fundamental biological processes and complex cellular mechanisms influenced by protein domain composition, and contribute to unveil new biomedical knowledge about the codifying genes.

  5. Expression analysis of Arabidopsis XH/XS-domain proteins indicates overlapping and distinct functions for members of this gene family.

    Science.gov (United States)

    Butt, Haroon; Graner, Sonja; Luschnig, Christian

    2014-03-01

    RNA-directed DNA methylation (RdDM) is essential for de novo DNA methylation in higher plants, and recent reports established novel elements of this silencing pathway in the model organism Arabidopsis thaliana. Involved in de novo DNA methylation 2 (IDN2) and the closely related factor of DNA methylation (FDM) are members of a plant-specific family of dsRNA-binding proteins characterized by conserved XH/XS domains and implicated in the regulation of RdDM at chromatin targets. Genetic analyses have suggested redundant as well as non-overlapping activities for different members of the gene family. However, detailed insights into the function of XH/XS-domain proteins are still elusive. By the generation and analysis of higher-order mutant combinations affected in IDN2 and further members of the gene family, we have provided additional evidence for their redundant activity. Distinct roles for members of the XH/XS-domain gene family were indicated by differences in their expression and subcellular localization. Fluorescent protein-tagged FDM genes were expressed either in nuclei or in the cytoplasm, suggestive of activities of XH/XS-domain proteins in association with chromatin as well as outside the nuclear compartment. In addition, we observed altered location of a functional FDM1-VENUS reporter from the nucleus into the cytoplasm under conditions when availability of further FDM proteins was limited. This is suggestive of a mechanism by which redistribution of XH/XS-domain proteins could compensate for the loss of closely related proteins.

  6. Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

    Science.gov (United States)

    Rinaldi, Jimena; Arrar, Mehrnoosh; Sycz, Gabriela; Cerutti, María Laura; Berguer, Paula M; Paris, Gastón; Estrín, Darío Ariel; Martí, Marcelo Adrián; Klinke, Sebastián; Goldbaum, Fernando Alberto

    2016-03-27

    In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK.

  7. Domain combination of the vertebrate-like TLR gene family: implications for their origin and evolution

    Indian Academy of Sciences (India)

    Baojun Wu; Tianxiao Huan; Jing Gong; Pin Zhou; Zengliang Bai

    2011-12-01

    Domain shuffling, which is an important mechanism in the evolution of multi-domain proteins, has shaped the evolutionary development of the immune system in animals. Toll and Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate and adaptive immune systems. Draft genome sequences provide the opportunity to compare the Toll/TLR gene repertoire among representative metazoans. In this study, we investigated the combination of Toll/interleukin-1 receptor (TIR) and leucine-rich repeat (LRR) domains of metazoan Toll/TLRs. Before Toll with both domains occurred in Cnidaria (sea anemone, Nematostella vectensis), through domain combinations, TIR-only and LRR-only proteins had already appeared in sponges (Amphimedon queenslandica). Although vertebrate-like TIR (V-TIR) domain already appeared in Cnidaria, the vertebrate-like TLR (V-TLR) with both domains appeared much later. The first combination between V-TIR domain and vertebrate-like LRR (V-LRR) domain for V-TLR may have occurred after the divergence of Cnidaria and bilateria. Then, another combination for V-TLR, a recombination of both domains, possibly occurred before or during the evolution of primitive vertebrates. Taken together, two rounds of domain combinations may thus have co-shaped the vertebrate TLRs.

  8. Comparative analysis of plant genomes allows the definition of the "Phytolongins": a novel non-SNARE longin domain protein family.

    Science.gov (United States)

    Vedovato, Marco; Rossi, Valeria; Dacks, Joel B; Filippini, Francesco

    2009-11-04

    Subcellular trafficking is a hallmark of eukaryotic cells. Because of their pivotal role in the process, a great deal of attention has been paid to the SNARE proteins. Most R-SNAREs, or "longins", however, also possess a highly conserved, N-terminal fold. This "longin domain" is known to play multiple roles in regulating SNARE activity and targeting via interaction with other trafficking proteins. However, the diversity and complement of longins in eukaryotes is poorly understood. Our comparative genome survey identified a novel family of longin-related proteins, dubbed the "Phytolongins" because they are specific to land plants. Phytolongins share with longins the N-terminal longin domain and the C-terminal transmembrane domain; however, in the central region, the SNARE motif is replaced by a novel region. Phylogenetic analysis pinpoints the Phytolongins as a derivative of the plant specific VAMP72 longin sub-family and allows elucidation of Phytolongin evolution. "Longins" have been defined as R-SNAREs composed of both a longin domain and a SNARE motif. However, expressed gene isoforms and splice variants of longins are examples of non-SNARE motif containing longins. The discovery of Phytolongins, a family of non-SNARE longin domain proteins, together with recent evidence on the conservation of the longin-like fold in proteins involved in both vesicle fusion (e.g. the Trs20 tether) and vesicle formation (e.g. sigma and mu adaptin) highlight the importance of the longin-like domain in protein trafficking and suggest that it was one of the primordial building blocks of the eukaryotic membrane-trafficking machinery.

  9. Comparative analysis of plant genomes allows the definition of the "Phytolongins": a novel non-SNARE longin domain protein family

    Directory of Open Access Journals (Sweden)

    Dacks Joel B

    2009-11-01

    Full Text Available Abstract Background Subcellular trafficking is a hallmark of eukaryotic cells. Because of their pivotal role in the process, a great deal of attention has been paid to the SNARE proteins. Most R-SNAREs, or "longins", however, also possess a highly conserved, N-terminal fold. This "longin domain" is known to play multiple roles in regulating SNARE activity and targeting via interaction with other trafficking proteins. However, the diversity and complement of longins in eukaryotes is poorly understood. Results Our comparative genome survey identified a novel family of longin-related proteins, dubbed the "Phytolongins" because they are specific to land plants. Phytolongins share with longins the N-terminal longin domain and the C-terminal transmembrane domain; however, in the central region, the SNARE motif is replaced by a novel region. Phylogenetic analysis pinpoints the Phytolongins as a derivative of the plant specific VAMP72 longin sub-family and allows elucidation of Phytolongin evolution. Conclusion "Longins" have been defined as R-SNAREs composed of both a longin domain and a SNARE motif. However, expressed gene isoforms and splice variants of longins are examples of non-SNARE motif containing longins. The discovery of Phytolongins, a family of non-SNARE longin domain proteins, together with recent evidence on the conservation of the longin-like fold in proteins involved in both vesicle fusion (e.g. the Trs20 tether and vesicle formation (e.g. σ and μ adaptin highlight the importance of the longin-like domain in protein trafficking and suggest that it was one of the primordial building blocks of the eukaryotic membrane-trafficking machinery.

  10. Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.

    Science.gov (United States)

    Speckman, R A; Garg, A; Du, F; Bennett, L; Veile, R; Arioglu, E; Taylor, S I; Lovett, M; Bowcock, A M

    2000-04-01

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

  11. Limited cross-reactivity among domains of the Plasmodium falciparum clone 3D7 erythrocyte membrane protein 1 family

    DEFF Research Database (Denmark)

    Joergensen, Louise; Turner, Louise; Magistrado, Pamela

    2006-01-01

    The var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family is responsible for antigenic variation and sequestration of infected erythrocytes during malaria. We have previously grouped the 60 PfEMP1 variants of P. falciparum clone 3D7 into groups A and B/A (category A...... from clone 3D7 by using a competition enzyme-linked immunosorbent assay and a pool of plasma from 63 malaria-exposed Tanzanian individuals. We conclude that naturally acquired antibodies are largely directed toward epitopes varying between different domains with a few, mainly category A, domains...

  12. Domain structure and pore loops in the 2-hydroxycarboxylate transporter family

    NARCIS (Netherlands)

    Lolkema, Juke S.

    2006-01-01

    The 2-hydroxycarboxylate transporter (2HCT) family is a family of bacterial secondary transporters for substrates like citrate, malate and lactate. The family is in class ST[3] of the MemGen classification system that groups membrane proteins in structural classes based on hydropathy profile analysi

  13. Direct binding of specific AUF1 isoforms to tandem zinc finger domains of tristetraprolin (TTP) family proteins.

    Science.gov (United States)

    Kedar, Vishram P; Zucconi, Beth E; Wilson, Gerald M; Blackshear, Perry J

    2012-02-17

    Tristetraprolin (TTP) is the prototype of a family of CCCH tandem zinc finger proteins that can bind to AU-rich elements in mRNAs and promote their decay. TTP binds to mRNA through its central tandem zinc finger domain; it then promotes mRNA deadenylation, considered to be the rate-limiting step in eukaryotic mRNA decay. We found that TTP and its related family members could bind to certain isoforms of another AU-rich element-binding protein, HNRNPD/AUF1, as well as a related protein, laAUF1. The interaction domain within AUF1p45 appeared to be a C-terminal "GY" region, and the interaction domain within TTP was the tandem zinc finger domain. Surprisingly, binding of AUF1p45 to TTP occurred even with TTP mutants that lacked RNA binding activity. In cell extracts, binding of AUF1p45 to TTP potentiated TTP binding to ARE-containing RNA probes, as determined by RNA gel shift assays; AUF1p45 did not bind to the RNA probes under these conditions. Using purified, recombinant proteins and a synthetic RNA target in FRET assays, we demonstrated that AUF1p45, but not AUF1p37, increased TTP binding affinity for RNA ∼5-fold. These data suggest that certain isoforms of AUF1 can serve as "co-activators" of TTP family protein binding to RNA. The results raise interesting questions about the ability of AUF1 isoforms to regulate the mRNA binding and decay-promoting activities of TTP and its family members as well as the ability of AUF1 proteins to serve as possible physical links between TTP and other mRNA decay proteins and structures.

  14. The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member of the β-tent fold.

    Directory of Open Access Journals (Sweden)

    Andrei N Lupas

    2015-01-01

    Full Text Available Despite having caused one of the greatest medical catastrophies of the last century through its teratogenic side-effects, thalidomide continues to be an important agent in the treatment of leprosy and cancer. The protein cereblon, which forms an E3 ubiquitin ligase compex together with damaged DNA-binding protein 1 (DDB1 and cullin 4A, has been recently indentified as a primary target of thalidomide and its C-terminal part as responsible for binding thalidomide within a domain carrying several invariant cysteine and tryptophan residues. This domain, which we name CULT (cereblon domain of unknown activity, binding cellular ligands and thalidomide, is also found in a family of secreted proteins from animals and in a family of bacterial proteins occurring primarily in δ-proteobacteria. Its nearest relatives are yippee, a highly conserved eukaryotic protein of unknown function, and Mis18, a protein involved in the priming of centromeres for recruitment of CENP-A. Searches for distant homologs point to an evolutionary relationship of CULT, yippee, and Mis18 to proteins sharing a common fold, which consists of two four-stranded β-meanders packing at a roughly right angle and coordinating a zinc ion at their apex. A β-hairpin inserted into the first β-meander extends across the bottom of the structure towards the C-terminal edge of the second β-meander, with which it forms a cradle-shaped binding site that is topologically conserved in all members of this fold. We name this the β-tent fold for the striking arrangement of its constituent β-sheets. The fold has internal pseudosymmetry, raising the possibility that it arose by duplication of a subdomain-sized fragment.

  15. The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member of the β-tent fold.

    Science.gov (United States)

    Lupas, Andrei N; Zhu, Hongbo; Korycinski, Mateusz

    2015-01-01

    Despite having caused one of the greatest medical catastrophies of the last century through its teratogenic side-effects, thalidomide continues to be an important agent in the treatment of leprosy and cancer. The protein cereblon, which forms an E3 ubiquitin ligase compex together with damaged DNA-binding protein 1 (DDB1) and cullin 4A, has been recently indentified as a primary target of thalidomide and its C-terminal part as responsible for binding thalidomide within a domain carrying several invariant cysteine and tryptophan residues. This domain, which we name CULT (cereblon domain of unknown activity, binding cellular ligands and thalidomide), is also found in a family of secreted proteins from animals and in a family of bacterial proteins occurring primarily in δ-proteobacteria. Its nearest relatives are yippee, a highly conserved eukaryotic protein of unknown function, and Mis18, a protein involved in the priming of centromeres for recruitment of CENP-A. Searches for distant homologs point to an evolutionary relationship of CULT, yippee, and Mis18 to proteins sharing a common fold, which consists of two four-stranded β-meanders packing at a roughly right angle and coordinating a zinc ion at their apex. A β-hairpin inserted into the first β-meander extends across the bottom of the structure towards the C-terminal edge of the second β-meander, with which it forms a cradle-shaped binding site that is topologically conserved in all members of this fold. We name this the β-tent fold for the striking arrangement of its constituent β-sheets. The fold has internal pseudosymmetry, raising the possibility that it arose by duplication of a subdomain-sized fragment.

  16. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.

    2014-11-11

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  17. Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis

    Directory of Open Access Journals (Sweden)

    Aragon Robert J

    2010-10-01

    Full Text Available Abstract Background The Ras association domain family 1 (RASSF1 gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. Methods Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. Results In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. Conclusion Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.

  18. A highly conserved family of domains related to the DNA-glycosylase fold helps predict multiple novel pathways for RNA modifications.

    Science.gov (United States)

    Burroughs, A Maxwell; Aravind, L

    2014-01-01

    A protein family including mammalian NEMF, Drosophila caliban, yeast Tae2, and bacterial FpbA-like proteins was first defined over a decade ago and found to be universally distributed across the three domains/superkingdoms of life. Since its initial characterization, this family of proteins has been tantalizingly linked to a wide range of biochemical functions. Tapping the enormous wealth of genome information that has accumulated since the initial characterization of these proteins, we perform a detailed computational analysis of the family, identifying multiple conserved domains. Domains identified include an enzymatic domain related to the formamidopyrimidine (Fpg), MutM, and Nei/EndoVIII family of DNA glycosylases, a novel, predicted RNA-binding domain, and a domain potentially mediating protein-protein interactions. Through this characterization, we predict that the DNA glycosylase-like domain catalytically operates on double-stranded RNA, as part of a hitherto unknown base modification mechanism that probably targets rRNAs. At least in archaea, and possibly eukaryotes, this pathway might additionally include the AMMECR1 family of proteins. The predicted RNA-binding domain associated with this family is also observed in distinct architectural contexts in other proteins across phylogenetically diverse prokaryotes. Here it is predicted to play a key role in a new pathway for tRNA 4-thiouridylation along with TusA-like sulfur transfer proteins.

  19. Correlation analysis for protein evolutionary family based on amino acid position mutations and application in PDZ domain.

    Directory of Open Access Journals (Sweden)

    Qi-Shi Du

    Full Text Available BACKGROUND: It has been widely recognized that the mutations at specific directions are caused by the functional constraints in protein family and the directional mutations at certain positions control the evolutionary direction of the protein family. The mutations at different positions, even distantly separated, are mutually coupled and form an evolutionary network. Finding the controlling mutative positions and the mutative network among residues are firstly important for protein rational design and enzyme engineering. METHODOLOGY: A computational approach, namely amino acid position conservation-mutation correlation analysis (CMCA, is developed to predict mutually mutative positions and find the evolutionary network in protein family. The amino acid position mutative function, which is the foundational equation of CMCA measuring the mutation of a residue at a position, is derived from the MSA (multiple structure alignment database of protein evolutionary family. Then the position conservation correlation matrix and position mutation correlation matrix is constructed from the amino acid position mutative equation. Unlike traditional SCA (statistical coupling analysis approach, which is based on the statistical analysis of position conservations, the CMCA focuses on the correlation analysis of position mutations. CONCLUSIONS: As an example the CMCA approach is used to study the PDZ domain of protein family, and the results well illustrate the distantly allosteric mechanism in PDZ protein family, and find the functional mutative network among residues. We expect that the CMCA approach may find applications in protein engineering study, and suggest new strategy to improve bioactivities and physicochemical properties of enzymes.

  20. Analysis of Organelle Targeting by DIL Domains of the Arabidopsis Myosin XI Family

    Science.gov (United States)

    Sattarzadeh, Amirali; Schmelzer, Elmon; Hanson, Maureen R.

    2011-01-01

    The Arabidopsis thaliana genome encodes 13 myosin XI motor proteins. Previous insertional mutant analysis has implicated substantial redundancy of function of plant myosin XIs in transport of intracellular organelles. Considerable information is available about the interaction of cargo with the myosin XI-homologous yeast myosin V protein myo2p. We identified a region in each of 12 myosin XI sequences that correspond to the yeast myo2p secretory-vesicle binding domain (the “DIL” domain). Structural modeling of the myosin DIL domain region of plant myosin XIs revealed significant similarity to the yeast myo2p and myo4p DIL domains. Transient expression of YFP fusions with the Arabidopsis myosin XI DIL domain resulted in fluorescent labeling of a variety of organelles, including the endoplasmic reticulum, peroxisomes, Golgi, and nuclear envelope. With the exception of the YFP::MYA1 DIL fusion, expression of the DIL–YFP fusions resulted in loss of motility of labeled organelles, consistent with a dominant-negative effect. Certain fusions resulted in localization to the cytoplasm, plasma membrane, or to unidentified vesicles. The same YFP-domain fusion sometimes labeled more than one organelle. Expression of a YFP fusion to a yeast myo2p DIL domain resulted in labeling of plant peroxisomes. Fusions with some of the myosin XI domains resulted in labeling of known cargoes of the particular myosin XI; however, certain myosin XI YFP fusions labeled organelles that had not previously been found to be detectably affected by mutations nor by expression of dominant-negative constructs. PMID:22645548

  1. Role of the C-Terminal SH3 Domain and N-Terminal Tyrosine Phosphorylation in Regulation of Tim and Related Dbl-Family Proteins†

    OpenAIRE

    Marielle E Yohe; Rossman, Kent; Sondek, John

    2008-01-01

    Dbl-related oncoproteins are guanine nucleotide exchange factors (GEFs) specific for Rho-family GTPases and typically possess tandem Dbl (DH) and pleckstrin homology (PH) domains that act in concert to catalyze exchange. Although the exchange potential of many Dbl-family proteins is constitutively activated by truncation, the precise mechanisms of regulation for many Dbl-family proteins are unknown. Tim and Vav are distantly related Dbl-family proteins that are similarly regulated; their Dbl ...

  2. Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins.

    Science.gov (United States)

    Wood, J D; Yuan, J; Margolis, R L; Colomer, V; Duan, K; Kushi, J; Kaminsky, Z; Kleiderlein, J J; Sharp, A H; Ross, C A

    1998-06-01

    Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy (DRPLA). The normal function of atrophin-1 is unknown. We have identified five atrophin-1 interacting proteins (AIPs) which bind to atrophin-1 in the vicinity of the polyglutamine tract using the yeast two-hybrid system. Four of the interactions were confirmed using in vitro binding assays. All five interactors contained multiple WW domains. Two are novel. The AIPs can be divided into two distinct classes. AIP1 and AIP3/WWP3 are MAGUK-like multidomain proteins containing a number of protein-protein interaction modules, namely a guanylate kinase-like region, two WW domains, and multiple PDZ domains. AIP2/WWP2, AIP4, and AIP5/WWP1 are highly homologous, each having four WW domains and a HECT domain characteristic of ubiquitin ligases. These interactors are similar to recently isolated huntingtin-interacting proteins, suggesting possible commonality of function between two proteins responsible for very similar diseases.

  3. Structure and function of the interacting domains of Spire and Fmn-family formins

    Energy Technology Data Exchange (ETDEWEB)

    Vizcarra, Christina L.; Kreutz, Barry; Rodal, Avital A.; Toms, Angela V.; Lu, Jun; Zheng, Wei; Quinlan, Margot E.; Eck, Michael J. (UCLA); (Brandeis); (DFCI)

    2012-07-11

    Evidence for cooperation between actin nucleators is growing. The WH2-containing nucleator Spire and the formin Cappuccino interact directly, and both are essential for assembly of an actin mesh during Drosophila oogenesis. Their interaction requires the kinase noncatalytic C-lobe domain (KIND) domain of Spire and the C-terminal tail of the formin. Here we describe the crystal structure of the KIND domain of human Spir1 alone and in complex with the tail of Fmn2, a mammalian ortholog of Cappuccino. The KIND domain is structurally similar to the C-lobe of protein kinases. The Fmn2 tail is coordinated in an acidic cleft at the base of the domain that appears to have evolved via deletion of a helix from the canonical kinase fold. Our functional analysis of Cappuccino reveals an unexpected requirement for its tail in actin assembly. In addition, we find that the KIND/tail interaction blocks nucleation by Cappuccino and promotes its displacement from filament barbed ends providing insight into possible modes of cooperation between Spire and Cappuccino.

  4. Familial hemiplegic migraine mutations affect Na,K-ATPase domain interactions

    National Research Council Canada - National Science Library

    Swarts, H.G.P; Weigand, K.M; Venselaar, H; Maagdenberg, A.M. van den; Russel, F.G.M; Koenderink, J.B

    2013-01-01

    Familial hemiplegic migraine (FHM) is a monogenic variant of migraine with aura. One of the three known causative genes, ATP1A2, which encodes the alpha2 isoform of Na,K-ATPase, causes FHM type 2 (FHM2...

  5. Domains of variability of Laurent coefficients and the convex hull for the family of concave univalent functions

    CERN Document Server

    Bhowmik, B; Wirths, K-J

    2010-01-01

    Let $\\ID$ denote the open unit disc and let $p\\in (0,1)$. We consider the family $Co(p)$ of functions $f:\\ID\\to \\overline{\\IC}$ that satisfy the following conditions: \\bee \\item[(i)] $f$ is meromorphic in $\\ID$ and has a simple pole at the point $p$. \\item[(ii)] $f(0)=f'(0)-1=0$. \\item[(iii)] $f$ maps $\\ID$ conformally onto a set whose complement with respect to $\\overline{\\IC}$ is convex. \\eee We determine the exact domains of variability of some coefficients $a_n(f)$ of the Laurent expansion

  6. Fast kinetics of nucleotide binding to Clostridium perfringens family II pyrophosphatase containing CBS and DRTGG domains.

    Science.gov (United States)

    Jämsen, J; Baykov, A A; Lahti, R

    2012-02-01

    We earlier described CBS-pyrophosphatase of Moorella thermoacetica (mtCBS-PPase) as a novel phosphohydrolase that acquired a pair of nucleotide-binding CBS domains during evolution, thus endowing the protein with the capacity to be allosterically regulated by adenine nucleotides (Jämsen, J., Tuominen, H., Salminen, A., Belogurov, G. A., Magretova, N. N., Baykov, A. A., and Lahti, R. (2007) Biochem. J., 408, 327-333). We herein describe a more evolved type of CBS-pyrophosphatase from Clostridium perfringens (cpCBS-PPase) that additionally contains a DRTGG domain between the two CBS domains in the regulatory part. cpCBS-PPase retained the ability of mtCBS-PPase to be inhibited by micromolar concentrations of AMP and ADP and activated by ATP and was additionally activated by diadenosine polyphosphates (AP(n)A) with n > 2. Stopped-flow measurements using a fluorescent nucleotide analog, 2'(3')-O-(N-methylanthranoyl)-AMP, revealed that cpCBS-PPase interconverts through two different conformations with transit times on the millisecond scale upon nucleotide binding. The results suggest that the presence of the DRTGG domain affords greater flexibility to the regulatory part, allowing it to more rapidly undergo conformational changes in response to binding.

  7. Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish.

    NARCIS (Netherlands)

    Meijer, A.H.; Krens, SF Gabby; Rodriguez, IA Medina; He, S; Bitter, W.; Snaar-Jagalska, B Ewa; Spaink, H.P.

    2004-01-01

    The zebrafish genomic sequence database was analysed for the presence of genes encoding members of the Toll-like receptors (TLR) and interleukin receptors (IL-R) and associated adaptor proteins containing a TIR domain. The resulting predictions show the presence of one or more counterparts for the

  8. Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain.

    Science.gov (United States)

    Jaradat, Saied A; Caccia, Sonia; Rawashdeh, Rifaat; Melhem, Motasem; Al-Hawamdeh, Ali; Carzaniga, Thomas; Haddad, Hazem

    2016-03-01

    Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype.

  9. Relationship of work-family conflict with burnout and marital satisfaction: cross-domain or source attribution relations?

    Science.gov (United States)

    Bagherzadeh, Razieh; Taghizadeh, Ziba; Mohammadi, Eesa; Kazemnejad, Anoshirvan; Pourreza, Abolghasem; Ebadi, Abbas

    2016-01-01

    Background: The present study was conducted to examine the relationship between two dimensions of work-family conflict (WFC) with marital satisfaction and burnout in a society in which few studies have been done about the consequences of WFC. Methods: A cross-sectional study was conducted in 2015. Surveys were distributed to 420 employed married women with various jobs living in Bushehr province, Iran. Data were collected using a questionnaire for demographic characteristic, the Netmeyer’s WFC questionnaire, Maslach Burnout Inventory: General Survey (MBI-GS), and Enrich maritalsatisfaction questionnaire. The data were analyzed using descriptive and inferential statistics. Results: There was a negatively significant association between work interference with family(WIF) and overall burnout as well as emotional exhaustion (P < .01). Family interference with work (FIW) was significantly associated with depersonalization (P < .01). The overall marital satisfaction and its subscales were significantly associated with WIF (P < .01) and FIW (P < .01 for overall marital satisfaction and P < .05 for its subscales). Conclusion: In terms of practical implication, to avoid creating disadvantages of WIF and FIW,facilitation in two domains of improving work and family conditions can be a useful means to prevent WFC and its consequences. PMID:27123434

  10. Domain specificity of MAP3K family members, MLK and Tak1, for JNK signaling in Drosophila.

    Science.gov (United States)

    Stronach, Beth; Lennox, Ashley L; Garlena, Rebecca A

    2014-06-01

    A highly diverse set of protein kinases functions as early responders in the mitogen- and stress-activated protein kinase (MAPK/SAPK) signaling pathways. For instance, humans possess 14 MAPK kinase kinases (MAP3Ks) that activate Jun kinase (JNK) signaling downstream. A major challenge is to decipher the selective and redundant functions of these upstream MAP3Ks. Taking advantage of the relative simplicity of Drosophila melanogaster as a model system, we assessed MAP3K signaling specificity in several JNK-dependent processes during development and stress response. Our approach was to generate molecular chimeras between two MAP3K family members, the mixed lineage kinase, Slpr, and the TGF-β activated kinase, Tak1, which share 32% amino acid identity across the kinase domain but otherwise differ in sequence and domain structure, and then test the contributions of various domains for protein localization, complementation of mutants, and activation of signaling. We found that overexpression of the wild-type kinases stimulated JNK signaling in alternate contexts, so cells were capable of responding to both MAP3Ks, but with distinct outcomes. Relative to wild-type, the catalytic domain swaps compensated weakly or not at all, despite having a shared substrate, the JNK kinase Hep. Tak1 C-terminal domain-containing constructs were inhibitory in Tak1 signaling contexts, including tumor necrosis factor-dependent cell death and innate immune signaling; however, depressing antimicrobial gene expression did not necessarily cause phenotypic susceptibility to infection. These same constructs were neutral in the context of Slpr-dependent developmental signaling, reflecting differential subcellular protein localization and by inference, point of activation. Altogether, our findings suggest that the selective deployment of a particular MAP3K can be attributed in part to its inherent sequence differences, cellular localization, and binding partner availability.

  11. Evolution of protein families: is it possible to distinguish between domains of life?

    Science.gov (United States)

    Sales-Pardo, Marta; Chan, Albert O B; Amaral, Luís A N; Guimerà, Roger

    2007-11-01

    Understanding evolutionary relationships between species can shed new light into the rooting of the tree of life and the origin of eukaryotes, thus, resulting in a long standing interest in accurately assessing evolutionary parameters at time scales on the order of a billion of years. Prior work suggests large variability in molecular substitution rates, however, we still do not know whether such variability is due to species-specific trends at a genomic scale, or whether it can be attributed to the fluctuations inherent in any stochastic process. Here, we study the statistical properties of gene and protein-family sizes in order to quantify the long time scale evolutionary differences and similarities across species. We first determine the protein families of 209 species of bacteria and 20 species of archaea. We find that we are unable to reject the null hypothesis that the protein-family sizes of these species are drawn from the same distribution. In addition, we find that for species classified in the same phylogenetic branch or in the same lifestyle group, family size distributions are not significantly more similar than for species in different branches. These two findings can be accounted for in terms of a dynamical birth, death, and innovation model that assumes identical protein-family evolutionary rates for all species. Our theoretical and empirical results thus strongly suggest that the variability empirically observed in protein-family size distributions is compatible with the expected stochastic fluctuations for an evolutionary process with identical genomic evolutionary rates. Our findings hold special importance for the plausibility of some theories of the origin of eukaryotes which require drastic changes in evolutionary rates for some period during the last 2 billion years.

  12. A divergent calponin homology (NN–CH) domain defines a novel family

    DEFF Research Database (Denmark)

    Schou, Kenneth Bødtker; Andersen, Jens S.; Pedersen, Lotte Bang

    2014-01-01

    and NUF2 share evolutionary ancestry with a novel protein family in mammals comprising, besides NDC80/HEC1 and NUF2, three Intraflagellar Transport (IFT) complex B subunits (IFT81, IFT57, CLUAP1) as well as six proteins with poorly defined function (FAM98A-C, CCDC22, CCDC93 and C14orf166). We show...

  13. Radically different thioredoxin domain arrangement of ERp46, an efficient disulfide bond introducer of the mammalian PDI family.

    Science.gov (United States)

    Kojima, Rieko; Okumura, Masaki; Masui, Shoji; Kanemura, Shingo; Inoue, Michio; Saiki, Masatoshi; Yamaguchi, Hiroshi; Hikima, Takaaki; Suzuki, Mamoru; Akiyama, Shuji; Inaba, Kenji

    2014-03-04

    The mammalian endoplasmic reticulum (ER) contains a diverse oxidative protein folding network in which ERp46, a member of the protein disulfide isomerase (PDI) family, serves as an efficient disulfide bond introducer together with Peroxiredoxin-4 (Prx4). We revealed a radically different molecular architecture of ERp46, in which the N-terminal two thioredoxin (Trx) domains with positively charged patches near their peptide-binding site and the C-terminal Trx are linked by unusually long loops and arranged extendedly, forming an opened V-shape. Whereas PDI catalyzes native disulfide bond formation by the cooperative action of two mutually facing redox-active sites on folding intermediates bound to the central cleft, ERp46 Trx domains are separated, act independently, and engage in rapid but promiscuous disulfide bond formation during early oxidative protein folding. Thus, multiple PDI family members likely contribute to different stages of oxidative folding and work cooperatively to ensure the efficient production of multi-disulfide proteins in the ER.

  14. Making sense of behavioral disturbances in persons with dementia: Latino family caregiver attributions of neuropsychiatric inventory domains.

    Science.gov (United States)

    Hinton, Ladson; Chambers, Darin; Velásquez, Alexandra

    2009-01-01

    The purpose of this study was to describe the nature and frequency of Latino family caregiver attributions for dementia-related neuropsychiatric symptoms. This is a cross-sectional study conducted in the Sacramento, California area. Participants were 30 Latino family caregivers of community-dwelling Latino elderly meeting research criteria for dementia who were selected from an ongoing cohort study of older Latinos (Sacramento Area Latino Study on Aging). Open-ended probes were used to elicit caregiver attributions for each symptom domain of the Neuropsychiatric Inventory. Across the 30 caregivers, 121 explanations for neuropsychiatric domains were present. Content analysis of these explanations revealed 7 different attribution categories (ie, Alzheimer disease, interpersonal problems, other medical conditions, personality, mental, aging, and genetics). Overall, Alzheimer disease was the most frequent attribution category but accounted for less than 30% of the total attributions. In conclusion, this study found that Latino caregivers were more likely to attribute neuropsychiatric symptoms to causes other than Alzheimer disease or a related dementia.

  15. Subunit interaction and regulation of activity through terminal domains of the family D DNA polymerase from Pyrococcus horikoshii.

    Science.gov (United States)

    Shen, Y; Tang, X-F; Matsui, E; Matsui, I

    2004-04-01

    Family D DNA polymerase (PolD) has recently been found in the Euryarchaeota subdomain of Archaea. Its genes are adjacent to several other genes related to DNA replication, repair and recombination in the genome, suggesting that this enzyme may be the major DNA replicase in Euryarchaeota. We successfully cloned, expressed, and purified the family D DNA polymerase from Pyrococcus horikoshii (PolDPho). By site-directed mutagenesis, we identified amino acid residues Asp-1122 and Asp-1124 of a large subunit as the essential residues responsible for DNA-polymerizing activity. We analysed the domain structure using proteins truncated at the N- and C-termini of both small and large subunits (DP1Pho and DP2Pho), and identified putative regions responsible for subunit interaction, oligomerization and regulation of the 3'-5' exonuclease activity in PolDPho. It was also found that the internal region of the putative zinc finger motif (cysteine cluster II) at the C-terminal of DP2Pho is involved in the 3'-5' exonuclease activity. Using gel filtration analysis, we determined the molecular masses of the recombinant PolDPho and the N-terminal putative dimerization domain of the large subunit, and proposed that PolD from P. horikoshii probably forms a heterotetrameric structure in solution. Based on these results, a model regarding the subunit interaction and regulation of activity of PolDPho is proposed.

  16. Structure of the C-terminal domain of AspA (antigen I/II-family protein from Streptococcus pyogenes

    Directory of Open Access Journals (Sweden)

    Michael Hall

    2014-01-01

    Full Text Available The pathogenic bacteria Streptococcus pyogenes can cause an array of diseases in humans, including moderate infections such as pharyngitis (strep throat as well as life threatening conditions such as necrotizing fasciitis and puerperal fever. The antigen I/II family proteins are cell wall anchored adhesin proteins found on the surfaces of most oral streptococci and are involved in host colonization and biofilm formation. In the present study we have determined the crystal structure of the C2–3-domain of the antigen I/II type protein AspA from S. pyogenes M type 28. The structure was solved to 1.8 Å resolution and shows that the C2–3-domain is comprised of two structurally similar DEv-IgG motifs, designated C2 and C3, both containing a stabilizing covalent isopeptide bond. Furthermore a metal binding site is identified, containing a bound calcium ion. Despite relatively low sequence identity, interestingly, the overall structure shares high similarity to the C2–3-domains of antigen I/II proteins from Streptococcus gordonii and Streptococcus mutans, although certain parts of the structure exhibit distinct features. In summary this work constitutes the first step in the full structure determination of the AspA protein from S. pyogenes.

  17. Identification and Expression Profiling of the BTB Domain-Containing Protein Gene Family in the Silkworm, Bombyx mori

    Directory of Open Access Journals (Sweden)

    Daojun Cheng

    2014-01-01

    Full Text Available The BTB domain is a conserved protein-protein interaction motif. In this study, we identified 56 BTB domain-containing protein genes in the silkworm, in addition to 46 in the honey bee, 55 in the red flour beetle, and 53 in the monarch butterfly. Silkworm BTB protein genes were classified into nine subfamilies according to their domain architecture, and most of them could be mapped on the different chromosomes. Phylogenetic analysis suggests that silkworm BTB protein genes may have undergone a duplication event in three subfamilies: BTB-BACK-Kelch, BTB-BACK-PHR, and BTB-FLYWCH. Comparative analysis demonstrated that the orthologs of each of 13 BTB protein genes present a rigorous orthologous relationship in the silkworm and other surveyed insects, indicating conserved functions of these genes during insect evolution. Furthermore, several silkworm BTB protein genes exhibited sex-specific expression in larval tissues or at different stages during metamorphosis. These findings not only contribute to a better understanding of the evolution of insect BTB protein gene families but also provide a basis for further investigation of the functions of BTB protein genes in the silkworm.

  18. The evolution of YidC/Oxa/Alb3 family in the three domains of life: a phylogenomic analysis

    Directory of Open Access Journals (Sweden)

    Tian Hai-Feng

    2009-06-01

    Full Text Available Abstract Background YidC/Oxa/Alb3 family includes a group of conserved translocases that are essential for protein insertion into inner membranes of bacteria and mitochondria, and thylakoid membranes of chloroplasts. Because mitochondria and chloroplasts are of bacterial origin, Oxa and Alb3, like many other mitochondrial/chloroplastic proteins, are hypothetically derived from the pre-existing protein (YidC of bacterial endosymbionts. Here, we test this hypothesis and investigate the evolutionary history of the whole YidC/Oxa/Alb3 family in the three domains of life. Results Our comprehensive analyses of the phylogenetic distribution and phylogeny of the YidC/Oxa/Alb3 family lead to the following findings: 1 In archaea, YidC homologs are only sporadically distributed in Euryarchaeota; 2 Most bacteria contain only one YidC gene copy; some species in a few taxa (Bacillus, Lactobacillales, Actinobacteria and Clostridia have two gene copies; 3 Eukaryotic Oxa and Alb3 have two separate prokaryotic origins, but they might not arise directly from the YidC of proteobacteria and cyanobacteria through the endosymbiosis origins of mitochondrium and chloroplast, respectively; 4 An ancient duplication occurred on both Oxa and Alb3 immediately after their origins, and thus most eukaryotes generally bear two Oxa and two Alb3. However, secondary loss, duplication or acquisition of new domain also occurred on the two genes in some lineages, especially in protists, resulting in a rich diversity or adaptive differentiation of the two translocases in these lineages. Conclusion YidC is distributed in bacteria and some Euryarchaeota. Although mitochondrial Oxa and chloroplastic Alb3 are derived from the prokaryotic YidC, their origin might be not related to the endosymbiosis events of the two organelles. In some eukaryotic lineages, especially in protists, Oxa and Alb3 have diverse evolutionary histories. Finally, a model for the evolutionary history of the entire

  19. The identification and structure of an N-terminal PR domain show that FOG1 is a member of the PRDM family of proteins.

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    Molly K Clifton

    Full Text Available FOG1 is a transcriptional regulator that acts in concert with the hematopoietic master regulator GATA1 to coordinate the differentiation of platelets and erythrocytes. Despite considerable effort, however, the mechanisms through which FOG1 regulates gene expression are only partially understood. Here we report the discovery of a previously unrecognized domain in FOG1: a PR (PRD-BF1 and RIZ domain that is distantly related in sequence to the SET domains that are found in many histone methyltransferases. We have used NMR spectroscopy to determine the solution structure of this domain, revealing that the domain shares close structural similarity with SET domains. Titration with S-adenosyl-L-homocysteine, the cofactor product synonymous with SET domain methyltransferase activity, indicated that the FOG PR domain is not, however, likely to function as a methyltransferase in the same fashion. We also sought to define the function of this domain using both pulldown experiments and gel shift assays. However, neither pulldowns from mammalian nuclear extracts nor yeast two-hybrid assays reproducibly revealed binding partners, and we were unable to detect nucleic-acid-binding activity in this domain using our high-diversity Pentaprobe oligonucleotides. Overall, our data demonstrate that FOG1 is a member of the PRDM (PR domain containing proteins, with zinc fingers family of transcriptional regulators. The function of many PR domains, however, remains somewhat enigmatic for the time being.

  20. Cystathionine β-synthase (CBS) domains confer multiple forms of Mg2+-dependent cooperativity to family II pyrophosphatases.

    Science.gov (United States)

    Salminen, Anu; Anashkin, Viktor A; Lahti, Matti; Tuominen, Heidi K; Lahti, Reijo; Baykov, Alexander A

    2014-08-15

    Regulated family II pyrophosphatases (CBS-PPases) contain a nucleotide-binding insert comprising a pair of cystathionine β-synthase (CBS) domains, termed a Bateman module. By binding with high affinity to the CBS domains, AMP and ADP usually inhibit the enzyme, whereas ATP activates it. Here, we demonstrate that AMP, ADP, and ATP bind in a positively cooperative manner to CBS-PPases from four bacteria: Desulfitobacterium hafniense, Clostridium novyi, Clostridium perfringens, and Eggerthella lenta. Enzyme interaction with substrate as characterized by the Michaelis constant (Km) also exhibited positive catalytic cooperativity that decreased in magnitude upon nucleotide binding. The degree of both types of cooperativity increased with increasing concentration of the cofactor Mg(2+) except for the C. novyi PPase where Mg(2+) produced the opposite effect on kinetic cooperativity. Further exceptions from these general rules were ADP binding to C. novyi PPase and AMP binding to E. lenta PPase, neither of which had any effect on activity. A genetically engineered deletion variant of D. hafniense PPase lacking the regulatory insert was fully active but differed from the wild-type enzyme in that it was insensitive to nucleotides and bound substrate non-cooperatively and with a smaller Km value. These results indicate that the regulatory insert acts as an internal inhibitor and confers dual positive cooperativity to CBS domain-containing PPases, making them highly sensitive regulators of the PPi level in response to the changes in cell energy status that control adenine nucleotide distribution. These regulatory features may be common among other CBS domain-containing proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. VAM-1: a new member of the MAGUK family binds to human Veli-1 through a conserved domain.

    Science.gov (United States)

    Tseng, T C; Marfatia, S M; Bryant, P J; Pack, S; Zhuang, Z; O'Brien, J E; Lin, L; Hanada, T; Chishti, A H

    2001-04-16

    The MAGUKs (membrane-associated guanylate kinase homologues) constitute a family of peripheral membrane proteins that function in tumor suppression and receptor clustering by forming multiprotein complexes containing distinct sets of transmembrane, cytoskeletal, and cytoplasmic signaling proteins. Here, we report the characterization of the human vam-1 gene that encodes a novel member of the p55 subfamily of MAGUKs. The complete cDNA sequence of VAM-1, tissue distribution of its mRNA, genomic structure, chromosomal localization, and Veli-1 binding properties are presented. The vam-1 gene is composed of 12 exons and spans approx. 115 kb. By fluorescence in situ hybridization the vam-1 gene was localized to 7p15-21, a chromosome region frequently disrupted in some human cancers. VAM-1 mRNA was abundant in human testis, brain, and kidney with lower levels detectable in other tissues. The primary structure of VAM-1, predicted from cDNA sequencing, consists of 540 amino acids including a single PDZ domain near the N-terminus, a central SH3 domain, and a C-terminal GUK (guanylate kinase-like) domain. Sequence alignment, heterologous transfection, GST pull-down experiments, and blot overlay assays revealed a conserved domain in VAM-1 that binds to Veli-1, the human homologue of the LIN-7 adaptor protein in Caenorhabditis. LIN-7 is known to play an essential role in the basolateral localization of the LET-23 tyrosine kinase receptor, by linking the receptor to LIN-2 and LIN-10 proteins. Our results therefore suggest that VAM-1 may function by promoting the assembly of a Veli-1 containing protein complex in neuronal as well as epithelial cells.

  2. Substrate specificity and recognition is conferred by the pleckstrin homology domain of the Dbl family guanine nucleotide exchange factor P-Rex2.

    Science.gov (United States)

    Joseph, Raji E; Norris, F A

    2005-07-29

    Dbl family guanine nucleotide exchange factors (GEFs) are characterized by the presence of a catalytic Dbl homology domain followed invariably by a lipid-binding pleckstrin homology (PH) domain. To date, substrate recognition and specificity of this family of GEFs has been reported to be mediated exclusively via the Dbl homology domain. Here we report the novel and unexpected finding that, in the Dbl family Rac-specific GEF P-Rex2, it is the PH domain that confers substrate specificity and recognition. Moreover, the beta3beta4 loop of the PH domain of P-Rex2 is the determinant for Rac1 recognition, as substitution of the beta3beta4 loop of the PH domain of Dbs (a RhoA- and Cdc42-specific GEF) with that of P-Rex2 confers Rac1-specific binding capability to the PH domain of Dbs. The contact interface between the PH domain of P-Rex2 and Rac1 involves the switch loop and helix 3 of Rac1. Moreover, substitution of helix 3 of Cdc42 with that of Rac1 now enables the PH domain of P-Rex2 to bind this Cdc42 chimera. Despite having the ability to recognize this chimeric Cdc42, P-Rex2 is unable to catalyze nucleotide exchange on Cdc42, suggesting that recognition of substrate and catalysis are two distinct events. Thus substrate recognition can now be added to the growing list of functions that are being attributed to the PH domain of Dbl family GEFs.

  3. A divergent calponin homology (NN–CH) domain defines a novel family

    DEFF Research Database (Denmark)

    Schou, Kenneth Bødtker; Andersen, Jens S.; Pedersen, Lotte Bang

    2014-01-01

    Microtubules are dynamic polymers of tubulin dimers that undergo continuous assembly and disassembly. A mounting number of microtubule-associated proteins (MAPs) regulate the dynamic behavior of microtubules and hence the assembly and disassembly of disparate microtubule structures within the cell...... and NUF2 share evolutionary ancestry with a novel protein family in mammals comprising, besides NDC80/HEC1 and NUF2, three Intraflagellar Transport (IFT) complex B subunits (IFT81, IFT57, CLUAP1) as well as six proteins with poorly defined function (FAM98A-C, CCDC22, CCDC93 and C14orf166). We show...

  4. Domain-orientation-controlled potassium niobate family piezoelectric materials with hydrothermal powders.

    Science.gov (United States)

    Fujiuchi, Yukiko; Morita, Takeshi

    2014-10-01

    Materials of the potassium niobate family, as lead-free piezoelectric materials, are expected to be alternative materials to Pb(Zr,Ti)O3 (PZT) because of their good piezoelectric properties, high Curie temperature, and so on. In particular, single-crystal potassium niobate is a promising ferroelectric material as a surface acoustic substrate and for functional optical effects. It is, however, well known that single crystals are difficult to fabricate because of the instability caused by temperature, external stress, and other factors.

  5. A Novel Mutation in the Pyrin Domain of the NOD-like Receptor Family Pyrin Domain Containing Protein 3 in Muckle-Wells Syndrome

    Science.gov (United States)

    Hu, Jian; Zhu, Yun; Zhang, Jian-Zhong; Zhang, Rong-Guang; Li, Hou-Min

    2017-01-01

    Background: Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin (IL)-1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease. CAPS is associated with gain-of-function missense mutations in NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), the gene encoding NLRP3. Moreover, most mutations leading to MWS occurred in exon 3 of NLRP3 gene. Here, we reported a novel mutation occurred in exon 1 of NLRP3 gene in an MWS patient and attempted to explore the pathogenic mechanism. Methods: Genetic sequence analysis of NLRP3 was performed in an MWS patient who presented with periodic fever, arthralgia, and multiform skin lesions. NLRP3 was also analyzed in this patient's parents and 50 healthy individuals. Clinical examinations including X-ray examination, skin biopsy, bone marrow aspiration smear, and blood test of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum levels of IL-1β, immunoglobulin E (IgE), antineutrophil cytoplasmic antibodies, antinuclear antibodies, and extractable nuclear antigen were also analyzed. The protein structure of mutant NLRP3 inflammasome was calculated by SWISS-MODEL software. Proteins of wild type and mutant components of NLRP3 inflammasome were expressed and purified, and the interaction abilities between these proteins were tested by surface plasmon resonance (SPR) assay. Results: X-ray examination showed no abnormality in the patient's knees. Laboratory tests indicated an elevation of CRP (233.24 mg/L) and ESR (67 mm/h) when the patient had fever. Serum IL-1β increased to 24.37 pg/ml, and serum IgE was higher than 2500.00 IU/ml. Other blood tests were

  6. The RST and PARP-like domain containing SRO protein family: analysis of protein structure, function and conservation in land plants

    Directory of Open Access Journals (Sweden)

    Salojärvi Jarkko

    2010-03-01

    Full Text Available Abstract Background The SROs (SIMILAR TO RCD-ONE are a group of plant-specific proteins which have important functions in stress adaptation and development. They contain the catalytic core of the poly(ADP-ribose polymerase (PARP domain and a C-terminal RST (RCD-SRO-TAF4 domain. In addition to these domains, several, but not all, SROs contain an N-terminal WWE domain. Results SROs are present in all analyzed land plants and sequence analysis differentiates between two structurally distinct groups; cryptogams and monocots possess only group I SROs whereas eudicots also contain group II. Group I SROs possess an N-terminal WWE domain (PS50918 but the WWE domain is lacking in group II SROs. Group I domain structure is widely represented in organisms as distant as humans (for example, HsPARP11. We propose a unified nomenclature for the SRO family. The SROs are able to interact with transcription factors through the C-terminal RST domain but themselves are generally not regulated at the transcriptional level. The most conserved feature of the SROs is the catalytic core of the poly(ADP-ribose polymerase (PS51059 domain. However, bioinformatic analysis of the SRO PARP domain fold-structure and biochemical assays of AtRCD1 suggested that SROs do not possess ADP-ribosyl transferase activity. Conclusions The SROs are a highly conserved family of plant specific proteins. Sequence analysis of the RST domain implicates a highly preserved protein structure in that region. This might have implications for functional conservation. We suggest that, despite the presence of the catalytic core of the PARP domain, the SROs do not possess ADP-ribosyl transferase activity. Nevertheless, the function of SROs is critical for plants and might be related to transcription factor regulation and complex formation.

  7. The RST and PARP-like domain containing SRO protein family: analysis of protein structure, function and conservation in land plants.

    Science.gov (United States)

    Jaspers, Pinja; Overmyer, Kirk; Wrzaczek, Michael; Vainonen, Julia P; Blomster, Tiina; Salojärvi, Jarkko; Reddy, Ramesha A; Kangasjärvi, Jaakko

    2010-03-12

    The SROs (SIMILAR TO RCD-ONE) are a group of plant-specific proteins which have important functions in stress adaptation and development. They contain the catalytic core of the poly(ADP-ribose) polymerase (PARP) domain and a C-terminal RST (RCD-SRO-TAF4) domain. In addition to these domains, several, but not all, SROs contain an N-terminal WWE domain. SROs are present in all analyzed land plants and sequence analysis differentiates between two structurally distinct groups; cryptogams and monocots possess only group I SROs whereas eudicots also contain group II. Group I SROs possess an N-terminal WWE domain (PS50918) but the WWE domain is lacking in group II SROs. Group I domain structure is widely represented in organisms as distant as humans (for example, HsPARP11). We propose a unified nomenclature for the SRO family. The SROs are able to interact with transcription factors through the C-terminal RST domain but themselves are generally not regulated at the transcriptional level. The most conserved feature of the SROs is the catalytic core of the poly(ADP-ribose) polymerase (PS51059) domain. However, bioinformatic analysis of the SRO PARP domain fold-structure and biochemical assays of AtRCD1 suggested that SROs do not possess ADP-ribosyl transferase activity. The SROs are a highly conserved family of plant specific proteins. Sequence analysis of the RST domain implicates a highly preserved protein structure in that region. This might have implications for functional conservation. We suggest that, despite the presence of the catalytic core of the PARP domain, the SROs do not possess ADP-ribosyl transferase activity. Nevertheless, the function of SROs is critical for plants and might be related to transcription factor regulation and complex formation.

  8. Satisfaction in different life domains in children receiving home parenteral nutrition and their families.

    Science.gov (United States)

    Gottrand, Frédéric; Staszewski, Pierre; Colomb, Virginie; Loras-Duclaux, Irène; Guimber, Dominique; Marinier, Evelyne; Breton, Anne; Magnificat, Sabine

    2005-06-01

    To assess the quality-of-life (QOL) of children receiving home parenteral nutrition (HPN). A national multicenter study of 72 patients (median age 4 years) presenting with a digestive disease requiring HPN, and 90 siblings, 67 fathers, and 69 mothers of these children. Median duration of HPN was 2 years (3 months-18 years). QOL was measured using validated, nondisease-specific questionnaires appropriate to the children's ages. The QOL scores were high in patients of all ages and were not significantly different from scores in a reference population of healthy children and adolescents. Lower QOL scores were recorded in the domains related to hospital, health, doctors, medications, and obligations. The QOL was not affected in siblings but was significantly impaired in parents, especially in mothers, who showed a lower level of satisfaction than did fathers for items related to work, inner life, and freedom. Presence of an ileostomy was the only factor that influenced QOL, especially of adolescents. QOL of HPN-dependent children and siblings is not different from that of healthy children, suggesting that these children actively use effective coping strategies. In contrast, the QOL of parents of HPN-dependent children is low.

  9. Heterogeneous dynamics in DNA site discrimination by the structurally homologous DNA-binding domains of ETS-family transcription factors.

    Science.gov (United States)

    He, Gaofei; Tolic, Ana; Bashkin, James K; Poon, Gregory M K

    2015-04-30

    The ETS family of transcription factors exemplifies current uncertainty in how eukaryotic genetic regulators with overlapping DNA sequence preferences achieve target site specificity. PU.1 and Ets-1 represent archetypes for studying site discrimination by ETS proteins because their DNA-binding domains are the most divergent in sequence, yet they share remarkably superimposable DNA-bound structures. To gain insight into the contrasting thermodynamics and kinetics of DNA recognition by these two proteins, we investigated the structure and dynamics of site discrimination by their DNA-binding domains. Electrophoretic mobilities of complexes formed by the two homologs with circularly permuted binding sites showed significant dynamic differences only for DNA complexes of PU.1. Free solution measurements by dynamic light scattering showed PU.1 to be more dynamic than Ets-1; moreover, dynamic changes are strongly coupled to site discrimination by PU.1, but not Ets-1. Interrogation of the protein/DNA interface by DNA footprinting showed similar accessibility to dimethyl sulfate for PU.1/DNA and Ets-1/DNA complexes, indicating that the dynamics of PU.1/DNA complexes reside primarily outside that interface. An information-based analysis of the two homologs' binding motifs suggests a role for dynamic coupling in PU.1's ability to enforce a more stringent sequence preference than Ets-1 and its proximal sequence homologs. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Taxonomic distribution, repeats, and functions of the S1 domain-containing proteins as members of the OB-fold family.

    Science.gov (United States)

    Deryusheva, Evgeniia I; Machulin, Andrey V; Selivanova, Olga M; Galzitskaya, Oxana V

    2017-04-01

    Proteins of the nucleic acid-binding proteins superfamily perform such functions as processing, transport, storage, stretching, translation, and degradation of RNA. It is one of the 16 superfamilies containing the OB-fold in protein structures. Here, we have analyzed the superfamily of nucleic acid-binding proteins (the number of sequences exceeds 200,000) and obtained that this superfamily prevalently consists of proteins containing the cold shock DNA-binding domain (ca. 131,000 protein sequences). Proteins containing the S1 domain compose 57% from the cold shock DNA-binding domain family. Furthermore, we have found that the S1 domain was identified mainly in the bacterial proteins (ca. 83%) compared to the eukaryotic and archaeal proteins, which are available in the UniProt database. We have found that the number of multiple repeats of S1 domain in the S1 domain-containing proteins depends on the taxonomic affiliation. All archaeal proteins contain one copy of the S1 domain, while the number of repeats in the eukaryotic proteins varies between 1 and 15 and correlates with the protein size. In the bacterial proteins, the number of repeats is no more than 6, regardless of the protein size. The large variation of the repeat number of S1 domain as one of the structural variants of the OB-fold is a distinctive feature of S1 domain-containing proteins. Proteins from the other families and superfamilies have either one OB-fold or change slightly the repeat numbers. On the whole, it can be supposed that the repeat number is a vital for multifunctional activity of the S1 domain-containing proteins. Proteins 2017; 85:602-613. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Genome-wide survey of prokaryotic serine proteases: Analysis of distribution and domain architectures of five serine protease families in prokaryotes

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    Tripathi Lokesh P

    2008-11-01

    Full Text Available Abstract Background Serine proteases are one of the most abundant groups of proteolytic enzymes found in all the kingdoms of life. While studies have established significant roles for many prokaryotic serine proteases in several physiological processes, such as those associated with metabolism, cell signalling, defense response and development, functional associations for a large number of prokaryotic serine proteases are relatively unknown. Current analysis is aimed at understanding the distribution and probable biological functions of the select serine proteases encoded in representative prokaryotic organisms. Results A total of 966 putative serine proteases, belonging to five families, were identified in the 91 prokaryotic genomes using various sensitive sequence search techniques. Phylogenetic analysis reveals several species-specific clusters of serine proteases suggesting their possible involvement in organism-specific functions. Atypical phylogenetic associations suggest an important role for lateral gene transfer events in facilitating the widespread distribution of the serine proteases in the prokaryotes. Domain organisations of the gene products were analysed, employing sensitive sequence search methods, to infer their probable biological functions. Trypsin, subtilisin and Lon protease families account for a significant proportion of the multi-domain representatives, while the D-Ala-D-Ala carboxypeptidase and the Clp protease families are mostly single-domain polypeptides in prokaryotes. Regulatory domains for protein interaction, signalling, pathogenesis, cell adhesion etc. were found tethered to the serine protease domains. Some domain combinations (such as S1-PDZ; LON-AAA-S16 etc. were found to be widespread in the prokaryotic lineages suggesting a critical role in prokaryotes. Conclusion Domain architectures of many serine proteases and their homologues identified in prokaryotes are very different from those observed in eukaryotes

  12. Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects.

    Science.gov (United States)

    Stepensky, Polina; Keller, Baerbel; Buchta, Mary; Kienzler, Anne-Kathrin; Elpeleg, Orly; Somech, Raz; Cohen, Sivan; Shachar, Idit; Miosge, Lisa A; Schlesier, Michael; Fuchs, Ilka; Enders, Anselm; Eibel, Hermann; Grimbacher, Bodo; Warnatz, Klaus

    2013-02-01

    Profound combined immunodeficiency can present with normal numbers of T and B cells, and therefore the functional defect of the cellular and humoral immune response is often not recognized until the first severe clinical manifestation. Here we report a patient of consanguineous descent presenting at 13 months of age with hypogammaglobulinemia, Pneumocystis jirovecii pneumonia, and a suggestive family history. We sought to identify the genetic alteration in a patient with combined immunodeficiency and characterize human caspase recruitment domain family, member 11 (CARD11), deficiency. Molecular, immunologic, and functional assays were performed. The immunologic characterization revealed only subtle changes in the T-cell and natural killer cell compartment, whereas B-cell differentiation, although normal in number, was distinctively blocked at the transitional stage. Genetic evaluation revealed a homozygous deletion of exon 21 in CARD11 as the underlying defect. This deletion abrogated protein expression and activation of the canonical nuclear factor κB (NF-κB) pathway in lymphocytes after antigen receptor or phorbol 12-myristate 13-acetate stimulation, whereas CD40 signaling in B cells was preserved. The abrogated activation of the canonical NF-κB pathway was associated with severely impaired upregulation of inducible T-cell costimulator, OX40, cytokine production, proliferation of T cells, and B cell-activating factor receptor expression on B cells. Thus in patients with CARD11 deficiency, the combination of impaired activation and especially upregulation of inducible T-cell costimulator on T cells, together with severely disturbed peripheral B-cell differentiation, apparently leads to a defective T-cell/B-cell cooperation and probably germinal center formation and clinically results in severe immunodeficiency. This report discloses the crucial and nonredundant role of canonical NF-κB activation and specifically CARD11 in the antigen-specific immune response

  13. Structural and evolutionary aspects of two families of non-catalytic domains present in starch and glycogen binding proteins from microbes, plants and animals

    DEFF Research Database (Denmark)

    Janeček, Štefan; Svensson, Birte; MacGregor, E. Ann

    2011-01-01

    Starch-binding domains (SBDs) comprise distinct protein modules that bind starch, glycogen or related carbohydrates and have been classified into different families of carbohydrate-binding modules (CBMs). The present review focuses on SBDs of CBM20 and CBM48 found in amylolytic enzymes from sever...

  14. Proteins with two SUMO-like domains in chromatin-associated complexes: The RENi (Rad60-Esc2-NIP45 family

    Directory of Open Access Journals (Sweden)

    Eisenhaber Birgit

    2005-02-01

    Full Text Available Abstract Background Post-translational modification by Small Ubiquitin-like Modifiers (SUMO has been implicated in protein targeting, in the maintenance of genomic integrity and in transcriptional control. But the specific molecular effects of SUMO modification on many target proteins remain to be elucidated. Recent findings point at the importance of SUMO-mediated histone NAD-dependent deacetylase (HDAC recruitment in transcriptional regulation. Results We describe the RENi family of SUMO-like domain proteins (SDP with the unique feature of typically containing two carboxy-terminal SUMO-like domains. Using sequence analytic evidence, we collect family members from animals, fungi and plants, most prominent being yeast Rad60, Esc2 and mouse NIP45 http://mendel.imp.univie.ac.at/SEQUENCES/reni/. Different proteins of the novel family are known to interact directly with histone NAD-dependent deacetylases (HDACs, structural maintenance of chromosomes (SMC proteins, and transcription factors. In particular, the highly non-trivial designation of the first of the two successive SUMO-domains in non-plant RENi provides a rationale for previously published functionally impaired mutant variants. Conclusions Till now, SUMO-like proteins have been studied exclusively in the context of their covalent conjugation to target proteins. Here, we present the exciting possibility that SUMO domain proteins, similarly to ubiquitin modifiers, have also evolved in a second line – namely as multi-domain proteins that are non-covalently attached to their target proteins. We suggest that the SUMO stable fusion proteins of the RENi family, which we introduce in this work, might mimic SUMO and share its interaction motifs (in analogy to the way that ubiquitin-like domains mimic ubiquitin. This presumption is supported by parallels in the spectrum of modified or bound proteins e.g. transcription factors and chromatin-associated proteins and in the recruitment of HDAC-activity.

  15. Differential sensitivity to methylated DNA by ETS-family transcription factors is intrinsically encoded in their DNA-binding domains.

    Science.gov (United States)

    Stephens, Dominique C; Poon, Gregory M K

    2016-10-14

    Transactivation by the ETS family of transcription factors, whose members share structurally conserved DNA-binding domains, is variably sensitive to methylation of their target genes. The mechanism by which DNA methylation controls ETS proteins remains poorly understood. Uncertainly also pervades the effects of hemi-methylated DNA, which occurs following DNA replication and in response to hypomethylating agents, on site recognition by ETS proteins. To address these questions, we measured the affinities of two sequence-divergent ETS homologs, PU.1 and Ets-1, to DNA sites harboring a hemi- and fully methylated CpG dinucleotide. While the two proteins bound unmethylated DNA with indistinguishable affinity, their affinities to methylated DNA are markedly heterogeneous and exhibit major energetic coupling between the two CpG methylcytosines. Analysis of simulated DNA and existing co-crystal structures revealed that hemi-methylation induced non-local backbone and groove geometries that were not conserved in the fully methylated state. Indirect readout of these perturbations was differentially achieved by the two ETS homologs, with the distinctive interfacial hydration in PU.1/DNA binding moderating the inhibitory effects of DNA methylation on binding. This data established a biophysical basis for the pioneering properties associated with PU.1, which robustly bound fully methylated DNA, but not Ets-1, which was substantially inhibited. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Amyloid-like fibrils from an 18-residue peptide analogue of a part of the central domain of the B-family of silkmoth chorion proteins.

    Science.gov (United States)

    Iconomidou, V A; Chryssikos, G D; Gionis, V; Vriend, G; Hoenger, A; Hamodrakas, S J

    2001-06-22

    Chorion is the major component of silkmoth eggshell. More than 95% of its dry mass consists of the A and B families of low molecular weight structural proteins, which have remarkable mechanical and chemical properties, and protect the oocyte and the developing embryo from the environment. We present data from negative staining, Congo red binding, X-ray diffraction, Fourier transform-Raman, attenuated total reflectance infrared spectroscopy and modelling studies of a synthetic peptide analogue of a part of the central domain of the B family of silkmoth chorion proteins, indicating that this peptide folds and self-assembles, forming amyloid-like fibrils. These results support further our proposal, based on experimental data from a synthetic peptide analogue of the central domain of the A family of chorion proteins, that silkmoth chorion is a natural, protective amyloid [Iconomidou et al., FEBS Lett. 479 (2000) 141-145].

  17. The bldC Developmental Locus of Streptomyces coelicolor Encodes a Member of a Family of Small DNA-Binding Proteins Related to the DNA-Binding Domains of the MerR Family

    OpenAIRE

    Hunt, AC; Servin-Gonzalez, L; Kelemen, GH; Buttner, MJ

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-n...

  18. Evolutionary and functional analysis of the invariant SWIM domain in the conserved Shu2/SWS1 protein family from Saccharomyces cerevisiae to Homo sapiens.

    Science.gov (United States)

    Godin, Stephen K; Meslin, Camille; Kabbinavar, Faiz; Bratton-Palmer, Dominique S; Hornack, Christina; Mihalevic, Michael J; Yoshida, Kyle; Sullivan, Meghan; Clark, Nathan L; Bernstein, Kara A

    2015-04-01

    The Saccharomyces cerevisiae Shu2 protein is an important regulator of Rad51, which promotes homologous recombination (HR). Shu2 functions in the Shu complex with Shu1 and the Rad51 paralogs Csm2 and Psy3. Shu2 belongs to the SWS1 protein family, which is characterized by its SWIM domain (CXC...Xn...CXH), a zinc-binding motif. In humans, SWS1 interacts with the Rad51 paralog SWSAP1. Using genetic and evolutionary analyses, we examined the role of the Shu complex in mitotic and meiotic processes across eukaryotic lineages. We provide evidence that the SWS1 protein family contains orthologous genes in early-branching eukaryote lineages (e.g., Giardia lamblia), as well as in multicellular eukaryotes including Caenorhabditis elegans and Drosophila melanogaster. Using sequence analysis, we expanded the SWIM domain to include an invariant alanine three residues after the terminal CXH motif (CXC…Xn…CXHXXA). We found that the SWIM domain is conserved in all eukaryotic orthologs, and accordingly, in vivo disruption of the invariant residues within the canonical SWIM domain inhibits DNA damage tolerance in yeast and protein-protein interactions in yeast and humans. Furthermore, using evolutionary analyses, we found that yeast and Drosophila Shu2 exhibit strong coevolutionary signatures with meiotic proteins, and in yeast, its disruption leads to decreased meiotic progeny. Together our data indicate that the SWS1 family is an ancient and highly conserved eukaryotic regulator of meiotic and mitotic HR.

  19. A two disulfide bridge Kazal domain from Phytophthora exhibits stable inhibitory activity against serine proteases of the subtilisin family

    Directory of Open Access Journals (Sweden)

    Kamoun Sophien

    2005-08-01

    Full Text Available Abstract Background Kazal-like serine protease inhibitors are defined by a conserved sequence motif. A typical Kazal domain contains six cysteine residues leading to three disulfide bonds with a 1–5/2–4/3–6 pattern. Most Kazal domains described so far belong to this class. However, a novel class of Kazal domains with two disulfide bridges resulting from the absence of the third and sixth cysteines have been found in biologically important molecules, such as human LEKTI, a 15-domain inhibitor associated with the severe congenital disease Netherton syndrome. These domains are referred to as atypical Kazal domains. Previously, EPI1, a Kazal-like protease inhibitor from the oomycete plant pathogen Phytophthora infestans, was shown to be a tight-binding inhibitor of subtilisin A. EPI1 also inhibits and interacts with the pathogenesis-related P69B subtilase of the host plant tomato, suggesting a role in virulence. EPI1 is composed of two Kazal domains, the four-cysteine atypical domain EPI1a and the typical domain EPI1b. Results In this study, we predicted the inhibition constants of EPI1a and EPI1b to subtilisin A using the additivity-based sequence to reactivity algorithm (Laskowski algorithm. The atypical domain EPI1a, but not the typical domain EPI1b, was predicted to have strong inhibitory activity against subtilisin A. Inhibition assays and coimmunoprecipitation experiments showed that recombinant domain EPI1a exhibited stable inhibitory activity against subilisin A and was solely responsible for inhibition and interaction with tomato P69B subtilase. Conclusion The finding that the two disulfide bridge atypical Kazal domain EPI1a is a stable inhibitor indicates that the missing two cysteines and their corresponding disulfide bond are not essential for inhibitor reactivity and stability. This report also suggests that the Laskowski algorithm originally developed and validated with typical Kazal domains might operate accurately for atypical

  20. Domains of quality of life: results of a three-stage Delphi consensus procedure among patients, family of patients, clinicians, scientists and the general public.

    Science.gov (United States)

    Pietersma, Suzanne; de Vries, Marieke; van den Akker-van Marle, M Elske

    2014-06-01

    Our key objective is to identify the core domains of health-related quality of life (QoL). Health-related QoL utility scales are commonly used in economic evaluations to assess the effectiveness of health-care interventions. However, health-care interventions are likely to affect QoL in a broader sense than is quantifiable with traditional scales. Therefore, measures need to go beyond these scales. Unfortunately, there is no consensus in the scientific literature on the essential domains of QoL. We conducted a three-stage online Delphi consensus procedure to identify the key domains of health-related QoL. Five stakeholder groups (i.e., patients, family of patients, clinicians, scientists and general public) were asked, on three consecutive occasions, what they perceive as the most important domains of health-related QoL. An analysis of existing (health-related) QoL and well-being measurements formed the basis of the Delphi-procedure. In total, 42 domains of QoL were judged, covering physical, mental and social aspects. All participants rated 'self-acceptance', 'self-esteem' and 'good social contacts' as essential. Strikingly, mental and social domains are perceived as more essential than physical domains across stakeholders groups. In traditionally used health-related QoL utility measures, physical domains like 'mobility' are prominently present. The Delphi-procedure shows that health-related QoL (utility) scales need to put sufficient emphasis on mental and social domains to capture aspects of QoL that are essential to people.

  1. Desmin myopathy with severe cardiomyopathy in a Uruguayan family due to a codon deletion in a new location within the desmin 1A rod domain.

    Science.gov (United States)

    Vernengo, Luis; Chourbagi, Oussama; Panuncio, Ana; Lilienbaum, Alain; Batonnet-Pichon, Sabrina; Bruston, Francine; Rodrigues-Lima, Fernando; Mesa, Rosario; Pizzarossa, Carlos; Demay, Laurence; Richard, Pascale; Vicart, Patrick; Rodriguez, Maria-Mirta

    2010-03-01

    Desmin myopathy is a heterogeneous neuromuscular disorder characterized by skeletal myopathy and cardiomyopathy, inherited mostly in an autosomal dominant pattern. We report a five generation Uruguayan family with severe cardiomyopathy and skeletal myopathy. Its most striking features are: atrial dilation, arrhythmia, conduction block and sudden death due to conduction impairment. Affected skeletal muscle shows alteration of mitochondria with paracrystallin inclusions and granulofilamentous material scattered in the muscle fibres. This family carries an unusual deletion p.E114del within the 1A rod domain of desmin. Transfected cells expressing the mutated desmin show punctuated and speckled cytoplasmic aggregates. The mutation causes a local conformational change in heptads a/d residues and charge positions. These findings lead to the hypothesis that coiled-coil interactions may be impaired, resulting in severe alterations in the desmin network. This is the first time that a mutation affecting this domain in the desmin molecule is described in a desminopathy.

  2. A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen

    Science.gov (United States)

    Gale, Daniel P.; Oygar, D. Deren; Lin, Fujun; Oygar, P. Derin; Khan, Nadia; Connor, Thomas M.F.; Lapsley, Marta; Maxwell, Patrick H.; Neild, Guy H.

    2016-01-01

    Background Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts. Methods We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses. Results We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested. Conclusions Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans. PMID:27190376

  3. An atypical segment swap in the DN and DC domains of the Acr_tran family resistance-nodulation-cell division pump.

    Science.gov (United States)

    Acharya, Giriraj; Kaur, Gurmeet; Subramanian, Srikrishna

    2016-12-01

    Domain/segment swapping is an exchange of equivalent secondary structure element(s) among two or more protein domains resulting in the reconstitution of the original fold while simultaneously causing oligomerization. Here we report an example of the outer membrane factor docking region of the Acr_tran family (PF00873) resistance-nodulation-cell division pump, in which a swapped, misfolded state, of the ferredoxin-like fold of the DN and DC domains, effectuates oligomerization. The atypical segment swap and the associated displacement of a region of the ferredoxin-like fold leads to a topology that is distinct from the original fold. To our knowledge, such segment swaps and associated fold change are rare. This exemplifies the role of functional constraints including oligomerization that determine the interplay between sequence and the three-dimensional structure of proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. A new family of receptor tyrosine kinases with a venus flytrap binding domain in insects and other invertebrates activated by aminoacids.

    Directory of Open Access Journals (Sweden)

    Arnaud Ahier

    Full Text Available BACKGROUND: Tyrosine kinase receptors (RTKs comprise a large family of membrane receptors that regulate various cellular processes in cell biology of diverse organisms. We previously described an atypical RTK in the platyhelminth parasite Schistosoma mansoni, composed of an extracellular Venus flytrap module (VFT linked through a single transmembrane domain to an intracellular tyrosine kinase domain similar to that of the insulin receptor. METHODS AND FINDINGS: Here we show that this receptor is a member of a new family of RTKs found in invertebrates, and particularly in insects. Sixteen new members of this family, named Venus Kinase Receptor (VKR, were identified in many insects. Structural and phylogenetic studies performed on VFT and TK domains showed that VKR sequences formed monophyletic groups, the VFT group being close to that of GABA(B receptors and the TK one being close to that of insulin receptors. We show that a recombinant VKR is able to autophosphorylate on tyrosine residues, and report that it can be activated by L-arginine. This is in agreement with the high degree of conservation of the alpha amino acid binding residues found in many amino acid binding VFTs. The presence of high levels of vkr transcripts in larval forms and in female gonads indicates a putative function of VKR in reproduction and/or development. CONCLUSION: The identification of RTKs specific for parasites and insect vectors raises new perspectives for the control of human parasitic and infectious diseases.

  5. Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects

    Science.gov (United States)

    Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling

    2017-01-01

    Abstract The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain–containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. PMID:28444351

  6. A new family of receptor tyrosine kinases with a venus flytrap binding domain in insects and other invertebrates activated by aminoacids.

    Science.gov (United States)

    Ahier, Arnaud; Rondard, Philippe; Gouignard, Nadège; Khayath, Naji; Huang, Siluo; Trolet, Jacques; Donoghue, Daniel J; Gauthier, Monique; Pin, Jean-Philippe; Dissous, Colette

    2009-05-21

    Tyrosine kinase receptors (RTKs) comprise a large family of membrane receptors that regulate various cellular processes in cell biology of diverse organisms. We previously described an atypical RTK in the platyhelminth parasite Schistosoma mansoni, composed of an extracellular Venus flytrap module (VFT) linked through a single transmembrane domain to an intracellular tyrosine kinase domain similar to that of the insulin receptor. Here we show that this receptor is a member of a new family of RTKs found in invertebrates, and particularly in insects. Sixteen new members of this family, named Venus Kinase Receptor (VKR), were identified in many insects. Structural and phylogenetic studies performed on VFT and TK domains showed that VKR sequences formed monophyletic groups, the VFT group being close to that of GABA(B) receptors and the TK one being close to that of insulin receptors. We show that a recombinant VKR is able to autophosphorylate on tyrosine residues, and report that it can be activated by L-arginine. This is in agreement with the high degree of conservation of the alpha amino acid binding residues found in many amino acid binding VFTs. The presence of high levels of vkr transcripts in larval forms and in female gonads indicates a putative function of VKR in reproduction and/or development. The identification of RTKs specific for parasites and insect vectors raises new perspectives for the control of human parasitic and infectious diseases.

  7. Mechanistic Heterogeneity in Site Recognition by the Structurally Homologous DNA-binding Domains of the ETS Family Transcription Factors Ets-1 and PU.1*

    Science.gov (United States)

    Wang, Shuo; Linde, Miles H.; Munde, Manoj; Carvalho, Victor D.; Wilson, W. David; Poon, Gregory M. K.

    2014-01-01

    ETS family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in terms of the role of hydration and counter ion release. The data suggest two distinct mechanisms wherein Ets-1 follows a “dry” mechanism that rapidly parses sites through electrostatic interactions and direct protein-DNA contacts, whereas PU.1 utilizes hydration to interrogate sequence-specific sites and form a long-lived complex relative to the Ets-1 counterpart. The kinetic persistence of the high affinity PU.1·DNA complex may be relevant to an emerging role of PU.1, but not Ets-1, as a pioneer transcription factor in vivo. In addition, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydration-dependent specificity may represent an important regulatory mechanism in vivo, a hypothesis that finds support in gene expression profiles of primary murine macrophages. PMID:24952944

  8. SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

    Directory of Open Access Journals (Sweden)

    Shchelkunov Sergei N

    2010-10-01

    Full Text Available Abstract Background Variola virus (VARV the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. Findings De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Conclusions Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

  9. Temperature inducible β-sheet structure in the transactivation domains of retroviral regulatory proteins of the Rev family

    Science.gov (United States)

    Thumb, Werner; Graf, Christine; Parslow, Tristram; Schneider, Rainer; Auer, Manfred

    1999-11-01

    The interaction of the human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev with cellular cofactors is crucial for the viral life cycle. The HIV-1 Rev transactivation domain is functionally interchangeable with analog regions of Rev proteins of other retroviruses suggesting common folding patterns. In order to obtain experimental evidence for similar structural features mediating protein-protein contacts we investigated activation domain peptides from HIV-1, HIV-2, VISNA virus, feline immunodeficiency virus (FIV) and equine infectious anemia virus (EIAV) by CD spectroscopy, secondary structure prediction and sequence analysis. Although different in polarity and hydrophobicity, all peptides showed a similar behavior with respect to solution conformation, concentration dependence and variations in ionic strength and pH. Temperature studies revealed an unusual induction of β-structure with rising temperatures in all activation domain peptides. The high stability of β-structure in this region was demonstrated in three different peptides of the activation domain of HIV-1 Rev in solutions containing 40% hexafluoropropanol, a reagent usually known to induce α-helix into amino acid sequences. Sequence alignments revealed similarities between the polar effector domains from FIV and EIAV and the leucine rich (hydrophobic) effector domains found in HIV-1, HIV-2 and VISNA. Studies on activation domain peptides of two dominant negative HIV-1 Rev mutants, M10 and M32, pointed towards different reasons for the biological behavior. Whereas the peptide containing the M10 mutation (L 78E 79→D 78L 79) showed wild-type structure, the M32 mutant peptide (L 78L 81L 83→A 78A 81A 83) revealed a different protein fold to be the reason for the disturbed binding to cellular cofactors. From our data, we conclude, that the activation domain of Rev proteins from different viral origins adopt a similar fold and that a β-structural element is involved in binding to a

  10. The velvet family of fungal regulators contains a DNA-binding domain structurally similar to NF-κB.

    Directory of Open Access Journals (Sweden)

    Yasar Luqman Ahmed

    2013-12-01

    Full Text Available Morphological development of fungi and their combined production of secondary metabolites are both acting in defence and protection. These processes are mainly coordinated by velvet regulators, which contain a yet functionally and structurally uncharacterized velvet domain. Here we demonstrate that the velvet domain of VosA is a novel DNA-binding motif that specifically recognizes an 11-nucleotide consensus sequence consisting of two motifs in the promoters of key developmental regulatory genes. The crystal structure analysis of the VosA velvet domain revealed an unforeseen structural similarity with the Rel homology domain (RHD of the mammalian transcription factor NF-κB. Based on this structural similarity several conserved amino acid residues present in all velvet domains have been identified and shown to be essential for the DNA binding ability of VosA. The velvet domain is also involved in dimer formation as seen in the solved crystal structures of the VosA homodimer and the VosA-VelB heterodimer. These findings suggest that defence mechanisms of both fungi and animals might be governed by structurally related DNA-binding transcription factors.

  11. The Clinical Spectrum of Missense Mutations of the First Aspartic Acid of cbEGF-like Domains in Fibrillin-1 Including a Recessive Family

    Science.gov (United States)

    Hilhorst-Hofstee, Yvonne; Rijlaarsdam, Marry EB; Scholte, Arthur JHA; Swart-van den Berg, Marietta; Versteegh, Michel IM; van der Schoot-van Velzen, Iris; Schäbitz, Hans-Joachim; Bijlsma, Emilia K; Baars, Marieke J; Kerstjens-Frederikse, Wilhelmina S; Giltay, Jacques C; Hamel, Ben C; Breuning, Martijn H; Pals, Gerard

    2010-01-01

    Marfan syndrome (MFS) is a dominant disorder with a recognizable phenotype. In most patients with the classical phenotype mutations are found in the fibrillin-1 gene (FBN1) on chromosome 15q21. It is thought that most mutations act in a dominant negative way or through haploinsufficiency. In 9 index cases referred for MFS we detected heterozygous missense mutations in FBN1 predicted to substitute the first aspartic acid of different calcium-binding Epidermal Growth Factor-like (cbEGF) fibrillin-1 domains. A similar mutation was found in homozygous state in 3 cases in a large consanguineous family. Heterozygous carriers of this mutation had no major skeletal, cardiovascular or ophthalmological features of MFS. In the literature 14 other heterozygous missense mutations are described leading to the substitution of the first aspartic acid of a cbEGF domain and resulting in a Marfan phenotype. Our data show that the phenotypic effect of aspartic acid substitutions in the first position of a cbEGF domain can range from asymptomatic to a severe neonatal phenotype. The recessive nature with reduced expression of FBN1 in one of the families suggests a threshold model combined with a mild functional defect of this specific mutation. © 2010 Wiley-Liss, Inc. PMID:20886638

  12. Crystal structure of calpain-3 penta-EF-hand (PEF) domain - a homodimerized PEF family member with calcium bound at the fifth EF-hand

    Energy Technology Data Exchange (ETDEWEB)

    Partha, Sarathy K.; Ravulapalli, Ravikiran; Allingham, John S.; Campbell, Robert L.; Davies, Peter L. [Queens

    2014-08-21

    Calpains are Ca2+dependent intracellular cysteine proteases that cleave a wide range of protein substrates to help implement Ca2+ signaling in the cell. The major isoforms of this enzyme family, calpain-1 and calpain-2, are heterodimers of a large and a small subunit, with the main dimer interface being formed through their C-terminal penta-EF hand (PEF) domains. Calpain-3, or p94, is a skeletal muscle-specific isoform that is genetically linked to limb-girdle muscular dystrophy. Biophysical and modeling studies with the PEF domain of calpain-3 support the suggestion that full-length calpain-3 exists as a homodimer. Here, we report the crystallization of calpain-3's PEF domain and its crystal structure in the presence of Ca2+, which provides evidence for the homodimer architecture of calpain-3 and supports the molecular model that places a protease core at either end of the elongated dimer. Unlike other calpain PEF domain structures, the calpain-3 PEF domain contains a Ca2+ bound at the EF5-hand used for homodimer association. Three of the four Ca2+-binding EF-hands of the PEF domains are concentrated near the protease core, and have the potential to radically change the local charge within the dimer during Ca2+ signaling. Examination of the homodimer interface shows that there would be steric clashes if the calpain-3 large subunit were to try to pair with a calpain small subunit.

  13. SorCS2 is required for BDNF-dependent plasticity in the hippocampus

    DEFF Research Database (Denmark)

    Glerup, S; Bolcho, U; Bøggild, S;

    2016-01-01

    SorCS2 is a member of the Vps10p-domain receptor gene family receptors with critical roles in the control of neuronal viability and function. Several genetic studies have suggested SORCS2 to confer risk of bipolar disorder, schizophrenia and attention deficit-hyperactivity disorder. Here we repor...

  14. Making sense of behavioral disturbances in persons with dementia: Latino family caregiver attributions of Neuropsychiatric Inventory domains

    OpenAIRE

    Hinton, Ladson; Chambers, Darin; Velásquez, Alexandra

    2009-01-01

    The purpose of this study was to describe the nature and frequency of Latino family caregiver attributions for dementia-related neuropsychiatric symptoms. This is a cross-sectional study conducted in the Sacramento, California area. Participants were 30 Latino family caregivers of community-dwelling Latino elderly meeting research criteria for dementia who were selected from an ongoing cohort study of older Latinos (Sacramento Area Latino Study on Aging). Open-ended probes were used to elicit...

  15. Arabidopsis RADICAL-INDUCED CELL DEATH1 belongs to the WWE protein-protein interaction domain protein family and modulates abscisic acid, ethylene, and methyl jasmonate responses.

    Science.gov (United States)

    Ahlfors, Reetta; Lång, Saara; Overmyer, Kirk; Jaspers, Pinja; Brosché, Mikael; Tauriainen, Airi; Kollist, Hannes; Tuominen, Hannele; Belles-Boix, Enric; Piippo, Mirva; Inzé, Dirk; Palva, E Tapio; Kangasjärvi, Jaakko

    2004-07-01

    Experiments with several Arabidopsis thaliana mutants have revealed a web of interactions between hormonal signaling. Here, we show that the Arabidopsis mutant radical-induced cell death1 (rcd1), although hypersensitive to apoplastic superoxide and ozone, is more resistant to chloroplastic superoxide formation, exhibits reduced sensitivity to abscisic acid, ethylene, and methyl jasmonate, and has altered expression of several hormonally regulated genes. Furthermore, rcd1 has higher stomatal conductance than the wild type. The rcd1-1 mutation was mapped to the gene At1g32230 where it disrupts an intron splice site resulting in a truncated protein. RCD1 belongs to the (ADP-ribosyl)transferase domain-containing subfamily of the WWE protein-protein interaction domain protein family. The results suggest that RCD1 could act as an integrative node in hormonal signaling and in the regulation of several stress-responsive genes.

  16. A new clan of CBM families based on bioinformatics of starch-binding domains from families CBM20 and CBM21

    DEFF Research Database (Denmark)

    Marhovic, M.; Svensson, Birte; MacGregor, E. A.;

    2005-01-01

    families: CBM20, CBM21, CBM25, CBM26, CBM34, and CBM41. This work is concentrated on CBM20 and CBM21. The CBM20 module was believed to be located almost exclusively at the C-terminal end of various amylases. The CBM21 module was known as the N-terminally positioned SBD of Rhizopus glucoamylase. Nowadays...

  17. Mechanistic heterogeneity in site recognition by the structurally homologous DNA-binding domains of the ETS family transcription factors Ets-1 and PU.1.

    Science.gov (United States)

    Wang, Shuo; Linde, Miles H; Munde, Manoj; Carvalho, Victor D; Wilson, W David; Poon, Gregory M K

    2014-08-01

    ETS family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in terms of the role of hydration and counter ion release. The data suggest two distinct mechanisms wherein Ets-1 follows a "dry" mechanism that rapidly parses sites through electrostatic interactions and direct protein-DNA contacts, whereas PU.1 utilizes hydration to interrogate sequence-specific sites and form a long-lived complex relative to the Ets-1 counterpart. The kinetic persistence of the high affinity PU.1 · DNA complex may be relevant to an emerging role of PU.1, but not Ets-1, as a pioneer transcription factor in vivo. In addition, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydration-dependent specificity may represent an important regulatory mechanism in vivo, a hypothesis that finds support in gene expression profiles of primary murine macrophages. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Relevance of the diversity among members of the Trypanosoma cruzi trans-sialidase family analyzed with camelids single-domain antibodies.

    Directory of Open Access Journals (Sweden)

    Laura Ratier

    Full Text Available The sialic acid present in the protective surface mucin coat of Trypanosoma cruzi is added by a membrane anchored trans-sialidase (TcTS, a modified sialidase that is expressed from a large gene family. In this work, we analyzed single domain camelid antibodies produced against trans-sialidase. Llamas were immunized with a recombinant trans-sialidase and inhibitory single-domain antibody fragments were obtained by phage display selection, taking advantage of a screening strategy using an inhibition test instead of the classic binding assay. Four single domain antibodies displaying strong trans-sialidase inhibition activity against the recombinant enzyme were identified. They share the same complementarity-determining region 3 length (17 residues and have very similar sequences. This result indicates that they likely derived from a unique clone. Probably there is only one structural solution for tight binding inhibitory antibodies against the TcTS used for immunization. To our surprise, this single domain antibody that inhibits the recombinant TcTS, failed to inhibit the enzymatic activity present in parasite extracts. Analysis of individual recombinant trans-sialidases showed that enzymes expressed from different genes were inhibited to different extents (from 8 to 98% by the llama antibodies. Amino acid changes at key positions are likely to be responsible for the differences in inhibition found among the recombinant enzymes. These results suggest that the presence of a large and diverse trans-sialidase family might be required to prevent the inhibitory response against this essential enzyme and might thus constitute a novel strategy of T. cruzi to evade the host immune system.

  19. A novel in-frame deletion affecting the BAR domain of OPHN1 in a family with intellectual disability and hippocampal alterations.

    Science.gov (United States)

    Santos-Rebouças, Cíntia Barros; Belet, Stefanie; Guedes de Almeida, Luciana; Ribeiro, Márcia Gonçalves; Medina-Acosta, Enrique; Bahia, Paulo Roberto Valle; Alves da Silva, Antônio Francisco; Lima dos Santos, Flávia; Borges de Lacerda, Glenda Corrêa; Pimentel, Márcia Mattos Gonçalves; Froyen, Guy

    2014-05-01

    Oligophrenin-1 (OPHN1) is one of at least seven genes located on chromosome X that take part in Rho GTPase-dependent signaling pathways involved in X-linked intellectual disability (XLID). Mutations in OPHN1 were primarily described as an exclusive cause of non-syndromic XLID, but the re-evaluation of the affected individuals using brain imaging displayed fronto-temporal atrophy and cerebellar hypoplasia as neuroanatomical marks. In this study, we describe clinical, genetic and neuroimaging data of a three generation Brazilian XLID family co-segregating a novel intragenic deletion in OPHN1. This deletion results in an in-frame loss of exon 7 at transcription level (c.781_891del; r.487_597del), which is predicted to abolish 37 amino acids from the highly conserved N-terminal BAR domain of OPHN1. cDNA expression analysis demonstrated that the mutant OPHN1 transcript is stable and no abnormal splicing was observed. Features shared by the affected males of this family include neonatal hypotonia, strabismus, prominent root of the nose, deep set eyes, hyperactivity and instability/intolerance to frustration. Cranial MRI scans showed large lateral ventricles, vermis hypoplasia and cystic dilatation of the cisterna magna in all affected males. Interestingly, hippocampal alterations that have not been reported in patients with loss-of-function OPHN1 mutations were found in three affected individuals, suggesting an important function for the BAR domain in the hippocampus. This is the first description of an in-frame deletion within the BAR domain of OPHN1 and could provide new insights into the role of this domain in relation to brain and cognitive development or function.

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

    OpenAIRE

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

    2000-01-01

    Familial partial lipodystrophy (FPLD), Dunnigan variety, is an autosomal dominant disorder characterized by marked loss of subcutaneous adipose tissue from the extremities and trunk but by excess fat deposition in the head and neck. The disease is frequently associated with profound insulin resistance, dyslipidemia, and diabetes. We have localized a gene for FPLD to chromosome 1q21-q23, and it has recently been proposed that nuclear lamin A/C is altered in FPLD, on the basis of a novel missen...

  1. Comparative analysis of plant genomes allows the definition of the "Phytolongins": a novel non-SNARE longin domain protein family

    OpenAIRE

    Dacks Joel B; Rossi Valeria; Vedovato Marco; Filippini Francesco

    2009-01-01

    Abstract Background Subcellular trafficking is a hallmark of eukaryotic cells. Because of their pivotal role in the process, a great deal of attention has been paid to the SNARE proteins. Most R-SNAREs, or "longins", however, also possess a highly conserved, N-terminal fold. This "longin domain" is known to play multiple roles in regulating SNARE activity and targeting via interaction with other trafficking proteins. However, the diversity and complement of longins in eukaryotes is poorly und...

  2. Comparative analysis of plant genomes allows the definition of the "Phytolongins": a novel non-SNARE longin domain protein family

    OpenAIRE

    Vedovato, Marco; Rossi, Valeria; Joel B Dacks; Filippini, Francesco

    2009-01-01

    Background Subcellular trafficking is a hallmark of eukaryotic cells. Because of their pivotal role in the process, a great deal of attention has been paid to the SNARE proteins. Most R-SNAREs, or "longins", however, also possess a highly conserved, N-terminal fold. This "longin domain" is known to play multiple roles in regulating SNARE activity and targeting via interaction with other trafficking proteins. However, the diversity and complement of longins in eukaryotes is poorly understood. ...

  3. Structure and expression of the maize (Zea mays L. SUN-domain protein gene family: evidence for the existence of two divergent classes of SUN proteins in plants

    Directory of Open Access Journals (Sweden)

    Simmons Carl R

    2010-12-01

    Full Text Available Abstract Background The nuclear envelope that separates the contents of the nucleus from the cytoplasm provides a surface for chromatin attachment and organization of the cortical nucleoplasm. Proteins associated with it have been well characterized in many eukaryotes but not in plants. SUN (Sad1p/Unc-84 domain proteins reside in the inner nuclear membrane and function with other proteins to form a physical link between the nucleoskeleton and the cytoskeleton. These bridges transfer forces across the nuclear envelope and are increasingly recognized to play roles in nuclear positioning, nuclear migration, cell cycle-dependent breakdown and reformation of the nuclear envelope, telomere-led nuclear reorganization during meiosis, and karyogamy. Results We found and characterized a family of maize SUN-domain proteins, starting with a screen of maize genomic sequence data. We characterized five different maize ZmSUN genes (ZmSUN1-5, which fell into two classes (probably of ancient origin, as they are also found in other monocots, eudicots, and even mosses. The first (ZmSUN1, 2, here designated canonical C-terminal SUN-domain (CCSD, includes structural homologs of the animal and fungal SUN-domain protein genes. The second (ZmSUN3, 4, 5, here designated plant-prevalent mid-SUN 3 transmembrane (PM3, includes a novel but conserved structural variant SUN-domain protein gene class. Mircroarray-based expression analyses revealed an intriguing pollen-preferred expression for ZmSUN5 mRNA but low-level expression (50-200 parts per ten million in multiple tissues for all the others. Cloning and characterization of a full-length cDNA for a PM3-type maize gene, ZmSUN4, is described. Peptide antibodies to ZmSUN3, 4 were used in western-blot and cell-staining assays to show that they are expressed and show concentrated staining at the nuclear periphery. Conclusions The maize genome encodes and expresses at least five different SUN-domain proteins, of which the PM3

  4. Membrane binding domains

    OpenAIRE

    Hurley, James H.

    2006-01-01

    Eukaryotic signaling and trafficking proteins are rich in modular domains that bind cell membranes. These binding events are tightly regulated in space and time. The structural, biochemical, and biophysical mechanisms for targeting have been worked out for many families of membrane binding domains. This review takes a comparative view of seven major classes of membrane binding domains, the C1, C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of specific headgroup inter...

  5. C-terminal domain phosphatase-like family members (AtCPLs) differentially regulate Arabidopsis thaliana abiotic stress signaling, growth, and development.

    Science.gov (United States)

    Koiwa, Hisashi; Barb, Adam W; Xiong, Liming; Li, Fang; McCully, Michael G; Lee, Byeong-Ha; Sokolchik, Irina; Zhu, Jianhua; Gong, Zhizhong; Reddy, Muppala; Sharkhuu, Altanbadralt; Manabe, Yuzuki; Yokoi, Shuji; Zhu, Jian-Kang; Bressan, Ray A; Hasegawa, Paul M

    2002-08-06

    Cold, hyperosmolarity, and abscisic acid (ABA) signaling induce RD29A expression, which is an indicator of the plant stress adaptation response. Two nonallelic Arabidopsis thaliana (ecotype C24) T-DNA insertional mutations, cpl1 and cpl3, were identified based on hyperinduction of RD29A expression that was monitored by using the luciferase (LUC) reporter gene (RD29ALUC) imaging system. Genetic linkage analysis and complementation data established that the recessive cpl1 and cpl3 mutations are caused by T-DNA insertions in AtCPL1 (Arabidopsis C-terminal domain phosphatase-like) and AtCPL3, respectively. Gel assays using recombinant AtCPL1 and AtCPL3 detected innate phosphatase activity like other members of the phylogenetically conserved family that dephosphorylate the C-terminal domain of RNA polymerase II (RNAP II). cpl1 mutation causes RD29ALUC hyperexpression and transcript accumulation in response to cold, ABA, and NaCl treatments, whereas the cpl3 mutation mediates hyperresponsiveness only to ABA. Northern analysis confirmed that LUC transcript accumulation also occurs in response to these stimuli. cpl1 plants accumulate biomass more rapidly and exhibit delayed flowering relative to wild type whereas cpl3 plants grow more slowly and flower earlier than wild-type plants. Hence AtCPL1 and AtCPL3 are negative regulators of stress responsive gene transcription and modulators of growth and development. These results suggest that C-terminal domain phosphatase regulation of RNAP II phosphorylation status is a focal control point of complex processes like plant stress responses and development. AtCPL family members apparently have both unique and overlapping transcriptional regulatory functions that differentiate the signal output that determines the plant response.

  6. Positive and negative social exchanges and cognitive aging in young-old adults: differential associations across family, friend, and spouse domains.

    Science.gov (United States)

    Windsor, Tim D; Gerstorf, Denis; Pearson, Elissa; Ryan, Lindsay H; Anstey, Kaarin J

    2014-03-01

    We examined how positive and negative social exchanges with friends, family, and spouses were related to cognitive aging in episodic and working memory, and perceptual speed. To do so, we used a large sample of cognitively intact young-old participants from the PATH Through Life Study (PATH; aged 60 to 64 years at baseline, n = 1,618) who were assessed on 3 occasions over 8 years. Additional replication analyses were conducted using the Health and Retirement Study (HRS), which provided data on episodic memory. The main analysis of PATH Through Life showed that positive exchanges with friends and family were associated with less decline in perceptual speed, with these associations attenuated by adjustment for physical functioning and depressive symptoms. Negative exchanges with spouses were associated with poorer working memory performance. Positive exchanges with friends were associated with better initial episodic memory in both PATH and HRS. More frequent negative exchanges with friends and family were associated with better episodic memory in the PATH sample. However, these findings were not replicated in HRS. Our findings provide indirect support for the role of social exchange quality in contributing to cognitive enrichment. However, the inconsistent pattern of results across cognitive and social exchange domains points to possibilities of reverse causality, and may also indicate that social exchange quality plays a less important role for cognitive enrichment than other psychosocial characteristics.

  7. Sequence and expression pattern of a novel human orphan G-protein-coupled receptor, GPRC5B, a family C receptor with a short amino-terminal domain

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Krogsgaard-Larsen, P

    2000-01-01

    the receptors currently assigned to family C. However, our results strongly indicate that RAIG1 and GPRC5B form a new subgroup of family C characterized by short ATDs. GPRC5B mRNA is widely expressed in peripheral and central tissues with highest abundance in kidney, pancreas, and testis. This mRNA expression...... from an expressed sequence tag clone that contained the entire open reading frame of the transcript encoding a protein of 395 amino acids. Analysis of the protein sequence reveal that GPRC5B contains a signal peptide and seven transmembrane alpha-helices, which is a hallmark of G......-protein-coupled receptors (GPCRs). GPRC5B displays homology to retinoic acid-inducible gene 1 (RAIG1, 33% sequence identity) and to several family C (mGluR-like) GPCRs (20-25% sequence identity). Both RAIG1 and GPRC5B have short extracellular amino-terminal domains (ATDs) that contrast the very long ATDs characterizing...

  8. Global analysis of ankyrin repeat domain C3HC4-type RING finger gene family in plants.

    Directory of Open Access Journals (Sweden)

    Xiaowei Yuan

    Full Text Available Ankyrin repeat (ANK C3HC4-type RING finger (RF genes comprise a large family in plants and play important roles in various physiological processes of plant life. In this study, we identified 187 ANK C3HC4-type RF proteins from 29 species with complete genomes and named the ANK C3HC4-type RF proteins the XB3-like proteins because they are structurally related to the rice (Oryza sativa XB3. A phylogenetic relationship analysis suggested that the XB3-like genes originated from ferns, and the encoded proteins fell into 3 major groups. Among these groups, we found that the spacing between the metal ligand position 6 and 7, and the conserved residues, which was in addition to the metal ligand amino acids, in the C3HC4-type RF were different. Using a wide range of protein structural analyses, protein models were established, and all XB3-like proteins were found to contain two to seven ANKs and a C3HC4-type RF. The microarray data for the XB3-like genes of Arabidopsis, Oryza sative, Zea mays and Glycine max revealed that the expression of XB3-like genes was in different tissues and during different life stages. The preferential expression of XB3-like genes in specified tissues and the response to phytohormone and abiotic stress treatments of Arabidopsis and Zea mays not only confirmed the microarray analysis data but also demonstrated that the XB3-like proteins play roles in plant growth and development as well as in stress responses. Our data provide a very useful reference for the identification and functional analysis of members of this gene family and also provide a new method for the genome-wide analysis of gene families.

  9. Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH

    Directory of Open Access Journals (Sweden)

    Xiaodong Gu

    2016-01-01

    Full Text Available DFNA9 is a late-onset, progressive, autosomal dominantly inherited sensorineural hearing loss with vestibular dysfunction, which is caused by mutations in the COCH (coagulation factor C homology gene. In this study, we investigated a Chinese family segregating autosomal dominant nonsyndromic sensorineural hearing loss. We identified a missense mutation c.T275A p.V92D in the LCCL domain of COCH cosegregating with the disease and absent in 100 normal hearing controls. This mutation leads to substitution of the hydrophobic valine to an acidic amino acid aspartic acid. Our data enriched the mutation spectrum of DFNA9 and implied the importance for mutation screening of COCH in age related hearing loss with vestibular dysfunctions.

  10. Crystal structure of a BCL-W domain-swapped dimer: implications for the function of BCL-2 family proteins.

    Science.gov (United States)

    Lee, Erinna F; Dewson, Grant; Smith, Brian J; Evangelista, Marco; Pettikiriarachchi, Anne; Dogovski, Con; Perugini, Matthew A; Colman, Peter M; Fairlie, W Douglas

    2011-10-12

    The prosurvival and proapoptotic proteins of the BCL-2 family share a similar three-dimensional fold despite their opposing functions. However, many biochemical studies highlight the requirement for conformational changes for the functioning of both types of proteins, although structural data to support such changes remain elusive. Here, we describe the X-ray structure of dimeric BCL-W that reveals a major conformational change involving helices α3 and α4 hinging away from the core of the protein. Biochemical and functional studies reveal that the α4-α5 hinge region is required for dimerization of BCL-W, and functioning of both pro- and antiapoptotic BCL-2 proteins. Hence, this structure reveals a conformational flexibility not seen in previous BCL-2 protein structures and provides insights into how these regulators of apoptosis can change conformation to exert their function.

  11. A novel approach for multi-domain and multi-gene family identification provides insights into evolutionary dynamics of disease resistance genes in core eudicot plants.

    Science.gov (United States)

    Hofberger, Johannes A; Zhou, Beifei; Tang, Haibao; Jones, Jonathan D G; Schranz, M Eric

    2014-11-08

    Recent advances in DNA sequencing techniques resulted in more than forty sequenced plant genomes representing a diverse set of taxa of agricultural, energy, medicinal and ecological importance. However, gene family curation is often only inferred from DNA sequence homology and lacks insights into evolutionary processes contributing to gene family dynamics. In a comparative genomics framework, we integrated multiple lines of evidence provided by gene synteny, sequence homology and protein-based Hidden Markov Modelling to extract homologous super-clusters composed of multi-domain resistance (R)-proteins of the NB-LRR type (for NUCLEOTIDE BINDING/LEUCINE-RICH REPEATS), that are involved in plant innate immunity. To assess the diversity of R-proteins within and between species, we screened twelve eudicot plant genomes including six major crops and found a total of 2,363 NB-LRR genes. Our curated R-proteins set shows a 50% average for tandem duplicates and a 22% fraction of gene copies retained from ancient polyploidy events (ohnologs). We provide evidence for strong positive selection and show significant differences in molecular evolution rates (Ka/Ks-ratio) among tandem- (mean = 1.59), ohnolog (mean = 1.36) and singleton (mean = 1.22) R-gene duplicates. To foster the process of gene-edited plant breeding, we report species-specific presence/absence of all 140 NB-LRR genes present in the model plant Arabidopsis and describe four distinct clusters of NB-LRR "gatekeeper" loci sharing syntenic orthologs across all analyzed genomes. By curating a near-complete set of multi-domain R-protein clusters in an eudicot-wide scale, our analysis offers significant insight into evolutionary dynamics underlying diversification of the plant innate immune system. Furthermore, our methods provide a blueprint for future efforts to identify and more rapidly clone functional NB-LRR genes from any plant species.

  12. Crystallization and preliminary X-ray crystallographic study of the extracellular domain of the 4-1BB ligand, a member of the TNF family

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Jung-Sue; Kim, Dong-Uk [Department of Biology, Yonsei University, Seoul 120-749 (Korea, Republic of); Ahn, Byungchan; Kwon, Byoung Se [Immunomodulation Research Center, Ulsan University, Ulsan 680-749 (Korea, Republic of); Cho, Hyun-Soo, E-mail: hscho8@yonsei.ac.kr [Department of Biology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2006-01-01

    The extracellular domain of the 4-1BB ligand fused with glutathione-S-transferase was expressed in Escherichia coli (Origami) and purified by using affinity and ion-exchange column chromatographic methods. Crystals of the 4-1BB ligand were obtained at 290 K by the hanging-drop vapour-diffusion method. The 4-1BB ligand, a member of the tumour necrosis factor (TNF) family, is an important co-stimulatory molecule that plays a key role in the clonal expansion and survival of CD8+ T cells. Signalling through binding of the 4-1BB ligand and 4-1BB has been reported to enhance CD8+ T-cell expansion and protect activated CD8+ T cells from death. The 4-1BB ligand is an integral protein expressed on activated antigen-presenting cells. The extracellular domain of the 4-1BB ligand fused with glutathione-S-transferase was expressed in Escherichia coli (Origami) and purified by using affinity and ion-exchange column chromatographic methods. Crystals of the 4-1BB ligand were obtained at 290 K by the hanging-drop vapour-diffusion method. X-ray diffraction data were collected from these crystals to 2.8 Å resolution and the crystals belong to space group C2, with unit-cell parameters a = 114.6, b = 73.8, c = 118.50 Å, β = 115.5°.

  13. Editing of misaligned 3'-termini by an intrinsic 3'-5' exonuclease activity residing in the PHP domain of a family X DNA polymerase.

    Science.gov (United States)

    Baños, Benito; Lázaro, José M; Villar, Laurentino; Salas, Margarita; de Vega, Miguel

    2008-10-01

    Bacillus subtilis gene yshC encodes a family X DNA polymerase (PolX(Bs)), whose biochemical features suggest that it plays a role during DNA repair processes. Here, we show that, in addition to the polymerization activity, PolX(Bs) possesses an intrinsic 3'-5' exonuclease activity specialized in resecting unannealed 3'-termini in a gapped DNA substrate. Biochemical analysis of a PolX(Bs) deletion mutant lacking the C-terminal polymerase histidinol phosphatase (PHP) domain, present in most of the bacterial/archaeal PolXs, as well as of this separately expressed protein region, allow us to state that the 3'-5' exonuclease activity of PolX(Bs) resides in its PHP domain. Furthermore, site-directed mutagenesis of PolX(Bs) His339 and His341 residues, evolutionary conserved in the PHP superfamily members, demonstrated that the predicted metal binding site is directly involved in catalysis of the exonucleolytic reaction. The implications of the unannealed 3'-termini resection by the 3'-5' exonuclease activity of PolX(Bs) in the DNA repair context are discussed.

  14. WRKY domain-encoding genes of a crop legume chickpea (Cicer arietinum): comparative analysis with Medicago truncatula WRKY family and characterization of group-III gene(s).

    Science.gov (United States)

    Kumar, Kamal; Srivastava, Vikas; Purayannur, Savithri; Kaladhar, V Chandra; Cheruvu, Purnima Jaiswal; Verma, Praveen Kumar

    2016-06-01

    The WRKY genes have been identified as important transcriptional modulators predominantly during the environmental stresses, but they also play critical role at various stages of plant life cycle. We report the identification of WRKY domain (WD)-encoding genes from galegoid clade legumes chickpea (Cicer arietinum L.) and barrel medic (Medicago truncatula). In total, 78 and 98 WD-encoding genes were found in chickpea and barrel medic, respectively. Comparative analysis suggests the presence of both conserved and unique WRKYs, and expansion of WRKY family in M. truncatula primarily by tandem duplication. Exclusively found in galegoid legumes, CaWRKY16 and its orthologues encode for a novel protein having a transmembrane and partial Exo70 domains flanking a group-III WD. Genomic region of galegoids, having CaWRKY16, is more dynamic when compared with millettioids. In onion cells, fused CaWRKY16-EYFP showed punctate fluorescent signals in cytoplasm. The chickpea WRKY group-III genes were further characterized for their transcript level modulation during pathogenic stress and treatments of abscisic acid, jasmonic acid, and salicylic acid (SA) by real-time PCR. Differential regulation of genes was observed during Ascochyta rabiei infection and SA treatment. Characterization of A. rabiei and SA inducible gene CaWRKY50 showed that it localizes to plant nucleus, binds to W-box, and have a C-terminal transactivation domain. Overexpression of CaWRKY50 in tobacco plants resulted in early flowering and senescence. The in-depth comparative account presented here for two legume WRKY genes will be of great utility in hastening functional characterization of crop legume WRKYs and will also help in characterization of Exo70Js. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  15. Characterization of TREM-3, an activating receptor on mouse macrophages: definition of a family of single Ig domain receptors on mouse chromosome 17.

    Science.gov (United States)

    Chung, Dong-Hui; Seaman, William E; Daws, Michael R

    2002-01-01

    We recently reported the cloning of two triggering receptors expressed by myeloid cells (TREM), TREM-2a and TREM-2b, which are highly homologous to each other. These receptors associate with DAP12, and ligation of TREM-2 on the surface of macrophages leads to the release of nitric oxide. Using the immunoglobulin (Ig) domain of TREM-2 to screen a mouse EST database we have isolated a novel receptor, derived from a WEHI-3 macrophage library, which shows homology to TREM-2 (20%). The DNA sequence of this receptor has been submitted to Genbank with the name TREM-3. The predicted amino acid sequence contains a single Ig domain and a transmembrane lysine residue. We found transcripts for TREM-3 in two macrophage cell lines (RAW264.7 and MT2) but not in P388D1 macrophage cells. TREM-3 transcripts could also be detected at low levels in T cell lines, but were not detectable in NK, B cell, or mast cell lines. Furthermore, in macrophage cells, transcripts for TREM-3 were up-regulated by LPS, but were down-regulated by IFN-gamma. Like TREM-1 and TREM-2, TREM-3 signals through DAP12, and when TREM-3 is transfected into an NK cell line it mediates redirected lysis. Thus, TREM-3 functions as an activating receptor. Analysis of the mouse genome reveals that the gene for TREM-3 lies adjacent to the gene for TREM-1 and in close proximity to a number of other single Ig domain receptors, including TREM-2. Thus, TREM-3 is a novel member of a family of immunoglobulin receptors that form an innate immune gene complex on chromosome 17.

  16. The Nucleotide-Binding Oligomerization Domain-Like Receptor Family Pyrin Domain-Containing 3 Inflammasome Regulates Bronchial Epithelial Cell Injury and Proapoptosis after Exposure to Biomass Fuel Smoke.

    Science.gov (United States)

    Li, Chen; Zhihong, Huang; Wenlong, Li; Xiaoyan, Liu; Qing, Chen; Wenzhi, Luo; Siming, Xie; Shengming, Liu

    2016-12-01

    The number of individuals in the population exposed to biomass fuel smoke (BS) is far greater than the number of cigarette smokers. About 20% of cigarette smokers develop chronic obstructive pulmonary disease (COPD) due to smoke-induced irreversible damage and sustained inflammation of the airway epithelium. However, the role of BS in COPD pathogenesis remains to be elucidated. In this study, we investigated the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 and caspase-1 in the bronchial epithelium from patients with COPD, and further determined the specific role of the NLRP3 inflammasome in bronchial epithelium injury using two in vitro models (BS and cigarette smoke [CS]) in the human bronchial epithelial (HBE) cell line (16HBE). After exposure to BS and CS, the release of damage-associated molecular patterns, the transcriptional and translational up-regulation of NLRP3, and the activation of caspase-1 were observed in cells at different time points. Because IL-1β secretion was dependent on the NLRP3 inflammasome, we assessed CXCL-8 production in response to smoke. Using a transwell migration assay in which 16HBE cells and human alveolar macrophages were cocultured, we showed that smoke-induced NLRP3 activation in 16HBE cells increased the migration of human alveolar macrophages. When the NLRP3 expression was silenced, the average migration distance of 16HBE was increased in scratch assay, because the activation of NLRP3 induced apoptosis by the p53-Bax mitochondrial pathway in the smoke-induced response. These results demonstrate the importance of the NLRP3 inflammasome in mediating BS- and CS-induced HBE cell damage and proapoptosis.

  17. The Popeye domain containing protein family – A novel class of cAMP effectors with important functions in multiple tissues

    Science.gov (United States)

    Schindler, Roland F.R.; Brand, Thomas

    2016-01-01

    Popeye domain containing (Popdc) proteins are a unique family, which combine several different properties and functions in a surprisingly complex fashion. They are expressed in multiple tissues and cell types, present in several subcellular compartments, interact with different classes of proteins, and are associated with a variety of physiological and pathophysiological processes. Moreover, Popdc proteins bind the second messenger cAMP with high affinity and it is thought that they act as a novel class of cAMP effector proteins. Here, we will review the most important findings about the Popdc family, which accumulated since its discovery about 15 years ago. We will be focussing on Popdc protein interaction and function in striated muscle tissue. However, as a full picture only emerges if all aspects are taken into account, we will also describe what is currently known about the role of Popdc proteins in epithelial cells and in various types of cancer, and discuss these findings with regard to their relevance for cardiac and skeletal muscle. PMID:26772438

  18. The Popeye domain containing protein family--A novel class of cAMP effectors with important functions in multiple tissues.

    Science.gov (United States)

    Schindler, Roland F R; Brand, Thomas

    2016-01-01

    Popeye domain containing (Popdc) proteins are a unique family, which combine several different properties and functions in a surprisingly complex fashion. They are expressed in multiple tissues and cell types, present in several subcellular compartments, interact with different classes of proteins, and are associated with a variety of physiological and pathophysiological processes. Moreover, Popdc proteins bind the second messenger cAMP with high affinity and it is thought that they act as a novel class of cAMP effector proteins. Here, we will review the most important findings about the Popdc family, which accumulated since its discovery about 15 years ago. We will be focussing on Popdc protein interaction and function in striated muscle tissue. However, as a full picture only emerges if all aspects are taken into account, we will also describe what is currently known about the role of Popdc proteins in epithelial cells and in various types of cancer, and discuss these findings with regard to their relevance for cardiac and skeletal muscle.

  19. Intronic mutations outside of Alu-repeat-rich domains of the LDL receptor gene are a cause of familial hypercholesterolemia.

    Science.gov (United States)

    Amsellem, Sabine; Briffaut, Dorothée; Carrié, Alain; Rabès, Jean Pierre; Girardet, Jean Philippe; Fredenrich, Alexandre; Moulin, Philippe; Krempf, Michel; Reznik, Yves; Vialettes, Bernard; de Gennes, Jean Luc; Brukert, Eric; Benlian, Pascale

    2002-12-01

    Familial hypercholesterolemia (FH), a frequent monogenic condition complicated by premature cardiovascular disease, is characterized by high allelic heterogeneity at the low-density lipoprotein receptor ( LDLR) locus. Despite more than a decade of genetic testing, knowledge about intronic disease-causing mutations has remained limited because of lack of available genomic sequences. Based on the finding from bioinformatic analysis that Alu repeats represent 85% of LDLR intronic sequences outside exon-intron junctions, we designed a strategy to improve the exploration of genomic regions in the vicinity of exons in 110 FH subjects from an admixed population. In the first group of 42 patients of negative mutation carriers, as previously established by former screening strategies (denaturing gradient gel electrophoresis, DNA sequencing with former primers overlapping splice-sites, Southern Blotting), about half ( n=22) were found to be carriers of at least one heterozygous mutation. Among a second group of 68 newly recruited patients, 27% of mutation carriers ( n=37) had a splicing regulatory mutation. Overall, out of the 54 mutations identified, 13 were intronic, and 18 were novel, out of which nearly half were intronic. Two novel intronic mutations (IVS8-10G-->A within the polypyrimidine tract and IVS7+10G-->A downstream of donor site) might create potential aberrant splice sites according to neural-network computed estimation, contrary to 31 common single nucleotide variations also identified at exon-intron junctions. This new strategy of detecting the most likely disease-causing LDLR mutations outside of Alu-rich genomic regions reveals that intronic mutations may have a greater impact than previously reported on the molecular basis of FH.

  20. Characterization of a single b-type heme, FAD, and metal binding sites in the transmembrane domain of six-transmembrane epithelial antigen of the prostate (STEAP) family proteins.

    Science.gov (United States)

    Kleven, Mark D; Dlakić, Mensur; Lawrence, C Martin

    2015-09-11

    Six-transmembrane epithelial antigen of the prostate 3 (Steap3) is the major ferric reductase in developing erythrocytes. Steap family proteins are defined by a shared transmembrane domain that in Steap3 has been shown to function as a transmembrane electron shuttle, moving cytoplasmic electrons derived from NADPH across the lipid bilayer to the extracellular face where they are used to reduce Fe(3+) to Fe(2+) and potentially Cu(2+) to Cu(1+). Although the cytoplasmic N-terminal oxidoreductase domain of Steap3 and Steap4 are relatively well characterized, little work has been done to characterize the transmembrane domain of any member of the Steap family. Here we identify high affinity FAD and iron biding sites and characterize a single b-type heme binding site in the Steap3 transmembrane domain. Furthermore, we show that Steap3 is functional as a homodimer and that it utilizes an intrasubunit electron transfer pathway through the single heme moiety rather than an intersubunit electron pathway through a potential domain-swapped dimer. Importantly, the sequence motifs in the transmembrane domain that are associated with the FAD and metal binding sites are not only present in Steap2 and Steap4 but also in Steap1, which lacks the N-terminal oxidoreductase domain. This strongly suggests that Steap1 harbors latent oxidoreductase activity.

  1. The bldC developmental locus of Streptomyces coelicolor encodes a member of a family of small DNA-binding proteins related to the DNA-binding domains of the MerR family.

    Science.gov (United States)

    Hunt, Alison C; Servín-González, Luis; Kelemen, Gabriella H; Buttner, Mark J

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed DeltabldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although DeltabldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein.

  2. Domains and domain loss

    DEFF Research Database (Denmark)

    Haberland, Hartmut

    2005-01-01

    The domain concept, originally suggested by Schmidt-Rohr in the 1930’s (as credited in Fishman’s writings in the 1970s), was an attempt to sort out different areas of language use in multilingual societies, which are relevant for language choice. In Fishman’s version, domains were considered...... not described in terms of domains, and recent research e.g. about the multilingual communities in the Danish-German border area seems to confirm this....

  3. Mutation G805R in the transmembrane domain of the LDL receptor gene causes familial hypercholesterolemia by inducing ectodomain cleavage of the LDL receptor in the endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Thea Bismo Strøm

    2014-01-01

    Full Text Available More than 1700 mutations in the low density lipoprotein receptor (LDLR gene have been found to cause familial hypercholesterolemia (FH. These are commonly divided into five classes based upon their effects on the structure and function of the LDLR. However, little is known about the mechanism by which mutations in the transmembrane domain of the LDLR gene cause FH. We have studied how the transmembrane mutation G805R affects the function of the LDLR. Based upon Western blot analyses of transfected HepG2 cells, mutation G805R reduced the amounts of the 120 kDa precursor LDLR in the endoplasmic reticulum. This led to reduced amounts of the mature 160 kDa LDLR at the cell surface. However, significant amounts of a secreted 140 kDa G805R-LDLR ectodomain fragment was observed in the culture media. Treatment of the cells with the metalloproteinase inhibitor batimastat largely restored the amounts of the 120 and 160 kDa forms in cell lysates, and prevented secretion of the 140 kDa ectodomain fragment. Together, these data indicate that a metalloproteinase cleaved the ectodomain of the 120 kDa precursor G805R-LDLR in the endoplasmic reticulum. It was the presence of the polar Arg805 and not the lack of Gly805 which led to ectodomain cleavage. Arg805 also prevented γ-secretase cleavage within the transmembrane domain. It is conceivable that introducing a charged residue within the hydrophobic membrane lipid bilayer, results in less efficient incorporation of the 120 kDa G805R-LDLR in the endoplasmic reticulum membrane and makes it a substrate for metalloproteinase cleavage.

  4. MicroRNA-181b inhibits thrombin-mediated endothelial activation and arterial thrombosis by targeting caspase recruitment domain family member 10.

    Science.gov (United States)

    Lin, Jibin; He, Shaolin; Sun, Xinghui; Franck, Gregory; Deng, Yihuan; Yang, Dafeng; Haemmig, Stefan; Wara, A K M; Icli, Basak; Li, Dazhu; Feinberg, Mark W

    2016-09-01

    Thrombogenic and inflammatory mediators, such as thrombin, induce NF-κB-mediated endothelial cell (EC) activation and dysfunction, which contribute to pathogenesis of arterial thrombosis. The role of anti-inflammatory microRNA-181b (miR-181b) on thrombosis remains unknown. Our previous study demonstrated that miR-181b inhibits downstream NF-κB signaling in response to TNF-α. Here, we demonstrate that miR-181b uniquely inhibits upstream NF-κB signaling in response to thrombin. Overexpression of miR-181b inhibited thrombin-induced activation of NF-κB signaling, demonstrated by reduction of phospho-IKK-β, -IκB-α, and p65 nuclear translocation in ECs. MiR-181b also reduced expression of NF-κB target genes VCAM-1, intercellular adhesion molecule-1, E-selectin, and tissue factor. Mechanistically, miR-181b targets caspase recruitment domain family member 10 (Card10), an adaptor protein that participates in activation of the IKK complex in response to signals transduced from protease-activated receptor-1. miR-181b reduced expression of Card10 mRNA and protein, but not protease-activated receptor-1. 3'-Untranslated region reporter assays, argonaute-2 microribonucleoprotein immunoprecipitation studies, and Card10 rescue studies revealed that Card10 is a bona fide direct miR-181b target. Small interfering RNA-mediated knockdown of Card10 expression phenocopied effects of miR-181b on NF-κB signaling and targets. Card10 deficiency did not affect TNF-α-induced activation of NF-κB signaling, which suggested stimulus-specific regulation of NF-κB signaling and endothelial responses by miR-181b in ECs. Finally, in response to photochemical injury-induced arterial thrombosis, systemic delivery of miR-181b reduced thrombus formation by 73% in carotid arteries and prolonged time to occlusion by 1.6-fold, effects recapitulated by Card10 small interfering RNA. These data demonstrate that miR-181b and Card10 are important regulators of thrombin-induced EC activation and

  5. The expression of the imprinted gene pleckstrin homology-like domain family A member 2 in placental tissues of preeclampsia and its effects on the proliferation, migration and invasion of trophoblast cells JEG-3.

    Science.gov (United States)

    Jin, Feng; Qiao, Chong; Luan, Nannan; Shang, Tao

    2015-11-01

    Preeclampsia (PE) is one of the most common hypertensive disorders and is a leading cause of morbidity and mortality for pregnant women and perinatal babies. Additionally, pleckstrin homology-like domain family A member 2 (PHLDA2) is associated with placental dysfunction. However, the effect of PHLDA2 on trophoblast cell proliferation, migration and invasion has not been investigated. In this study, 15 PE patients and 15 normal pregnant women were recruited and clinical characteristics were summarized. Pleckstrin homology-like domain family A member 2 levels in placental tissues were examined using real-time PCR and western blot. Overexpression plasmid and PHLDA2 siRNA was introduced into JEG-3 cells, respectively. Cell proliferation was measured using MTT assay and flow cytometry. Cell migration and invasion capacities were assessed by wound healing and Transwell assays. It was found that PE patients collectively presented proteinuria, elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP), and lower gestational ages and birth weights. Pleckstrin homology-like domain family A member 2 levels in the preeclamptic placenta were significantly upregulated. Pleckstrin homology-like domain family A member 2 overexpression significantly arrested cells in the G0/G1 phase, inhibited cell proliferation and suppressed the migration and invasion of JEG-3 cells. Pleckstrin homology-like domain family A member 2 knockdown significantly blocked the cells in the S phase of the cell cycle. Knockdown of PHLDA2 alleviated the inhibition on the migration and invasion of trophoblast cells JEG-3. These findings illustrate that PHLDA2 may participate in PE pathogenesis and indicate its potential application in the early diagnosis of PE. © 2015 Wiley Publishing Asia Pty Ltd.

  6. Genome cartography through domain annotation.

    Science.gov (United States)

    Ponting, C P; Dickens, N J

    2001-01-01

    The evolutionary history of eukaryotic proteins involves rapid sequence divergence, addition and deletion of domains, and fusion and fission of genes. Although the protein repertoires of distantly related species differ greatly, their domain repertoires do not. To account for the great diversity of domain contexts and an unexpected paucity of ortholog conservation, we must categorize the coding regions of completely sequenced genomes into domain families, as well as protein families.

  7. A CHASE domain containing protein kinase OsCRL4, represents a new AtCRE1-like gene family in rice

    Institute of Scientific and Technical Information of China (English)

    韩秋敏; 姜华武; 齐晓朋; 于洁; 吴平

    2004-01-01

    AtCRE1 is known to be a cytokinin receptor in Arabidopsis. The AtCRE1 protein contains CHASE domain at the N-terminal part, followed by a transmitter (histidine kinase) domain and two receiver domains. The N-terminal CHASE domain of AtCRE1 contains putative recognition sites for cytokinin. Five CHASE domains containing proteins were found in rice, OsCRL1a, OsCRL1b, OsCRL2, OsCRL3, and OsCRL4. OsCRL1a, OsCRL1b, OsCRL2 and OsCRL3 contain the four domains existing in CRE1, whereas OsCRL4 only contains the CHASE domain and a putative Ser/Thr protein kinase domain. The authors cloned the encoding gene OsCRL4 and found that it represents a new member of the cytokinin receptor protein in rice.

  8. A CHASE domain containing protein kinase OsCRL4, represents a new AtCRE1-like gene family in rice

    Institute of Scientific and Technical Information of China (English)

    韩秋敏; 姜华武; 齐晓朋; 丁洁; 吴平

    2004-01-01

    AtCRE1 is known to be a cytokinin receptor inArabidopsis. The AtCRE1 protein contains CHASE domain at the N-terminal part, followed by a transmitter (histidine kinase) domain and two receiver domains. The N-terminal CHASE domain of AtCRE1 contains putative recognition sites for cytokinin. Five CHASE domains containing proteins were found in rice, OsCRLla, OsCRLlb, OsCRL2, OsCRL3, and OsCRL4. OsCRL1a, OsCRL1b, OsCRL2 and OsCRL3 contain the four domains existing in CRE1, whereas OsCRL4 only contains the CHASE domain and a putative Ser/Thr protein kinase domain The authors cloned the encoding gene OsCRL4 and found that it represents a new member of the cytokinin receptor protein in rice.

  9. Genome-Wide Identification of Calcium Dependent Protein Kinase Gene Family in Plant Lineage Shows Presence of Novel D-x-D and D-E-L Motifs in EF-Hand Domain.

    Science.gov (United States)

    Mohanta, Tapan K; Mohanta, Nibedita; Mohanta, Yugal K; Bae, Hanhong

    2015-01-01

    Calcium ions are considered ubiquitous second messengers in eukaryotic signal transduction pathways. Intracellular Ca(2+) concentration are modulated by various signals such as hormones and biotic and abiotic stresses. Modulation of Ca(2+) ion leads to stimulation of calcium dependent protein kinase genes (CPKs), which results in regulation of gene expression and therefore mediates plant growth and development as well as biotic and abiotic stresses. Here, we reported the CPK gene family of 40 different plant species (950 CPK genes) and provided a unified nomenclature system for all of them. In addition, we analyzed their genomic, biochemical and structural conserved features. Multiple sequence alignment revealed that the kinase domain, auto-inhibitory domain and EF-hands regions of regulatory domains are highly conserved in nature. Additionally, the EF-hand domains of higher plants were found to contain four D-x-D and two D-E-L motifs, while lower eukaryotic plants had two D-x-D and one D-x-E motifs in their EF-hands. Phylogenetic analysis showed that CPK genes are clustered into four different groups. By studying the CPK gene family across the plant lineage, we provide the first evidence of the presence of D-x-D motif in the calcium binding EF-hand domain of CPK proteins.

  10. Characterization of a gene family encoding SEA (sea-urchin sperm protein, enterokinase and agrin-domain proteins with lectin-like and heme-binding properties from Schistosoma japonicum.

    Directory of Open Access Journals (Sweden)

    Evaristus Chibunna Mbanefo

    Full Text Available BACKGROUND: We previously identified a novel gene family dispersed in the genome of Schistosoma japonicum by retrotransposon-mediated gene duplication mechanism. Although many transcripts were identified, no homolog was readily identifiable from sequence information. METHODOLOGY/PRINCIPAL FINDINGS: Here, we utilized structural homology modeling and biochemical methods to identify remote homologs, and characterized the gene products as SEA (sea-urchin sperm protein, enterokinase and agrin-domain containing proteins. A common extracellular domain in this family was structurally similar to SEA-domain. SEA-domain is primarily a structural domain, known to assist or regulate binding to glycans. Recombinant proteins from three members of this gene family specifically interacted with glycosaminoglycans with high affinity, with potential implication in ligand acquisition and immune evasion. Similar approach was used to identify a heme-binding site on the SEA-domain. The heme-binding mode showed heme molecule inserted into a hydrophobic pocket, with heme iron putatively coordinated to two histidine axial ligands. Heme-binding properties were confirmed using biochemical assays and UV-visible absorption spectroscopy, which showed high affinity heme-binding (K D = 1.605×10(-6 M and cognate spectroscopic attributes of hexa-coordinated heme iron. The native proteins were oligomers, antigenic, and are localized on adult worm teguments and gastrodermis; major host-parasite interfaces and site for heme detoxification and acquisition. CONCLUSIONS: The results suggest potential role, at least in the nucleation step of heme crystallization (hemozoin formation, and as receptors for heme uptake. Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism. Thus, assessing prospects for application in disease intervention is warranted.

  11. NLR family pyrin domain containing 3 (NLRP3) inflammasome gene polymorphism rs7512998 (C>T) predicts aging-related increase of blood pressure, the TAMRISK study.

    Science.gov (United States)

    Kunnas, Tarja; Määttä, Kirsi; Nikkari, Seppo T

    2015-01-01

    The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome by cellular stress leads to activation of the inflammasome, and NLRP3 gene polymorphisms have been associated with autoinflammatory diseases. Inflammasomes have also been implicated in the initiation or progression of metabolic disorders such as atherosclerosis, type 2 diabetes and obesity. The association of NLRP3 genetic variant rs7512998 with blood pressure and hypertension was studied in a 50-year-old Finnish cohort with a subpopulation who had available data on blood pressure measurements also at the age of 45 years. NLRP3 gene polymorphism rs7512998 C-allele was associated with higher systolic (p = 0.006) and diastolic (p = 0.011) blood pressure compared to the TT-genotype carriers in 50-year-old subjects. In addition, by analysis of variance for repeated measures between ages of 45- and 50 years there was a significant time by genotype interaction; blood pressure increased more in subjects with the C-allele both in systolic (p = 0.035) and diastolic (p = 0.012) values. However, no association with diagnosed hypertension was found. We report for the first time that NLRP3 gene polymorphism rs7512998 was associated with systolic and diastolic blood pressure in 50-year-old subjects. In addition, an effect of this variation upon blood pressure was seen in these same subjects in a 5-year follow-up from a 45-year-old cohort to 50 years of age.

  12. Genomic structure of metabotropic glutamate receptor 7 and comparison of genomic structures of extracellular domains of mGluR family

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Metabotropic glutamate receptor 7, coupled with a chemical neurotransmitter L-glutamate, plays an important role in the development of many psychiatric and neurological disorders. To study the biological and genetic mechanism of the mGluR7-related diseases, a physical map covering the full-length mGluR7 genomic sequence has been constructed through seed clone screening and fingerprinting database searching. These BAC clones in the physical map have been sequenced with shotgun strategy and assembled by Phred-Phrap-Consed software; the error rate of the final genomic sequence is less than 0.01%. mGluR7 spans 880 kb genomic region, the GC content and repeat content of mGluR7 genomic sequence are 38% and 37.5% respectively. mGluR7 has a typical "house-keeping" promoter and consists of 11 exons, with introns ranging from 6 kb to 285 kb. mGluR7a and mGluR7b are two known alternatively splicing variants. Comparing the genomic structures of extracellular domains of mGluR family, their genomic structures can be subdivided into three groups, which are consistent with that of proteins. Although the genomic organization of mGluR7's group is conserved, the majority of introns in the extracellular segments vary dramatically. It is an obvious trend of the increasing intron size inverse proportion to phylogenetic time. Variation of genomic structure is higher than that of protein, which is attributed to the species characteristic regulation of gene expression.

  13. Yes-associated protein/TEA domain family member and hepatocyte nuclear factor 4-alpha (HNF4α) repress reciprocally to regulate hepatocarcinogenesis in rats and mice.

    Science.gov (United States)

    Cai, Wang-Yu; Lin, Ling-Yun; Hao, Han; Zhang, Sai-Man; Ma, Fei; Hong, Xin-Xin; Zhang, Hui; Liu, Qing-Feng; Ye, Guo-Dong; Sun, Guang-Bin; Liu, Yun-Jia; Li, Sheng-Nan; Xie, Yuan-Yuan; Cai, Jian-Chun; Li, Bo-An

    2017-04-01

    Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between Yes-associated protein/TEA domain family member (YAP-TEAD) and hepatocyte nuclear factor 4-alpha (HNF4α) in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells by a ubiquitin proteasome pathway. By contrast, HNF4α was found to directly associate with TEAD4 to compete with YAP1 for binding to TEAD4, thus inhibiting the transcriptional activity of YAP-TEAD and expression of their target genes. Moreover, overexpression of HNF4α was found to significantly compromise YAP-TEAD-induced HCC cell proliferation and stem cell expansion. Finally, we documented the regulatory mechanism between YAP-TEAD and HNF4α in rat and mouse tumor models, which confirmed our in vitro results. There is a double-negative feedback mechanism that controls TEAD-YAP and HNF4α expression in vitro and in vivo, thereby regulating cellular proliferation and differentiation. Given that YAP acts as a dominant oncogene in HCC and plays a crucial role in stem cell homeostasis and tissue regeneration, manipulating the interaction between YAP, TEADs, and HNF4α may provide a new approach for HCC treatment and regenerative medicine. (Hepatology 2017;65:1206-1221). © 2016 by the American Association for the Study of Liver Diseases.

  14. Buffers and Risks in Temperament and Family for Early Adolescent Psychopathology : Generic, Conditional, or Domain-Specific Effects? The TRAILS Study

    NARCIS (Netherlands)

    Sentse, Miranda; Veenstra, Rene; Lindenberg, Siegwart; Verhulst, Frank C.; Ormel, Johan

    2009-01-01

    This study examined the possible risk-buffering and risk-enhancing role of family characteristics on the association between temperament and early adolescent externalizing and internalizing problems, adjusted for familial vulnerability for psychopathology and early childhood problem behavior. Furthe

  15. A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family.

    Science.gov (United States)

    Morell, R; Friedman, T B; Moeljopawiro, S; Hartono; Soewito; Asher, J H

    1992-07-01

    Waardenburg syndrome type 1 (WS1) is an autosomal dominant disorder characterized by deafness, dystopia canthorum, heterochromia iridis, white forelock, and premature greying. A similar phenotype is caused in the mouse by mutations in the Pax-3 gene. This observation, together with comparisons of conserved syntenies in the murine and human genetic maps, suggested that at least some WS1 mutations should occur in HuP2, the probable human homolog of Pax-3. Two mutations in the HuP2 sequence of individuals with WS1 have been reported recently. Both of them occur in the highly conserved paired box region of the gene, which encodes a DNA binding domain. The functional consequences of these mutations are at present speculative. We report here a 14 bp deletion in the paired domain encoded by exon 2 of HuP2 in an Indonesian family segregating for WS1. This frameshift mutation results in a premature termination codon in exon 3. The HuP2 product is a truncated protein lacking most of the paired domain and all of the predicted homeo domain. We propose that the WS1 phenotype in this family is due to loss of function of HuP2 and discuss two mechanisms for the dominant effect of this mutation.

  16. Probing the electrostatics and pharmacological modulation of sequence-specific binding by the DNA-binding domain of the ETS family transcription factor PU.1: a binding affinity and kinetics investigation.

    Science.gov (United States)

    Munde, Manoj; Poon, Gregory M K; Wilson, W David

    2013-05-27

    Members of the ETS family of transcription factors regulate a functionally diverse array of genes. All ETS proteins share a structurally conserved but sequence-divergent DNA-binding domain, known as the ETS domain. Although the structure and thermodynamics of the ETS-DNA complexes are well known, little is known about the kinetics of sequence recognition, a facet that offers potential insight into its molecular mechanism. We have characterized DNA binding by the ETS domain of PU.1 by biosensor-surface plasmon resonance (SPR). SPR analysis revealed a striking kinetic profile for DNA binding by the PU.1 ETS domain. At low salt concentrations, it binds high-affinity cognate DNA with a very slow association rate constant (≤10(5)M(-)(1)s(-)(1)), compensated by a correspondingly small dissociation rate constant. The kinetics are strongly salt dependent but mutually balance to produce a relatively weak dependence in the equilibrium constant. This profile contrasts sharply with reported data for other ETS domains (e.g., Ets-1, TEL) for which high-affinity binding is driven by rapid association (>10(7)M(-)(1)s(-)(1)). We interpret this difference in terms of the hydration properties of ETS-DNA binding and propose that at least two mechanisms of sequence recognition are employed by this family of DNA-binding domain. Additionally, we use SPR to demonstrate the potential for pharmacological inhibition of sequence-specific ETS-DNA binding, using the minor groove-binding distamycin as a model compound. Our work establishes SPR as a valuable technique for extending our understanding of the molecular mechanisms of ETS-DNA interactions as well as developing potential small-molecule agents for biotechnological and therapeutic purposes.

  17. Increased Expression of the NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome in Dermatomyositis and Polymyositis is a Potential Contributor to Their Pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Xi Yin; Gen-Cheng Han; Xing-Wei Jiang; Qiang Shi; Chuan-Qiang Pu

    2016-01-01

    Background:Dermatomyositis (DM) and polymyositis (PM) are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood.The NOD-like receptor family,pyrin domain containing 3 (NLRP3) inflammasome is a type of cytoplasmic multiprotein inflammasome and is responsible for the activation of inflammatory reactivations.Responding to a wide range of exogenous and endogenous microbial or sterile stimuli,NLRP3 inflammasomes can cleave pro-caspase-1 into active caspase-1,which processes the pro-inflammatory cytokines pro-interleukin (IL)-1 β and pro-IL-18 into active and secreted IL-1 β and IL-18.The NLRP3 inflammasome is implicated in infectious and sterile inflammatory diseases.However,it remains unclear whether it is involved in the pathogenesis of DM/PM,which we aim to address in our research.Methods:In this study,22 DM/PM patients and 24 controls were recruited.The protein and RNA expression of IL-1β,IL-18,NLRP3,and caspase-1 in serum and muscle samples were tested and compared between the two groups.Results:The serum IL-1β and IL-18 levels were significantly higher in DM/PM patients than those in the controls by enzyme linked immunosorbent assay (ELISA,DM vs.control,25.02 ± 8.29 ng/ml vs.16.49 ± 3.30 ng/ml,P < 0.001; PM vs.control,26.49 ± 7.79 ng/ml vs.16.49 ± 3.30 ng/ml,P < 0.001).Moreover,the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed that DM/PM patients exhibited higher RNA expression of IL-1 β,IL-18,and NLRP3 in the muscle (for IL-1β,DM vs.control,P =0.0012,PM vs.control,P =0.0021; for IL-18,DM vs.control,P =0.0045,PM vs.control,P =0.0031; for NLRP3,DM vs.control,P =0.0017,PM vs.control,P =0.0006).Moreover,the protein expression of NLRP3 and caspase-1 in muscle samples of DM/PM patients were also significantly elevated compared to that in the muscles of the controls.Conclusions:Our findings demonstrate that the NLRP3 inflammasome is implicated in the pathogenesis of DM

  18. HCV NS5A protein containing potential ligands for both Src homology 2 and 3 domains enhances autophosphorylation of Src family kinase Fyn in B cells.

    Directory of Open Access Journals (Sweden)

    Kenji Nakashima

    Full Text Available Hepatitis C virus (HCV infects B lymphocytes and induces mixed cryoglobulinemia and B cell non-Hodgkin's lymphoma. The molecular mechanism for the pathogenesis of HCV infection-mediated B cell disorders remains obscure. To identify the possible role for HCV nonstructural 5A (NS5A protein in B cells, we generated the stable B cell lines expressing Myc-His tagged NS5A. Immunoprecipitation study in the presence or absence of pervanadate (PV implied that NS5A was tyrosine phosphorylated by pervanadate (PV treatment of the cells. Therefore we examined pull-down assay by using glutathione S-transferase (GST-fusion proteins of various Src homology 2 (SH2 domains, which associates with phosphotyrosine within a specific amino acid sequence. The results showed that NS5A specifically bound to SH2 domain of Fyn from PV-treated B cells in addition to Src homology 3 (SH3 domain. Substitution of Arg(176 to Lys in the SH2 domain of Fyn abrogated this interaction. Deletion mutational analysis demonstrated that N-terminal region of NS5A was not required for the interaction with the SH2 domain of Fyn. Tyr(334 was identified as a tyrosine phosphorylation site in NS5A. Far-western analysis revealed that SH2 domain of Fyn directly bound to NS5A. Fyn and NS5A were colocalized in the lipid raft. These results suggest that NS5A directly binds to the SH2 domain of Fyn in a tyrosine phosphorylation-dependent manner. Lastly, we showed that the expression of NS5A in B cells increased phosphorylation of activation loop tyrosine in the kinase domain of Fyn. NS5A containing ligand for both SH2 and SH3 domains enhances an aberrant autophosphorylation and kinase activity of Fyn in B cells.

  19. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  20. Ligand binding by PDZ domains

    OpenAIRE

    Celestine N. Chi; Bach, Anders; Stromgaard, Kristian; Gianni, Stefano; Jemth, Per

    2012-01-01

    The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common proteinprotein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, s...

  1. A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans

    DEFF Research Database (Denmark)

    Stattin, Eva-Lena; Wiklund, Fredrik; Lindblom, Karin;

    2010-01-01

    Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identifi...

  2. Buffers and Risks in Temperament and Family for Early Adolescent Psychopathology: Generic, Conditional, or Domain-Specific Effects? The Trails Study

    Science.gov (United States)

    Sentse, Miranda; Veenstra, Rene; Lindenberg, Siegwart; Verhulst, Frank C.; Ormel, Johan

    2009-01-01

    This study examined the possible risk-buffering and risk-enhancing role of family characteristics on the association between temperament and early adolescent externalizing and internalizing problems, adjusted for familial vulnerability for psychopathology and early childhood problem behavior. Furthermore, it explored whether these effects were…

  3. Domain analysis

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

    The domain-analytic approach to knowledge organization (KO) (and to the broader field of library and information science, LIS) is outlined. The article reviews the discussions and proposals on the definition of domains, and provides an example of a domain-analytic study in the field of art studie....... Varieties of domain analysis as well as criticism and controversies are presented and discussed....

  4. Ga(3+)/Ln(3+) Metallacrowns: A Promising Family of Highly Luminescent Lanthanide Complexes That Covers Visible and Near-Infrared Domains.

    Science.gov (United States)

    Chow, Chun Y; Eliseeva, Svetlana V; Trivedi, Evan R; Nguyen, Tu N; Kampf, Jeff W; Petoud, Stéphane; Pecoraro, Vincent L

    2016-04-20

    Luminescent lanthanide(III)-based molecular scaffolds hold great promises for materials science and for biological applications. Their fascinating photophysical properties enable spectral discrimination of emission bands that range from the visible to the near-infrared (NIR) regions. In addition, their strong resistance to photobleaching makes them suitable for long duration or repeated biological experiments using a broad range of sources of excitation including intense and focalized systems such as lasers (e.g., confocal microscopy). A main challenge in the creation of luminescent lanthanide(III) complexes lies in the design of a ligand framework that combines two main features: (i) it must include a chromophoric moiety that possesses a large molar absorptivity and is able to sensitize several different lanthanide(III) ions emitting in the visible and/or in the near-infrared, and (ii) it must protect the Ln(3+) cation by minimizing nonradiative deactivation pathways due to the presence of -OH, -NH and -CH vibrations. Herein, a new family of luminescent Ga(3+)/Ln(3+) metallacrown (MC) complexes is reported. The MCs with the general composition [LnGa4(shi)4(C6H5CO2)4(C5H5N) (CH3OH)] (Ln-1, Ln = Sm(3+)-Yb(3+)) were synthesized in a one pot reaction using salicylhydroxamic acid (H3shi) with Ga(3+) and Ln(3+) nitrates as reagents. The molecular structure of [DyGa4(shi)4(C6H5CO2)4(C5H5N) (CH3OH)] was obtained by X-ray analysis of single crystals and shows that the complex is formed as a [12-MCGa(III)shi-4] core with four benzoate molecules bridging the central Dy(3+) ion to the Ga(3+) ring metals. The powder X-ray diffraction analysis demonstrates that all other isolated complexes are isostructural. The extended analysis of the luminescence properties of these complexes, excited by the electronic states of the chromophoric ligands, showed the presence of characteristic, sharp f-f transitions that can be generated not only in the NIR (Sm, Dy, Ho, Er, Yb) but also in the

  5. Evolutionarily evolved discriminators in the 3-TPR domain of the Toc64 family involved in protein translocation at the outer membrane of chloroplasts and mitochondria.

    Science.gov (United States)

    Mirus, Oliver; Bionda, Tihana; von Haeseler, Arndt; Schleiff, Enrico

    2009-08-01

    Transport of polypeptides across membranes is a general and essential cellular process utilised by molecular machines. At least one component of these complexes contains a domain composed of three tetratricopeptide repeat (3-TPR) motifs. We have focussed on the receptor Toc64 to elucidate the evolved functional specifications of its 3-TPR domain. Toc64 is a component of the Toc core complex and functionally replaces Tom70 at the outer membrane of mitochondria in plants. Its 3-TPR domain recognises the conserved C-terminus of precursor-bound chaperones. We built homology models of the 3-TPR domain of chloroplastic Toc64 from different species and of the mitochondrial isoform from Arabidopsis. Guided by modelling, we identified residues essential for functional discrimination of the differently located isoforms to be located almost exclusively on the convex surface of the 3-TPR domain. The only exception is at568Ser/ps557Met, which is positioned in the ligand-binding groove. The functional implications of the homology models are discussed.

  6. Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training

    DEFF Research Database (Denmark)

    Vind, B. F.; Pehmøller, Christian; Treebak, Jonas Thue

    2011-01-01

    AIMS/HYPOTHESIS: Insulin-mediated glucose disposal rates (R (d)) are reduced in type 2 diabetic patients, a process in which intrinsic signalling defects are thought to be involved. Phosphorylation of TBC1 domain family, member 4 (TBC1D4) is at present the most distal insulin receptor signalling...... mU min(-1) m(-2)) clamp, we obtained M. vastus lateralis biopsies from 13 obese type 2 diabetic and 13 obese, non-diabetic control individuals before and after 10 weeks of endurance exercise-training. RESULTS: Before training, reductions in insulin-stimulated R (d), together with impaired insulin...

  7. Domains of quality of life: Results of a three-stage Delphi consensus-procedure amongst patients, family of patients, clinicians, scientists and the general public

    NARCIS (Netherlands)

    Pietersma, S.; de Vries, M.; Akker van den, M.E.

    2014-01-01

    Purpose Our key objective is to identify the core domains of health-related quality of life (QoL). Health-related QoL utility scales are commonly used in economic evaluations to assess the effectiveness of health-care interventions. However, health-care interventions are likely to affect QoL in a

  8. A starch-binding domain identified in α-amylase (AmyP) represents a new family of carbohydrate-binding modules that contribute to enzymatic hydrolysis of soluble starch.

    Science.gov (United States)

    Peng, Hui; Zheng, Yunyun; Chen, Maojiao; Wang, Ying; Xiao, Yazhong; Gao, Yi

    2014-04-02

    A novel starch-binding domain (SBD) that represents a new carbohydrate-binding module family (CBM69) was identified in the α-amylase (AmyP) of the recently established alpha-amylase subfamily GH13_37. The SBD and its homologues come mostly from marine bacteria, and phylogenetic analysis indicates that they are closely related to the CBM20 and CBM48 families. The SBD exhibited a binding preference toward raw rice starch, but the truncated mutant (AmyPΔSBD) still retained similar substrate preference. Kinetic analyses revealed that the SBD plays an important role in soluble starch hydrolysis because different catalytic efficiencies have been observed in AmyP and the AmyPΔSBD.

  9. The methyltransferase NSD3 has chromatin-binding motifs, PHD5-C5HCH, that are distinct from other NSD (nuclear receptor SET domain) family members in their histone H3 recognition.

    Science.gov (United States)

    He, Chao; Li, Fudong; Zhang, Jiahai; Wu, Jihui; Shi, Yunyu

    2013-02-15

    The NSD (nuclear receptor SET domain-containing) family members, consisting of NSD1, NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1), are SET domain-containing methyltransferases and aberrant expression of each member has been implicated in multiple diseases. They have specific mono- and dimethylase activities for H3K36, whereas play nonredundant roles during development. Aside from the well characterized catalytic SET domain, NSD proteins have multiple potential chromatin-binding motifs that are clinically relevant, including the fifth plant homeodomain (PHD5) and the adjacent Cys-His-rich domain (C5HCH) located at the C terminus. Herein, we report the crystal structures of the PHD5-C5HCH module of NSD3, in the free state and in complex with H3(1-7) (H3 residues 1-7), H3(1-15) (H3 residues 1-15), and H3(1-15)K9me3 (H3 residues 1-15 with trimethylation on K9) peptides. These structures reveal that the PHD5 and C5HCH domains fold into a novel integrated PHD-PHD-like structural module with H3 peptide bound only on the surface of PHD5 and provide the molecular basis for the recognition of unmodified H3K4 and trimethylated H3K9 by NSD3 PHD5. Structural studies and binding assays show that differences exist in histone binding specificity of the PHD5 domain between three members of the NSD family. For NSD2, the PHD5-C5HCH:H3 N terminus interaction is largely conserved, although with a stronger preference for unmethylated H3K9 (H3K9me0) than trimethylated H3K9 (H3K9me3), and NSD1 PHD5-C5HCH does not bind to H3 peptides. Our results shed light on how NSD proteins that mediate H3K36 methylation are localized to specific genomic sites and provide implications for the mechanism of functional diversity of NSD proteins.

  10. Non-syndromic tooth agenesis in two Chinese families associated with novel missense mutations in the TNF domain of EDA (ectodysplasin A.

    Directory of Open Access Journals (Sweden)

    Shufeng Li

    Full Text Available Here we report two unrelated Chinese families with congenital missing teeth inherited in an X-linked manner. We mapped the affected locus to chromosome Xp11-Xq21 in one family. In the defined region, both families were found to have novel missense mutations in the ectodysplasin-A (EDA gene. The mutation of c.947A>G caused the D316G substitution of the EDA protein. The mutation of c.1013C>T found in the other family resulted in the Thr to Met mutation at position 338 of EDA. The EDA gene has been reported responsible for X-linked hypohidrotic ectodermal dysplasia (XLHED in humans characterized by impaired development of hair, eccrine sweat glands, and teeth. In contrast, all the affected individuals in the two families that we studied here had normal hair and skin. Structural analysis suggests that these two novel mutants may account for the milder phenotype by affecting the stability of EDA trimers. Our results indicate that these novel missense mutations in EDA are associated with the isolated tooth agenesis and provide preliminary explanation for the abnormal clinical phenotype at a molecular structural level.

  11. GTPase domains of ras p21 oncogene protein and elongation factor Tu: analysis of three-dimensional structures, sequence families, and functional sites.

    Science.gov (United States)

    Valencia, A; Kjeldgaard, M; Pai, E F; Sander, C

    1991-06-15

    GTPase domains are functional and structural units employed as molecular switches in a variety of important cellular functions, such as growth control, protein biosynthesis, and membrane traffic. Amino acid sequences of more than 100 members of different subfamilies are known, but crystal structures of only mammalian ras p21 and bacterial elongation factor Tu have been determined. After optimal superposition of these remarkably similar structures, careful multiple sequence alignment, and calculation of residue-residue interactions, we analyzed the two subfamilies in terms of structural conservation, sequence conservation, and residue contact strength. There are three main results. (i) A structure-based alignment of p21 and elongation factor Tu. (ii) The definition of a common conserved structural core that may be useful as the basis of model building by homology of the three-dimensional structure of any GTPase domain. (iii) Identification of sequence regions, other than the effector loop and the nucleotide binding site, that may be involved in the functional cycle: they are loop L4, known to change conformation after GTP hydrolysis; helix alpha 2, especially Arg-73 and Met-67 in ras p21; loops L8 and L10, including ras p21 Arg-123, Lys-147, and Leu-120; and residues located spatially near the N and C termini. These regions are candidate sites for interaction either with the GTP/GDP exchange factor, with a GTPase-affected function, or with a molecule delivered to a destination site with the aid of the GTPase domain.

  12. Predicting adolescent posttraumatic stress in the aftermath of war: differential effects of coping strategies across trauma reminder, loss reminder, and family conflict domains.

    Science.gov (United States)

    Howell, Kathryn H; Kaplow, Julie B; Layne, Christopher M; Benson, Molly A; Compas, Bruce E; Katalinski, Ranka; Pasalic, Hafiza; Bosankic, Nina; Pynoos, Robert

    2015-01-01

    The vast majority of youth who lived through the Bosnian war were exposed to multiple traumatic events, including interpersonal violence, community destruction, and the loss of a loved one. This study examined factors that predict post-war psychological adjustment, specifically posttraumatic stress, in Bosnian adolescents. Regression analyses evaluated theorized differential relations between three types of post-war stressors - exposure to trauma reminders, loss reminders, and intrafamilial conflict - specific coping strategies, and posttraumatic stress symptom dimensions. We examined 555 Bosnian adolescents, aged 15-19 years, to predict their long-term posttraumatic stress reactions in the aftermath of war. Findings indicated that post-war exposure to trauma reminders, loss reminders, and family conflict, as well as engagement and disengagement coping strategies, predicted posttraumatic stress symptoms. Secondary control engagement coping responses to all three types of post-war stressors were inversely associated with posttraumatic stress symptoms, whereas primary control engagement coping responses to family conflict were inversely associated with hyperarousal symptoms. Disengagement responses to trauma reminders and family conflict were positively associated with re-experiencing symptoms. These findings shed light on ways in which trauma reminders, loss reminders, and family conflict may intersect with coping responses to influence adolescent postwar adjustment.

  13. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common protein-protein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins......, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...

  14. A novel missense mutation in the C-terminal domain of lipoprotein lipase (Glu410-->Val) leads to enzyme inactivation and familial chylomicronemia.

    Science.gov (United States)

    Previato, L; Guardamagna, O; Dugi, K A; Ronan, R; Talley, G D; Santamarina-Fojo, S; Brewer, H B

    1994-09-01

    Lipoprotein lipase (LPL) is a complex enzyme consisting of multiple functional domains essential for the initial hydrolysis of triglycerides present in plasma lipoproteins. Previous studies have localized the catalytic domain of LPL, responsible for the hydrolytic function of the enzyme, to the N-terminus whereas the C-terminal end may play a role in lipid and heparin binding. To date, most described missense mutations resulting in a nonfunctional LPL have been located in the N-terminal region of the enzyme. In this manuscript we describe the defect in the LPL gene of a patient with triglycerides ranging from normal to 12,000 mg/dl, low LPL mass, and no LPL activity in post-heparin plasma. Sequencing of patient PCR-amplified DNA identified two separate mutations in the C-terminal domain of LPL: an A-->T transversion at nucleotide 1484 resulting in a Glu410-->Val substitution and a C-->G mutation at position 1595 that introduces a premature stop codon at position 447. Digestion with MaeIII and MnII established that the patient is a true homozygote for both mutations. In order to investigate the functional significance of these defects, mutant enzymes containing either the Val410 or the Ter447 mutations as well as both Val410 and Ter447, were expressed in vitro. Compared to the wild-type enzyme, LPL447 demonstrated a moderate reduction of specific activity using triolein (70% of normal) and tributyrin (74% of normal) substrates, while LPL410 had a significant (11% and 23% of normal) reduction of the normal lipase and esterase specific activities, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Multimerization of GPIHBP1 and Familial Chylomicronemia from a Serine-to-Cysteine Substitution in GPIHBP1's Ly6 Domain

    DEFF Research Database (Denmark)

    Plengpanich, Wanee; Young, Stephen G; Khovidhunkit, Weerapan

    2014-01-01

    -fingered structure containing 10 cysteines and a conserved pattern of disulfide bond formation. Here, we report a patient with severe hypertriglyceridemia who was homozygous for a GPIHBP1 point mutation that converted a serine in GPIHBP1's Ly6 domain (Ser-107) to a cysteine. Two hypertriglyceridemic siblings were...... monomers bind LPL. In keeping with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free binding assays. We conclude that an extra cysteine in GPIHBP1's Ly6 motif results in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia....

  16. The Lectin Domain of the Polypeptide GalNAc Transferase Family of Glycosyltransferases (ppGalNAc Ts) Acts as a Switch Directing Glycopeptide Substrate Glycosylation in an N- or C-terminal Direction, Further Controlling Mucin Type O-Glycosylation

    DEFF Research Database (Denmark)

    Gerken, Thomas A; Revoredo, Leslie; Thome, Joseph J C

    2013-01-01

    Mucin type O-glycosylation is initiated by a large family of polypeptide GalNAc transferases (ppGalNAc Ts) that add α-GalNAc to the Ser and Thr residues of peptides. Of the 20 human isoforms, all but one are composed of two globular domains linked by a short flexible linker: a catalytic domain...... relative to the nonglycosylated control peptides. This N- and/or C-terminal selectivity is presumably due to weak glycopeptide binding to the lectin domain, whose orientation relative to the catalytic domain is dynamic and isoform-dependent. Such N- or C-terminal glycopeptide selectivity provides...

  17. A conserved sequence extending motif III of the motor domain in the Snf2-family DNA translocase Rad54 is critical for ATPase activity.

    Directory of Open Access Journals (Sweden)

    Xiao-Ping Zhang

    Full Text Available Rad54 is a dsDNA-dependent ATPase that translocates on duplex DNA. Its ATPase function is essential for homologous recombination, a pathway critical for meiotic chromosome segregation, repair of complex DNA damage, and recovery of stalled or broken replication forks. In recombination, Rad54 cooperates with Rad51 protein and is required to dissociate Rad51 from heteroduplex DNA to allow access by DNA polymerases for recombination-associated DNA synthesis. Sequence analysis revealed that Rad54 contains a perfect match to the consensus PIP box sequence, a widely spread PCNA interaction motif. Indeed, Rad54 interacts directly with PCNA, but this interaction is not mediated by the Rad54 PIP box-like sequence. This sequence is located as an extension of motif III of the Rad54 motor domain and is essential for full Rad54 ATPase activity. Mutations in this motif render Rad54 non-functional in vivo and severely compromise its activities in vitro. Further analysis demonstrated that such mutations affect dsDNA binding, consistent with the location of this sequence motif on the surface of the cleft formed by two RecA-like domains, which likely forms the dsDNA binding site of Rad54. Our study identified a novel sequence motif critical for Rad54 function and showed that even perfect matches to the PIP box consensus may not necessarily identify PCNA interaction sites.

  18. Crystal structures of starch binding domain from Rhizopus oryzae glucoamylase in complex with isomaltooligosaccharide: insights into polysaccharide binding mechanism of CBM21 family.

    Science.gov (United States)

    Chu, Chen-Hsi; Li, Kun-Mou; Lin, Shih-Wei; Chang, Margaret Dah-Tsyr; Jiang, Ting-Ying; Sun, Yuh-Ju

    2014-06-01

    Glucoamylases are responsible for hydrolysis of starch and polysaccharides to yield β-D-glucose. Rhizopus oryzae glucoamylase (RoGA) is composed of an N-terminal starch binding domain (SBD) and a C-terminal catalytic domain connected by an O-glycosylated linker. Two carbohydrate binding sites in RoSBD have been identified, site I is created by three highly conserved aromatic residues, Trp47, Tyr83, and Tyr94, and site II is built up by Tyr32 and Phe58. Here, the two crystal structures of RoSBD in complex with only α-(1,6)-linked isomaltotriose (RoSBD-isoG3) and isomaltotetraose (RoSBD-isoG4) have been determined at 1.2 and 1.3 Å, respectively. Interestingly, site II binding is observed in both complexes, while site I binding is only found in the RoSBD-isoG4 complex. Hence, site II acts as the recognition binding site for carbohydrate and site I accommodates site II to bind isoG4. Site I participates in sugar binding only when the number of glucosyl units of oligosaccharides is more than three. Taken together, two carbohydrate binding sites in RoSBD cooperate to reinforce binding mode of glucoamylase with polysaccharides as well as the starch.

  19. Educational needs of family physicians in the domains of health and conformity with continuing education in Fasa University of Medical Sciences

    Directory of Open Access Journals (Sweden)

    NAHID ZARIF SANAIEY

    2015-04-01

    Full Text Available Introduction: Assessment and prioritization are the first steps of planning. According to the family physician’s idea, evaluating programs in order to improve them is one of the necessities of promoting quality and increases the efficiency and effectiveness of continuing education. This study aimed to determine family physicians’ educational needs regarding health and its applicability in continuous medical education in Fasa University of Medical Sciences. Methods: In this cross-sectional study, viewpoints of 45 general physicians working at Fasa University of Medical Sciences in 2013 were studied. Samples were selected through census. Data collection was done using a researcher-made questionnaire using 10-point Likert scale and a checklist with Delphi technique. Content validity of the questionnaire and its reliability were confirmed by the experts’ opinion and Cronbach’s alpha of 80%. The data were analyzed through SPSS software version 16, using both descriptive and inferential statistics (mean and standard deviation, standard score (SQ, t-test, ANOVAs. A significance level of 0.05. The most educational conformity with continuing education was in the diseases area (topic 27%, content 37%. In the areas of environmental and professional health and health education, compliance was zero. Conclusions: The physicians stated that mental health was the first educational need and environmental and professional health was the last one. According to the results, proper continuing medical programs should be coordinated with educational needs.

  20. Targeting the BH3 domain of Bcl-2 family proteins. A brief history from natural products to foldamers as promising cancer therapeutic avenues.

    Science.gov (United States)

    De Giorgi, M; Voisin-Chiret, A S; Rault, S

    2013-01-01

    For many years the spotlight in drug discovery has been on a relatively small number of validated therapeutic target classes, such as G-protein coupled receptors and enzymes such as protein kinases, with well characterized enzymatic and cellular activities. However, with recent progress in genomics and proteomics, protein-protein interactions (PPIs) provide new way of finding novel bioactive molecules acting on their interfaces. This review addresses the current case studies and state of the art in the development of small chemical modulators controlling interactions of proteins that have pathological implications in various human diseases and in particular in cancer. The attention is focused on Bcl-2 family protein modulators ranging from natural products to synthetic ones with particular interest in foldamers as BH3 alpha helix mimetics.

  1. Amino acid substitutions of conserved residues in the carboxyl-terminal domain of the [alpha]I(X) chain of type X collagen occur in two unrelated families with metaphyseal chondrodysplasia type Schmid

    Energy Technology Data Exchange (ETDEWEB)

    Wallis, G.A.; Rash, B.; Sweetman, W.A.; Thomas, J.T.; Grant, M.E.; Boot-Handford, R.P. (Univ. of Manchester (United Kingdom)); Super, M. (Royal Manchester Children' s Hospital, Manchester (United Kingdom)); Evans, G. (Robert Jones Orthopaedic Hospital, Oswestry (United Kingdom))

    1994-02-01

    Type X collagen is a homotrimeric, short-chain, nonfibrillar extracellular-matrix component that is specifically and transiently synthesized by hypertrophic chondrocytes at the site of endochondral ossification. The precise function of type X collagen is not known, but its specific pattern of expression suggests that mutations within the encoding gene (COL10A1) that alter the structure or synthesis of the protein may cause heritable forms of chondrodysplasia. The authors used the PCR and the SSCP techniques to analyze the coding and upstream promoter regions of the COL10A1 gene in a number of individuals with forms of chondrodysplasia. Using this approach, they identified two individuals with metaphyseal chondrodysplasia type Schmid (MCDS) with SSCP changes in the region of the gene encoding the carboxyl-terminal domain. Sequence analysis demonstrated that the individuals were heterozygous for two unique single-base-pair transitions that led to the substitution of the highly conserved amino acid residue tyrosine at position 598 by aspartic acid in one person and of leucine at position 614 by proline in the other. The substitution at residue 598 segregated with the phenotype in a family of eight (five affected and three unaffected) related persons. The substitutions at residue 614 occurred in a sporadically affected individual but not in her unaffected mother and brother. Additional members of this family were not available for further study. These results suggest that certain amino acid substitutions within the carboxyl-terminal domain of the chains of the type X collagen molecule cause MCDS. These amino acid substitutions are likely to alter either chain recognition or assembly of the type X collagen molecule, thereby depleting the amount of normal type X collagen deposited in the extracellular matrix, with consequent aberrations in bone growth and development. 36 refs., 5 figs.

  2. Allelic Analyses of the Arabidopsis YUC1 Locus Reveal Residues and Domains Essential for the Functions of YUC Family of Flavin Monooxygenases

    Institute of Scientific and Technical Information of China (English)

    Xianhui Hou; Sainan Liu; Florencia Pierri; Xinhua Dai; Li-Jia Qu; Yunde Zhao

    2011-01-01

    Flavin monooxygenases(FMOs)play critical roles in plant growth and development by synthesizing auxin and other signaling molecules.However,the structure and function relationship within plant FMOs is not understood.Here we defined the important residues and domains of the Arabidopsis YUC1 FMO,a key enzyme in auxin biosynthesis.We previously showed that simultaneous inactivation of YUC1 and its homologue YUC4 caused severe defects in vascular and floral development.We mutagenized the yuc4 mutant and screened for mutants with phenotypes similar to those of yuc1 yuc4 double mutants.Among the isolated mutants,five of them contained mutations in the YUC1 gene.Interestingly,the mutations identified in the new yuc1 alleles were concentrated in the two GXGXXG motifs that are highly conserved among the plant FMOs.One such motif presumably binds to flavin adenine dinucleotide(FAD) cofactor and the other binds to nicotinamide adenine dinucleotide phosphate (NADPH).We also identified the Ser139 to Phe conversion in yuc1,a mutation that is located between the two nucleotide-binding sites.By analyzing a series of yuc1 mutants,we identified key residues and motifs essential for the functions of YUC1 FMO.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-07-15

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

  4. Editing of misaligned 3′-termini by an intrinsic 3′–5′ exonuclease activity residing in the PHP domain of a family X DNA polymerase

    Science.gov (United States)

    Baños, Benito; Lázaro, José M.; Villar, Laurentino; de Vega, Miguel

    2008-01-01

    Bacillus subtilis gene yshC encodes a family X DNA polymerase (PolXBs), whose biochemical features suggest that it plays a role during DNA repair processes. Here, we show that, in addition to the polymerization activity, PolXBs possesses an intrinsic 3′–5′ exonuclease activity specialized in resecting unannealed 3′-termini in a gapped DNA substrate. Biochemical analysis of a PolXBs deletion mutant lacking the C-terminal polymerase histidinol phosphatase (PHP) domain, present in most of the bacterial/archaeal PolXs, as well as of this separately expressed protein region, allow us to state that the 3′–5′ exonuclease activity of PolXBs resides in its PHP domain. Furthermore, site-directed mutagenesis of PolXBs His339 and His341 residues, evolutionary conserved in the PHP superfamily members, demonstrated that the predicted metal binding site is directly involved in catalysis of the exonucleolytic reaction. The implications of the unannealed 3′-termini resection by the 3′–5′ exonuclease activity of PolXBs in the DNA repair context are discussed. PMID:18776221

  5. Hypoxia influences expression profile of Pleckstrin homology-like domain, family A, member 2 in Indian catfish, Clarias batrachus (Linnaeus, 1758): A new candidate gene for hypoxia tolerance in fish

    Indian Academy of Sciences (India)

    Vindhya Mohindra; Ratnesh K Tripathi; Prabhaker Yadav; Rajeev K Singh; Kuldeep K Lal

    2014-06-01

    Several physiologically important genes were found to be regulated by hypoxia at the transcriptional level. The Pleckstrin homology-like domain, family A, member 2 (PHLDA2) gene was previously identified as an imprinted gene. The present study was aimed to determine the structure of complete cDNA and the deduced protein of PHLDA2 along with analysing the changes in its mRNA expression in Clarias batrachus tissues under hypoxic conditions. The complete cDNA of CbPHLDA2 gene consisted of 1009 nucleotides with an open reading frame of 417 nucleotides. The deduced CbPHLDA2 protein of 139 amino acids shared high homology with PHLD2A of other fishes as well as that of vertebrates. Importantly, a single amino acid (asparagine/lysine) insertion was identified in the PH domain of CbPHLDA2 and other fishes, which was absent in other vertebrates studied. Furthermore, under normoxic conditions, CbPHLDA2 was constitutively expressed with varying levels in analysed tissues. Short- and long-term hypoxia exposure resulted in significant changes in the expression of CbPHLDA2 in liver, spleen, head kidney, brain and muscle in a time-dependent manner. The results suggested that CbPHLDA2 might play an important role for adaptive significance under hypoxia.

  6. The YARHG domain: an extracellular domain in search of a function.

    Directory of Open Access Journals (Sweden)

    Penny Coggill

    Full Text Available We have identified a new bacterial protein domain that we hypothesise binds to peptidoglycan. This domain is called the YARHG domain after the most highly conserved sequence-segment. The domain is found in the extracellular space and is likely to be composed of four alpha-helices. The domain is found associated with protein kinase domains, suggesting it is associated with signalling in some bacteria. The domain is also found associated with three different families of peptidases. The large number of different domains that are found associated with YARHG suggests that it is a useful functional module that nature has recombined multiple times.

  7. The Bcl-2 homology domain 3 (BH3)-only proteins Bim and bid are functionally active and restrained by anti-apoptotic Bcl-2 family proteins in healthy liver.

    Science.gov (United States)

    Kodama, Takahiro; Hikita, Hayato; Kawaguchi, Tsukasa; Saito, Yoshinobu; Tanaka, Satoshi; Shigekawa, Minoru; Shimizu, Satoshi; Li, Wei; Miyagi, Takuya; Kanto, Tatsuya; Hiramatsu, Naoki; Tatsumi, Tomohide; Takehara, Tetsuo

    2013-10-18

    An intrinsic pathway of apoptosis is regulated by the B-cell lymphoma-2 (Bcl-2) family proteins. We previously reported that a fine rheostatic balance between the anti- and pro-apoptotic multidomain Bcl-2 family proteins controls hepatocyte apoptosis in the healthy liver. The Bcl-2 homology domain 3 (BH3)-only proteins set this rheostatic balance toward apoptosis upon activation in the diseased liver. However, their involvement in healthy Bcl-2 rheostasis remains unknown. In the present study, we focused on two BH3-only proteins, Bim and Bid, and we clarified the Bcl-2 network that governs hepatocyte life and death in the healthy liver. We generated hepatocyte-specific Bcl-xL- or Mcl-1-knock-out mice, with or without disrupting Bim and/or Bid, and we examined hepatocyte apoptosis under physiological conditions. We also examined the effect of both Bid and Bim disruption on the hepatocyte apoptosis caused by the inhibition of Bcl-xL and Mcl-1. Spontaneous hepatocyte apoptosis in Bcl-xL- or Mcl-1-knock-out mice was significantly ameliorated by Bim deletion. The disruption of both Bim and Bid completely prevented hepatocyte apoptosis in Bcl-xL-knock-out mice and weakened massive hepatocyte apoptosis via the additional in vivo knockdown of mcl-1 in these mice. Finally, the hepatocyte apoptosis caused by ABT-737, which is a Bcl-xL/Bcl-2/Bcl-w inhibitor, was completely prevented in Bim/Bid double knock-out mice. The BH3-only proteins Bim and Bid are functionally active but are restrained by the anti-apoptotic Bcl-2 family proteins under physiological conditions. Hepatocyte integrity is maintained by the dynamic and well orchestrated Bcl-2 network in the healthy liver.

  8. Trusted Domain

    DEFF Research Database (Denmark)

    Hjorth, Theis Solberg; Torbensen, Rune

    2012-01-01

    that enables secure end-to-end communication with home automation devices, and it supports device revocations as well as a structure of intersecting sets of nodes for scalability. Devices in the Trusted Domain are registered in a list that is distributed using a robust epidemic protocol optimized...

  9. Domain crossing

    DEFF Research Database (Denmark)

    Schraefel, M. C.; Rouncefield, Mark; Kellogg, Wendy

    2012-01-01

    In CSCW, how much do we need to know about another domain/culture before we observe, intersect and intervene with designs. What optimally would that other culture need to know about us? Is this a “how long is a piece of string” question, or an inquiry where we can consider a variety of contexts a...

  10. Ubiquitin domain proteins in disease

    DEFF Research Database (Denmark)

    Klausen, Louise Kjær; Schulze, Andrea; Seeger, Michael

    2007-01-01

    The human genome encodes several ubiquitin-like (UBL) domain proteins (UDPs). Members of this protein family are involved in a variety of cellular functions and many are connected to the ubiquitin proteasome system, an essential pathway for protein degradation in eukaryotic cells. Despite their s...... and cancer. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).......The human genome encodes several ubiquitin-like (UBL) domain proteins (UDPs). Members of this protein family are involved in a variety of cellular functions and many are connected to the ubiquitin proteasome system, an essential pathway for protein degradation in eukaryotic cells. Despite...

  11. Ras-Association Domain Family 1 Isoform A (RASSF1A) Gene Polymorphism rs1989839 is Associated with Risk and Metastatic Potential of Osteosarcoma in Young Chinese Individuals: A Multi-Center, Case-Control Study.

    Science.gov (United States)

    Xu, Hongwei; Zhan, Wang; Chen, Zhiyuan

    2016-11-23

    BACKGROUND The ras-association domain family 1 isoform A (RASSF1A) gene serves as a bona fide tumor suppressor gene. The polymorphisms in RASSF1A were previously reported to be associated with the risk of solid malignant tumors. We hypothesized herein that RASSF1A gene polymorphisms are involved in the risk and prognosis of osteosarcoma (OS). MATERIAL AND METHODS We recruited 279 young OS cases and 286 tumor-free controls from the east Chinese population. Five tagSNPs of RASSF1A gene (rs2236947A/C, rs2073497A/C, rs1989839C/T, rs72932987C/T, and rs4688728G/T) were genotyped. DNA was isolated from blood samples and then underwent PCR analysis for genotyping. RESULTS rs1989839C/T is an important predictor of osteosarcoma risk and outcome. The CT genotype of rs1989839 is highly related to elevated risk of osteosarcoma. Furthermore, rs1989839C/T is also associated with the Enneking stage of osteosarcoma and risk of lung metastasis. One of the other 4 SNPs, rs2236947A/C, shows a borderline significance in predicting osteosarcoma risk. CONCLUSIONS Our study is the first to prove that RASSF1A gene polymorphisms may potentially be predictive for osteosarcoma risk and prognosis.

  12. Detection of a novel mutation in the SRC homology domain 2 (SH2) of Bruton`s tyrosine kinase and direct female carrier evaluation in a family with x-linked agammaglobulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Schuster, V.; Seidenspinner, S.; Wolfgang Kreth, H. [Univ. of Wuerzburg (Germany)

    1996-05-03

    X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency disease with a block in differentiation from pre-B to B cells resulting in a selective defect in the humoral immune response. Affected males have very low concentrations of serum immunoglobulins leading predominantly to recurrent bacterial infections beginning at age 6 to 18 months. The gene responsible for XLA was identified recently to encode a cytoplasmatic tyrosine kinase (Bruton`s tyrosine kinase, BTK). We have analyzed the BTK gene in a large family in which two brothers presented with the severe phenotype of XLA. Genomic DNA of affected boys and from healthy relatives was amplified by PCR with primers specific for the putative promoter region and for all 19 exons, including flanking intron boundaries, and subsequently screened for mutations using single strand conformation polymorphism (SSCP) analysis. Altered single strand band patterns were found using primers specific for exon 10, 15, and 18. Direct cycle-sequencing of these BTK segments detected two known polymorphisms in intron 14 and in exon 18. Sequencing of exon 10 from two boys with XLA demonstrated a novel point mutation in the SH2 domain of BTK. Direct identification of healthy female carriers in three generations was performed by amplification mutagenesis using PCR with a modified first primer. This method can easily be applied also to prenatal diagnosis. 25 refs., 3 figs.

  13. Domain-specific language design requires feature descriptions

    NARCIS (Netherlands)

    A. van Deursen (Arie); P. Klint (Paul)

    2001-01-01

    textabstractA domain-specific language (DSL) provides a notation tailored towards an application domain and is based on the relevant concepts and features of that domain. As such, a DSL is a means to describe and generate members of a family of programs in the domain. A prerequisite for the design

  14. Nuclear transfer alters placental gene expression and associated histone modifications of the placental-specific imprinted gene pleckstrin homology-like domain, family A, member 2 (PHLDA2) in cattle.

    Science.gov (United States)

    Arnold, Daniel R; Gaspar, Roberta C; da Rocha, Carlos V; Sangalli, Juliano R; de Bem, Tiago H C; Corrêa, Carolina A P; Penteado, João C T; Meirelles, Flavio V; Lopes, Flavia L

    2017-03-01

    Abnormal placental development is frequent in nuclear transfer (NT) pregnancies and is likely to be associated with altered epigenetic reprogramming. In the present study, fetal and placental measurements were taken on Day 60 of gestation in cows with pregnancies produced by AI, IVF and NT. Placentas were collected and subjected to histological evaluation, the expression of genes important in trophoblast differentiation and expression of the placental imprinted gene pleckstrin homology-like domain, family A, member 2 (PHLDA2), as well as chromatin immunoprecipitation (ChIP) for histone marks within the promoter of PHLDA2. Fewer binucleated cells were observed in NT cotyledons, followed by IVF and AI cotyledons (P<0.05). Expression of heart and neural crest derivatives expressed 1 (HAND1), placental lactogen (PL), pregnancy-associated glycoprotein 9 (PAG-9) and PHLDA2 was elevated in NT cotyledons compared with AI cotyledons. Expression of PHLDA2 was higher in IVF than AI samples (P<0.05). ChIP revealed an increase in the permissive mark dimethylation of lysine 4 on histone H3 (H3K4me2), surprisingly associated with the silent allele of PHLDA2, and a decrease in the inhibitory mark H3K9me2 in NT samples. Thus, genes critical for placental development were altered in NT placentas, including an imprinted gene. Allele-specific changes in the permissive histone mark in the PHLDA2 promoter indicate misregulation of imprinting in clones. Abnormal trophoblast differentiation could have resulted in lower numbers of binucleated cells following NT. These results suggest that the altered expression of imprinted genes associated with NT are also caused by changes in histone modifications.

  15. Upregulated expression of La ribonucleoprotein domain family member 6 and collagen type I gene following water-filtered broad-spectrum near-infrared irradiation in a 3-dimensional human epidermal tissue culture model as revealed by microarray analysis.

    Science.gov (United States)

    Tanaka, Yohei; Nakayama, Jun

    2017-02-27

    Water-filtered broad-spectrum near-infrared irradiation can induce various biological effects, as our previous clinical, histological, and biochemical investigations have shown. However, few studies that examined the changes thus induced in gene expression. The aim was to investigate the changes in gene expression in a 3-dimensional reconstructed epidermal tissue culture exposed to water-filtered broad-spectrum near-infrared irradiation. DNA microarray and quantitative real-time polymerase chain reaction (PCR) analysis was used to assess gene expression levels in a 3-dimensional reconstructed epidermal model composed of normal human epidermal cells exposed to water-filtered broad-spectrum near-infrared irradiation. The water filter allowed 1000-1800 nm wavelengths and excluded 1400-1500 nm wavelengths, and cells were exposed to 5 or 10 rounds of near-infrared irradiation at 10 J/cm(2) . A DNA microarray with over 50 000 different probes showed 18 genes that were upregulated or downregulated by at least twofold after irradiation. Quantitative real-time PCR revealed that, relative to control cells, the gene encoding La ribonucleoprotein domain family member 6 (LARP6), which regulates collagen expression, was significantly and dose-dependently upregulated (P < 0.05) by water-filtered broad-spectrum near-infrared exposure. Gene encoding transcripts of collagen type I were significantly upregulated compared with controls (P < 0.05). This study demonstrates the ability of water-filtered broad-spectrum near-infrared irradiation to stimulate the production of type I collagen. © 2017 The Australasian College of Dermatologists.

  16. DNA-Encoded Flagellin Activates Toll-Like Receptor 5 (TLR5, Nod-like Receptor Family CARD Domain-Containing Protein 4 (NRLC4, and Acts as an Epidermal, Systemic, and Mucosal-Adjuvant

    Directory of Open Access Journals (Sweden)

    Steven E. Applequist

    2013-09-01

    Full Text Available Eliciting effective immune responses using non-living/replicating DNA vaccines is a significant challenge. We have previously shown that ballistic dermal plasmid DNA-encoded flagellin (FliC promotes humoral as well as cellular immunity to co-delivered antigens. Here, we observe that a plasmid encoding secreted FliC (pFliC(-gly produces flagellin capable of activating two innate immune receptors known to detect flagellin; Toll-like Receptor 5 (TLR5 and Nod-like Receptor family CARD domain-containing protein 4 (NRLC4. To test the ability of pFliC(-gly to act as an adjuvant we immunized mice with plasmid encoding secreted FliC (pFliC(-gly and plasmid encoding a model antigen (ovalbumin by three different immunization routes representative of dermal, systemic, and mucosal tissues. By all three routes we observed increases in antigen-specific antibodies in serum as well as MHC Class I-dependent cellular immune responses when pFliC(-gly adjuvant was added. Additionally, we were able to induce mucosal antibody responses and Class II-dependent cellular immune responses after mucosal vaccination with pFliC(-gly. Humoral immune responses elicited by heterologus prime-boost immunization with a plasmid encoding HIV-1 from gp160 followed by protein boosting could be enhanced by use of pFliC(-gly. We also observed enhancement of cross-clade reactive IgA as well as a broadening of B cell epitope reactivity. These observations indicate that plasmid-encoded secreted flagellin can activate multiple innate immune responses and function as an adjuvant to non-living/replicating DNA immunizations. Moreover, the capacity to elicit mucosal immune responses, in addition to dermal and systemic properties, demonstrates the potential of flagellin to be used with vaccines designed to be delivered by various routes.

  17. Concept Convergence in Empirical Domains

    Science.gov (United States)

    Ontañón, Santiago; Plaza, Enric

    How to achieve shared meaning is a significant issue when more than one intelligent agent is involved in the same domain. We define the task of concept convergence, by which intelligent agents can achieve a shared, agreed-upon meaning of a concept (restricted to empirical domains). For this purpose we present a framework that, integrating computational argumentation and inductive concept learning, allows a pair of agents to (1) learn a concept in an empirical domain, (2) argue about the concept's meaning, and (3) reach a shared agreed-upon concept definition. We apply this framework to marine sponges, a biological domain where the actual definitions of concepts such as orders, families and species are currently open to discussion. An experimental evaluation on marine sponges shows that concept convergence is achieved, within a reasonable number of interchanged arguments, and reaching short and accurate definitions (with respect to precision and recall).

  18. EuPathDomains: the divergent domain database for eukaryotic pathogens.

    Science.gov (United States)

    Ghouila, Amel; Terrapon, Nicolas; Gascuel, Olivier; Guerfali, Fatma Z; Laouini, Dhafer; Maréchal, Eric; Bréhélin, Laurent

    2011-06-01

    Eukaryotic pathogens (e.g. Plasmodium, Leishmania, Trypanosomes, etc.) are a major source of morbidity and mortality worldwide. In Africa, one of the most impacted continents, they cause millions of deaths and constitute an immense economic burden. While the genome sequence of several of these organisms is now available, the biological functions of more than half of their proteins are still unknown. This is a serious issue for bringing to the foreground the expected new therapeutic targets. In this context, the identification of protein domains is a key step to improve the functional annotation of the proteins. However, several domains are missed in eukaryotic pathogens because of the high phylogenetic distance of these organisms from the classical eukaryote models. We recently proposed a method, co-occurrence domain detection (CODD), that improves the sensitivity of Pfam domain detection by exploiting the tendency of domains to appear preferentially with a few other favorite domains in a protein. In this paper, we present EuPathDomains (http://www.atgc-montpellier.fr/EuPathDomains/), an extended database of protein domains belonging to ten major eukaryotic human pathogens. EuPathDomains gathers known and new domains detected by CODD, along with the associated confidence measurements and the GO annotations that can be deduced from the new domains. This database significantly extends the Pfam domain coverage of all selected genomes, by proposing new occurrences of domains as well as new domain families that have never been reported before. For example, with a false discovery rate lower than 20%, EuPathDomains increases the number of detected domains by 13% in Toxoplasma gondii genome and up to 28% in Cryptospordium parvum, and the total number of domain families by 10% in Plasmodium falciparum and up to 16% in C. parvum genome. The database can be queried by protein names, domain identifiers, Pfam or Interpro identifiers, or organisms, and should become a valuable

  19. Multi-domain proteins in the three kingdoms of life: orphan domains and other unassigned regions.

    Science.gov (United States)

    Ekman, Diana; Björklund, Asa K; Frey-Skött, Johannes; Elofsson, Arne

    2005-04-22

    Comparative studies of the proteomes from different organisms have provided valuable information about protein domain distribution in the kingdoms of life. Earlier studies have been limited by the fact that only about 50% of the proteomes could be matched to a domain. Here, we have extended these studies by including less well-defined domain definitions, Pfam-B and clustered domains, MAS, in addition to Pfam-A and SCOP domains. It was found that a significant fraction of these domain families are homologous to Pfam-A or SCOP domains. Further, we show that all regions that do not match a Pfam-A or SCOP domain contain a significantly higher fraction of disordered structure. These unstructured regions may be contained within orphan domains or function as linkers between structured domains. Using several different definitions we have re-estimated the number of multi-domain proteins in different organisms and found that several methods all predict that eukaryotes have approximately 65% multi-domain proteins, while the prokaryotes consist of approximately 40% multi-domain proteins. However, these numbers are strongly dependent on the exact choice of cut-off for domains in unassigned regions. In conclusion, all eukaryotes have similar fractions of multi-domain proteins and disorder, whereas a high fraction of repeating domain is distinguished only in multicellular eukaryotes. This implies a role for repeats in cell-cell contacts while the other two features are important for intracellular functions.

  20. Linking Team Resources to Work-Family Enrichment and Satisfaction

    Science.gov (United States)

    Hunter, Emily M.; Perry, Sara Jansen; Carlson, Dawn S.; Smith, Steven A.

    2010-01-01

    Work-family scholars now recognize the potential positive effects of participation in one life domain (i.e., work or family) on performance in other life domains. We examined how employees might benefit from team resources, which are highly relevant to the modern workplace, in both work and nonwork domains via work-family enrichment. Using the…

  1. .Gov Domains API

    Data.gov (United States)

    General Services Administration — This dataset offers the list of all .gov domains, including state, local, and tribal .gov domains. It does not include .mil domains, or other federal domains outside...

  2. Complete mitochondrial genome of the Tristram's Bunting, Emberiza tristrami (Aves: Passeriformes): the first representative of the family Emberizidae with six boxes in the central conserved domain II of control region.

    Science.gov (United States)

    Kan, Xianzhao; Yuan, Jian; Zhang, Liqin; Li, Xifeng; Yu, Lei; Chen, Lei; Guo, Zhichun; Yang, Jianke

    2013-12-01

    Mitochondrial genome has proven to be a powerful tool for phylogenetic inference, phylogeography, and molecular evolution. In this study, we determined the complete mitochondrial genome of Emberiza tristrami (Passeriformes: Emberizidae) for use in future phylogenetic analyses. This circular mitochondrial genome is 16,789 bp in length and composed of 13 typical protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 putative control region (CR). One extra nucleotide "C" of nad3 is not detected in the mitogenome of E. tristrami. The CR of E. tristrami can be divided into three domains: ETAS (extended termination-associated sequence) domain I (nt 1-431), central conserved domain II (nt 432-847), and CSB (conserved sequence block) domain III (nt 848-1217). Six conserved sequence boxes in the central conserved domain II were identified as boxes F, E, D, C, b, and B.

  3. Protectin D1 reduces concanavalin A-induced liver injury by inhibiting NF-κB-mediated CX3CL1/CX3CR1 axis and NLR family, pyrin domain containing 3 inflammasome activation.

    Science.gov (United States)

    Ren, Jun; Meng, Shanshan; Yan, Bingdi; Yu, Jinyan; Liu, Jing

    2016-04-01

    Protectin D1 (PD1) is a bioactive product generated from docosahexaenoic acid, which may exert anti-inflammatory effects in various inflammatory diseases. However, the underlying molecular mechanism of its anti‑inflammatory activity on concanavalin A (Con A)-induced hepatitis remains unknown. The aim of the present study was to investigate the protective effects of PD1 against Con A‑induced liver injury and the underlying mechanisms via intravenous injection of PD1 prior to Con A administration. C57BL/6 mice were randomly divided into four experimental groups as follows: Control group, Con A group (30 mg/kg), 20 µg/kg PD1 + Con A (30 mg/kg) group and 10 µg/kg PD1 + Con A (30 mg/kg) group. PD1 pretreatment was demonstrated to significantly inhibit elevated plasma aminotransferase levels, high mobility group box 1 and liver necrosis, which were observed in Con A‑induced hepatitis. Furthermore, compared with the Con A group, PD1 pretreatment prevented the production of pro‑inflammatory cytokines, including tumor necrosis factor‑α, interferon‑γ and interleukin‑2, ‑1β and ‑6. In addition, pretreatment with PD1 markedly downregulated cluster of differentiation (CD)4+, CD8+ and natural killer T (NKT) cell infiltration in the liver. PD1 pretreatment was observed to suppress the messenger RNA and protein expression levels of NLR family, pyrin domain containing 3 and Toll‑like receptor (TLR) 4 in liver tissue samples. Further data indicated that PD1 pretreatment inhibited the activation of the nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) signaling pathway and chemokine (C‑X3‑C motif) ligand 1 (CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1) axis by preventing phosphorylation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α and NF‑κB in Con A‑induced liver injury. Therefore, these results suggest that PD1 administration protects mice against Con A‑induced liver injury via

  4. Discoidin Domain Receptors Role in Human Diseases

    Directory of Open Access Journals (Sweden)

    Iker BADIOLA

    2011-11-01

    Full Text Available Discoidin Domain Receptor 1 and Discodin Domain Receptor 2 are the two only members of the DDR family. The DDR family is a Tyrosine Kinase Receptor (TKR family with some peculiarities compared with other Tyrosine Kinase Receptors such as their natural ligand; which in this case is the fibrillar collagen; or the slow phosphorylation pattern. These peculiarities confer a special role to the receptors present in many diseases development processes as cancer, cirrhosis or lung fibrosis. In this review it is described the overview of the DDRs structure and their role in the different disease development and the possibility to consider them as therapeutic targets.

  5. WOMEN IN FAMILY BUSINESS

    OpenAIRE

    Anshu,

    2012-01-01

    The role of women in family businesses is explored in the paper. Although recognized as generally very important players, the role of women is often defined as invisible in business decision-making, supportive in men’s traditional business domains and only rarelyadequately recognized and rewarded. The paper explores possible differences in the views of men and women who manage small family firms. Their attitudes opposing the traditional business roles ofwomen, different views on managerial, o...

  6. The lectin domain of the polypeptide GalNAc transferase family of glycosyltransferases (ppGalNAc Ts) acts as a switch directing glycopeptide substrate glycosylation in an N- or C-terminal direction, further controlling mucin type O-glycosylation.

    Science.gov (United States)

    Gerken, Thomas A; Revoredo, Leslie; Thome, Joseph J C; Tabak, Lawrence A; Vester-Christensen, Malene Bech; Clausen, Henrik; Gahlay, Gagandeep K; Jarvis, Donald L; Johnson, Roy W; Moniz, Heather A; Moremen, Kelley

    2013-07-01

    Mucin type O-glycosylation is initiated by a large family of polypeptide GalNAc transferases (ppGalNAc Ts) that add α-GalNAc to the Ser and Thr residues of peptides. Of the 20 human isoforms, all but one are composed of two globular domains linked by a short flexible linker: a catalytic domain and a ricin-like lectin carbohydrate binding domain. Presently, the roles of the catalytic and lectin domains in peptide and glycopeptide recognition and specificity remain unclear. To systematically study the role of the lectin domain in ppGalNAc T glycopeptide substrate utilization, we have developed a series of novel random glycopeptide substrates containing a single GalNAc-O-Thr residue placed near either the N or C terminus of the glycopeptide substrate. Our results reveal that the presence and N- or C-terminal placement of the GalNAc-O-Thr can be important determinants of overall catalytic activity and specificity that differ between transferase isoforms. For example, ppGalNAc T1, T2, and T14 prefer C-terminally placed GalNAc-O-Thr, whereas ppGalNAc T3 and T6 prefer N-terminally placed GalNAc-O-Thr. Several transferase isoforms, ppGalNAc T5, T13, and T16, display equally enhanced N- or C-terminal activities relative to the nonglycosylated control peptides. This N- and/or C-terminal selectivity is presumably due to weak glycopeptide binding to the lectin domain, whose orientation relative to the catalytic domain is dynamic and isoform-dependent. Such N- or C-terminal glycopeptide selectivity provides an additional level of control or fidelity for the O-glycosylation of biologically significant sites and suggests that O-glycosylation may in some instances be exquisitely controlled.

  7. Structural and Histone Binding Ability Characterizations of Human PWWP Domains

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Amaya, Maria F.; Xu, Chao; Dombrovski, Ludmila; Qiu, Wei; Wang, Yanming; Min, Jinrong (Toronto); (Penn)

    2013-09-25

    The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.

  8. Dissolved families

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The situation in the family preceding a family separation is studied here, to identify risk factors for family dissolution. Information registers covering prospective statistics about health aspects, demographic variables, family violence, self-destructive behaviour, unemployment, and the spousal...

  9. Dissolved families

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The situation in the family preceding a family separation is studied here, to identify risk factors for family dissolution. Information registers covering prospective statistics about health aspects, demographic variables, family violence, self-destructive behaviour, unemployment, and the spousal...

  10. Family Life

    Science.gov (United States)

    ... With Family and Friends > Family Life Request Permissions Family Life Approved by the Cancer.Net Editorial Board , ... your outlook on the future. Friends and adult family members The effects of cancer on your relationships ...

  11. Characterizing Class I WW domains defines key specificity determinants and generates mutant domains with novel specificities.

    Science.gov (United States)

    Kasanov, J; Pirozzi, G; Uveges, A J; Kay, B K

    2001-03-01

    WW domains are small protein interaction modules found in a wide range of eukaryotic signaling and structural proteins. Five classes of WW domains have been annotated to date, where each class is largely defined by the type of peptide ligand selected, rather than by similarities within WW domains. Class I WW domains bind Pro-Pro-Xxx-Tyr containing ligands, and it would be of interest to determine residues within the domains that determine this specificity. Fourteen WW domains selected Leu/Pro-Pro-Xxx-Tyr containing peptides ligands via phage display and were thus designated as Class 1 WW domains. These domains include those present in human YAP (hYAP) and WWP3, as well as those found in ubiquitin protein ligases of the Nedd4 family, including mouse Nedd4 (mNedd4), WWP1, WWP2 and Rsp5. Comparing the primary structures of these WW domains highlighted a set of highly conserved residues, in addition to those originally noted to occur within WW domains. Substitutions at two of these conserved positions completely inhibited ligand binding, whereas substitution at a non-conserved position did not. Moreover, mutant WW domains containing substitutions at conserved positions bound novel peptide ligands. Class I WW domains contain a highly conserved set of residues that are important in selecting Pro-Xxx-Tyr containing peptide ligands. The presence of these residues within an uncharacterized WW domain can be used to predict its ability to bind Pro-Xxx-Tyr containing peptide ligands.

  12. The CW domain, a structural module shared amongst vertebrates, vertebrate-infecting parasites and higher plants.

    Science.gov (United States)

    Perry, Jason; Zhao, Yunde

    2003-11-01

    A previously undetected domain, named CW for its conserved cysteine and tryptophan residues, appears to be a four-cysteine zinc-finger motif found exclusively in vertebrates, vertebrate-infecting parasites and higher plants. Of the twelve distinct nuclear protein families that comprise the CW domain-containing superfamily, only the microrchida (MORC) family has begun to be characterized. However, several families contain other domains suggesting a relationship between the CW domain and either chromatin methylation status or early embryonic development.

  13. 基于知识图谱的国内家族企业研究可视化分析%The Visualization Analysis on Family Business Research in China Based on Mapping Knowledge Domains

    Institute of Scientific and Technical Information of China (English)

    郑迪松; 王河森

    2016-01-01

    为梳理国内家族企业领域研究状况,以CSSCI数据库收录的1998-2014年间国内家族企业研究领域的1043篇文献为样本,运用信息可视化软件CiteSpace Ⅲ进行统计与可视化分析,结果显示:研究机构以高校为主;机构和作者合作具有比较明显的区域特征;费孝通、储小平、陈凌、李新春等学者在该领域具有较大的影响力;《管理世界》、Family Business Review、《经济研究》等期刊受到国内研究者的高度关注;家族企业经营管理、家族控制与家族治理、家族企业治理与代理、家族企业制度安排、产权与家族化管理、家族企业继承与成长等问题是家族企业研究热点。%Taking 1043 papers on family business research from CSSCI database published during 1998-2014 as data sample, this paper used CiteSpaceⅢ to do statistic analyse and draw the knowledge maps. It shows that the research institutions are mainly colleges and universities; the cooperation between the institutions and the authors has obvious regional characteristics; Fei Xiaotong, Chu Xiaoping, Chen Ling and Li Xinchun have great inlfuences in the ifeld; Management World(Chinese) , Family Business Review(English) , Economic Research Journal(Chinese) are highly attracted by domestic researchers; family business management, family control and family governance, family business governance and agency relationship, family business system arrangement, property rights and family management, family business succession and growth are the hot points of family business research.

  14. Chicken Ig-like receptor B2, a member of a multigene family, is mainly expressed on B lymphocytes, recruits both Src homology 2 domain containing protein tyrosine phosphatase (SHP)-1 and SHP-2, and inhibits proliferation

    NARCIS (Netherlands)

    Viertlboeck, B.C.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Gobel, T.W.

    2004-01-01

    Ig-like inhibitory receptors have been the focus of intensive research particularly in mouse and human. We report the cloning and characterization of three novel inhibitory chicken Ig-like receptors (CHIR) that display a two Ig-domain extracellular structure, a transmembrane region lacking charged

  15. Protein domain prediction

    NARCIS (Netherlands)

    Ingolfsson, Helgi; Yona, Golan

    2008-01-01

    Domains are considered to be the building blocks of protein structures. A protein can contain a single domain or multiple domains, each one typically associated with a specific function. The combination of domains determines the function of the protein, its subcellular localization and the interacti

  16. Canonical metrics on Cartan--Hartogs domains

    CERN Document Server

    Zedda, Michela

    2011-01-01

    In this paper we address two problems concerning a family of domains $M_{\\Omega}(\\mu) \\subset \\C^n$, called Cartan-Hartogs domains, endowed with a natural Kaehler metric $g(\\mu)$. The first one is determining when the metric $g(\\mu)$ is extremal (in the sense of Calabi), while the second one studies when the coefficient $a_2$ in the Engli\\v{s} expansion of Rawnsley $\\epsilon$-function associated to $g(\\mu)$ is constant.

  17. The LIM domain protein FHL2 interacts with the NR5A family of nuclear receptors and CREB to activate the inhibin-α subunit gene in ovarian granulosa cells.

    Science.gov (United States)

    Matulis, Christina K; Mayo, Kelly E

    2012-08-01

    Nuclear receptor transcriptional activity is enhanced by interaction with coactivators. The highly related nuclear receptor 5A (NR5A) subfamily members liver receptor homolog 1 and steroidogenic factor 1 bind to and activate several of the same genes, many of which are important for reproductive function. To better understand transcriptional activation by these nuclear receptors, we sought to identify interacting proteins that might function as coactivators. The LIM domain protein four and a half LIM domain 2 (FHL2) was identified as interacting with the NR5A receptors in a yeast two-hybrid screen of a human ovary cDNA library. FHL2, and the closely related FHL1, are both expressed in the rodent ovary and in granulosa cells. Small interfering RNA-mediated knockdown of FHL1 and FHL2 in primary mouse granulosa cells reduced expression of the NR5A target genes encoding inhibin-α and P450scc. In vitro assays confirmed the interaction between the FHL and NR5A proteins and revealed that a single LIM domain of FHL2 is sufficient for this interaction, whereas determinants in both the ligand binding domain and DNA binding domain of NR5A proteins are important. FHL2 enhances the ability of both liver receptor homolog 1 and steroidogenic factor 1 to activate the inhibin-α subunit gene promoter in granulosa cells and thus functions as a transcriptional coactivator. FHL2 also interacts with cAMP response element-binding protein and substantially augments activation of inhibin gene expression by the combination of NR5A receptors and forskolin, suggesting that FHL2 may facilitate integration of these two signals. Collectively these results identify FHL2 as a novel coactivator of NR5A nuclear receptors in ovarian granulosa cells and suggest its involvement in regulating target genes important for mammalian reproduction.

  18. Differential effect on TCR:CD3 stimulation of a 90-kD glycoprotein (gp90/Mac-2BP), a member of the scavenger receptor cysteine-rich domain protein family

    DEFF Research Database (Denmark)

    Silvestri, B; Calderazzo, F; Coppola, V;

    1998-01-01

    We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non-specific ......We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non...

  19. Family Therapy

    Science.gov (United States)

    ... may be credentialed by the American Association for Marriage and Family Therapy (AAMFT). Family therapy is often short term. ... challenging situations in a more effective way. References Marriage and family therapists: The friendly mental health professionals. American Association ...

  20. Familial hypertriglyceridemia

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000397.htm Familial hypertriglyceridemia To use the sharing features on this page, please enable JavaScript. Familial hypertriglyceridemia is a common disorder passed down through families. ...

  1. Family Meals

    Science.gov (United States)

    ... Teaching Kids to Be Smart About Social Media Family Meals KidsHealth > For Parents > Family Meals Print A ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  2. Family Arguments

    Science.gov (United States)

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

  3. Family History

    Science.gov (United States)

    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 ...

  4. Domain similarity based orthology detection.

    Science.gov (United States)

    Bitard-Feildel, Tristan; Kemena, Carsten; Greenwood, Jenny M; Bornberg-Bauer, Erich

    2015-05-13

    Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time. We propose to speed up the detection of orthologous proteins by using strings of domains to characterize the proteins. We present two new protein similarity measures, a cosine and a maximal weight matching score based on domain content similarity, and new software, named porthoDom. The qualities of the cosine and the maximal weight matching similarity measures are compared against curated datasets. The measures show that domain content similarities are able to correctly group proteins into their families. Accordingly, the cosine similarity measure is used inside porthoDom, the wrapper developed for proteinortho. porthoDom makes use of domain content similarity measures to group proteins together before searching for orthologs. By using domains instead of amino acid sequences, the reduction of the search space decreases the computational complexity of an all-against-all sequence comparison. We demonstrate that representing and comparing proteins as strings of discrete domains, i.e. as a concatenation of their unique identifiers, allows a drastic simplification of search space. porthoDom has the advantage of speeding up orthology detection while maintaining a degree of accuracy similar to proteinortho. The implementation of porthoDom is released using python and C++ languages and is available under the GNU GPL licence 3 at http://www.bornberglab.org/pages/porthoda .

  5. Domains via Graphs

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guoqiang; CHEN Yixiang

    2001-01-01

    This paper provides a concrete and simple introduction to two pillars of domain theory: (1) solving recursive domain equations, and (2) universal and saturated domains. Our exposition combines Larsen and Winskel's idea on solving domain equations using information systems with Girard's idea of stable domain theory in the form of coherence spaces, or graphs.Detailed constructions are given for universal and even homogeneous objects in two categories of graphs: one representing binary complete, prime algebraic domains with complete primes covering the bottom; the other representing ω-algebraic, prime algebraic lattices. The backand-forth argument in model theory helps to enlighten the constructions.

  6. Changing Family Practices with Assistive Technology

    DEFF Research Database (Denmark)

    Sonne, Tobias; Müller, Jörg; Marshall, Paul

    2016-01-01

    Families of children with Attention Deficit Hyperactivity Disorder (ADHD) often report morning and bedtime routines to be stressful and frustrating. Through a design process involving domain professionals and families we designed MOBERO, a smartphone-based system that assists families in establis...

  7. The Rafita asteroid family

    Science.gov (United States)

    Aljbaae, S.; Carruba, V.; Masiero, J. R.; Domingos, R. C.; Huaman, M.

    2017-01-01

    The Rafita asteroid family is an S-type group located in the middle main belt, on the right side of the 3J:-1A mean-motion resonance. The proximity of this resonance to the family left side in semi-major axis caused many former family members to be lost. As a consequence, the family shape in the (a, 1/D) domain is quite asymmetrical, with a preponderance of objects on the right side of the distribution. The Rafita family is also characterized by a leptokurtic distribution in inclination, which allows the use of methods of family age estimation recently introduced for other leptokurtic families such as Astrid, Hansa, Gallia, and Barcelona. In this work we propose a new method based on the behavior of an asymmetry coefficient function of the distribution in the (a, 1/D) plane to date incomplete asteroid families such as Rafita. By monitoring the time behavior of this coefficient for asteroids simulating the initial conditions at the time of the family formation, we were able to estimate that the Rafita family should have an age of 490 ± 200 Myr, in good agreement with results from independent methods such as Monte Carlo simulations of Yarkovsky and Yorp dynamical induced evolution and the time behaviour of the kurtosis of the sin (i) distribution. Asteroids from the Rafita family can reach orbits similar to 8% of the currently known near Earth objects. ≃1% of the simulated objects are present in NEO-space during the final 10 Myr of the simulation, and thus would be comparable to objects in the present-day NEO population.

  8. Safe domain and elementary geometry

    CERN Document Server

    Richard, J M

    2004-01-01

    A classical problem of mechanics involves a projectile fired from a given point with a given velocity whose direction is varied. This results in a family of trajectories whose envelope defines the border of a 'safe' domain. In the simple cases of a constant force, harmonic potential and Kepler or Coulomb motion, the trajectories are conic curves whose envelope in a plane is another conic section which can be derived either by simple calculus or by geometrical considerations. The case of harmonic forces reveals a subtle property of the maximal sum of distances within an ellipse.

  9. Domains of laminin

    DEFF Research Database (Denmark)

    Engvall, E; Wewer, U M

    1996-01-01

    Extracellular matrix molecules are often very large and made up of several independent domains, frequently with autonomous activities. Laminin is no exception. A number of globular and rod-like domains can be identified in laminin and its isoforms by sequence analysis as well as by electron...... microscopy. Here we present the structure-function relations in laminins by examination of their individual domains. This approach to viewing laminin is based on recent results from several laboratories. First, some mutations in laminin genes that cause disease have affected single laminin domains, and some...... laminin isoforms lack particular domains. These mutants and isoforms are informative with regard to the activities of the mutated and missing domains. These mutants and isoforms are informative with regard to the activities of the mutated and missing domains. Second, laminin-like domains have now been...

  10. Family Privilege

    Science.gov (United States)

    Seita, John R.

    2014-01-01

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

  11. Family Privilege

    Science.gov (United States)

    Seita, John R.

    2014-01-01

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

  12. Bioinformatics of the TULIP domain superfamily.

    Science.gov (United States)

    Kopec, Klaus O; Alva, Vikram; Lupas, Andrei N

    2011-08-01

    Proteins of the BPI (bactericidal/permeability-increasing protein)-like family contain either one or two tandem copies of a fold that usually provides a tubular cavity for the binding of lipids. Bioinformatic analyses show that, in addition to its known members, which include BPI, LBP [LPS (lipopolysaccharide)-binding protein)], CETP (cholesteryl ester-transfer protein), PLTP (phospholipid-transfer protein) and PLUNC (palate, lung and nasal epithelium clone) protein, this family also includes other, more divergent groups containing hypothetical proteins from fungi, nematodes and deep-branching unicellular eukaryotes. More distantly, BPI-like proteins are related to a family of arthropod proteins that includes hormone-binding proteins (Takeout-like; previously described to adopt a BPI-like fold), allergens and several groups of uncharacterized proteins. At even greater evolutionary distance, BPI-like proteins are homologous with the SMP (synaptotagmin-like, mitochondrial and lipid-binding protein) domains, which are found in proteins associated with eukaryotic membrane processes. In particular, SMP domain-containing proteins of yeast form the ERMES [ER (endoplasmic reticulum)-mitochondria encounter structure], required for efficient phospholipid exchange between these organelles. This suggests that SMP domains themselves bind lipids and mediate their exchange between heterologous membranes. The most distant group of homologues we detected consists of uncharacterized animal proteins annotated as TM (transmembrane) 24. We propose to group these families together into one superfamily that we term as the TULIP (tubular lipid-binding) domain superfamily.

  13. 14-3-3 Proteins, FHA Domains and BRCT Domains in the DNA Damage Response

    OpenAIRE

    Mohammad, Duaa H.; Yaffe, Michael B.

    2009-01-01

    The DNA damage response depends on the concerted activity of protein serine/threonine kinases and modular phosphoserine/threonine binding domains to relay the damage signal and recruit repair proteins. The PIKK family of protein kinases, which includes ATM/ATR/DNA-PK, preferentially phosphorylate Ser-Gln sites, while their basophilic downstream effecter kinases, Chk1/Chk2/MK2 preferentially phosphorylate hydrophobic-X-Arg-X-X-Ser/Thr-hydrophobic sites. A subset of tandem BRCT domains act as p...

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

    Science.gov (United States)

    Ho, Joyce; Birman, Dina

    2009-01-01

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

  15. Effective formulas for invariant functions -- case of elementary Reinhardt domains

    OpenAIRE

    Pflug, Peter; Zwonek, Wlodzimierz

    1996-01-01

    In the paper we find effective formulas for the invariant functions, appearing in the theory of several complex variables, of the elementary Reinhardt domains. This gives us the first example of a large family of domains for which the functions are calculated explicitly.

  16. Familial gigantism

    NARCIS (Netherlands)

    W.W. de Herder (Wouter)

    2012-01-01

    textabstractFamilial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  17. Familial gigantism

    Directory of Open Access Journals (Sweden)

    Wouter W. de Herder

    2012-01-01

    Full Text Available Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  18. Familial dermographism.

    Science.gov (United States)

    Jedele, K B; Michels, V V

    1991-05-01

    Urticaria in response to various physical stimuli has been reported in sporadic and familial patterns. The most common of these physical urticarias, dermographism, is a localized urticarial response to stroking or scratching of the skin and has not been reported previously to be familial. A four-generation family with dermographism, probably inherited as an autosomal dominant trait, is presented along with a discussion of sporadic dermographism and other types of familial physical urticarias.

  19. Simple connectivity of the D-stability Domain and D-stability of polynomial families%D-稳定性区域的单连通性与多项式族的D-稳定性

    Institute of Scientific and Technical Information of China (English)

    段广仁

    2001-01-01

    It is proved that all monic polynomials of order n with roots lying in some open region on the complex plane forms a simply connected set in the polynomial parameter space. Based on this result, Edge Theorems for D-stability of general polyhedrons of polynomials and Boundary Theorems for D-stability of compact sets of polynomials are obtained. Both cases of families of polynomials with dependent and independent coefficients are considered. Different from the previous ones, our Edge Theorems and Boundary Theorems do not require the convexity orthe connectivity of the set of polynomials. Moreover, our Boundary Theorem for families of polynomials with dependent coefficients does not require the coefficient dependency relation to be affine%证明了其根位于复平面中某开域的所有n阶多项式的全体构成多项式参数空间中的一个单连通集,并基于这一结果进一步提出了关于一般多面体多项式族D-稳定性的棱边定理和关于一般多项式紧集D-稳定性的边界定理.所得结果包含了多项式参数无关和相关两种情形.不同于已有结果,作者提出的棱边定理和边界定理不要求多项式集的凸性与单连通性.另外,关于相关参数的多项式集的边界定理还突破了现有结果中关于参数相关关系为仿射映射的限制.

  20. Translation domains in multiferroics

    OpenAIRE

    Meier, D; Leo, N; Jungk, T.; Soergel, E.; Becker, P.; Bohaty, L.; Fiebig, M.

    2010-01-01

    Translation domains differing in the phase but not in the orientation of the corresponding order parameter are resolved in two types of multiferroics. Hexagonal (h-) YMnO$_3$ is a split-order-parameter multiferroic in which commensurate ferroelectric translation domains are resolved by piezoresponse force microscopy whereas MnWO$_4$ is a joint-order-parameter multiferroic in which incommensurate magnetic translation domains are observed by optical second harmonic generation. The pronounced ma...

  1. Frustratingly Easy Domain Adaptation

    CERN Document Server

    Daumé, Hal

    2009-01-01

    We describe an approach to domain adaptation that is appropriate exactly in the case when one has enough ``target'' data to do slightly better than just using only ``source'' data. Our approach is incredibly simple, easy to implement as a preprocessing step (10 lines of Perl!) and outperforms state-of-the-art approaches on a range of datasets. Moreover, it is trivially extended to a multi-domain adaptation problem, where one has data from a variety of different domains.

  2. Staggered domain wall fermions

    CERN Document Server

    Hoelbling, Christian

    2016-01-01

    We construct domain wall fermions with a staggered kernel and investigate their spectral and chiral properties numerically in the Schwinger model. In some relevant cases we see an improvement of chirality by more than an order of magnitude as compared to usual domain wall fermions. Moreover, we present first results for four-dimensional quantum chromodynamics, where we also observe significant reductions of chiral symmetry violations for staggered domain wall fermions.

  3. CDD/SPARCLE: functional classification of proteins via subfamily domain architectures

    Science.gov (United States)

    Marchler-Bauer, Aron; Bo, Yu; Han, Lianyi; He, Jane; Lanczycki, Christopher J.; Lu, Shennan; Chitsaz, Farideh; Derbyshire, Myra K.; Geer, Renata C.; Gonzales, Noreen R.; Gwadz, Marc; Hurwitz, David I.; Lu, Fu; Marchler, Gabriele H.; Song, James S.; Thanki, Narmada; Wang, Zhouxi; Yamashita, Roxanne A.; Zhang, Dachuan; Zheng, Chanjuan; Geer, Lewis Y.; Bryant, Stephen H.

    2017-01-01

    NCBI's Conserved Domain Database (CDD) aims at annotating biomolecular sequences with the location of evolutionarily conserved protein domain footprints, and functional sites inferred from such footprints. An archive of pre-computed domain annotation is maintained for proteins tracked by NCBI's Entrez database, and live search services are offered as well. CDD curation staff supplements a comprehensive collection of protein domain and protein family models, which have been imported from external providers, with representations of selected domain families that are curated in-house and organized into hierarchical classifications of functionally distinct families and sub-families. CDD also supports comparative analyses of protein families via conserved domain architectures, and a recent curation effort focuses on providing functional characterizations of distinct subfamily architectures using SPARCLE: Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. PMID:27899674

  4. Structural and histone binding ability characterizations of human PWWP domains.

    Directory of Open Access Journals (Sweden)

    Hong Wu

    Full Text Available BACKGROUND: The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. METHODOLOGY/PRINCIPAL FINDINGS: The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. CONCLUSIONS: PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical β-barrel core, an insertion motif between the second and third β-strands and a C-terminal α-helix bundle. Both the canonical β-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web

  5. Pragmatic circuits frequency domain

    CERN Document Server

    Eccles, William

    2006-01-01

    Pragmatic Circuits: Frequency Domain goes through the Laplace transform to get from the time domain to topics that include the s-plane, Bode diagrams, and the sinusoidal steady state. This second of three volumes ends with a-c power, which, although it is just a special case of the sinusoidal steady state, is an important topic with unique techniques and terminology. Pragmatic Circuits: Frequency Domain is focused on the frequency domain. In other words, time will no longer be the independent variable in our analysis. The two other volumes in the Pragmatic Circuits series include titles on DC

  6. The Impact of Emotional Labor on Work-Family Outcomes

    Science.gov (United States)

    Yanchus, Nancy J.; Eby, Lilian T.; Lance, Charles E.; Drollinger, Sabrina

    2010-01-01

    Theory and research on emotional labor at work is applied to the study of the work-family interface to explore how emotional experiences in both the work and the family domain relate to the experience of work-family conflict and work-family enrichment, and ultimately attitudinal and health outcomes. Emotional intelligence is also examined as a…

  7. Visualizing domain wall and reverse domain superconductivity.

    Science.gov (United States)

    Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D

    2014-08-28

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.

  8. The chicken SLAM family.

    Science.gov (United States)

    Straub, Christian; Viertlboeck, Birgit C; Göbel, Thomas W

    2013-01-01

    The signaling lymphocytic activation molecule (SLAM) family of receptors is critically involved in the immune regulation of lymphocytes but has only been detected in mammals, with one member being present in Xenopus. Here, we describe the identification, cloning, and analysis of the chicken homologues to the mammalian SLAMF1 (CD150), SLAMF2 (CD48), and SLAMF4 (CD244, 2B4). Two additional chicken SLAM genes were identified and designated SLAMF3like and SLAM5like in order to stress that those two receptors have no clear mammalian counterpart but share some features with mammalian SLAMF3 and SLAMF5, respectively. Three of the chicken SLAM genes are located on chromosome 25, whereas two are currently not yet assigned. The mammalian and chicken receptors share a common structure with a V-like domain that lacks conserved cysteine residues and a C2-type Ig domain with four cysteines forming two disulfide bonds. Chicken SLAMF2, like its mammalian counterpart, lacks a transmembrane and cytoplasmic domain and thus represents a glycosyl-phosphatidyl-inositol-anchored protein. The cytoplasmic tails of SLAMF1 and SLAMF4 display two and four conserved immunoreceptor tyrosine-based switch motifs (ITSMs), respectively, whereas both chicken SLAMF3like and SLAMF5like have only a single ITSM. We have also identified the chicken homologues of the SLAM-associated protein family of adaptors (SAP), SAP and EAT-2. Chicken SAP shares about 70 % identity with mammalian SAP, and chicken EAT-2 is homologous to mouse EAT-2, whereas human EAT-2 is much shorter. The characterization of the chicken SLAM family of receptors and the SAP adaptors demonstrates the phylogenetic conservation of this family, in particular, its signaling capacities.

  9. Genome-Wide Analysis of PDZ Domain Binding Reveals Inherent Functional Overlap within the PDZ Interaction Network

    NARCIS (Netherlands)

    Te Veldhuis, A.J.W.; Sakalis, P.A.; Fowler, D.A.; Bagowski, C.P.

    2011-01-01

    Binding selectivity and cross-reactivity within one of the largest and most abundant interaction domain families, the PDZ family, has long been enigmatic. The complete human PDZ domain complement (the PDZome) consists of 267 domains and we applied here a Bayesian selectivity model to predict hundred

  10. The enterprise engineering domain

    CSIR Research Space (South Africa)

    De Vries, M

    2015-06-01

    Full Text Available representation of the EE domain within the emerging EE discipline. We used a questionnaire to gather the views of EE and enterprise architecture (EA) researchers and practitioners on the EE domain. The main contributions of this article include: (1...

  11. Domain wall filters

    CERN Document Server

    Bär, O; Neuberger, H; Witzel, O; Baer, Oliver; Narayanan, Rajamani; Neuberger, Herbert; Witzel, Oliver

    2007-01-01

    We propose using the extra dimension separating the domain walls carrying lattice quarks of opposite handedness to gradually filter out the ultraviolet fluctuations of the gauge fields that are felt by the fermionic excitations living in the bulk. This generalization of the homogeneous domain wall construction has some theoretical features that seem nontrivial.

  12. Domain Walls on Singularities

    CERN Document Server

    Halyo, Edi

    2009-01-01

    We describe domain walls that live on $A_2$ and $A_3$ singularities. The walls are BPS if the singularity is resolved and non--BPS if it is deformed and fibered. We show that these domain walls may interpolate between vacua that support monopoles and/or vortices.

  13. Domains of Learning.

    Science.gov (United States)

    Gagne, Robert M.

    In planning educational research, recognition needs to be made of five domains of learning: (1) motor skills, (2) verbal information, (3) intellectual skills, (4) cognitive strategies, and (5) attitudes. In being cognizant of these domains, the researcher is able to distinguish the parts of a content area which are subject to different…

  14. A Domain Analysis Bibliography

    Science.gov (United States)

    1990-06-01

    Bauhaus , a prototype CASE workstation for D-SAPS development. [ARAN88A] Guillermo F. Arango. Domain Engineering for Software Reuse. PhD thesis...34 VITA90B: Domain Analysis within the ISEC Rapid Center 48 CMU/SEI-90-SR-3 Appendix III Alphabetical by Organization/Project BAUHAUS * ALLE87A

  15. The Roco protein family : a functional perspective

    NARCIS (Netherlands)

    Marin, Ignacio; van Egmond, Wouter N.; van Haastert, Peter J. M.

    2008-01-01

    In this review, we discuss the evolutionary, biochemical, and functional data available for members of the Roco protein family. They are characterized by having a conserved supradomain that contains a Ras-like GTPase domain, called Roc, and a characteristic COR (C-terminal of Roc) domain. A kinase d

  16. Domain relationships in thiamine diphosphate-dependent enzymes.

    Science.gov (United States)

    Duggleby, Ronald G

    2006-08-01

    Three-dimensional structures have been determined for 13 different enzymes that use thiamine diphosphate (ThDP) as a cofactor. These enzymes fall into five families, where members within a family have similar structures. In different families, there are similarities between some domains that clearly point to a common ancestor for all of these enzymes. Where the enzyme structures differ, evolutionary relationships between families can be discerned. Here, I present an analysis of these families and propose an evolutionary pathway to explain the diversity of structures that are now known.

  17. Normal Families and Shared Functions

    Institute of Scientific and Technical Information of China (English)

    WANG Xue-qin; LEI Chun-lin

    2015-01-01

    Let k be a positive integer, let h be a holomorphic function in a domain D, h 6≡0 and let F be a family of nonvanishing meromorphic functions in D. If each pair of functions f and g in F , f (k) and g(k) share h in D, then F is normal in D.

  18. WOMEN IN FAMILY BUSINESS

    Directory of Open Access Journals (Sweden)

    Mr Anshu

    2012-04-01

    Full Text Available The role of women in family businesses is explored in the paper. Although recognized as generally very important players, the role of women is often defined as invisible in business decision-making, supportive in men’s traditional business domains and only rarelyadequately recognized and rewarded. The paper explores possible differences in the views of men and women who manage small family firms. Their attitudes opposing the traditional business roles ofwomen, different views on managerial, ownership and transition issues and possible gender discrimination are examined. The findings support the paradigm of a different, more feminine style of management, while signs of discrimination are not clearly revealed. This paper is based on a research intended to provide acomparative analysis of the status of women entrepreneurs and men entrepreneurs in Family Business in India. It first draws demographic & psychographic profiles of women and men entrepreneurs in family business, identifies & addresses operational problems faced by women and men entrepreneurs in family business, draws theirinclination for future plans for growth and expansion and also for the furtherance of research on women entrepreneurs in India.

  19. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  20. My Family

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Everyone has a family.We live in it and feel very warm.There are three persons in my family,my mother,father and I.We live together very happily and there are many interesting stories about my family. My father is a hard-working man.He works as a doctor.He always tries his best to help every,patient and make patients comfortable.But sonetimes he works so hard

  1. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  2. Family literacy

    DEFF Research Database (Denmark)

    Sehested, Caroline

    2012-01-01

    I Projekt familielæsning, der er et samarbejde mellem Nationalt Videncenter for Læsning og Hillerød Bibliotek, arbejder vi med at få kontakt til de familier, som biblioteket ellers aldrig ser som brugere og dermed også de børn, der vokser op i familier, for hvem bøger og oplæsningssituationer ikke...... er en selvfølgelig del af barndommen. Det, vi vil undersøge og ønsker at være med til at udvikle hos disse familier, er det, man kan kalde family literacy....

  3. Pleckstrin homology domains and the cytoskeleton.

    Science.gov (United States)

    Lemmon, Mark A; Ferguson, Kathryn M; Abrams, Charles S

    2002-02-20

    Pleckstrin homology (PH) domains are 100-120 amino acid protein modules best known for their ability to bind phosphoinositides. All possess an identical core beta-sandwich fold and display marked electrostatic sidedness. The binding site for phosphoinositides lies in the center of the positively charged face. In some cases this binding site is well defined, allowing highly specific and strong ligand binding. In several of these cases the PH domains specifically recognize 3-phosphorylated phosphoinositides, allowing them to drive membrane recruitment in response to phosphatidylinositol 3-kinase activation. Examples of these PH domain-containing proteins include certain Dbl family guanine nucleotide exchange factors, protein kinase B, PhdA, and pleckstrin-2. PH domain-mediated membrane recruitment of these proteins contributes to regulated actin assembly and cell polarization. Many other PH domain-containing cytoskeletal proteins, such as spectrin, have PH domains that bind weakly, and to all phosphoinositides. In these cases, the individual phosphoinositide interactions may not be sufficient for membrane association, but appear to require self-assembly of their host protein and/or cooperation with other anchoring motifs within the same molecule to drive membrane attachment.

  4. The different roles of aggrecan interaction domains

    DEFF Research Database (Denmark)

    Aspberg, Anders

    2012-01-01

    is vital in that it binds the proteoglycan to hyaluronan in ternary complex with link protein, retaining the proteoglycan in the tissue. The importance of the C-terminal G3 domain interactions has recently been emphasized by two different human hereditary disorders: autosomal recessive aggrecan......The aggregating proteoglycans of the lectican family are important components of extracellular matrices. Aggrecan is the most well studied of these and is central to cartilage biomechanical properties and skeletal development. Key to its biological function is the fixed charge of the many......-type spondyloepimetaphyseal dysplasia and autosomal dominant familial osteochondritis dissecans. In these two conditions, different missense mutations in the aggrecan C-type lectin repeat have been described. The resulting amino acid replacements affect the ligand interactions of the G3 domain, albeit with widely different...

  5. Chronic illness and family: impact of schizophrenia and Crohn's disease on the family quality of life.

    Science.gov (United States)

    Loga, Slobodan; Sošić, Bojan; Kulenović, Alma Džubur; Svraka, Emira; Bosankić, Nina; Kučukalić, Abdulah; Cemalović, Omer; Hadžić, Alma

    2012-12-01

    Quality of life assessments are increasingly present in health research. Chronic and progressive illness of a family member unavoidably affects quality of life of a family as a whole. The goals of this study were to gain insight into the family burden of chronic disorders, especially possible differences in family quality of life (FQOL) in families that have members suffering from either schizophrenia or Crohn's disease, and families in which none of the members have chronic somatic or mental illness, as well as to pilot an instrument for this purpose. The sample consisted of 53 families with a member suffering from schizophrenia, 50 families with a member suffering from Crohn's disease, and 45 families with no identifiable chronic illnesses. An informant from each family underwent a structured face to face interview, using a questionnaire specially adapted from Family Quality of Life Survey, an instrument widely used to assess FQOL in families with members with disabilities, and which addresses nine areas of family life. In the domain of health, both groups of families with chronic illnesses believe they have significantly different conditions when compared to members of the Control group. In the Crohn's disease group, families had a great deal more of challenges in accessing healthcare services; and see themselves at a disadvantage when compared to both other groups in the domain of finances. Control group offered lowest rating in the domain of support from others. Overall measures of FQOL show significant variation among the three groups, Crohn's disease group offering lowest ratings, followed by families of mental health service users. Overall, FQOL seems to be lower in families that have members diagnosed with Crohn's disease than in families with members suffering from schizophrenia. Illness-specific studies are required, as well as instruments with stronger psychometric properties and studies of determinants of FQOL. Qualitative approach should be emphasised

  6. Unsharp Values, Domains and Topoi

    CERN Document Server

    Doering, Andreas

    2011-01-01

    The so-called topos approach provides a radical reformulation of quantum theory. Structurally, quantum theory in the topos formulation is very similar to classical physics. There is a state object, analogous to the state space of a classical system, and a quantity-value object, generalising the real numbers. Physical quantities are maps from the state object to the quantity-value object -- hence the `values' of physical quantities are not just real numbers in this formalism. Rather, they are families of real intervals, interpreted as `unsharp values'. We will motivate and explain these aspects of the topos approach and show that the structure of the quantity-value object can be analysed using tools from domain theory, a branch of order theory that originated in theoretical computer science. Moreover, the base category of the topos associated with a quantum system turns out to be a domain if the underlying von Neumann algebra is a matrix algebra. For general algebras, the base category still is a highly struct...

  7. Small Families

    Science.gov (United States)

    ... easier for both parents to combine careers with family life. The general stress level is lower because there often are fewer ... can help replace the missing ties. For many families, religious congregational ... such as youth and neighborhood activity centers also can fulfill these ...

  8. FAMILY PLATYSTOMATIDAE.

    Science.gov (United States)

    Wendt, Lisiane Dilli

    2016-06-14

    Platystomatidae (Signal Flies) are one of the largest families of Tephritoidea, with about 1200 species and four subfamilies, worldwide distributed. However, Platystomatidae are not well represented in the New World, and in the Neotropical Region only four genera and 26 species, belonging to Platystomatinae, are recorded. The family is a group understudied in Colombia and only one species is recorded to the country.

  9. Beyond Conflict: Functional Facets of the Work-Family Interplay

    Science.gov (United States)

    Wiese, Bettina S.; Seiger, Christine P.; Schmid, Christian M.; Freund, Alexandra M.

    2010-01-01

    The present paper deals with three positive facets of the work-family interplay, i.e., transfer of competencies, transfer of positive mood, and cross-domain compensation. The latter refers to the experience that engagement in one domain helps dealing with failures in the other domain. In two correlational studies (N[subscript 1] = 107 working…

  10. Domain-Specific Multimodeling

    DEFF Research Database (Denmark)

    Hessellund, Anders

    Enterprise systems are complex artifacts. They are hard to build, manage, understand, and evolve. Existing software development paradigms fail to properly address challenges such as system size, domain complexity, and software evolution when development is scaled to enterprise systems. We propose...... domain-specific multimodeling as a development paradigm to tackle these challenges in a language-oriented manner. The different concerns of a system are conceptually separated and made explicit as independent domain-specific languages. This approach increases productivity and quality by raising...... the overall level of abstraction. It does, however, also introduce a new problem of coordinating multiple different languages in a single system. We call this problem the coordination problem. In this thesis, we present the coordination method for domain-specific multimodeling that explicitly targets...

  11. Conserved Domain Database (CDD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — CDD is a protein annotation resource that consists of a collection of well-annotated multiple sequence alignment models for ancient domains and full-length proteins.

  12. The laminin family.

    Science.gov (United States)

    Aumailley, Monique

    2013-01-01

    Laminins are large molecular weight glycoproteins constituted by the assembly of three disulfide-linked polypeptides, the α, β and γ chains. The human genome encodes 11 genetically distinct laminin chains. Structurally, laminin chains differ by the number, size and organization of a few constitutive domains, endowing the various members of the laminin family with common and unique important functions. In particular, laminins are indispensable building blocks for cellular networks physically bridging the intracellular and extracellular compartments and relaying signals critical for cellular behavior, and for extracellular polymers determining the architecture and the physiology of basement membranes.

  13. Work-family enrichment among dual-earner couples: can work improve our family life?

    Science.gov (United States)

    Dunn, Marianne G; O'Brien, Karen M

    2013-10-01

    The extent to which resources generated at work and positive affect were associated with enrichment in the family domain among 107 dual-earner couples was investigated. Grounded in work-family enrichment theory (Greenhaus & Powell, 2006), this study examined the indirect effect of workplace organizational support on family satisfaction through positive affect at work. Organizational support for work-family management was associated with positive affect at work for both women and men, and positive affect at work was related to family satisfaction for women. One interpersonal effect emerged: women's positive affect at work was associated with family satisfaction for men. Implications for theory, practice, research, and workplace policy are discussed.

  14. Strongly Semicontinuous Domains and Semi-FS Domains

    Directory of Open Access Journals (Sweden)

    Qingyu He

    2014-01-01

    Full Text Available We are mainly concerned with some special kinds of semicontinuous domains and relationships between them. New concepts of strongly semicontinuous domains, meet semicontinuous domains and semi-FS domains are introduced. It is shown that a dcpo L is strongly semicontinuous if and only if L is semicontinuous and meet semicontinuous. It is proved that semi-FS domains are strongly semicontinuous. Some interpolation properties of semiway-below relations in (strongly semicontinuous bc-domains are given. In terms of these properties, it is proved that strongly semicontinuous bc-domains, in particular strongly semicontinuous lattices, are all semi-FS domains.

  15. Domains in Ferroelectric Nanostructures

    Science.gov (United States)

    Gregg, Marty

    2010-03-01

    Ferroelectric materials have great potential in influencing the future of small scale electronics. At a basic level, this is because ferroelectric surfaces are charged, and so interact strongly with charge-carrying metals and semiconductors - the building blocks for all electronic systems. Since the electrical polarity of the ferroelectric can be reversed, surfaces can both attract and repel charges in nearby materials, and can thereby exert complete control over both charge distribution and movement. It should be no surprise, therefore, that microelectronics industries have already looked very seriously at harnessing ferroelectric materials in a variety of applications, from solid state memory chips (FeRAMs) to field effect transistors (FeFETs). In all such applications, switching the direction of the polarity of the ferroelectric is a key aspect of functional behavior. The mechanism for switching involves the field-induced nucleation and growth of domains. Domain coarsening, through domain wall propagation, eventually causes the entire ferroelectric to switch its polar direction. It is thus the existence and behavior of domains that determine the switching response, and ultimately the performance of the ferroelectric device. A major issue, associated with the integration of ferroelectrics into microelectronic devices, has been that the fundamental properties associated with ferroelectrics, when in bulk form, appear to change quite dramatically and unpredictably when at the nanoscale: new modes of behaviour, and different functional characteristics from those seen in bulk appear. For domains, in particular, the proximity of surfaces and boundaries have a dramatic effect: surface tension and depolarizing fields both serve to increase the equilibrium density of domains, such that minor changes in scale or morphology can have major ramifications for domain redistribution. Given the importance of domains in dictating the overall switching characteristics of a device

  16. Four Essays on Family Life Events

    DEFF Research Database (Denmark)

    Loft, Lisbeth Trille Gylling

    . In addition, the present thesis underlines the need for an improved understanding of the role of health and caregiving as fundamental aspects of family life, and in doing so allocates increased attention to how children’s characteristics are central to family-level outcomes. Just as the lives of family...... and institutional settings, and c) the significance of the interconnectedness of family life events across life domains and over time. Taken together the analyses included in the present thesis combine the need to understand conditions and consequences of contemporary family life with a renewed attention...... to the social mechanisms associated with social differentiation. One contribution of the present thesis is that it highlights the need for family research in general, and Danish family studies in particular, to pay greater theoretical and methodological attention to the dynamic nature of family life events...

  17. Factors associated with family-centered involvement in family practice--a cross-sectional multivariate analysis.

    Science.gov (United States)

    Deutsch, Tobias; Frese, Thomas; Sandholzer, Hagen

    2014-01-01

    The importance of a family-centered approach in family practice has been emphasized. Knowledge about factors associated with higher family-centered involvement seems beneficial to stimulate its realization. German office-based family physicians completed a questionnaire addressing several aspects of family-centered care. Logistic regression was used to identify associations with the involvement overall and in different domains: routine inquiry and documentation of family-related information, family orientation regarding diagnosis and treatment, family-oriented dialogues, family conferences, and case-related collaboration with marriage and family therapists. We found significant associations between physicians' family-centered involvement and expected patient receptiveness, perceived impact of the family's influence on health, self-perceived psychosocial family-care competences (overall and concerning concepts for family orientation, psychosocial intervention in family conferences, and the communication of the idea of family counseling), advanced training in psychosocial primary care (PPC), personal acquaintance with family therapists (regarding case-related collaboration), and rural office environment. Increased emphasis on the family's influence on health in medical education and training, the provision of concepts for a family-centered perspective, and versatile skills for psychosocial intervention and inquiry of patient preferences, as well as the strengthening of networking between family physicians and family therapists, might promote the family-centered approach in family practice.

  18. Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, James M.; Korzhnev, Dmitry M.; Ceccarelli, Derek F.; Briant, Douglas J.; Zarrine-Afsar, Arash; Sicheri, Frank; Kay, Lewis E.; Pawson, Tony (Mount Sinai Hospital); (Toronto)

    2012-10-23

    The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studies of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.

  19. Family Disruptions

    Science.gov (United States)

    ... stay angry, or avoid fights altogether? Your children model themselves on you. Departures and Returns Do you or your spouse frequently travel on business? These can be disruptive times for your child and for the family ...

  20. Familial hypercholesterolemia

    Science.gov (United States)

    ... hypercholesterolemia or early heart attacks High level of LDL cholesterol in either or both parents People from families ... called fibroblasts to see how the body absorbs LDL cholesterol Genetic test for the defect associated with this ...

  1. Family matters

    DEFF Research Database (Denmark)

    Kieffer-Kristensen, Rikke; Siersma, Volkert Dirk; Teasdale, Thomas William

    2013-01-01

    OBJECTIVES: To relate illness and family factors to emotional and behavioural problems in school-age children (7–14 years old) of parents with acquired brain injury and their healthy spouses. PARTICIPANTS, MATERIALS/METHODS: Members of 35 families in which a parent had been diagnosed with acquired...... brain injury participated. Family and brain injury characteristics were reported by the ill and healthy parents. Children self-reported post-traumatic stress symptoms (PSS) using the Child Impact of Events revised (CRIES). Emotional and behavioural problems among the children were also identified...... by the parents using the Achenbach’s Child Behaviour Checklist (CBCL). RESULTS: The family stress variables relating to the healthy spouse in all six comparisons were significant (p

  2. Just how versatile are domains?

    Directory of Open Access Journals (Sweden)

    Bornberg-Bauer Erich

    2008-10-01

    Full Text Available Abstract Background Creating new protein domain arrangements is a frequent mechanism of evolutionary innovation. While some domains always form the same combinations, others form many different arrangements. This ability, which is often referred to as versatility or promiscuity of domains, its a random evolutionary model in which a domain's promiscuity is based on its relative frequency of domains. Results We show that there is a clear relationship across genomes between the promiscuity of a given domain and its frequency. However, the strength of this relationship differs for different domains. We thus redefine domain promiscuity by defining a new index, DV I ("domain versatility index", which eliminates the effect of domain frequency. We explore links between a domain's versatility, when unlinked from abundance, and its biological properties. Conclusion Our results indicate that domains occurring as single domain proteins and domains appearing frequently at protein termini have a higher DV I. This is consistent with previous observations that the evolution of domain re-arrangements is primarily driven by fusion of pre-existing arrangements and single domains as well as loss of domains at protein termini. Furthermore, we studied the link between domain age, defined as the first appearance of a domain in the species tree, and the DV I. Contrary to previous studies based on domain promiscuity, it seems as if the DV I is age independent. Finally, we find that contrary to previously reported findings, versatility is lower in Eukaryotes. In summary, our measure of domain versatility indicates that a random attachment process is sufficient to explain the observed distribution of domain arrangements and that several views on domain promiscuity need to be revised.

  3. Beyond the trailing spouse: The commuter partnership as an alternative to family migration

    NARCIS (Netherlands)

    van der Klis, M.; Mulder, C.H.

    2008-01-01

    Combining commitments in the domains of work, family, and residence has become a complex puzzle for the contemporary (dual-earner) family, especially when these choices concern family migration. For some families, non-standard alternatives to family migration, such as a commuter partnership in which

  4. Axion domain wall baryogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Daido, Ryuji; Kitajima, Naoya [Department of Physics, Tohoku University,Sendai 980-8578 (Japan); Takahashi, Fuminobu [Department of Physics, Tohoku University,Sendai 980-8578 (Japan); Kavli IPMU, TODIAS, University of Tokyo,Kashiwa 277-8583 (Japan)

    2015-07-28

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m≃10{sup 8}–10{sup 13} GeV and f≃10{sup 13}–10{sup 16} GeV. Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  5. Families in the Military

    Science.gov (United States)

    ... Contents Facts For Families Guide - View by Topic Chinese Facts for Families Guide Facts For Families Guide - Search Spanish Facts for Families Guide Facts for Families - Vietnamese Military Families No. 88; updated March 2017 Global conflict ...

  6. Limiting behavior of non-autonomous stochastic reaction-diffusion equations on thin domains

    Science.gov (United States)

    Li, Dingshi; Wang, Bixiang; Wang, Xiaohu

    2017-02-01

    This paper deals with the limiting behavior of stochastic reaction-diffusion equations driven by multiplicative noise and deterministic non-autonomous terms defined on thin domains. We first prove the existence, uniqueness and periodicity of pullback tempered random attractors for the equations in an (n + 1)-dimensional narrow domain, and then establish the upper semicontinuity of these attractors when a family of (n + 1)-dimensional thin domains collapses onto an n-dimensional domain.

  7. Development and Validation of the Family Influence Scale

    Science.gov (United States)

    Fouad, Nadya A.; Cotter, Elizabeth W.; Fitzpatrick, Mary E.; Kantamneni, Neeta; Carter, Laura; Bernfeld, Steve

    2010-01-01

    This article describes the development and validation of the Family Influence Scale (FIS). The FIS is designed to assess perceptions of how one's family of origin influences career and work choices. The purpose of Study 1 was to identify the domains of family influence. A 57-item scale was completed by a sample of 205 college students. Results…

  8. The antecedents and outcomes of work-family enrichment amongst female workers

    OpenAIRE

    Esandre Marais; Marissa de Klerk; Jan Alewyn Nel; Leon de Beer

    2014-01-01

    Orientation: Women are involved in both a work and a family domain. Work-family enrichment is a concept that describes how these domains can enrich each other through the transfer of resources from one domain to the other.Research purpose: The objective was to determine the relationship between work resources,home resources, work engagement, family engagement and work-family enrichment. The aim was also to test two models representing work-to-family and family-to-work enrichment as mediators....

  9. Family eating habits, family support and subjective well-being in university students in Chile

    DEFF Research Database (Denmark)

    Schnettler, Berta; Höger, Yesly; Orellana, Ligia

    2016-01-01

    included: the Family Eating Habits Questionnaire (FEHQ), the Satisfaction with Life Scale (SWLS), the Satisfaction with Food-related Life Scale (SWFL) and the Family Resources Scale (FRS). Estimated weight and height were asked about as well as sociodemographic variables. Results: Using an exploratory...... as with the overall satisfaction with life and in the food domain....

  10. Documenting Different Domains of Promotion of Autonomy in Families

    Science.gov (United States)

    Manzi, Claudia; Regalia, Camillo; Pelucchi, Sara; Fincham, Frank D.

    2012-01-01

    Parental promotion of autonomy for offspring well-being has been widely recognized in developmental psychology. Recent studies, however, show that this association varies across cultures. Such variation may reflect inappropriate measurement of this dimension of parenting. Therefore, three existing measures of promotion of autonomy were used to…

  11. Documenting Different Domains of Promotion of Autonomy in Families

    Science.gov (United States)

    Manzi, Claudia; Regalia, Camillo; Pelucchi, Sara; Fincham, Frank D.

    2012-01-01

    Parental promotion of autonomy for offspring well-being has been widely recognized in developmental psychology. Recent studies, however, show that this association varies across cultures. Such variation may reflect inappropriate measurement of this dimension of parenting. Therefore, three existing measures of promotion of autonomy were used to…

  12. The ING family tumor suppressors: from structure to function.

    Science.gov (United States)

    Aguissa-Touré, Almass-Houd; Wong, Ronald P C; Li, Gang

    2011-01-01

    The Inhibitor of Growth (ING) proteins belong to a well-conserved family which presents in diverse organisms with several structural and functional domains for each protein. The ING family members are found in association with many cellular processes. Thus, the ING family proteins are involved in regulation of gene transcription, DNA repair, tumorigenesis, apoptosis, cellular senescence and cell cycle arrest. The ING proteins have multiple domains that are potentially capable of binding to many partners. It is conceivable, therefore, that such proteins could function similarly within protein complexes. In this case, within this family, each function could be attributed to a specific domain. However, the role of ING domains is not definitively clear. In this review, we summarize recent advances in structure-function relationships in ING proteins. For each domain, we describe the known biological functions and the approaches utilized to identify the functions associated with ING proteins.

  13. Domain Modeling: NP_001001417.5 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001001417.5 chr17 Crystal structure of the putative RabGAP domain of human TBC1 ...domain family member 14 p2qq8a_ chr17/NP_001001417.5/NP_001001417.5_holo_78-368.pdb psi-blast 153L,156H,201F,202P,205D,278S,279L,307V,308Q,337D,338T,339V UNX 0 ...

  14. On Binding Domains

    NARCIS (Netherlands)

    Everaert, M.B.H.

    2005-01-01

    In this paper I want to explore reasons for replacing Binding Theory based on the anaphor-pronoun dichotomy by a Binding Theory allowing more domains restricting/defining anaphoric dependencies. This will, thus, have consequences for the partitioning of anaphoric elements, presupposing more types of

  15. Cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  16. Domain: Labour market

    NARCIS (Netherlands)

    Oude Mulders, J.; Wadensjö, E.; Hasselhorn, H.M.; Apt, W.

    This domain chapter is dedicated to summarize research on the effects of labour market contextual factors on labour market participation of older workers (aged 50+) and identify research gaps. While employment participation and the timing of (early) retirement is often modelled as an individual

  17. Normed Domains of Holomorphy

    Directory of Open Access Journals (Sweden)

    Steven G. Krantz

    2010-01-01

    Full Text Available We treat the classical concept of domain of holomorphy in ℂn when the holomorphic functions considered are restricted to lie in some Banach space. Positive and negative results are presented. A new view of the case n=1 is considered.

  18. Domain: Labour market

    NARCIS (Netherlands)

    Oude Mulders, J.; Wadensjö, E.; Hasselhorn, H.M.; Apt, W.

    2015-01-01

    This domain chapter is dedicated to summarize research on the effects of labour market contextual factors on labour market participation of older workers (aged 50+) and identify research gaps. While employment participation and the timing of (early) retirement is often modelled as an individual deci

  19. Family Literacy

    Directory of Open Access Journals (Sweden)

    Livija Knaflič

    1999-12-01

    Full Text Available Research in child and adult literacy demonstrates that the achievement and the level of literacy that children attain at school is connected with the social and cultural characteristics and the level of literacy of the child's family. This intergenerational transfer of the level of literacy has motivated the search for different ways of improving the level of literacy.The concept of family literacy is based on the assumption that a higher level of parent literacy means that the children may achieve the same, and it also offers better schooling prospects. Family literacy programmes help fami­lies to develop different activities, in­cluding reading and writing skills, both in their community and in everyday life.

  20. Family Structure and Family Processes in Mexican American Families

    OpenAIRE

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

    2011-01-01

    Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct,...

  1. A common Greenlandic Inuit BRCA1 RING domain founder mutation

    DEFF Research Database (Denmark)

    Hansen, T.v.O.; Ejlertsen, B.; Albrechtsen, Anders;

    2009-01-01

    Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We examined 32 breast and/or ovarian cancer patients from Greenland for mutations in BRCA1 and BRCA2. Whereas no mutations were identified in 19 families, 13 families exhibited a BRCA1...... exon 3 nucleotide 234 T > G mutation, which has not previously been reported in the breast cancer information core (BIC) database. The mutation changes a conserved cysteine 39 to a glycine in the Zn(2+) site II of the RING domain, which is essential for BRCA1 ubiquitin ligase activity. Eight...... of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit...

  2. ACRATA: a novel electron transfer domain associated to apoptosis and cancer

    Directory of Open Access Journals (Sweden)

    Martinez-A Carlos

    2004-12-01

    Full Text Available Abstract Background Recently, several members of a vertebrate protein family containing a six trans-membrane (6TM domain and involved in apoptosis and cancer (e.g. STEAP, STAMP1, TSAP6, have been identified in Golgi and cytoplasmic membranes. The exact function of these proteins remains unknown. Methods We related this 6TM domain to distant protein families using intermediate sequences and methods of iterative profile sequence similarity search. Results Here we show for the first time that this 6TM domain is homolog to the 6TM heme binding domain of both the NADPH oxidase (Nox family and the YedZ family of bacterial oxidoreductases. Conclusions This finding gives novel insights about the existence of a previously undetected electron transfer system involved in apoptosis and cancer, and suggests further steps in the experimental characterization of these evolutionarily related families.

  3. What's for dinner? Types of food served at family dinner differ across parent and family characteristics.

    Science.gov (United States)

    Neumark-Sztainer, Dianne; MacLehose, Rich; Loth, Katie; Fulkerson, Jayne A; Eisenberg, Marla E; Berge, Jerica

    2014-01-01

    To examine the types of food served at family dinner in the homes of adolescents and correlations with parent and family sociodemographic characteristics, psychosocial factors and meal-specific variables. A cross-sectional population-based survey completed by mail or telephone by parents participating in Project F-EAT (Families and Eating and Activity in Teens) in 2009-2010. Homes of families with adolescents in Minneapolis/St. Paul urban area, MN, USA. Participants included 1923 parents/guardians (90·8% female; 68·5% from ethnic/racial minorities) of adolescents who participated in EAT 2010. Less than a third (28%) of parents reported serving a green salad at family dinner on a regular basis, but 70% reported regularly serving vegetables (other than potatoes). About one-fifth (21%) of families had fast food at family dinners two or more times per week. Variables from within the sociodemographic domain (low educational attainment) psychosocial domain (high work-life stress, depressive symptoms, low family functioning) and meal-specific domain (low value of family meals, low enjoyment of cooking, low meal planning, high food purchasing barriers and fewer hours in food preparation) were associated with lower healthfulness of foods served at family dinners, in analyses adjusted for sociodemographic characteristics. There is a need for interventions to improve the healthfulness of food served at family meals. Interventions need to be suitable for parents with low levels of education; take parent and family psychosocial factors into account; promote more positive attitudes toward family meals; and provide skills to make it easier to plan and prepare healthful family meals.

  4. [Family dynamics and chronic illness: children with diabetes in the context of their families].

    Science.gov (United States)

    Wirlach-Bartosik, S; Schubert, M T; Freilinger, M; Schober, E

    2005-01-01

    The present study is based on the assumption of an interaction between family functioning and chronic illness. Using a systemic approach, the intra-familial situation of families with a diabetes-affected child is examined. 44 families were evaluated using a family diagnostic instrument ("Familienbögen") and compared with 31 control families with a healthy child. Furthermore, the study looked at the influence of the level of family functioning on glycemic control, as measured by HbA1c values, and vice versa. Families with a child affected by diabetes showed significantly more dysfunctional domains and higher discrepancies of the ratings in the family diagnostic instrument (p family functioning and glycemic control was found. Poor glycemic control therefore did not have any negative effects on the family dynamics, in fact, the opposite was often the case. Also, the relationship between siblings was judged more positively when one of the siblings was chronically ill (p familial dynamics, it may, at the same time, offer opportunities for an improvement of family relationships. However, if physiological parameters deteriorate in the child (poor glycemic control), family problems seem to become less important. Success in the treatment of diabetes patients should therefore not only be measured by the quality of glycemic control, but also by considering psychological factors and aspects of family dynamics.

  5. Family Circle

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Foster care is conducive to giving orphaned children a better life For most children living in orphanages, having a real home is just a pipe dream. Although they may be well looked after, receive a good education and proper nutrition, the love and care that come from being part of a real family just aren't there.

  6. My Family

    Institute of Scientific and Technical Information of China (English)

    刘才来

    2002-01-01

    There are four people in my family. They are grandma, father,mother and I. Now we all live in Wuhan. They are from different places. My grandma comes from Sichuan. She likes hot(辣4的) meat very much. She doesn't like bread or noodles at all. She likes vegetables a little. My father is from Guang Zhou.

  7. My Family

    Institute of Scientific and Technical Information of China (English)

    李梅

    2012-01-01

    There are four people in my family--my parents, my brother and I. My name is Li Mei. I'm fifteen years old. I am of medium height and build. I like English very much. It's very interesting. I can play the piano very well. It makes me feel very happy.

  8. Finding Family

    Institute of Scientific and Technical Information of China (English)

    LIU YUNYUN

    2010-01-01

    @@ It took 14 years--and just two min-utes-for an adopted Chinese girl to find her biological family. July 21 this year marked the first anniversary of Haley Butler's finding of her biological parents in Maanshan in east China's Anhui Province.

  9. FAMILY RICHARDIIDAE.

    Science.gov (United States)

    Wendt, Lisiane Dilli; Ale-Rocha, Rosaly

    2016-06-14

    Richardiidae are a family of "acalyptrate" Diptera represented by ca. 180 species distributed in the New World, mostly in the Neotropical region. The species that occur in Colombia have received little attention from taxonomists, and the great majority of them are known only from their type localities. Currently, 14 genera and 23 species are known to occur in the country.

  10. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  11. Finding Family

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Discovering her birth parents was an exciting adventure for a 15-year-old girl It took 14 years-and just two minutes-for an adopted Chinese girl to find her biological family.July 21 this year marked the first

  12. Familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Versmissen, Jorie; Vongpromek, Ranitha; Yahya, Reyhana

    2016-01-01

    cholesterol efflux capacity between male familial hypercholesterolaemia (FH) patients with and without CHD relative to their non-FH brothers, and examined HDL constituents including sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (apoM). RESULTS: Seven FH patients were asymptomatic and six had...

  13. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  14. Asymptotic behaviour of optimal spectral planar domains with fixed perimeter

    Science.gov (United States)

    Bucur, Dorin; Freitas, Pedro

    2013-05-01

    We consider the problem of minimizing the kth Dirichlet eigenvalue of planar domains with fixed perimeter and show that, as k goes to infinity, the optimal domain converges to the ball with the same perimeter. We also consider this problem within restricted classes of domains such as n-polygons and tiling domains, for which we show that the optimal asymptotic domain is that which maximises the area for fixed perimeter within the given family, i.e., the regular n-polygon and the regular hexagon, respectively. Physically, the above problems correspond to the determination of the shapes within a given class which will support the largest number of modes below a given frequency.

  15. Functional Implications of Domain Organization Within Prokaryotic Rhomboid Proteases.

    Science.gov (United States)

    Panigrahi, Rashmi; Lemieux, M Joanne

    2015-01-01

    Intramembrane proteases are membrane embedded enzymes that cleave transmembrane substrates. This interesting class of enzyme and its water mediated substrate cleavage mechanism occurring within the hydrophobic lipid bilayer has drawn the attention of researchers. Rhomboids are a family of ubiquitous serine intramembrane proteases. Bacterial forms of rhomboid proteases are mainly composed of six transmembrane helices that are preceded by a soluble N-terminal domain. Several crystal structures of the membrane domain of the E. coli rhomboid protease ecGlpG have been solved. Independently, the ecGlpG N-terminal cytoplasmic domain structure was solved using both NMR and protein crystallography. Despite these structures, we still do not know the structure of the full-length protein, nor do we know the functional role of these domains in the cell. This chapter will review the structural and functional roles of the different domains associated with prokaryotic rhomboid proteases. Lastly, we will address questions remaining in the field.

  16. Time Domain Induced Polarization

    DEFF Research Database (Denmark)

    Fiandaca, Gianluca; Auken, Esben; Christiansen, Anders Vest

    2012-01-01

    Time-domain-induced polarization has significantly broadened its field of reference during the last decade, from mineral exploration to environmental geophysics, e.g., for clay and peat identification and landfill characterization. Though, insufficient modeling tools have hitherto limited the use...... of time-domaininduced polarization for wider purposes. For these reasons, a new forward code and inversion algorithm have been developed using the full-time decay of the induced polarization response, together with an accurate description of the transmitter waveform and of the receiver transfer function......%. Furthermore, the presence of low-pass filters in time-domain-induced polarization instruments affects the early times of the acquired decays (typically up to 100 ms) and has to be modeled in the forward response to avoid significant loss of resolution. The developed forward code has been implemented in a 1D...

  17. Novel predicted RNA-binding domains associated with the translation machinery.

    Science.gov (United States)

    Aravind, L; Koonin, E V

    1999-03-01

    Two previously undetected domains were identified in a variety of RNA-binding proteins, particularly RNA-modifying enzymes, using methods for sequence profile analysis. A small domain consisting of 60-65 amino acid residues was detected in the ribosomal protein S4, two families of pseudouridine synthases, a novel family of predicted RNA methylases, a yeast protein containing a pseudouridine synthetase and a deaminase domain, bacterial tyrosyl-tRNA synthetases, and a number of uncharacterized, small proteins that may be involved in translation regulation. Another novel domain, designated PUA domain, after PseudoUridine synthase and Archaeosine transglycosylase, was detected in archaeal and eukaryotic pseudouridine synthases, archaeal archaeosine synthases, a family of predicted ATPases that may be involved in RNA modification, a family of predicted archaeal and bacterial rRNA methylases. Additionally, the PUA domain was detected in a family of eukaryotic proteins that also contain a domain homologous to the translation initiation factor eIF1/SUI1; these proteins may comprise a novel type of translation factors. Unexpectedly, the PUA domain was detected also in bacterial and yeast glutamate kinases; this is compatible with the demonstrated role of these enzymes in the regulation of the expression of other genes. We propose that the S4 domain and the PUA domain bind RNA molecules with complex folded structures, adding to the growing collection of nucleic acid-binding domains associated with DNA and RNA modification enzymes. The evolution of the translation machinery components containing the S4, PUA, and SUI1 domains must have included several events of lateral gene transfer and gene loss as well as lineage-specific domain fusions.

  18. SLAM-family receptors: immune regulators with or without SAP-family adaptors.

    Science.gov (United States)

    Veillette, André

    2010-03-01

    The signaling lymphocytic activation molecule (SLAM) family of receptors and the SLAM-associated protein (SAP) family of intracellular adaptors are expressed in immune cells. By way of their cytoplasmic domain, SLAM-related receptors physically associate with SAP-related adaptors. Evidence is accumulating that the SLAM and SAP families play crucial roles in multiple immune cell types. Moreover, the prototype of the SAP family, that is SAP, is mutated in a human immunodeficiency, X-linked lymphoproliferative (XLP) disease. In the presence of SAP-family adaptors, the SLAM family usually mediates stimulatory signals that promote immune cell activation or differentiation. In the absence of SAP-family adaptors, though, the SLAM family undergoes a "switch-of-function," thereby mediating inhibitory signals that suppress immune cell functions. The molecular basis and significance of this mechanism are discussed herein.

  19. A structural genomics analysis of histidine kinase sensor domains

    Science.gov (United States)

    Cheung, Jonah

    2005-11-01

    Histidine kinase sensors are a part of a two-component system of protein signaling in prokaryotes and lower eukaryotes that relay an external environmental signal to an adaptive internal cellular response. Signal transduction occurs via phosphotransfer between a sensor protein and a response regulator which interact in tandem. The sensor is usually a transmembrane protein that contains a conserved cytoplasmic histidine kinase transmitter domain and a modular periplasmic sensor domain. The response regulator is cytoplasmic protein that contains a receiver domain that interacts with the histidine kinase, and an output domain that interacts with regulators of transcription or chemotaxis. My work focuses on the X-ray structure determination of a variety of bacterial sensor domains, based on a structural genomics analysis of the entire sensor domain family. Structures of the NarX, DcuS, LisK, and DctB sensor domains have been solved to atomic resolution, some in both ligand-bound and ligand-free states. Two distinct structural folds have been revealed---all-alpha helical and mixed alpha-beta. An analysis of the structures reveals a possible mechanism of transmembrane signaling in histidine kinase sensors as a sliding-piston motion between transmembrane helices. Although there is great diversity in ligand binding, there appears to be a small number of distinct sensor domain folds for which structural representatives of two have been solved. A final synthesis of the structural information with a comprehensive bio-informatics analysis of all histidine kinase sensor domain sequences allows fold prediction for over 400 sensor domains, in a step towards mapping the entire structural landscape of this protein family.

  20. Learning about Familial Hypercholesterolemia

    Science.gov (United States)

    ... terms used on this page Learning About Familial Hypercholesterolemia What is familial hypercholesterolemia? What are the symptoms ... Additional Resources About Familial Hypercholesterolemia What is familial hypercholesterolemia? Familial hypercholesterolemia is an inherited condition that causes ...

  1. Natural Family Planning

    Science.gov (United States)

    ... Sex and Birth Control Birth Control Natural Family Planning Natural Family Planning Birth ControlPrevention and WellnessSex and Birth Control Share Natural Family Planning Natural Family PlanningWhat is natural family planning?Natural ...

  2. Child in hospital: family experiences and expectations of how nurses can promote family health.

    Science.gov (United States)

    Hopia, Hanna; Tomlinson, Patricia S; Paavilainen, Eija; Astedt-Kurki, Päivi

    2005-02-01

    This study set out to explore, from the family's point of view, ways in which nursing staff can promote family health during the child's hospital stay. Having a child in hospital is a major source of stress and anxiety for the whole family. Earlier studies have described parental coping strategies, ways to strengthen those strategies and to support parental participation in child care, but no one has studied the promotion of family health during the child's hospitalization from the family's point of view. Interviews were conducted in 2002 with 29 families who had a child with a chronic illness which were receiving or had received treatment on the paediatric wards of two Finnish hospitals. Data analysis was based on the grounded theory method, proceeding to the stage of axial coding. Data collection and analysis phases proceeded simultaneously. Five domains were distinguished in the promotion of family health: (1) reinforcing parenthood, (2) looking after the child's welfare, (3) sharing the emotional burden, (4) supporting everyday coping and (5) creating a confidential care relationship. The results strengthen the knowledge base of family nursing by showing how nursing staff can promote family health during the child's hospital stay. The results have a number of practical applications for nursing, both for clinical practice and research. The results can be used in paediatric hospital wards caring for chronically ill children and their families. The five domains of family health promotion described here should be tested in other paediatric wards and in other geographical locations.

  3. The CRM domain: an RNA binding module derived from an ancient ribosome-associated protein.

    Science.gov (United States)

    Barkan, Alice; Klipcan, Larik; Ostersetzer, Oren; Kawamura, Tetsuya; Asakura, Yukari; Watkins, Kenneth P

    2007-01-01

    The CRS1-YhbY domain (also called the CRM domain) is represented as a stand-alone protein in Archaea and Bacteria, and in a family of single- and multidomain proteins in plants. The function of this domain is unknown, but structural data and the presence of the domain in several proteins known to interact with RNA have led to the proposal that it binds RNA. Here we describe a phylogenetic analysis of the domain, its incorporation into diverse proteins in plants, and biochemical properties of a prokaryotic and eukaryotic representative of the domain family. We show that a bacterial member of the family, Escherichia coli YhbY, is associated with pre-50S ribosomal subunits, suggesting that YhbY functions in ribosome assembly. GFP fused to a single-domain CRM protein from maize localizes to the nucleolus, suggesting that an analogous activity may have been retained in plants. We show further that an isolated maize CRM domain has RNA binding activity in vitro, and that a small motif shared with KH RNA binding domains, a conserved "GxxG" loop, contributes to its RNA binding activity. These and other results suggest that the CRM domain evolved in the context of ribosome function prior to the divergence of Archaea and Bacteria, that this function has been maintained in extant prokaryotes, and that the domain was recruited to serve as an RNA binding module during the evolution of plant genomes.

  4. [Family violence].

    Science.gov (United States)

    Manoudi, F; Chagh, R; Es-soussi, M; Asri, F; Tazi, I

    2013-09-01

    Family violence is a serious public health problem, the scale of which is seriously increasing in Morocco. Although it has existed for a long time, we ignore the real characteristics of this plague in our country; our work consisted in an epidemiological approach of family violence in Marrakech during 2006. After elaborating a questionnaire, which allows the study of the demographic and social profile of the families, the study of violence exercised in the family and the evaluation of the depression in the women, we led an inquiry amongst 265 women. Analysis of the results obtained has allowed us to underline the following characteristics: 16.6% of the women in our sample had been physically beaten; the young age is a risk factor; the age range most affected by violence is in women between the ages of 30 and 40 and which represent 39% of the battered women; domestic violence touches all the social, economic and cultural classes: in our study, 63% of the women having undergone violence were housewives, 25% were managers and 3% senior executives; family problems were the most important cause of violence in our study, representing 32.32%. Requests for money was the cause in 11.3% of the cases, and imposed sexual relations were found in 6.8% of the cases; alcoholism is an aggravating factor of family violence; 27.3% of the spouses who assaulted their wives were drunk; 52% of the assaulted women were victims of violence in childhood and 36% had been witness to their father's violence; in 63.6% of the cases of violence, the children were witnesses, and in 25% of the cases the children were victims of violence at the same time as their mothers; 50% of the women victims of violence did not react, while 38.6% left home, and 9.1 filed for divorce. Thirty-two percent of the assaulted woman had been traumatised by the aggression; the association of depression and violence was very high, 343% of the battered women in our study suffered from severe depression. This work

  5. Comparison of the domain and frequency domain state feedbacks

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, S.Y.

    1986-01-01

    In this paper, we present explicitly the equivalence of the time domain and frequency domain state feedbacks, as well as the dynamic state feedback and a modified frequency domain state feedback, from the closed-loop transfer function point of view. The difference of the two approaches is also shown.

  6. My family

    Institute of Scientific and Technical Information of China (English)

    陈君怡

    2011-01-01

    I have a happy fam_ly.Lookthis is my family photo.This is mydad.He often wears a pair Ofglasses(戴着一副眼镜I_This ismy mum.She is very pretty.Sheloves me very much.The little girlin a red blouse is me.I’m smiling(微笑).I love my family.

  7. A Minimal Rac Activation Domain in the Unconventional Guanine Nucleotide Exchange Factor Dock180†

    OpenAIRE

    Xin WU; Ramachandran, Sekar; Cerione, Richard A.; Erickson, Jon W.

    2011-01-01

    Guanine nucleotide exchange factors (GEFs) activate Rho GTPases by catalyzing the exchange of bound GDP for GTP, thereby resulting in downstream effector recognition. Two metazoan families of GEFs have been described: Dbl-GEF family members that share conserved Dbl homology (DH) and Pleckstrin homology (PH) domains and the more recently described Dock180 family members that share little sequence homology with the Dbl family and are characterized by conserved Dock homology regions 1 and 2 (DHR...

  8. Enrichment between the Work and Nonwork Domain : A Look at the Bright Side of Life

    OpenAIRE

    Daniel, Stefanie

    2013-01-01

    Research on the work-family interface repeatedly demonstrated that combining multiple roles such as being an employee as well as a parent can lead to detrimental consequences due to competing demands emerging from both the work and the family domain. However, in recent years, research found that combining multiple roles can also have positive consequences. This positive perspective on the work-family interface is specified in the model of work-family enrichment (Greenhaus & Powell, 2006). Wor...

  9. [Familial hypercholesterolemia].

    Science.gov (United States)

    Turpin, G; Bruckert, E

    1999-12-01

    Familial hypercholesterolemia is characterized by a high plasma LDL-cholesterol level. The low-density particles are the end-product of the triglyceride-rich particles, i.e. VLDL, synthetized by the liver. These triglyceride-rich particles are subsequently transformed into intermediate density lipoprotein by the lipoprotein lipase and LDL after further triglyceride hydrolysis by the hepatic lipase. The LDL particles are taken up in all cells by the mean of the LDL receptor. A large body of evidence (including experimental, clinical, epidemiological data as well as the results of large trial with lipid lowering drugs) has accumulated to establish that these particles are one of the major causative factor of atherosclerosis and its complications. Two different mechanisms may be at work in the familial hypercholesterolemia: a mutation in the LDL receptor or a single mutation in the apolipoprotein B100. Specific therapeutic intervention should be undertaken to decrease the risk to develop cardiovascular disease, mainly coronary heart disease. The therapeutic intervention includes both a diet low in saturated fatty acids and cholesterol and statins which are now the first line therapy. Fibrates are proposed to those who do not tolerate statins and LDL-apheresis is associated to statin in the rare homozygous familial hypercholesterolemia.

  10. Domains of Disoriented Chiral Condensate

    CERN Document Server

    Amado, R D; Lu, Yang

    1996-01-01

    The probability distribution of neutral pion fraction from independent domains of disoriented chiral condensate is characterized. The signal for the condensate is clear for a small number of domains but is greatly reduced for more than three.

  11. Summarization by domain ontology navigation

    DEFF Research Database (Denmark)

    Andreasen, Troels; Bulskov, Henrik

    2013-01-01

    of the subject. In between these two extremes, conceptual summaries encompass selected concepts derived using background knowledge. We address in this paper an approach where conceptual summaries are provided through a conceptualization as given by an ontology. The ontology guiding the summarization can...... be a simple taxonomy or a generative domain ontology. A domain ontology can be provided by a preanalysis of a domain corpus and can be used to condense improved summaries that better reflects the conceptualization of a given domain....

  12. Domain Modeling: NP_001092096.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001092096.1 chr19 Solution structure of the tandem four zf-C2H2 domain repeats o...f murine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_001092096.1/NP_001092096.1_holo_175-290.pdb blast 3

  13. Domain Modeling: NP_085116.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_085116.2 chr5 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr5/NP_085116.2/NP_085116.2_holo_209-322.pdb blast 216C,218E,21

  14. Domain Modeling: NP_940886.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_940886.1 chr3 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr3/NP_940886.1/NP_940886.1_holo_320-436.pdb psi-blast 321C,323

  15. Domain Modeling: NP_852466.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_852466.1 chr3 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr3/NP_852466.1/NP_852466.1_holo_673-813.pdb blast 926R,928P,92

  16. Domain Modeling: NP_056154.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_056154.1 chr20 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr20/NP_056154.1/NP_056154.1_holo_623-739.pdb psi-blast 624C,6

  17. Domain Modeling: NP_065184.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_065184.2 chr1 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr1/NP_065184.2/NP_065184.2_holo_267-376.pdb psi-blast 274A,276

  18. Domain Modeling: NP_055062.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available formation of the Tandem PDZ Domains c1u3ba_ chr4/NP_055062.1/NP_055062.1_apo_249-480.pdb swppa 0 ... ...NP_055062.1 chr4 Auto-inhibition Mechanism of X11s/Mints Family Scaffold Proteins Revealed by the Closed Con

  19. Domain Modeling: NP_001154.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available formation of the Tandem PDZ Domains c1u3ba_ chr9/NP_001154.2/NP_001154.2_apo_655-837.pdb blast 0 ... ...NP_001154.2 chr9 Auto-inhibition Mechanism of X11s/Mints Family Scaffold Proteins Revealed by the Closed Con

  20. Domain Modeling: NP_005494.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available Revealed by the Closed Conformation of the Tandem PDZ Domains c1u3ba_ chr15/NP_005494.2/NP_005494.2_apo_567-749.pdb blast 0 ... ...NP_005494.2 chr15 Auto-inhibition Mechanism of X11s/Mints Family Scaffold Proteins

  1. Domain Modeling: NP_066971.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_066971.2 chr7 Solution structure of the tandem four zf-C2H2 domain repeats of mu...rine GLI-Kruppel family member HKR3 c2dlqa_ chr7/NP_066971.2/NP_066971.2_holo_341-454.pdb blast 348C,350E,35

  2. Domain Modeling: NP_006291.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_006291.2 chr19 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_006291.2/NP_006291.2_holo_163-276.pdb blast 170C,172E,

  3. Domain Modeling: NP_071911.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_071911.3 chr10 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr10/NP_071911.3/NP_071911.3_holo_111-217.pdb psi-blast 112C,1

  4. Domain Modeling: NP_775751.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_775751.1 chr19 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_775751.1/NP_775751.1_holo_331-443.pdb blast 338C,340H,

  5. Domain Modeling: NP_037512.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_037512.3 chr19 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_037512.3/NP_037512.3_holo_542-655.pdb blast 549C,551E,

  6. Domain Modeling: NP_001098547.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001098547.2 chr3 Solution structure of the tandem four zf-C2H2 domain repeats of... murine GLI-Kruppel family member HKR3 c2dlqa_ chr3/NP_001098547.2/NP_001098547.2_holo_540-654.pdb psi-blast

  7. Domain Modeling: NP_001074421.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001074421.1 chr6 Solution structure of the tandem four zf-C2H2 domain repeats of... murine GLI-Kruppel family member HKR3 c2dlqa_ chr6/NP_001074421.1/NP_001074421.1_holo_6-118.pdb blast 6C,8L

  8. Domain Modeling: NP_006201.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_006201.1 chr19 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr19/NP_006201.1/NP_006201.1_holo_165-272.pdb psi-blast 1308P,

  9. Domain Modeling: NP_899051.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_899051.1 chr17 Solution structure of the tandem four zf-C2H2 domain repeats of m...urine GLI-Kruppel family member HKR3 c2dlqa_ chr17/NP_899051.1/NP_899051.1_holo_199-297.pdb psi-blast 200L,2

  10. Chaotic domains: A numerical investigation

    OpenAIRE

    Cross, M. C.; Meiron, D.; Tu, Yuhai

    1994-01-01

    We study the chaotic domain state in rotating convection using a model equation that allows for a continuous range of roll orientations as in the experimental system. Methods are developed for extracting the domain configuration from the resulting patterns that should be applicable to a wide range of domain states. Comparison with the truncated three mode amplitude equation description is made.

  11. Gershgorin domains for partitioned matrices

    NARCIS (Netherlands)

    Sluis, A. van der

    1979-01-01

    Inclusion domains for the eigenvalues of a partitioned matrix are specified in terms of perturbations of its diagonal blocks. The size of such perturbations is measured using the Kantorovitch-Robert-Deutsch vectorial norms. The inclusion domains obtained thereby are compared with inclusion domains o

  12. Feature-level domain adaptation

    DEFF Research Database (Denmark)

    Kouw, Wouter M.; Van Der Maaten, Laurens J P; Krijthe, Jesse H.

    2016-01-01

    Domain adaptation is the supervised learning setting in which the training and test data are sampled from different distributions: training data is sampled from a source domain, whilst test data is sampled from a target domain. This paper proposes and studies an approach, called feature...

  13. Classification of Noncommutative Domain Algebras

    CERN Document Server

    Arias, Alvaro

    2012-01-01

    Noncommutative domain algebras are noncommutative analogues of the algebras of holomorphic functions on domains of $\\C^n$ defined by holomorphic polynomials, and they generalize the noncommutative Hardy algebras. We present here a complete classification of these algebras based upon techniques inspired by multivariate complex analysis, and more specifically the classification of domains in hermitian spaces up to biholomorphic equivalence.

  14. Family, employment, and individual resource-based antecedents of maternal work-family enrichment from infancy through middle childhood.

    Science.gov (United States)

    Zhou, Nan; Buehler, Cheryl

    2016-07-01

    This study used data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (N = 1,019) to examine family, employment, and individual antecedents of maternal work-family enrichment from infancy through middle childhood. Work-family conflict and important confounding factors were controlled. From the family domain, higher income-to-needs ratio and social support were associated with higher work-family enrichment. From the employment domain, greater job rewards, benefits of employment for children, and work commitment were associated with higher work-family enrichment. From the individual domain, higher maternal education and extroversion were associated with higher work-family enrichment. No family, employment, and individual characteristics were associated with work-family conflict across time except for partner intimacy. In general, the results supported antecedents of work-family enrichment that supply needed resources. The present study contributed to the literature by identifying antecedents of maternal work-family enrichment across early child developmental stages, which goes beyond examinations of particular life stages and a work-family conflict perspective. Implications for theory and practice are discussed. (PsycINFO Database Record

  15. The history of the CATH structural classification of protein domains.

    Science.gov (United States)

    Sillitoe, Ian; Dawson, Natalie; Thornton, Janet; Orengo, Christine

    2015-12-01

    This article presents a historical review of the protein structure classification database CATH. Together with the SCOP database, CATH remains comprehensive and reasonably up-to-date with the now more than 100,000 protein structures in the PDB. We review the expansion of the CATH and SCOP resources to capture predicted domain structures in the genome sequence data and to provide information on the likely functions of proteins mediated by their constituent domains. The establishment of comprehensive function annotation resources has also meant that domain families can be functionally annotated allowing insights into functional divergence and evolution within protein families. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Is work-family balance more than conflict and enrichment?

    Science.gov (United States)

    Carlson, Dawn S; Grzywacz, Joseph G; Zivnuska, Suzanne

    2009-10-01

    This study deepens our theoretical and practical understanding of work-family balance, defined as the 'accomplishment of role-related expectations that are negotiated and shared between an individual and his/her role-related partners in the work and family domains' (Grzywacz & Carlson, 2007: 458). We develop a new measure of work-family balance and establish discriminant validity between it, work-family conflict, and work-family enrichment. Further, we examine the relationship of work-family balance with six key work and family outcomes. Results suggest that balance explains variance beyond that explained by traditional measures of conflict and enrichment for five of six outcomes tested: job satisfaction, organizational commitment, family satisfaction, family performance, and family functioning. We conclude with a discussion of the applications of our work.

  17. Metaphors, domains and embodiment

    Directory of Open Access Journals (Sweden)

    M.E. Botha

    2005-07-01

    Full Text Available Investigations of metaphorical meaning constitution and meaning (in- variance have revealed the significance of semantic and semiotic domains and the contexts within which they function as basis for the grounding of metaphorical meaning. In this article some of the current views concerning the grounding of metaphorical meaning in experience and embodiment are explored. My provisional agreement with Lakoff, Johnson and others about the “conceptual” nature of metaphor rests on an important caveat, viz. that this bodily based conceptual structure which lies at the basis of linguistic articulations of metaphor, is grounded in a deeper ontic structure of the world and of human experience. It is the “metaphorical” (actually “analogical” ontological structure of this grounding that is of interest for the line of argumentation followed in this article. Because Johnson, Lakoff and other’s proposal to ground metaphorical meaning in embodiment and neural processes is open to being construed as subjectivist and materialist, I shall attempt to articulate the contours of an alternative theory of conceptual metaphor, meaning and embodiment which counteracts these possibilities. This theory grounds metaphorical meaning and meaning change in an ontological and anthropological framework which recognises the presence and conditioning functioning of radially ordered structures for reality. These categorisations in which humankind, human knowledge and reality participate, condition and constrain (ground analogical and metaphorical meaning transfer, cross-domain mappings, and blends in cognition and in language, provide the basis for the analogical concepts found in these disciplines.

  18. The Role of the Family in Genetic Testing: Theoretical Perspectives, Current Knowledge, and Future Directions

    Science.gov (United States)

    Peterson, Susan K.

    2005-01-01

    This article addresses conceptual challenges and theoretical approaches for examining the role of the family in responding and adapting to genetic testing for inherited conditions. Using a family systems perspective, family-based constructs that are relevant to genetic testing may be organized into three domains: family communication, organization…

  19. Homogenization of a Parabolic Equation in Perforated Domain with Neumann Boundary Condition

    Indian Academy of Sciences (India)

    A K Nandakumaran; M Rajesh

    2002-02-01

    In this article, we study the homogenization of the family of parabolic equations over periodically perforated domains \\begin{align*}_tb\\left(\\frac{x}{}, u_{}\\right)-\\mathrm{div} a\\left(\\frac{x}{}, u_{},\

  20. Delimiting family in syntheses of research on childhood chronic conditions and family life.

    Science.gov (United States)

    Knafl, Kathleen; Leeman, Jennifer; Havill, Nancy; Crandell, Jamie; Sandelowski, Margarete

    2015-03-01

    Synthesis of family research presents unique challenges to investigators who must delimit what will be included as a family study in the proposed review. In this paper, the authors discuss the conceptual and pragmatic challenges of conducting systematic reviews of the literature on the intersection between family life and childhood chronic conditions. A proposed framework for delimiting the family domain of interest is presented. The framework addresses both topical salience and level of relevance and provides direction to future researchers, with the goal of supporting the overall quality of family research synthesis efforts. For users of synthesis studies, knowledge of how investigators conceptualize the boundaries of family research is important contextual information for understanding the limits and applicability of the results. © 2014 Family Process Institute.

  1. The framing of scientific domains

    DEFF Research Database (Denmark)

    Dam Christensen, Hans

    2014-01-01

    Purpose: By using the UNISIST models this article argues for the necessity of domain analysis in order to qualify scientific information seeking. The models better understanding of communication processes in a scientific domain and embraces the point that domains are always both unstable over time...... and changeable according to the specific perspective. This understanding is even more important today as numerous digitally generated information tools as well as collaborative and interdisciplinary research are blurring the domain borders. Nevertheless, researchers navigate “intuitively” in “their” specific...... as according to the agents that are charting them. As such, power in a Foucauldian sense is unavoidable in outlining a domain. Originality/value 1. The UNISIST models are applied to the domain of art history; and 2. the article discusses the instability of a scientific domain as well as, at the same time...

  2. The framing of scientific domains

    DEFF Research Database (Denmark)

    Dam Christensen, Hans

    2014-01-01

    Purpose: By using the UNISIST models this article argues for the necessity of domain analysis in order to qualify scientific information seeking. The models better understanding of communication processes in a scientific domain and embraces the point that domains are always both unstable over time...... as according to the agents that are charting them. As such, power in a Foucauldian sense is unavoidable in outlining a domain. Originality/value 1. The UNISIST models are applied to the domain of art history; and 2. the article discusses the instability of a scientific domain as well as, at the same time......, the significance of framing a domain; an implication which is often neglected in scientific information seeking....

  3. [The press and family planning].

    Science.gov (United States)

    Abraham De D'ornellas, R

    1987-01-01

    The treatment in the press of family planning hinges on two fundamental factors: the taboo of the leftist groups and the taboo of the Catholic Church, whose head is against abortion under any circumstances. Leftist views insinuate that family planning is the genocidal plan of North American imperialists against the Third World and, in particular, against Latin America. This genocidal plan is supposed to subject poor populations to international schemes. In the press family planning is often treated in a sanctimonious fashion, lumping it together with topics like pornography, sex, and violence. In 1983 the daily newspaper Expreso published a supplement running every week for almost three months about the issue of population, which dealt fairly extensively with such topics as population and housing, education, employment, and urban proliferation, as well as responsible parenthood and child survival. In addition, there was a detailed description of contraceptive methods. In October 1986 another surprising thing happened: the President of Peru talked about the topic of family planning, which at the time was an act of courage. Since then much has changed; the whole world is interested in family planning and certain aspects of population. Since October 1986 more has been published in this domain than during the preceding 20 years. In contrast, the Church reacted differently to this issue: after some initial caution, the conference of Peruvian bishops attacked all methods of modern contraceptives and private institutions of family planning. The information boom in family planning will certainly continue. At the moment this flood of articles and editorials about the issue is an expression of the anxiety of families related to uncontrolled reproduction and the fear of overpopulation in large cities devoid of minimal services.

  4. ADAM-15 Disintegrin-Like Domain Structure and Function

    Directory of Open Access Journals (Sweden)

    Dong Lu

    2010-10-01

    Full Text Available The ADAM (a disintegrin-like and metalloproteinase proteins are a family of transmembrane cell-surface proteins with important functions in adhesion and proteolytic processing in all animals. Human ADAM-15 is the only member of the ADAM family with the integrin binding motif Arg-Gly-Asp (RGD in its disintegrin-like domain. This motif is also found in most snake venom disintegrins and other disintegrin-like proteins. This unique RGD motif within ADAM-15 serves as an integrin ligand binding site, through which it plays a pivotal role in interacting with integrin receptors, a large family of heterodimeric transmembrane glycoproteins. This manuscript will present a review of the RGD-containing disintegrin-like domain structures and the structural features responsible for their activity as antagonists of integrin function in relation to the canonical RGD template.

  5. Quality of Family Relationships: The Contributions of Family Structures and Gender – Role Orientations

    Directory of Open Access Journals (Sweden)

    Adebayo Sulaiman Olanrewaju

    2015-06-01

    Full Text Available Since the whole human population are products of the family, it may be deduced that a substantial proportion of the social-vices besieging the modern world emanate from maladaptive socialization process of the family domain. To achieve a capable and positive functioning socialization process, harmonious and healthy relationships must be ensured among and between each member of the family. Taking into consideration the overarching positive influence of valuable family relationship on healthy family lives, it is highly essential to investigate the predicting factors of good family relationships. Accordingly, this study tested whether family structures and gender role orientations would predict quality of family relationships. Ninety-eight participants who were selected using cluster sampling method from Ekiti State University, Ado-Ekiti, Nigeria, completed self-report instruments comprising of Index of Family Relations (IFR, Bem Sex-Role Inventory (BSRI and the Personal Data Sheet (PDS. Hypotheses were tested using one-way ANOVA and multiple regressions. Findings suggest that participants from traditional marriage families reported better family relationships than those from single-parent, divorced and court/legal marriage families. Additionally, the expression of feminine traits by family members (regardless of sex seems to account for a well knitted family relationship than the expression of the nearly feminine trait, androgynous trait and nearly masculine trait. Results were discussed in line with previous literature and it was recommended that traditional/customary marriage should not be jettisoned in the process of family formation but should be done in conjunction with court/legal marriage. Similarly, the expression of feminine traits by each family member regardless of their sex should be encouraged to forestall family conflicts and ensure good family relations.

  6. The cullin protein family.

    Science.gov (United States)

    Sarikas, Antonio; Hartmann, Thomas; Pan, Zhen-Qiang

    2011-01-01

    Cullin proteins are molecular scaffolds that have crucial roles in the post-translational modification of cellular proteins involving ubiquitin. The mammalian cullin protein family comprises eight members (CUL1 to CUL7 and PARC), which are characterized by a cullin homology domain. CUL1 to CUL7 assemble multi-subunit Cullin-RING E3 ubiquitin ligase (CRL) complexes, the largest family of E3 ligases with more than 200 members. Although CUL7 and PARC are present only in chordates, other members of the cullin protein family are found in Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana and yeast. A cullin protein tethers both a substrate-targeting unit, often through an adaptor protein, and the RING finger component in a CRL. The cullin-organized CRL thus positions a substrate close to the RING-bound E2 ubiquitin-conjugating enzyme, which catalyzes the transfer of ubiquitin to the substrate. In addition, conjugation of cullins with the ubiquitin-like molecule Nedd8 modulates activation of the corresponding CRL complex, probably through conformational regulation of the interactions between cullin's carboxy-terminal tail and CRL's RING subunit. Genetic studies in several model organisms have helped to unravel a multitude of physiological functions associated with cullin proteins and their respective CRLs. CRLs target numerous substrates and thus have an impact on a range of biological processes, including cell growth, development, signal transduction, transcriptional control, genomic integrity and tumor suppression. Moreover, mutations in CUL7 and CUL4B genes have been linked to hereditary human diseases.

  7. Correlation between aberrant methylation status of ras association domain family 1A and alteration of DNA methyltransferases, hepatitis B virus infection in hepatocellular carcinoma%原发性肝癌组织RASSF1A异常甲基化与DNMTs及HBV的关系

    Institute of Scientific and Technical Information of China (English)

    赵强子; 窦科峰; 祁志芳; 魏万礼; 杨雁灵; 李开宗

    2006-01-01

    目的探讨原发性肝癌ras相关结构域家族1A(ras association domain family 1A,RASSF1A)异常甲基化与肿瘤组织中DNA甲基转移酶(DNA methyltransferases,DNMTs)转录水平变化及HBV感染的关系.方法采用甲基化特异性PCR(methylation specific PCR,MSP)技术检测61例原发性肝癌组织RASSF1A基因异常甲基化情况,RT-PCR法检测其中三种主要DNA甲基转移酶(DNMT1、DNMT3A、DNMT3B)水平的变化.结果61例肝癌标本中RASSF1A基因启动子区异常甲基化45例(73.8%);HBV感染者47例(77.1%),其中MSP阳性32例;无HBV感染者14例,其中MSP阳性13例,RASSF1A基因异常甲基化与HBV感染之间的关系无统计学意义(x2=2.260,P=0.133).肝癌组、肝癌细胞系组及HBV感染组DNMTs表达水平与正常对照组相比均显著升高;组内比较显示肝癌组中DNMT3A、DNMT3B在MSP阳性患者中较阴性患者升高(分别为t=3.494,P<0.01;t=4.258,P<0.01),而DNMT1下降(t=3.221,P<0.05);HBV感染组中,MSP阳性组织其DNMT3B较阴性者升高(t=12.171,P<0.01).结论肝癌组织DNMTs水平变化与RASSF1A异常甲基化有密切关系;HBV感染与DNMT3B转录水平变化相关.

  8. A family of inversion formulas in thermoacoustic tomography

    KAUST Repository

    Nguyen, Linh

    2009-10-01

    We present a family of closed form inversion formulas in thermoacoustic tomography in the case of a constant sound speed. The formulas are presented in both time-domain and frequency-domain versions. As special cases, they imply most of the previously known filtered backprojection type formulas. © 2009 AMERICAN INSTITUTE OF MATHEMATICAL SCIENCES.

  9. SLIDE, the Protein Interacting Domain of Imitation Switch Remodelers, Binds DDT-Domain Proteins of Different Subfamilies in Chromatin Remodeling Complexes

    Institute of Scientific and Technical Information of China (English)

    Jiaqiang Dong; Zheng Gao; Shujing Liu; Guang Li; Zhongnan Yang; Hai Huang; Lin Xu

    2013-01-01

    The Imitation Switch (ISWI) type adenosine triphosphate (ATP)-dependent chromatin remodeling factors are conserved proteins in eukaryotes, and some of them are known to form stable remodeling complexes with members from a family of proteins, termed DDT-domain proteins. Although it is well documented that ISWIs play important roles in different biological processes in many eukaryotic species, the molecular basis for protein interactions in ISWI complexes has not been fully addressed. Here, we report the identification of interaction domains for both ISWI and DDT-domain proteins. By analyzing CHROMATIN REMODELING11 (CHR11) and RINGLET1 (RLT1), an Arabidopsis thaliana ISWI (AtISWI) and AtDDT-domain protein, respectively, we show that the SLIDE domain of CHR11 and the DDT domain together with an adjacent sequence of RLT1 are responsible for their binding. The Arabidopsis genome contains at least 12 genes that encode DDT-domain proteins, which could be grouped into five subfamilies based on the sequence similarity. The SLIDE domain of AtISWI is able to bind members from different AtDDT subfamilies. Moreover, a human ISWI protein SNF2H is capable of binding AtDDT-domain proteins through its SLIDE domain, suggesting that binding to DDT-domain proteins is a conserved biochemical function for the SLIDE domain of ISWIs in eukaryotes.

  10. Phylogenetic Analysis of RhoGAP Domain-Containing Proteins

    Institute of Scientific and Technical Information of China (English)

    Marcelo M.Brand(a)o; Karina L.Silva-Brand(a)o; Fernando F.Costa; Sara T.O.Saad

    2006-01-01

    Proteins containing an Rho GTPase-activating protein (RhoGAP) domain work as molecular switches involved in the regulation of diverse cellular functions. The ability of these GTPases to regulate a wide number of cellular processes comes from their interactions with multiple effectors and inhibitors, including the RhoGAP family, which stimulates their intrinsic GTPase activity. Here, a phylogenetic approach was applied to study the evolutionary relationship among 59 RhoGAP domain-containing proteins. The sequences were aligned by their RhoGAP domains and the phylogenetic hypotheses were generated using Maximum Parsimony and Bayesian analyses. The character tracing of two traits, GTPase activity and presence of other domains, indicated a significant phylogenetic signal for both of them.

  11. Structure of the kinase domain of Gilgamesh from Drosophila melanogaster.

    Science.gov (United States)

    Han, Ni; Chen, CuiCui; Shi, Zhubing; Cheng, Dianlin

    2014-04-01

    The CK1 family kinases regulate multiple cellular aspects and play important roles in Wnt/Wingless and Hedgehog signalling. The kinase domain of Drosophila Gilgamesh isoform I (Gilgamesh-I), a homologue of human CK1-γ, was purified and crystallized. Crystals of methylated Gilgamesh-I kinase domain with a D210A mutation diffracted to 2.85 Å resolution and belonged to space group P43212, with unit-cell parameters a = b = 52.025, c = 291.727 Å. The structure of Gilgamesh-I kinase domain, which was determined by molecular replacement, has conserved catalytic elements and an active conformation. Structural comparison indicates that an extended loop between the α1 helix and the β4 strand exists in the Gilgamesh-I kinase domain. This extended loop may regulate the activity and function of Gilgamesh-I.

  12. Structure of synaptophysin: a hexameric MARVEL-domain channel protein.

    Science.gov (United States)

    Arthur, Christopher P; Stowell, Michael H B

    2007-06-01

    Synaptophysin I (SypI) is an archetypal member of the MARVEL-domain family of integral membrane proteins and one of the first synaptic vesicle proteins to be identified and cloned. Most all MARVEL-domain proteins are involved in membrane apposition and vesicle-trafficking events, but their precise role in these processes is unclear. We have purified mammalian SypI and determined its three-dimensional (3D) structure by using electron microscopy and single-particle 3D reconstruction. The hexameric structure resembles an open basket with a large pore and tenuous interactions within the cytosolic domain. The structure suggests a model for Synaptophysin's role in fusion and recycling that is regulated by known interactions with the SNARE machinery. This 3D structure of a MARVEL-domain protein provides a structural foundation for understanding the role of these important proteins in a variety of biological processes.

  13. SPOC: A widely distributed domain associated with cancer, apoptosis and transcription

    Directory of Open Access Journals (Sweden)

    Martinez-A Carlos

    2004-07-01

    Full Text Available Abstract Background The Split ends (Spen family are large proteins characterised by N-terminal RNA recognition motifs (RRMs and a conserved SPOC (Spen paralog and ortholog C-terminal domain. The aim of this study is to characterize the family at the sequence level. Results We describe undetected members of the Spen family in other lineages (Plasmodium and Plants and localise SPOC in a new domain context, in a family that is common to all eukaryotes using profile-based sequence searches and structural prediction methods. Conclusions The widely distributed DIO (Death inducer-obliterator family is related to cancer and apoptosis and offers new clues about SPOC domain functionality.

  14. Protein domain organisation: adding order

    Directory of Open Access Journals (Sweden)

    Kummerfeld Sarah K

    2009-01-01

    Full Text Available Abstract Background Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. Results We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Conclusion Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected

  15. Roles within the Family

    Science.gov (United States)

    ... Life Listen Español Text Size Email Print Share Roles Within the Family Page Content Article Body Families ... family unit, and which rights, privileges, obligations, and roles are assigned to each family member. In most ...

  16. Dbl family guanine nucleotide exchange factors.

    Science.gov (United States)

    Zheng, Y

    2001-12-01

    The Dbl family of guanine nucleotide exchange factors are multifunctional molecules that transduce diverse intracellular signals leading to the activation of Rho GTPases. The tandem Dbl-homology and pleckstrin-homology domains shared by all members of this family represent the structural module responsible for catalyzing the GDP-GTP exchange reaction of Rho proteins. Recent progress in genomic, genetic, structural and biochemical studies has implicated Dbl family members in diverse biological processes, including growth and development, skeletal muscle formation, neuronal axon guidance and tissue organization. The detailed pictures of their autoregulation, agonist-controlled activation and mechanism of interaction with Rho GTPase substrates, have begun to emerge.

  17. Individual and Contextual Parameters Associated with Adolescents' Domain Specific Self-Perceptions

    Science.gov (United States)

    Kokkinos, Constantinos M.; Hatzinikolaou, Stamatia

    2011-01-01

    The present study examined the role of adolescents' self-esteem and perceptions of family and classroom contexts on their domain specific self-perceptions. 345 Greek junior high school adolescents aged 14-16 completed measures of domain specific self-perceptions, self-esteem, parenting styles and classroom climate. Hierarchical regression analyses…

  18. Global minimizing domains for the first eigenvalue of an elliptic operator with non-constant coefficients

    Directory of Open Access Journals (Sweden)

    Dorin Bucur

    2000-05-01

    Full Text Available We consider an elliptic operator, in divergence form, that is a uniformly elliptic matrix. We describe the behavior of every sequence of domains which minimizes the first Dirichlet eigenvalue over a family of fixed measure domains of $R^N$. The existence of minimizers is proved in some particular situations, for example when the operator is periodic.

  19. Phosphorylation and Functional Properties of the IIA Domain of the Lactose Transport Protein of Streptococcus thermophilus

    NARCIS (Netherlands)

    Gunnewijk, M.G W; Postma, P.W.; Poolman, B.

    1999-01-01

    The lactose-H+ symport protein (LacS) of Streptococcus thermophilus has a carboxyl-terminal regulatory domain (IIALacS) that is homologous to a family of proteins and protein domains of the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS) in various organisms, of which IIAGlc of Esc

  20. Individual and Contextual Parameters Associated with Adolescents' Domain Specific Self-Perceptions

    Science.gov (United States)

    Kokkinos, Constantinos M.; Hatzinikolaou, Stamatia

    2011-01-01

    The present study examined the role of adolescents' self-esteem and perceptions of family and classroom contexts on their domain specific self-perceptions. 345 Greek junior high school adolescents aged 14-16 completed measures of domain specific self-perceptions, self-esteem, parenting styles and classroom climate. Hierarchical regression analyses…

  1. Oligomerization of DH Domain Is Essential for Dbl-Induced Transformation

    OpenAIRE

    Zhu, Kejin; Debreceni, Balazs; Bi, Feng; Zheng, Yi

    2001-01-01

    The dbl oncogene product (onco-Dbl) is the prototype member of a family of guanine nucleotide exchange factors (GEFs) for Rho GTPases. The Dbl homology (DH) domain of onco-Dbl is responsible for the GEF catalytic activity, and the DH domain, together with the immediately adjacent pleckstrin homology (PH) domain, constitutes the minimum module bearing transforming function. In the present study, we demonstrate that the onco-Dbl protein exists in oligomeric form in vitro and in cells. The oligo...

  2. Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein

    DEFF Research Database (Denmark)

    Jacobsen, Linda; Madsen, P; Moestrup, S K;

    1996-01-01

    the corresponding cDNA. The gene, designated SORL1, maps to chromosome 11q 23/24 and encodes a 2214-residue type 1 receptor containing a furin cleavage site immediately preceding the N terminus determined in the purified protein. The receptor, designated sorLA-1, has a short cytoplasmic tail containing a tyrosine......-based internalization signal and a large external part containing (from the N-terminal): 1) a segment homologous to domains in the yeast vacuolar protein sorting 10 protein, Vps10p, that binds carboxypeptidase Y, 2) five tandemly arranged YWTD repeats and a cluster of 11 class A repeats characteristic of the low...... density lipoprotein receptor gene family receptors, and 3) six tandemly arranged fibronectin type III repeats also found in certain neural adhesion proteins. sorLA-1 may therefore be classified as a hybrid receptor. Northern blotting revealed specific mRNA transcripts in brain, spinal cord, and testis...

  3. Integrating Family Resilience and Family Stress Theory.

    Science.gov (United States)

    Patterson, Joan M.

    2002-01-01

    The construct, family resilience, is defined differently by practitioners and researchers. This study tries to clarify the concept of family resilience. The foundation is family stress and coping theory, particularly the stress models that emphasize adaptation processes in families exposed to major adversities. (JDM)

  4. A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange

    OpenAIRE

    Rossman, Kent L.; Worthylake, David K.; Snyder, Jason T; Siderovski, David P.; Campbell, Sharon L; Sondek, John

    2002-01-01

    Dbl-related oncoproteins are guanine nucleotide exchange factors (GEFs) specific for Rho guanosine triphosphatases (GTPases) and invariably possess tandem Dbl (DH) and pleckstrin homology (PH) domains. While it is known that the DH domain is the principal catalytic subunit, recent biochemical data indicate that for some Dbl-family proteins, such as Dbs and Trio, PH domains may cooperate with their associated DH domains in promoting guanine nucleotide exchange of Rho GTPases. In order to gain ...

  5. 血浆Ras相关区域家族蛋白1A基因甲基化在肝细胞癌分子诊断中的价值%Clinical significance of methylation of plasma Ras-association domain family 1A gene in the molecular diagnosis of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    费伯健; 黄朝晖; 华东; 胡瑜; 程之红; 余坚

    2011-01-01

    Objective: To establish a methylation-sensitive restriction enzymes-based quantitative PCR (MSRE-qPCR) method for methylation analysis of Ras-association domain family 1A (RASSF1A) gene, and to further assess the clinical value of plasma methylation analysis using this method for noninvasive diagnosis of hepatocellutar carcinoma (HCC). Methods: MRSE Hha I was used to digest genomic DNA samples, and the digestion result was evaluated by using qPCR. Then the MSRE-qPCR method for methylation analysis of RASSF\\A gene was established. The efficacy of this method was tested in 45 liver tissues (20 surgically resected HCC specimens and the matched non-cancerous tissues, as well as 5 normal liver tissues), and which was further validated by using bisulfite sequencing PCR (BSP). The results of MRSE-qPCR were compared with those of methylation-specific PCR (MSP) assay. The established MSRE-qPCR method was used to detect the RASSF]A methylation levels in 150 plasma samples from 72 cases of HCC, 37 cases of benign liver diseases such as liver cirrhosis and chronic hepatitis, and 41 normal controls, and the associations of RASSF1A methylation level with the clinicopathological parameters of patients with HCC were evaluated.Results: The established MSRE-qPCR method could detect as low as 1% methylated target sites in given DNA samples. Of the 20 HCC tissues, 14 (70%) were hypermethylated in the target CpC of RASSF]A promoter. Five matched non-cancerous tissues were also found to be methylated, whereas no methylated RASSF]A sequence was detected in 5 normal liver tissues. The result of MSRE-qPCR was accurate and comparable with that of MSP. The positive rate of RASSF\\A methylation in plasma samples from patients with HCC was 65.3% (47/72), which was significantly higher than those from patients with benign liver diseases (3/37, 8.1%) and normal controls (1/41, 2.4%) (f<0.000 1). Combined analysis of plasma RASSF\\A methylation and serum AFP revealed an increased diagnostic

  6. Protein domains and architectural innovation in plant-associated Proteobacteria

    Directory of Open Access Journals (Sweden)

    Downie J Allan

    2005-02-01

    Full Text Available Abstract Background Evolution of new complex biological behaviour tends to arise by novel combinations of existing building blocks. The functional and evolutionary building blocks of the proteome are protein domains, the function of a protein being dependent on its constituent domains. We clustered completely-sequenced proteomes of prokaryotes on the basis of their protein domain content, as defined by Pfam (release 16.0. This revealed that, although there was a correlation between phylogeny and domain content, other factors also have an influence. This observation motivated an investigation of the relationship between an organism's lifestyle and the complement of domains and domain architectures found within its proteome. Results We took a census of all protein domains and domain combinations (architectures encoded in the completely-sequenced proteobacterial genomes. Nine protein domain families were identified that are found in phylogenetically disparate plant-associated bacteria but are absent from non-plant-associated bacteria. Most of these are known to play a role in the plant-associated lifestyle, but they also included domain of unknown function DUF1427, which is found in plant symbionts and pathogens of the alpha-, beta- and gamma-Proteobacteria, but not known in any other organism. Further, several domains were identified as being restricted to phytobacteria and Eukaryotes. One example is the RolB/RolC glucosidase family, which is found only in Agrobacterium species and in plants. We identified the 0.5% of Pfam protein domain families that were most significantly over-represented in the plant-associated Proteobacteria with respect to the background frequencies in the whole set of available proteobacterial proteomes. These included guanylate cyclase, domains implicated in aromatic catabolism, cellulase and several domains of unknown function. We identified 459 unique domain architectures found in phylogenetically diverse plant pathogens

  7. Structural basis of Smoothened regulation by its extracellular domains

    Science.gov (United States)

    Byrne, Eamon F. X.; Sircar, Ria; Miller, Paul S.; Hedger, George; Luchetti, Giovanni; Nachtergaele, Sigrid; Tully, Mark D.; Mydock-McGrane, Laurel; Covey, Douglas F.; Rambo, Robert P.; Sansom, Mark S. P.; Newstead, Simon; Rohatgi, Rajat; Siebold, Christian

    2016-07-01

    Developmental signals of the Hedgehog (Hh) and Wnt families are transduced across the membrane by Frizzled-class G-protein-coupled receptors (GPCRs) composed of both a heptahelical transmembrane domain (TMD) and an extracellular cysteine-rich domain (CRD). How the large extracellular domains of GPCRs regulate signalling by the TMD is unknown. We present crystal structures of the Hh signal transducer and oncoprotein Smoothened, a GPCR that contains two distinct ligand-binding sites: one in its TMD and one in the CRD. The CRD is stacked atop the TMD, separated by an intervening wedge-like linker domain. Structure-guided mutations show that the interface between the CRD, linker domain and TMD stabilizes the inactive state of Smoothened. Unexpectedly, we find a cholesterol molecule bound to Smoothened in the CRD binding site. Mutations predicted to prevent cholesterol binding impair the ability of Smoothened to transmit native Hh signals. Binding of a clinically used antagonist, vismodegib, to the TMD induces a conformational change that is propagated to the CRD, resulting in loss of cholesterol from the CRD-linker domain-TMD interface. Our results clarify the structural mechanism by which the activity of a GPCR is controlled by ligand-regulated interactions between its extracellular and transmembrane domains.

  8. Domain imaging in FINEMET ribbons

    Energy Technology Data Exchange (ETDEWEB)

    Silveyra, J.M., E-mail: jsilveyra@fi.uba.a [Laboratorio de Solidos Amorfos, INTECIN, Facultad de Ingenieria, UBA-CONICET, Paseo Colon 850, (C1063ACV) Buenos Aires (Argentina); Vlasak, G.; Svec, P.; Janickovic, D. [Institute of Physics, Slovak Academy of Sciences, Dubravska cesta 9, 845 11 Bratislava (Slovakia); Cremaschi, V.J., E-mail: vcremas@gmail.co [Laboratorio de Solidos Amorfos, INTECIN, Facultad de Ingenieria, UBA-CONICET, Paseo Colon 850, (C1063ACV) Buenos Aires (Argentina); Member of Carrera del Investigador, CONICET (Argentina)

    2010-09-15

    The magnetization behaviour of a ferromagnetic material depends on its domain structure, which in turn is largely determined by magnetic anisotropies. In this work, domain patterns were observed by a quite forgotten but still the simplest and the cheapest technique: the Bitter method. A systematic study of the evolution of the domain structure in FINEMET ribbons after thermal annealing is presented, correlating the results with the crystalline structure, magnetostriction and coercivity measurements.

  9. Dynamical domain wall and localization

    Directory of Open Access Journals (Sweden)

    Yuta Toyozato

    2016-03-01

    Full Text Available Based on the previous works (Toyozato et al., 2013 [24]; Higuchi and Nojiri, 2014 [25], we investigate the localization of the fields on the dynamical domain wall, where the four-dimensional FRW universe is realized on the domain wall in the five-dimensional space–time. Especially we show that the chiral spinor can localize on the domain wall, which has not been succeeded in the past works as the seminal work in George et al. (2009 [23].

  10. The human protein disulfide isomerase gene family

    Directory of Open Access Journals (Sweden)

    Galligan James J

    2012-07-01

    Full Text Available Abstract Enzyme-mediated disulfide bond formation is a highly conserved process affecting over one-third of all eukaryotic proteins. The enzymes primarily responsible for facilitating thiol-disulfide exchange are members of an expanding family of proteins known as protein disulfide isomerases (PDIs. These proteins are part of a larger superfamily of proteins known as the thioredoxin protein family (TRX. As members of the PDI family of proteins, all proteins contain a TRX-like structural domain and are predominantly expressed in the endoplasmic reticulum. Subcellular localization and the presence of a TRX domain, however, comprise the short list of distinguishing features required for gene family classification. To date, the PDI gene family contains 21 members, varying in domain composition, molecular weight, tissue expression, and cellular processing. Given their vital role in protein-folding, loss of PDI activity has been associated with the pathogenesis of numerous disease states, most commonly related to the unfolded protein response (UPR. Over the past decade, UPR has become a very attractive therapeutic target for multiple pathologies including Alzheimer disease, Parkinson disease, alcoholic and non-alcoholic liver disease, and type-2 diabetes. Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR.

  11. Mapping the Moral Domain

    Science.gov (United States)

    Graham, Jesse; Nosek, Brian A.; Haidt, Jonathan; Iyer, Ravi; Koleva, Spassena; Ditto, Peter H.

    2010-01-01

    The moral domain is broader than the empathy and justice concerns assessed by existing measures of moral competence, and it is not just a subset of the values assessed by value inventories. To fill the need for reliable and theoretically-grounded measurement of the full range of moral concerns, we developed the Moral Foundations Questionnaire (MFQ) based on a theoretical model of five universally available (but variably developed) sets of moral intuitions: Harm/care, Fairness/reciprocity, Ingroup/loyalty, Authority/respect, and Purity/sanctity. We present evidence for the internal and external validity of the scale and the model, and in doing so present new findings about morality: 1. Comparative model fitting of confirmatory factor analyses provides empirical justification for a five-factor structure of moral concerns. 2. Convergent/discriminant validity evidence suggests that moral concerns predict personality features and social group attitudes not previously considered morally relevant. 3. We establish pragmatic validity of the measure in providing new knowledge and research opportunities concerning demographic and cultural differences in moral intuitions. These analyses provide evidence for the usefulness of Moral Foundations Theory in simultaneously increasing the scope and sharpening the resolution of psychological views of morality. PMID:21244182

  12. Discoidin Domain Receptor 1

    Science.gov (United States)

    Song, Sunmi; Shackel, Nicholas A.; Wang, Xin M.; Ajami, Katerina; McCaughan, Geoffrey W.; Gorrell, Mark D.

    2011-01-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell–collagen interactions in chronic liver injury. PMID:21356365

  13. Family Trajectories and Health : A Life Course Perspective

    NARCIS (Netherlands)

    Barban, Nicola

    2013-01-01

    This paper investigates the role of family trajectory, i.e., the whole sequence of family events during the life course of early adults in shaping their health outcomes. Union formation and childbearing are jointly considered, since the two life domains are highly connected and their intersections

  14. Family Trajectories and Health : A Life Course Perspective

    NARCIS (Netherlands)

    Barban, Nicola

    2013-01-01

    This paper investigates the role of family trajectory, i.e., the whole sequence of family events during the life course of early adults in shaping their health outcomes. Union formation and childbearing are jointly considered, since the two life domains are highly connected and their intersections m

  15. Life Satisfaction and Family Structure among Adolescents in Hong Kong

    Science.gov (United States)

    Kwan, Ying-Keung

    2008-01-01

    Relationships between family structure and perceived life satisfaction in overall life and five domains of the Brief Multidimensional Students' Life Satisfaction Scale, family life, friendships, school experience, myself, and where I live were examined among 4,502 Chinese adolescent secondary school students in Hong Kong. Bivariate analyses showed…

  16. Domain walls and ferroelectric reversal in corundum derivatives

    Science.gov (United States)

    Ye, Meng; Vanderbilt, David

    2017-01-01

    Domain walls are the topological defects that mediate polarization reversal in ferroelectrics, and they may exhibit quite different geometric and electronic structures compared to the bulk. Therefore, a detailed atomic-scale understanding of the static and dynamic properties of domain walls is of pressing interest. In this work, we use first-principles methods to study the structures of 180∘ domain walls, both in their relaxed state and along the ferroelectric reversal pathway, in ferroelectrics belonging to the family of corundum derivatives. Our calculations predict their orientation, formation energy, and migration energy and also identify important couplings between polarization, magnetization, and chirality at the domain walls. Finally, we point out a strong empirical correlation between the height of the domain-wall-mediated polarization reversal barrier and the local bonding environment of the mobile A cations as measured by bond-valence sums. Our results thus provide both theoretical and empirical guidance for future searches for ferroelectric candidates in materials of the corundum derivative family.

  17. Family Matters

    Directory of Open Access Journals (Sweden)

    Isabel de Riquer

    2011-04-01

    Full Text Available The scene is at the court of James I of Aragon in the mid-13th c., the place is the royal palace of Barcelona or any of the crown's other possessions, and the dramatis personae include the heir to the throne, prince Peire (future king Peire the Great, and the court's most famous troubadour, Cerverí de Girona (fl. 1259-85. Author of the largest corpus of any Occitan troubadour (114 poems, Cerverì distinguishes himself by the surprises and challenges he presents to his audience: an alba (the most openly erotic genre to the Virgin Mary, the Cobla in sis lengatges (Cobla in Six Languages, the apparently nonsensical Vers estrayn. Cerverì borrows equally from the folk-inspired Galician-Portuguese poetry and from the French tradition, including the chanson de malmariée, where a young woman bemoans being sold off by her family to an old man (gilos, "Jealous" and separated from her youthful doulz amis, some even praying for the death of their husband. Both within that tradition and among Cerverì's three chansons de malmariée, the Gelosesca stands out as "especially determined" to lose her husband, using every "solution" (prayer, black magic, potion or experimenta.

  18. Bossa Nova: Introducing modularity into the Bossa Nova domain-specific language

    DEFF Research Database (Denmark)

    Lawall, Julia Laetitia; Duschene, Hervé; Muller, Gilles;

    2005-01-01

    Domain-specific languages (DSLs) have been proposed as a solution to ease the development of programs within a program family. Sometimes, however, experience with the use of a DSL reveals the presence of subfamilies within the family targeted by the language. We are then faced with the question...... modular language, Bossa Nova, and assess the language quantitatively and qualitatively....

  19. Hmong Students’ Perceptions of Their Family Environment: A Consensual Qualitative Analysis of Family Photos

    Directory of Open Access Journals (Sweden)

    Dung Mao

    2012-01-01

    Full Text Available Although various studies have examined the home environment of low-income families and its impact on children’s development, limited research has been done to investigate the impact of home environment on Hmong American families, especially those who live below the federal poverty line. The purpose of this study was to document from the students’ perspective what it is like to live and grow up in a poor family. Fifteen Hmong students in 5th through 8th grades tookpart in the photovoice project. The consensual qualitative analyses of the photos and interviews revealed two domains (family physical home environment and family activities, seven themes (crowded space, unkempt space, equipped with media, generational and gender separation, parental involvement, organization of daily life, and social connections and 38 core ideas. Some implications of the study are proposed for educators who work with Hmong families.

  20. Development and testing of the Survey of Family Environment (SFE): a novel instrument to measure family functioning and needs for family support.

    Science.gov (United States)

    Hohashi, Naohiro; Honda, Junko

    2012-01-01

    Hohashi's Concentric Sphere Family Environment Model (CSFEM; Hohashi & Honda, 2011) is a newly proposed family nursing theory for holistically understanding the family environment that acts on family well-being. The purpose of this article is to develop and psychometrically test the Japanese version of the Survey of Family Environment (SFE-J), grounded in the CSFEM, for measuring family's perceived family functioning and family's perceived needs for family support. The SFE-J is a 30-item self-administered instrument that assesses five domains (suprasystem, macrosystem, microsystem, family internal environment system, and chronosystem) and has been subjected to rigorous reliability and validity investigations among paired partners in child-rearing families (N of family = 1,990). Internal consistency reliability was high as measured by Cronbach's alpha coefficients. Temporal stability over a 2-week interval was supported by high (substantial or perfect) and significant intraclass correlation coefficients. The total score for the SFE-J was significantly correlated with the Japanese version of the Feetham Family Functioning Survey (FFFS-J), indicating an acceptable concurrent validity. Construct validity was supported by a confirmatory factor analysis that evaluated the five-factor structure to measure the concept of CSFEM. Results also demonstrate that the SFE-J family functioning scores show no significant differences between paired partners. The SFE-J is a reliable and valid instrument to assess not only intrafamily functioning but also interfamily functioning and, by identifying items/domains with high requirements for family support, serves to facilitate the providing of appropriate support to families.

  1. Ontology development for Sufism domain

    Science.gov (United States)

    Iqbal, Rizwan

    2012-01-01

    Domain ontology is a descriptive representation of any particular domain which in detail describes the concepts in a domain, the relationships among those concepts and organizes them in a hierarchal manner. It is also defined as a structure of knowledge, used as a means of knowledge sharing to the community. An Important aspect of using ontologies is to make information retrieval more accurate and efficient. Thousands of domain ontologies from all around the world are available online on ontology repositories. Ontology repositories like SWOOGLE currently have over 1000 ontologies covering a wide range of domains. It was found that up to date there was no ontology available covering the domain of "Sufism". This unavailability of "Sufism" domain ontology became a motivation factor for this research. This research came up with a working "Sufism" domain ontology as well a framework, design of the proposed framework focuses on the resolution to problems which were experienced while creating the "Sufism" ontology. The development and working of the "Sufism" domain ontology are covered in detail in this research. The word "Sufism" is a term which refers to Islamic mysticism. One of the reasons to choose "Sufism" for ontology creation is its global curiosity. This research has also managed to create some individuals which inherit the concepts from the "Sufism" ontology. The creation of individuals helps to demonstrate the efficient and precise retrieval of data from the "Sufism" domain ontology. The experiment of creating the "Sufism" domain ontology was carried out on a tool called Protégé. Protégé is a tool which is used for ontology creation, editing and it is open source.

  2. Genome-Wide Identification and Evolutionary Analysis of the Animal Specific ETS Transcription Factor Family

    OpenAIRE

    Wang, Zhipeng; Zhang, Qin

    2009-01-01

    The ETS proteins are a family of transcription factors (TFs) that regulate a variety of biological processes. We made genome-wide analyses to explore the classification of the ETS gene family. We identified 207 ETS genes which encode 321 ETS TFs from ten animal species. Of the 321 ETS TFs, 155 contain only an ETS domain, about 50% contain a ETS_PEA3_N or a SAM_PNT domain in addition to an ETS domain, the rest (only four) contain a second ETS domain or a second ETS_PEA3_N domain or an another ...

  3. Domain-wall spin dynamics in kagome antiferromagnets.

    Science.gov (United States)

    Lhotel, E; Simonet, V; Ortloff, J; Canals, B; Paulsen, C; Suard, E; Hansen, T; Price, D J; Wood, P T; Powell, A K; Ballou, R

    2011-12-16

    We report magnetization and neutron scattering measurements down to 60 mK on a new family of Fe based kagome antiferromagnets, in which a strong local spin anisotropy combined with a low exchange path network connectivity lead to domain walls intersecting the kagome planes through strings of free spins. These produce unfamiliar slow spin dynamics in the ordered phase, evolving from exchange-released spin flips towards a cooperative behavior on decreasing the temperature, probably due to the onset of long-range dipolar interaction. A domain structure of independent magnetic grains is obtained that could be generic to other frustrated magnets.

  4. 'Time-out' with the family: the shaping of family leisure in the new urban consumption spaces of cafes, bars and restaurants

    NARCIS (Netherlands)

    Karsten, L.; Kamphuis, A.; Remeijnse, C.

    2015-01-01

    In many north-western European countries, the family practices of drinking and eating used to be largely located in the private domain of the home. This situation has recently begun to change, particularly in gentrified urban areas where middle-class families are growing in number and family outings

  5. On Probability Domains

    Science.gov (United States)

    Frič, Roman; Papčo, Martin

    2010-12-01

    Motivated by IF-probability theory (intuitionistic fuzzy), we study n-component probability domains in which each event represents a body of competing components and the range of a state represents a simplex S n of n-tuples of possible rewards-the sum of the rewards is a number from [0,1]. For n=1 we get fuzzy events, for example a bold algebra, and the corresponding fuzzy probability theory can be developed within the category ID of D-posets (equivalently effect algebras) of fuzzy sets and sequentially continuous D-homomorphisms. For n=2 we get IF-events, i.e., pairs ( μ, ν) of fuzzy sets μ, ν∈[0,1] X such that μ( x)+ ν( x)≤1 for all x∈ X, but we order our pairs (events) coordinatewise. Hence the structure of IF-events (where ( μ 1, ν 1)≤( μ 2, ν 2) whenever μ 1≤ μ 2 and ν 2≤ ν 1) is different and, consequently, the resulting IF-probability theory models a different principle. The category ID is cogenerated by I=[0,1] (objects of ID are subobjects of powers I X ), has nice properties and basic probabilistic notions and constructions are categorical. For example, states are morphisms. We introduce the category S n D cogenerated by Sn=\\{(x1,x2,ldots ,xn)in In;sum_{i=1}nxi≤ 1\\} carrying the coordinatewise partial order, difference, and sequential convergence and we show how basic probability notions can be defined within S n D.

  6. The Pfam protein families database.

    Science.gov (United States)

    Finn, Robert D; Tate, John; Mistry, Jaina; Coggill, Penny C; Sammut, Stephen John; Hotz, Hans-Rudolf; Ceric, Goran; Forslund, Kristoffer; Eddy, Sean R; Sonnhammer, Erik L L; Bateman, Alex

    2008-01-01

    Pfam is a comprehensive collection of protein domains and families, represented as multiple sequence alignments and as profile hidden Markov models. The current release of Pfam (22.0) contains 9318 protein families. Pfam is now based not only on the UniProtKB sequence database, but also on NCBI GenPept and on sequences from selected metagenomics projects. Pfam is available on the web from the consortium members using a new, consistent and improved website design in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/), as well as from mirror sites in France (http://pfam.jouy.inra.fr/) and South Korea (http://pfam.ccbb.re.kr/).

  7. Genetic Analysis of MEFV Gene Pyrin Domain in Patients With Behçet's Disease

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Objectives. Behçet's disease (BD is a systemic vasculitis with recurrent oral and genital ulcers and uveitis. MEFV gene, which is the main factor in familial Mediterranean fever (FMF, is also reported to be a susceptibility gene for BD. The pyrin domain of MEFV gene is a member of death-domain superfamily and has been proposed to regulate inflammatory signaling in myeloid cells. This study was designed to determine if mutations in pyrin domain of MEFV gene are involved in BD. Methods. We analyzed the pyrin domain of MEFV gene in 54 Turkish patients with BD by PCR-analysis and direct sequencing. Results. Neither deletion or insertion mutations nor point mutations in pyrin domain were found in any patient. Conclusion. Although pyrin gene mutations have been reported in patients with BD, pyrin domain is not mutated. However, alterations in other regions of MEFV gene and interaction between pyrin domains are needed to be further investigated.

  8. Taxonomies of Educational Objective Domain

    OpenAIRE

    Eman Ghanem Nayef; Nik Rosila Nik Yaacob; Hairul Nizam Ismail

    2013-01-01

    This paper highlights an effort to study the educational objective domain taxonomies including Bloom’s taxonomy, Lorin Anderson’s taxonomy, and Wilson’s taxonomy. In this study a comparison among these three taxonomies have been done. Results show that Bloom’s taxonomy is more suitable as an analysis tool to Educational Objective domain.

  9. Crystal structure studies of NADP+ dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain.

    Science.gov (United States)

    Kumar, S M; Pampa, K J; Manjula, M; Abdoh, M M M; Kunishima, Naoki; Lokanath, N K

    2014-06-20

    NADP(+) dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP(+) was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH's. And, small domain and clasp domain showing significant differences when compared to other IDH's of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH's. Also, helices/beta sheets are absent in the small domain, when compared to other IDH's of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit-subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.

  10. Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

    Science.gov (United States)

    Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

    2008-08-22

    CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

  11. The EMILIN/Multimerin family

    Directory of Open Access Journals (Sweden)

    Alfonso eColombatti

    2012-01-01

    Full Text Available EMILINs and Multimerins (EMILIN1, EMILIN2, Multimerin1, and Multimerin2 constitute a four member family that in addition to the shared C-terminus gC1q domain typical of the gC1q/TNF superfamily members contain a N-terminus unique cysteine-rich EMI domain. These glycoproteins are homotrimeric and assemble into high molecular weight multimers. They are predominantly expressed in the extracellular matrix and contribute to several cellular functions in part associated with the gC1q domain and in part not yet assigned nor linked to other specific regions of the sequence. Among the latter is the control of arterial blood pressure, the inhibition of Bacillus anthracis cell cytotoxicity, the promotion of cell death, the proangiogenetic function and a role in platelet hemostasis. The focus of this review is to highlight the multiplicity of functions and domains of the EMILIN/Multimerin family with a particular emphasis on the regulatory role played by the ligand-receptor interactions of the gC1q domain.EMILIN1 is the most extensively studied member both from the structural and functional point of view. The structure of the gC1q of EMILIN1 solved by NMR highlights unique characteristics compared to other gC1q domains: it shows a marked decrease of the contact surface of the trimeric assembly and while conserving the jelly-roll topology with two β-sheets of antiparallel strands it presents a nine-stranded β-sandwich fold instead of the usual ten-stranded fold. This is likely due to the insertion of nine residues that disrupt the ordered strand organization and forma a highly dynamic protruding loop.. In this loop the residue E933 is the site of interaction between gC1q and the α4β1 and α9β1 integrins, and contrary to integrin occupancy that usually upregulates cell growth, when gC1q is ligated by the integrin the cells reduce their proliferative activity.

  12. Phase-domain photoacoustic sensing

    Science.gov (United States)

    Gao, Fei; Zhang, Ruochong; Feng, Xiaohua; Liu, Siyu; Ding, Ran; Kishor, Rahul; Qiu, Lei; Zheng, Yuanjin

    2017-01-01

    As one of the fastest-growing imaging modalities in recent years, photoacoustic imaging has attracted tremendous research interest for various applications including anatomical, functional, and molecular imaging. The majority of the photoacoustic imaging systems are based on the time-domain pulsed photoacoustic method, which utilizes a pulsed laser source to induce a wideband photoacoustic signal, revealing optical absorption contrast. An alternative way is the frequency-domain photoacoustic method utilizing the chirping modulation of laser intensity to achieve lower system cost. In this paper, we report another way of the photoacoustic method, called phase-domain photoacoustic sensing, which explores the phase difference between two consequent intensity-modulated laser pulse induced photoacoustic measurements to reveal the optical properties. The basic principle is introduced, modeled, and experimentally validated in this paper, which opens another potential pathway to perform photoacoustic sensing and imaging, eliminating acoustic detection variations beyond the conventional time-domain and frequency-domain photoacoustic methods.

  13. Domain wall description of superconductivity

    CERN Document Server

    Brito, F A; Silva, J C M

    2012-01-01

    In the present work we shall address the issue of electrical conductivity in superconductors in the perspective of superconducting domain wall solutions in the realm of field theory. We take our set up made out of a dynamical complex scalar field coupled to gauge field to be responsible for superconductivity and an extra scalar real field that plays the role of superconducting domain walls. The temperature of the system is interpreted as the parameter to move type I to type II domain walls. Alternatively, this means that the domain wall surface is suffering an acceleration as one goes from one type to another. On the other hand, changing from type I to type II state means a formation of a condensate what is in perfect sense of lowering the temperature around the superconductor. One can think of this scenario as an analog of holographic scenarios where this set up is replaced by a black hole near the domain wall.

  14. Texture of lipid bilayer domains

    DEFF Research Database (Denmark)

    Jensen, Uffe Bernchou; Brewer, Jonathan R.; Midtiby, Henrik Skov

    2009-01-01

    chains. By imaging the intensity variations as a function of the polarization angle, we map the lateral variations of the lipid tilt within domains. Results reveal that gel domains are composed of subdomains with different lipid tilt directions. We have applied a Fourier decomposition method......We investigate the texture of gel (g) domains in binary lipid membranes composed of the phospholipids DPPC and DOPC. Lateral organization of lipid bilayer membranes is a topic of fundamental and biological importance. Whereas questions related to size and composition of fluid membrane domain...... are well studied, the possibility of texture in gel domains has so far not been examined. When using polarized light for two-photon excitation of the fluorescent lipid probe Laurdan, the emission intensity is highly sensitive to the angle between the polarization and the tilt orientation of lipid acyl...

  15. Family and family therapy in Russia.

    Science.gov (United States)

    Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

    2012-04-01

    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.

  16. Family influence on volunteering intention and behavior among Chinese adolescents in Hong Kong.

    Science.gov (United States)

    Law, Ben M F; Shek, Daniel T L

    2009-01-01

    Based on the responses of 5,946 adolescents (mean age = 14.77), the relationships among family influence, adolescents' volunteering intention, and volunteering behavior in a Chinese context were examined. A 9-item Chinese Family Influence on Adolescent Volunteerism Scale (C-FIAV) was used to measure nine kinds of influence of the family (such as family support) which could be subsumed under two underlying domains (positive family influence and extrinsic family influence). Results showed that family support, family belief, and family modeling were positively associated with both intention and behavior. Family reward and coercion were negatively associated with both intention and behavior. Family belief in volunteerism was the most critical factor. Grade and gender differences were found only in the associations between family influence and volunteering intention. Path models showed that positive and extrinsic family influence had an effect on volunteering behavior directly or via the mediation of volunteering intention. Implications and limitations are discussed.

  17. Glutamine versus ammonia utilization in the NAD synthetase family.

    Directory of Open Access Journals (Sweden)

    Jessica De Ingeniis

    Full Text Available NAD is a ubiquitous and essential metabolic redox cofactor which also functions as a substrate in certain regulatory pathways. The last step of NAD synthesis is the ATP-dependent amidation of deamido-NAD by NAD synthetase (NADS. Members of the NADS family are present in nearly all species across the three kingdoms of Life. In eukaryotic NADS, the core synthetase domain is fused with a nitrilase-like glutaminase domain supplying ammonia for the reaction. This two-domain NADS arrangement enabling the utilization of glutamine as nitrogen donor is also present in various bacterial lineages. However, many other bacterial members of NADS family do not contain a glutaminase domain, and they can utilize only ammonia (but not glutamine in vitro. A single-domain NADS is also characteristic for nearly all Archaea, and its dependence on ammonia was demonstrated here for the representative enzyme from Methanocaldococcus jannaschi. However, a question about the actual in vivo nitrogen donor for single-domain members of the NADS family remained open: Is it glutamine hydrolyzed by a committed (but yet unknown glutaminase subunit, as in most ATP-dependent amidotransferases, or free ammonia as in glutamine synthetase? Here we addressed this dilemma by combining evolutionary analysis of the NADS family with experimental characterization of two representative bacterial systems: a two-subunit NADS from Thermus thermophilus and a single-domain NADS from Salmonella typhimurium providing evidence that ammonia (and not glutamine is the physiological substrate of a typical single-domain NADS. The latter represents the most likely ancestral form of NADS. The ability to utilize glutamine appears to have evolved via recruitment of a glutaminase subunit followed by domain fusion in an early branch of Bacteria. Further evolution of the NADS family included lineage-specific loss of one of the two alternative forms and horizontal gene transfer events. Lastly, we identified NADS

  18. Bequeathing Family Continuity.

    Science.gov (United States)

    Spanier, Graham B.

    1989-01-01

    Notes that many children who experience abuse, family disruption, or poverty reach adulthood with a strong commitment to family life. Questions whether changes in American families are indicators of pathology, deterioration, and instability; and asks how dysfunctional families transmit commitment to the concept of family to succeeding generations.…

  19. Family Reading Night

    Science.gov (United States)

    Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

    2007-01-01

    This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

  20. Importance of the Alternative Five and Trait Emotional Intelligence for Agentic and Communal Domains of Satisfaction

    Directory of Open Access Journals (Sweden)

    Andreja Avsec

    2011-12-01

    Full Text Available Many studies supported the importance of trait emotional intelligence (EI for subjective well-being but specific domains of life-satisfaction were rarely of interest. Our study investigated whether emotional intelligence is more important for interpersonal or communal-related domains (e.g. satisfaction with friends, intimate partners than for agentic domains of satisfaction (e.g. satisfaction with finances, work. Due to the problematic differential validity of trait EI from personality, the relationship between trait EI and domains of satisfaction was controlled for by personality. Slovene students and young adults (N=442 completed the Emotional Skills and Competence Questionnaire and the Zuckerman-Kuhlman Personality Questionnaire, and rated their satisfaction with 12 aspects of life. Principal component analysis of these domains revealed three components, explaining 62% of total variance. The communal domains included self-reported satisfaction with popularity, respect, influence on others, family relationships, and intimate relationship. The agentic domains included satisfaction with professional carrier, financial situation, academic education, and achieved goals. The physical domains component was comprised of satisfaction with appearance, fitness, and health. After accounting for personality, trait EI explained 16% of variance in communal domain and 10% of variance in agentic domain, thus suggesting greater importance of trait EI for interpersonal domains. However, trait EI seems to play an important role for satisfaction in the agentic domains also, as successful management of our emotions can help us reach our goals and thus be more satisfied.

  1. Comparison of CD45 extracellular domain sequences from divergent vertebrate species suggests the conservation of three fibronectin type III domains.

    Science.gov (United States)

    Okumura, M; Matthews, R J; Robb, B; Litman, G W; Bork, P; Thomas, M L

    1996-08-15

    Mammalian CD45 is a transmembrane protein tyrosine phosphatase expressed by all nucleated cells of hematopoietic origin. In lymphocytes, CD45 is required for Ag-induced signal transduction due to its ability to positively regulate Src family members. The mechanisms by which CD45 function is regulated are unknown. Indeed, the interactions of CD45 extracellular domains are largely undefined. To gain insight into potentially important regions of the extracellular domain, we sought to identify conserved features from divergent species. cDNAs encoding the putative CD45 homologue from Heterodontus francisci (horned shark) were isolated. The cDNA sequence predicts a protein of 1200 amino acids that contains a 452-amino acid extracellular domain, a 22-amino acid transmembrane region, and a 703-amino acid cytoplasmic domain. Alignment searches revealed that the Heterodontus cytoplasmic domain sequence was most identical to mammalian CD45 and a transmembrane protein tyrosine phosphatase sequence identified from chickens, ChPTP lambda. A dendrogram with other transmembrane protein tyrosine phosphatase sequences suggest that the Heterodontus and chicken sequences represents CD45 orthologues for their respective species. Analysis of vertebrate CD45 extracellular domain sequences indicates the conservation of three structural regions: a region containing potential O-linked carbohydrate sites, a cysteine-containing region, and a region containing three fibronectin type III domains. For each vertebrate species, multiple isoforms are generated by alternative splicing of three exons that encode a portion of the region containing potential O-linked glycosylation sites. These studies provide evidence for a conservation in CD45 extracellular domain structure between divergent species and provide a basis for understanding CD45 extracellular domain interactions.

  2. Family Factors in Small Family Business Growth

    National Research Council Canada - National Science Library

    Jim Cater; Marilyn Young

    2016-01-01

    .... We suggest that while all three patterns of small family business growth may lead to individual company success and sustainability, businesses with units in multiple trade areas may be most adept at managing the six family factors.

  3. What’s for dinner? Types of food served at family dinner differ across parent and family characteristics

    Science.gov (United States)

    Neumark-Sztainer, Dianne; MacLehose, Rich; Loth, Katie; Fulkerson, Jayne A.; Eisenberg, Marla E.; Berge, Jerica

    2013-01-01

    Objective To examine the types of food served at family dinner in the homes of adolescents and correlations with parent and family sociodemographic characteristics, psychosocial factors, and meal-specific variables. Design A cross-sectional population-based survey completed by mail or telephone by parents participating in Project F-EAT (Families and Eating and Activity in Teens) in 2009–2010. Setting Homes of families with adolescents in Minneapolis/St Paul urban area. Subjects Participants included 1,923 parents/guardians (90.8% female; 68.5% from ethnic/racial minorities) of adolescents who participated in EAT 2010. Results Less than a third (28%) of parents reported serving a green salad at family dinner on a regular basis, but 70% reported regularly serving vegetables (other than potatoes). About one-fifth (21%) of families had fast food at family dinners two or more times a week. Variables from within the sociodemographic domain (low educational attainment); psychosocial domain (high work-life stress, depressive symptoms, low family functioning); and meal-specific domain (low value of family meals, low enjoyment of cooking, low meal planning, high food purchasing barriers, and fewer hours in food preparation) were associated with lower healthfulness of foods served at family dinners, in analyses adjusted for sociodemographic characteristics. Conclusions There is a need for interventions to improve the healthfulness of food served at family meals. Interventions need to be suitable for parents with low levels of education; take parent and family psychosocial factors into account; promote more positive attitudes toward family meals; and provide skills to make it easier to plan and prepare healthful family meals. PMID:23083836

  4. Mutation of domain III and domain VI in L gene conserved domain of Nipah virus

    Science.gov (United States)

    Jalani, Siti Aishah; Ibrahim, Nazlina

    2016-11-01

    Nipah virus (NiV) is the etiologic agent responsible for the respiratory illness and causes fatal encephalitis in human. NiV L protein subunit is thought to be responsible for the majority of enzymatic activities involved in viral transcription and replication. The L protein which is the viral RNA dependent RNA polymerase has high sequence homology among negative sense RNA viruses. In negative stranded RNA viruses, based on sequence alignment six conserved domain (domain I-IV) have been determined. Each domain is separated on variable regions that suggest the structure to consist concatenated functional domain. To directly address the roles of domains III and VI, site-directed mutations were constructed by the substitution of bases at sequences 2497, 2500, 5528 and 5532. Each mutated L gene can be used in future studies to test the ability for expression on in vitro translation.

  5. Domain Walls in SU(5)

    CERN Document Server

    Poghosian, L E; Pogosian, Levon; Vachaspati, Tanmay

    2000-01-01

    We consider the Grand Unified SU(5) model with a small or vanishing cubic term in the adjoint scalar field in the potential. This gives the model an approximate or exact Z$_2$ symmetry whose breaking leads to domain walls. The simplest domain wall has the structure of a kink across which the Higgs field changes sign ($\\Phi \\to -\\Phi$) and inside which the full SU(5) is restored. The kink is shown to be perturbatively unstable for all parameters. We then construct a domain wall solution that is lighter than the kink and show it to be perturbatively stable for a range of parameters. The symmetry in the core of this domain wall is smaller than that outside. The interactions of the domain wall with magnetic monopole is discussed and it is shown that magnetic monopoles with certain internal space orientations relative to the wall pass through the domain wall. Magnetic monopoles in other relative internal space orientations are likely to be swept away on collision with the domain walls, suggesting a scenario where ...

  6. Empowerment variables for rehabilitation clients on perceived beliefs concerning work quality of life domains.

    Science.gov (United States)

    Tschopp, Molly K; Frain, Michael P; Bishop, Malachy

    2009-01-01

    This article describes and presents an initial analysis of variables generally associated with empowerment towards perceived beliefs concerning quality of life work domains for individuals with disabilities. The model examines the domains of importance, satisfaction, control and degree of interference of disability that an individual feels towards work. The internet based study used results from 70 individuals with disabilities in varying aspects of work. The variables composing empowerment that correlated strongly with the work domains include: self-advocacy, self-efficacy, perceived stigma, and family resiliency as measured through coping. Quality of Life concerning work was measured through the DSC-C a domain specific QOL instrument.

  7. Fitting hidden Markov models of protein domains to a target species: application to Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Terrapon Nicolas

    2012-05-01

    Full Text Available Abstract Background Hidden Markov Models (HMMs are a powerful tool for protein domain identification. The Pfam database notably provides a large collection of HMMs which are widely used for the annotation of proteins in new sequenced organisms. In Pfam, each domain family is represented by a curated multiple sequence alignment from which a profile HMM is built. In spite of their high specificity, HMMs may lack sensitivity when searching for domains in divergent organisms. This is particularly the case for species with a biased amino-acid composition, such as P. falciparum, the main causal agent of human malaria. In this context, fitting HMMs to the specificities of the target proteome can help identify additional domains. Results Using P. falciparum as an example, we compare approaches that have been proposed for this problem, and present two alternative methods. Because previous attempts strongly rely on known domain occurrences in the target species or its close relatives, they mainly improve the detection of domains which belong to already identified families. Our methods learn global correction rules that adjust amino-acid distributions associated with the match states of HMMs. These rules are applied to all match states of the whole HMM library, thus enabling the detection of domains from previously absent families. Additionally, we propose a procedure to estimate the proportion of false positives among the newly discovered domains. Starting with the Pfam standard library, we build several new libraries with the different HMM-fitting approaches. These libraries are first used to detect new domain occurrences with low E-values. Second, by applying the Co-Occurrence Domain Discovery (CODD procedure we have recently proposed, the libraries are further used to identify likely occurrences among potential domains with higher E-values. Conclusion We show that the new approaches allow identification of several domain families previously absent in

  8. Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines

    Directory of Open Access Journals (Sweden)

    Liao Li

    2010-10-01

    Full Text Available Abstract Background Protein-protein interaction (PPI plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs, based on domains represented as interaction profile hidden Markov models (ipHMM where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB. Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD. Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure, an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on

  9. Consuming Family Dinner Time

    National Research Council Canada - National Science Library

    Kelli Gutierrez; Linda Price; Eric Arnould

    2008-01-01

      Our study examines whether and how family dinners are embedded in the centrifugal and centripetal dynamics of everyday family life, the diversity of meanings they have for families and the intentions...

  10. Family Adjustment to Aphasia

    Science.gov (United States)

    ... Public / Speech, Language and Swallowing / Disorders and Diseases Family Adjustment to Aphasia Richard S. was a senior manager ... It also presents a great challenge to the family. There may be tension among family members and ...

  11. Improving Family Communications

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Listen Español Text Size Email Print Share Improving Family Communications Page Content Article Body How can I ...

  12. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  13. Family Activities for Fitness

    Science.gov (United States)

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  14. Wavefield extrapolation in pseudodepth domain

    KAUST Repository

    Ma, Xuxin

    2013-02-01

    Wavefields are commonly computed in the Cartesian coordinate frame. Its efficiency is inherently limited due to spatial oversampling in deep layers, where the velocity is high and wavelengths are long. To alleviate this computational waste due to uneven wavelength sampling, we convert the vertical axis of the conventional domain from depth to vertical time or pseudodepth. This creates a nonorthognal Riemannian coordinate system. Isotropic and anisotropic wavefields can be extrapolated in the new coordinate frame with improved efficiency and good consistency with Cartesian domain extrapolation results. Prestack depth migrations are also evaluated based on the wavefield extrapolation in the pseudodepth domain.© 2013 Society of Exploration Geophysicists. All rights reserved.

  15. Anatomy of Mammalian Replication Domains

    Science.gov (United States)

    Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

    2017-01-01

    Genetic information is faithfully copied by DNA replication through many rounds of cell division. In mammals, DNA is replicated in Mb-sized chromosomal units called “replication domains.” While genome-wide maps in multiple cell types and disease states have uncovered both dynamic and static properties of replication domains, we are still in the process of understanding the mechanisms that give rise to these properties. A better understanding of the molecular basis of replication domain regulation will bring new insights into chromosome structure and function. PMID:28350365

  16. Clustering of protein domains for functional and evolutionary studies

    Directory of Open Access Journals (Sweden)

    Long Paul F

    2009-10-01

    Full Text Available Abstract Background The number of protein family members defined by DNA sequencing is usually much larger than those characterised experimentally. This paper describes a method to divide protein families into subtypes purely on sequence criteria. Comparison with experimental data allows an independent test of the quality of the clustering. Results An evolutionary split statistic is calculated for each column in a protein multiple sequence alignment; the statistic has a larger value when a column is better described by an evolutionary model that assumes clustering around two or more amino acids rather than a single amino acid. The user selects columns (typically the top ranked columns to construct a motif. The motif is used to divide the family into subtypes using a stochastic optimization procedure related to the deterministic annealing EM algorithm (DAEM, which yields a specificity score showing how well each family member is assigned to a subtype. The clustering obtained is not strongly dependent on the number of amino acids chosen for the motif. The robustness of this method was demonstrated using six well characterized protein families: nucleotidyl cyclase, protein kinase, dehydrogenase, two polyketide synthase domains and small heat shock proteins. Phylogenetic trees did not allow accurate clustering for three of the six families. Conclusion The method clustered the families into functional subtypes with an accuracy of 90 to 100%. False assignments usually had a low specificity score.

  17. Branding a family business

    OpenAIRE

    Pohjola, Matti

    2016-01-01

    This master’s thesis main object was to understand better the very little researched topic: branding a family business. The main aim was to seek the values used behind family business that are the family values used in the brand and how the branding has been implemented in a family company. A qualitative method was chosen for this research for an interpretative analysis of the subject. Five family companies were chosen for the interviews. All these family companies are known Fi...

  18. Domains involved in TAF15 subcellular localisation

    DEFF Research Database (Denmark)

    Marko, Marija; Vlassis, Arsenios; Guialis, Apostolia

    2012-01-01

    TAF15 (TBP associated factor 15) is a member of the highly conserved TET (also known as FET) protein family of RNA binding proteins (RBP), which comprises in addition FUS (fused in sarcoma, also known as TLS, translocated in liposarcoma) and EWS (Ewing sarcoma protein). The TET proteins are impli...... regulated in the HeLa and the neuronal HT22 cell lines and that TAF15 co-localised with a minor subset of RNA granules in the cytoplasm of HT22 cells, supporting a model whereupon TAF15 plays a role in RNA transport and/or local RNA translation....... to play important roles in the onset of specific tumours, certain forms of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In this study we identified the domains of TAF15 responsible for its subcellular localisation in human (HeLa) cells and experimentally confirmed......, capable of being targeted to stress granules. We, moreover, showed that TAF15 cellular localisation depended on ongoing transcription and that independent domains of TAF15 engaged in nucleolar capping upon transcription inhibition. Finally, we demonstrated that TAF15 localisation was differentially...

  19. Selective targeting of epigenetic reader domains.

    Science.gov (United States)

    Greschik, Holger; Schüle, Roland; Günther, Thomas

    2017-05-01

    Epigenetic regulators including writers, erasers, and readers of chromatin marks have been implicated in numerous diseases and are therefore subject of intense academic and pharmaceutical research. While several small-molecule inhibitors targeting writers or erasers are either approved drugs or are currently being evaluated in clinical trials, the targeting of epigenetic readers has lagged behind. Proof-of-principle that epigenetic readers are also relevant drug targets was provided by landmark discoveries of selective inhibitors targeting the BET family of acetyl-lysine readers. More recently, high affinity chemical probes for non-BET acetyl- and methyl-lysine reader domains have also been developed. Areas covered: This article covers recent advances with the identification and validation of inhibitors and chemical probes targeting epigenetic reader domains. Issues related to epigenetic reader druggability, quality requirements for chemical probes, interpretation of cellular action, unexpected cross-talk, and future challenges are also discussed. Expert opinion: Chemical probes provide a powerful means to unravel biological functions of epigenetic readers and evaluate their potential as drug targets. To yield meaningful results, potency, selectivity, and cellular target engagement of chemical probes need to be stringently validated. Future chemical probes will probably need to fulfil additional criteria such as strict target specificity or the targeting of readers within protein complexes.

  20. Family Health History and Diabetes

    Science.gov (United States)

    ... Diabetes Diabetes Risk Test Family Health History Quiz Family Health History Quiz Family health history is an ... health problems. Four Questions You Should Ask Your Family About Diabetes & Family Health History Knowing your family ...

  1. Domain Modeling: NP_079291.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_079291.2 chr10 Crystal structure of ATPase domain of Ssb1 chaperone, a member of... the HSP70 family, from Saccharomyces cerevisiae p3gl1b_ chr10/NP_079291.2/NP_079291.2_holo_53-521.pdb psi-blast 62D,133W,284R,285R,287R,315D,481V,486E,488P,491Q,512L _MG 0 ...

  2. Domain Modeling: NP_443202.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_443202.3 chr20 Crystal structure of ATPase domain of Ssb1 chaperone, a member of... the HSP70 family, from Saccharomyces cerevisiae p3gl1b_ chr20/NP_443202.3/NP_443202.3_holo_57-527.pdb psi-blast 66D,242E,318V,319A,320D,388T,486V,491E,493A,496Q,509R _MG 0 ...

  3. Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain.

    Science.gov (United States)

    Kintner, C

    1992-04-17

    Differential adhesion between embryonic cells has been proposed to be mediated by a family of closely related glycoproteins called the cadherins. The cadherins mediate adhesion in part through an interaction between the cadherin cytoplasmic domain and intracellular proteins, called the catenins. To determine whether these interactions could regulate cadherin function in embryos, a form of N-cadherin was generated that lacks an extracellular domain. Expression of this mutant in Xenopus embryos causes a dramatic inhibition of cell adhesion. Analysis of the mutant phenotype shows that at least two regions of the N-cadherin cytoplasmic domain can inhibit adhesion and that the mutant cadherin can inhibit catenin binding to E-cadherin. These results suggest that cadherin-mediated adhesion can be regulated by cytoplasmic interactions and that this regulation may contribute to morphogenesis when emerging tissues coexpress several cadherin types.

  4. Conserved domains and SINE diversity during animal evolution.

    Science.gov (United States)

    Luchetti, Andrea; Mantovani, Barbara

    2013-10-01

    Eukaryotic genomes harbour a number of mobile genetic elements (MGEs); moving from one genomic location to another, they are known to impact on the host genome. Short interspersed elements (SINEs) are well-represented, non-autonomous retroelements and they are likely the most diversified MGEs. In some instances, sequence domains conserved across unrelated SINEs have been identified; remarkably, one of these, called Nin, has been conserved since the Radiata-Bilateria splitting. Here we report on two new domains: Inv, derived from Nin, identified in insects and in deuterostomes, and Pln, restricted to polyneopteran insects. The identification of Inv and Pln sequences allowed us to retrieve new SINEs, two in insects and one in a hemichordate. The diverse structural combination of the different domains in different SINE families, during metazoan evolution, offers a clearer view of SINE diversity and their frequent de novo emergence through module exchange, possibly underlying the high evolutionary success of SINEs. © 2013 Elsevier Inc. All rights reserved.

  5. Adaptive evolution in the GAF domain of phytochromes in gymnosperms.

    Science.gov (United States)

    Wang, Jing; Yan, Boqian; Chen, Guopei; Su, Yingjuan; Wang, Ting

    2010-04-01

    The GAF domain of phytochrome is essential for photoconversion and signal transduction. In gymnosperms, it exists in all members of the phytochrome family that experience gene duplication. Maximum-likelihood models of codon substitution can provide a framework for constructing likelihood ratio tests of changes in selective pressure and make clear predictions about patterns of genetic change following gene duplication. In this study, 68 gymnosperm GAF sequences were analyzed to identify lineages and sites under positive selection. Our results indicate that (1) positive selection at a few sites (3.6%), rather than relaxation of selective constraints, has played a major role in the evolution of the gymnosperm GAF domain; (2) strong positive selective pressure tends to occur in the recent PHYP lineages of cogeneric species, but is absent in old lineages consisting of distantly related species; and (3) the selective pressure indicated by the omega ratio varies greatly among lineages and sites in the GAF domain.

  6. Untangling spider silk evolution with spidroin terminal domains

    Directory of Open Access Journals (Sweden)

    Garb Jessica E

    2010-08-01

    Full Text Available Abstract Background Spidroins are a unique family of large, structural proteins that make up the bulk of spider silk fibers. Due to the highly variable nature of their repetitive sequences, spidroin evolutionary relationships have principally been determined from their non-repetitive carboxy (C-terminal domains, though they offer limited character data. The few known spidroin amino (N-terminal domains have been difficult to obtain, but potentially contain critical phylogenetic information for reconstructing the diversification of spider silks. Here we used silk gland expression data (ESTs from highly divergent species to evaluate the functional significance and phylogenetic utility of spidroin N-terminal domains. Results We report 11 additional spidroin N-termini found by sequencing ~1,900 silk gland cDNAs from nine spider species that shared a common ancestor > 240 million years ago. In contrast to their hyper-variable repetitive regions, spidroin N-terminal domains have retained striking similarities in sequence identity, predicted secondary structure, and hydrophobicity. Through separate and combined phylogenetic analyses of N-terminal domains and their corresponding C-termini, we find that combined analysis produces the most resolved trees and that N-termini contribute more support and less conflict than the C-termini. These analyses show that paralogs largely group by silk gland type, except for the major ampullate spidroins. Moreover, spidroin structural motifs associated with superior tensile strength arose early in the history of this gene family, whereas a motif conferring greater extensibility convergently evolved in two distantly related paralogs. Conclusions A non-repetitive N-terminal domain appears to be a universal attribute of spidroin proteins, likely retained from the origin of spider silk production. Since this time, spidroin N-termini have maintained several features, consistent with this domain playing a key role in silk

  7. Families and family therapy in Hong Kong.

    Science.gov (United States)

    Tse, Samson; Ng, Roger M K; Tonsing, Kareen N; Ran, Maosheng

    2012-04-01

    Family therapy views humans not as separate entities, but as embedded in a network of relationships, highlighting the reciprocal influences of one's behaviours on one another. This article gives an overview of family demographics and the implementation of family therapy in Hong Kong. We start with a review of the family demographics in Hong Kong and brief notes on families in mainland China. Demographics show that the landscape has changed markedly in the past decade, with more cross-border marriages, an increased divorce rate, and an ageing overall population - all of which could mean that there is increasing demand for professional family therapy interventions. However, only a limited number of professionals are practising the systems-based approach in Hong Kong. Some possible reasons as to why family therapy is not well disseminated and practised are discussed. These reasons include a lack of mental health policy to support family therapy, a lack of systematic family therapy training, and a shortage of skilled professionals. Furthermore, challenges in applying the western model in Chinese culture are also outlined. We conclude that more future research is warranted to investigate how family therapy can be adapted for Chinese families.

  8. Family psychology and family therapy in Japan.

    Science.gov (United States)

    Kameguchi, K; Murphy-Shigematsu, S

    2001-01-01

    The development of family psychology and family therapy in Japan has occurred mostly since the 1980s. This development was originally activated by the major social issue in contemporary Japan of school refusal, in which more than 127,000 children either overtly refuse to or claim that they cannot go to school. From a family perspective, this problem is analyzed as it relates to the confusion that children experience from unbalanced and unclear boundaries in family relations or "membranes." An approach to family therapy that adapts systems theory and integrates a clay sculpting medium has been developed to work with Japanese families confronting this problem. The design and implementation of preventative family psychology programs applied at the community level are also an important part of the future development in these fields.

  9. Critical SQG in bounded domains

    OpenAIRE

    Constantin, Peter; Ignatova, Mihaela

    2016-01-01

    We consider the critical dissipative SQG equation in bounded domains, with the square root of the Dirichlet Laplacian dissipation. We prove global a priori interior $C^{\\alpha}$ and Lipschitz bounds for large data.

  10. Structure of axionic domain walls

    Science.gov (United States)

    Huang, M. C.; Sikivie, P.

    1985-09-01

    The structure of axionic domain walls is investigated using the low-energy effective theory of axions and pions. We derive the spatial dependence of the phases of the Peccei-Quinn scalar field and the QCD quark-antiquark condensates inside an axionic domain wall. Thence an accurate estimate of the wall surface energy density is obtained. The equations of motion for axions, photons, leptons, and baryons in the neighborhood of axionic domain walls are written down and estimates are given for the wall reflection and transmission coefficients of these particles. Finally, we discuss the energy dissipation by axionic domain walls oscillating in the early universe due to the reflection of particles in the primordial soup.

  11. Structure of axionic domain walls

    Energy Technology Data Exchange (ETDEWEB)

    Huang, M.C.; Sikivie, P.

    1985-09-15

    The structure of axionic domain walls is investigated using the low-energy effective theory of axions and pions. We derive the spatial dependence of the phases of the Peccei-Quinn scalar field and the QCD quark-antiquark condensates inside an axionic domain wall. Thence an accurate estimate of the wall surface energy density is obtained. The equations of motion for axions, photons, leptons, and baryons in the neighborhood of axionic domain walls are written down and estimates are given for the wall reflection and transmission coefficients of these particles. Finally, we discuss the energy dissipation by axionic domain walls oscillating in the early universe due to the reflection of particles in the primordial soup.

  12. Toeplitz operators on connected domains

    Institute of Scientific and Technical Information of China (English)

    CAO; Guangfu

    2006-01-01

    The proof of the index formula of the Toeplitz operator with a continuous symbol on the Hardy space for the unit circle in the complex plane depends on the Hopftheorem. However,the analogue result of the Hopf theorem does not hold on a general connected domain. Hence,the extension of the index formula of the Toeplitz operator on a general domain needs a method which is different from that for the case of the unit circle. In the present paper, the index formula of the Toeplitz operator with a continuous symbol on the finite complex connected domain in the complex plane is obtained, and the cohomology groups of Toeplitz algebras on general domains are discussed. In addition, the Toeplitz operators with symbols in QC are also discussed.

  13. Modulation of oncogenic DBL activity by phosphoinositol phosphate binding to pleckstrin homology domain.

    Science.gov (United States)

    Russo, C; Gao, Y; Mancini, P; Vanni, C; Porotto, M; Falasca, M; Torrisi, M R; Zheng, Y; Eva, A

    2001-06-01

    The Dbl family guanine nucleotide exchange factors (GEFs) contain a region of sequence similarity consisting of a catalytic Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. PH domains are involved in the regulated targeting of signaling molecules to plasma membranes by protein-protein and/or protein-lipid interactions. Here we show that Dbl PH domain binding to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-triphosphate results in the inhibition of Dbl GEF activity on Rho family GTPase Cdc42. Phosphatidylinositol 4,5-bisphosphate binding to the PH domain significantly inhibits the Cdc42 interactive activity of the DH domain suggesting that the DH domain is subjected to the PH domain modulation under the influence of phosphoinositides (PIPs). We generated Dbl mutants unable to interact with PIPs. These mutants retained GEF activity on Cdc42 in the presence of PIPs and showed a markedly enhanced activating potential for both Cdc42 and RhoA in vivo while displaying decreased cellular transforming activity. Immunofluorescence analysis of NIH3T3 transfectants revealed that whereas the PH domain localizes to actin stress fibers and plasma membrane, the PH mutants are no longer detectable on the plasma membrane. These results suggest that modulation of PIPs in both the GEF catalytic activity and the targeting to plasma membrane determines the outcome of the biologic activity of Dbl.

  14. Family doctors' involvement with families in Estonia

    Directory of Open Access Journals (Sweden)

    Lember Margus

    2004-10-01

    Full Text Available Abstract Background Family doctors should care for individuals in the context of their family. Family has a powerful influence on health and illness and family interventions have been shown to improve health outcomes for a variety of health problems. The aim of the study was to investigate the Estonian family doctors' (FD attitudes to the patients' family-related issues in their work: to explore the degree of FDs involvement in family matters, their preparedness for management of family-related issues and their self-assessment of the ability to manage different family-related problems. Methods A random sample (n = 236 of all FDs in Estonia was investigated using a postal questionnaire. Altogether 151 FDs responded to the questionnaire (response rate 64%, while five of them were excluded as they did not actually work as FDs. Results Of the respondents, 90% thought that in managing the health problems of patients FDs should communicate and cooperate with family members. Although most of the family doctors agreed that modifying of the health damaging risk factors (smoking, alcohol and drug abuse of their patients and families is their task, one third of them felt that dealing with these problems is ineffective, or perceived themselves as poorly prepared or having too little time for such activities. Of the respondents, 58% (n = 83 were of the opinion that they could modify also relationship problems. Conclusions Estonian family doctors are favourably disposed to involvement in family-related problems, however, they need some additional training, especially in the field of relationship management.

  15. The Relationship between Family Education and Support Services and Parent and Child Outcomes over Time

    Science.gov (United States)

    Kutash, Krista; Garraza, Lucas Godoy; Ferron, John M.; Duchnowski, Albert J.; Walrath, Christine; Green, Amy L.

    2013-01-01

    The purpose of the current study is to contribute to the knowledge base on the use of family education and support (FES) services by examining the longitudinal trajectories of FES receipt and multiple domains of child and family functioning. Using an extant data set of more than 9,000 youth and their caregivers, results indicate that families who…

  16. The Relationship between Family Education and Support Services and Parent and Child Outcomes over Time

    Science.gov (United States)

    Kutash, Krista; Garraza, Lucas Godoy; Ferron, John M.; Duchnowski, Albert J.; Walrath, Christine; Green, Amy L.

    2013-01-01

    The purpose of the current study is to contribute to the knowledge base on the use of family education and support (FES) services by examining the longitudinal trajectories of FES receipt and multiple domains of child and family functioning. Using an extant data set of more than 9,000 youth and their caregivers, results indicate that families who…

  17. Siblings' Power and Influence in Polyadic Family Conflict during Early Childhood

    Science.gov (United States)

    Della Porta, Sandra; Howe, Nina

    2017-01-01

    This study examined sibling behavior during polyadic family conflicts (involving three or more family members) by identifying operational conflict elements (i.e., roles, topic), power strategies, effective influence of power, and social domain argumentation. Polyadic conflict sequences (n = 210) were identified in 35/39 families with two siblings…

  18. Language Choice and Language Policies in Filipino-Malaysian Families in Multilingual Malaysia

    Science.gov (United States)

    Dumanig, Francisco Perlas; David, Maya Khemlani; Shanmuganathan, Thilagavathi

    2013-01-01

    Personal, social, cultural, economic, and political factors influence the language/s used by family members in the home domain. This study examines how family language policies are planned and developed in Filipino-Malaysian families in Malaysia. The language used at home in such mixed or exogamous marriages is also influenced by the ethnicity of…

  19. Evolutionary history and genome organization of DUF1220 protein domains.

    Science.gov (United States)

    O'Bleness, Majesta S; Dickens, C Michael; Dumas, Laura J; Kehrer-Sawatzki, Hildegard; Wyckoff, Gerald J; Sikela, James M

    2012-09-01

    DUF1220 protein domains exhibit the most extreme human lineage-specific (HLS) copy number increase of any protein coding region in the human genome and have recently been linked to evolutionary and pathological changes in brain size (e.g., 1q21-associated microcephaly). These findings lend support to the view that DUF1220 domain dosage is a key factor in the determination of primate (and human) brain size. Here we analyze 41 animal genomes and present the most complete account to date of the evolutionary history and genome organization of DUF1220 domains and the gene family that encodes them (NBPF). Included among the novel features identified by this analysis is a DUF1220 domain precursor in nonmammalian vertebrates, a unique predicted promoter common to all mammalian NBPF genes, six distinct clades into which DUF1220 sequences can be subdivided, and a previously unknown member of the NBPF gene family (NBPF25). Most importantly, we show that the exceptional HLS increase in DUF1220 copy number (from 102 in our last common ancestor with chimp to 272 in human; an average HLS increase of ~28 copies every million years since the Homo/Pan split) was driven by intragenic domain hyperamplification. This increase primarily involved a 4.7 kb, tandemly repeated three DUF1220 domain unit we have named the HLS DUF1220 triplet, a motif that is a likely candidate to underlie key properties unique to the Homo sapiens brain. Interestingly, all copies of the HLS DUF1220 triplet lie within a human-specific pericentric inversion that also includes the 1q12 C-band, a polymorphic heterochromatin expansion that is unique to the human genome. Both cytogenetic features likely played key roles in the rapid HLS DUF1220 triplet hyperamplification, which is among the most striking genomic changes specific to the human lineage.

  20. Stretching the rules: monocentric chromosomes with multiple centromere domains.

    Science.gov (United States)

    Neumann, Pavel; Navrátilová, Alice; Schroeder-Reiter, Elizabeth; Koblížková, Andrea; Steinbauerová, Veronika; Chocholová, Eva; Novák, Petr; Wanner, Gerhard; Macas, Jiří

    2012-01-01

    The centromere is a functional chromosome domain that is essential for faithful chromosome segregation during cell division and that can be reliably identified by the presence of the centromere-specific histone H3 variant CenH3. In monocentric chromosomes, the centromere is characterized by a single CenH3-containing region within a morphologically distinct primary constriction. This region usually spans up to a few Mbp composed mainly of centromere-specific satellite DNA common to all chromosomes of a given species. In holocentric chromosomes, there is no primary constriction; the centromere is composed of many CenH3 loci distributed along the entire length of a chromosome. Using correlative fluorescence light microscopy and high-resolution electron microscopy, we show that pea (Pisum sativum) chromosomes exhibit remarkably long primary constrictions that contain 3-5 explicit CenH3-containing regions, a novelty in centromere organization. In addition, we estimate that the size of the chromosome segment delimited by two outermost domains varies between 69 Mbp and 107 Mbp, several factors larger than any known centromere length. These domains are almost entirely composed of repetitive DNA sequences belonging to 13 distinct families of satellite DNA and one family of centromeric retrotransposons, all of which are unevenly distributed among pea chromosomes. We present the centromeres of Pisum as novel "meta-polycentric" functional domains. Our results demonstrate that the organization and DNA composition of functional centromere domains can be far more complex than previously thought, do not require single repetitive elements, and do not require single centromere domains in order to segregate properly. Based on these findings, we propose Pisum as a useful model for investigation of centromere architecture and the still poorly understood role of repetitive DNA in centromere evolution, determination, and function.

  1. Nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 inflammasomes and the ;relationship between it and periodontal diseases%核苷酸结合寡聚化结构域样受体热蛋白结构域亚家族成员3炎症小体的活化调节与牙周疾病的关系

    Institute of Scientific and Technical Information of China (English)

    吴冷; 王骏; 赵蕾; 吴亚菲

    2015-01-01

     The nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing(NLRP)3 inflammasome is an intracellular multi-protein complex that is assembled after its central component, NLRP3, and senses pathogens and host danger signals. The NLRP3 inflammasome induces maturation and secretion of inflammatory cytokines interleukin(IL)-1β by activating cysteinyl aspartale specific protease-1, thereby participating in immunoinflammatory responses. Periodontal diseases are caused by local immunoinflammatory responses against periodontal pathogens, with IL-1βbeing one of the critical factors. Furthermore, the processing and secretion of IL-1βis closely related to the NLRP3 inflammasome. Periodontal pathogens can regulate expression and activation of NLRP3 inflammasome. Therefore, NLRP3 inflammasome is significant to the development and treatment of periodontal diseases. This article focuses on the biological function and activation mechanism of the NLRP3 inflammasome and the relevant research progress on periodontal diseases.%核苷酸结合寡聚化结构域样受体热蛋白结构域亚家族成员(NLRP)3炎症小体是一种位于细胞质内的多蛋白质复合体,由其核心成分感知病原体和宿主危险信号后组装而成,通过激活半胱氨酸天冬酰胺特异蛋白酶-1致促炎因子白细胞介素(IL)-1β成熟与分泌参与免疫炎症反应。牙周病是由宿主和微生物因素相互作用导致的局部炎症反应,而IL-1β又是牙周炎发病的关键因素之一。IL-1β的成熟和分泌与NLRP3炎症小体密切相关,且牙周致病菌可调节该炎症小体的表达及活化,因此NLRP3炎症小体对牙周疾病的发生发展和治疗具有重要意义。本文就NLRP3炎症小体的生物学功能、

  2. A segmental labeling strategy for unambiguous determination of domain-domain interactions of large multi-domain proteins

    Energy Technology Data Exchange (ETDEWEB)

    Chen Jianglei; Wang Jianjun, E-mail: jjwang@med.wayne.edu [Wayne State University, Department of Biochemistry and Molecular Biology, School of Medicine (United States)

    2011-08-15

    NMR structural determination of large multi-domain proteins is a challenging task due to significant spectral overlap with a particular difficulty in unambiguous identification of domain-domain interactions. Segmental labeling is a NMR strategy that allows for isotopically labeling one domain and leaves the other domain unlabeled. This significantly simplifies spectral overlaps and allows for quick identification of domain-domain interaction. Here, a novel segmental labeling strategy is presented for detection of inter-domain NOEs. To identify domain-domain interactions in human apolipoprotein E (apoE), a multi-domain, 299-residues {alpha}-helical protein, on-column expressed protein ligation was utilized to generate a segmental-labeled apoE samples in which the N-terminal (NT-) domain was {sup 2}H(99%)/{sup 15}N-labeled whereas the C-terminal (CT-) domain was either {sup 15}N- or {sup 15}N/{sup 13}C-labeled. 3-D {sup 15}N-edited NOESY spectra of these segmental-labeled apoE samples allow for direct observation of the inter-domain NOEs between the backbone amide protons of the NT-domain and the aliphatic protons of the CT-domain. This straightforward approach permits unambiguous identification of 78 inter-domain NOEs, enabling accurate definition of the relative positions of both the NT- and the CT-domains and determination of the NMR structure of apoE.

  3. Work-family interface from a life and career stage perspective: the role of demands and resources.

    Science.gov (United States)

    Demerouti, Evangelia; Peeters, Maria C W; van der Heijden, Beatrice I J M

    2012-01-01

    Work-family conflict and enrichment are experiences that occur daily and have substantial consequences for employees, their families, and the organizations that employ them. The aim of the current review is to make a link between life and career stage, work and family conditions, and the work-family interface. The basic proposition is that life stages partly determine career development, and consequently the specific working conditions (job demands and job resources) and family conditions (family demands and family resources) that individuals are exposed to. As a result, the specific demands and resources in the work and family domains determine to what extent individuals experience that work and family are conflicting or enriching life domains. In this review we suggest that individuals in early adulthood will experience high inter-role conflict and low facilitation due to high demands and low resources in both life domains, while individuals in late adulthood will experience the opposite pattern; that is, low conflict and high facilitation due to low demands and high resources in both domains. Individuals in middle adulthood will experience high work-family conflict but also high family-work facilitation due to the presence of high job demands and resources in both life domains. Integrating life and career stage perspectives and the experience of work-family interface is of notable practical utility because it provides a mechanism to make more informed decisions about the relative need for and corresponding benefits of work-family programs.

  4. Structure and evolutionary history of a large family of NLR proteins in the zebrafish.

    Science.gov (United States)

    Howe, Kerstin; Schiffer, Philipp H; Zielinski, Julia; Wiehe, Thomas; Laird, Gavin K; Marioni, John C; Soylemez, Onuralp; Kondrashov, Fyodor; Leptin, Maria

    2016-04-01

    Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins. Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families. We describe a family of nearly 400 NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system. © 2016 The Authors.

  5. Diversity in domain architectures of Ser/Thr kinases and their homologues in prokaryotes

    Directory of Open Access Journals (Sweden)

    Krupa A

    2005-09-01

    Full Text Available Abstract Background Ser/Thr/Tyr kinases (STYKs commonly found in eukaryotes have been recently reported in many bacterial species. Recent studies elucidating their cellular functions have established their roles in bacterial growth and development. However functions of a large number of bacterial STYKs still remain elusive. The organisation of domains in a large dataset of bacterial STYKs has been investigated here in order to recognise variety in domain combinations which determine functions of bacterial STYKs. Results Using sensitive sequence and profile search methods, domain organisation of over 600 STYKs from 125 prokaryotic genomes have been examined. Kinase catalytic domains of STYKs tethered to a wide range of enzymatic domains such as phosphatases, HSP70, peptidyl prolyl isomerases, pectin esterases and glycoproteases have been identified. Such distinct preferences for domain combinations are not known to be present in either the Histidine kinase or the eukaryotic STYK families. Domain organisation of STYKs specific to certain groups of bacteria has also been noted in the current anlaysis. For example, Hydrophobin like domains in Mycobacterial STYK and penicillin binding domains in few STYKs of Gram-positive organisms and FHA domains in cyanobacterial STYKs. Homologues of characterised substrates of prokaryotic STYKs have also been identified. Conclusion The domains and domain architectures of most of the bacterial STYKs identified are very different from the known domain organisation in STYKs of eukaryotes. This observation highlights distinct biological roles of bacterial STYKs compared to eukaryotic STYKs. Bacterial STYKs reveal high diversity in domain organisation. Some of the modular organisations conserved across diverse bacterial species suggests their central role in bacterial physiology. Unique domain architectures of few other groups of STYKs reveal recruitment of functions specific to the species.

  6. Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Bennett, Eric P; Schjoldager, Katrine T-B G;

    2011-01-01

    UDP-GalNAc:polypeptide a-N-acetylgalactosaminyltransferases (GalNAc-Ts) constitute a family of up to 20 transferases that initiate mucin-type O-glycosylation. The transferases are structurally composed of catalytic and lectin domains. Two modes have been identified for the selection...... of glycosylation sites by GalNAc-Ts: confined sequence recognition by the catalytic domain alone, and concerted recognition of acceptor sites and adjacent GalNAc-glycosylated sites by the catalytic and lectin domains, respectively. Thus far, only the catalytic domain has been shown to have peptide sequence...... on sequences of mucins MUC1, MUC2, MUC4, MUC5AC, MUC6, and MUC7 as well as a random glycopeptide bead library, we examined the binding properties of four different lectin domains. The lectin domains of GalNAc-T1, -T2, -T3, and -T4 bound different subsets of small glycopeptides. These results indicate...

  7. Structure-Function Study of the N-terminal Domain of Exocyst Subunit Sec3

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Kyuwon; Knödler, Andreas; Lee, Sung Haeng; Zhang, Xiaoyu; Orlando, Kelly; Zhang, Jian; Foskett, Trevor J.; Guo, Wei; Dominguez, Roberto (UPENN)

    2010-04-19

    The exocyst is an evolutionarily conserved octameric complex involved in polarized exocytosis from yeast to humans. The Sec3 subunit of the exocyst acts as a spatial landmark for exocytosis through its ability to bind phospholipids and small GTPases. The structure of the N-terminal domain of Sec3 (Sec3N) was determined ab initio and defines a new subclass of pleckstrin homology (PH) domains along with a new family of proteins carrying this domain. Respectively, N- and C-terminal to the PH domain Sec3N presents an additional {alpha}-helix and two {beta}-strands that mediate dimerization through domain swapping. The structure identifies residues responsible for phospholipid binding, which when mutated in cells impair the localization of exocyst components at the plasma membrane and lead to defects in exocytosis. Through its ability to bind the small GTPase Cdc42 and phospholipids, the PH domain of Sec3 functions as a coincidence detector at the plasma membrane.

  8. Comparative Study of Lectin Domains in Model Species: New Insights into Evolutionary Dynamics

    Directory of Open Access Journals (Sweden)

    Sofie Van Holle

    2017-05-01

    Full Text Available Lectins are present throughout the plant kingdom and are reported to be involved in diverse biological processes. In this study, we provide a comparative analysis of the lectin families from model species in a phylogenetic framework. The analysis focuses on the different plant lectin domains identified in five representative core angiosperm genomes (Arabidopsis thaliana, Glycine max, Cucumis sativus, Oryza sativa ssp. japonica and Oryza sativa ssp. indica. The genomes were screened for genes encoding lectin domains using a combination of Basic Local Alignment Search Tool (BLAST, hidden Markov models, and InterProScan analysis. Additionally, phylogenetic relationships were investigated by constructing maximum likelihood phylogenetic trees. The results demonstrate that the majority of the lectin families are present in each of the species under study. Domain organization analysis showed that most identified proteins are multi-domain proteins, owing to the modular rearrangement of protein domains during evolution. Most of these multi-domain proteins are widespread, while others display a lineage-specific distribution. Furthermore, the phylogenetic analyses reveal that some lectin families evolved to be similar to the phylogeny of the plant species, while others share a closer evolutionary history based on the corresponding protein domain architecture. Our results yield insights into the evolutionary relationships and functional divergence of plant lectins.

  9. Evolution and potential function of fibrinogen-like domains across twelve Drosophila species

    Directory of Open Access Journals (Sweden)

    Middha Sumit

    2008-05-01

    Full Text Available Abstract Background The fibrinogen-like (FBG domain consists of approximately 200 amino acid residues, which has high sequence similarity to the C-terminal halves of fibrinogen β and γ chains. Fibrinogen-related proteins (FREPs containing one or more FBG domains are found universally in vertebrates and invertebrates. In invertebrates, FREPs are involved in immune responses and other aspects of physiology. To understand the complexity of this gene family in Drosophila, we analyzed FREPs in twelve Drosophila species. Results Using the genome data from 12 Drosophila species, we identified FBG domains in each species. The results show that the gene numbers in each species vary from 14 genes up to 43 genes. Using sequence profile analysis, we found that FBG domains have high sequence similarity and are highly conserved throughout. By comparison of structure and sequence conservation, some of the FBG domains in Drosophila melanogaster are predicted to function in recognition of carbohydrates and their derivatives on the surface of microorganisms in innate immunity. Conclusion Sequence and structural analyses show that FREP family across 12 Drosophila species contains conserved FBG domains. Expansion of the FREP families in Drosophila is mainly accounted by a major expansion of FBG domains.

  10. Plant NAC-type transcription factor proteins contain a NARD domain for repression of transcriptional activation.

    Science.gov (United States)

    Hao, Yu-Jun; Song, Qing-Xin; Chen, Hao-Wei; Zou, Hong-Feng; Wei, Wei; Kang, Xu-Sheng; Ma, Biao; Zhang, Wan-Ke; Zhang, Jin-Song; Chen, Shou-Yi

    2010-10-01

    Plant-specific transcription factor NAC proteins play essential roles in many biological processes such as development, senescence, morphogenesis, and stress signal transduction pathways. In the NAC family, some members function as transcription activators while others act as repressors. In the present study we found that though the full-length GmNAC20 from soybean did not have transcriptional activation activity, the carboxy-terminal activation domain of GmNAC20 had high transcriptional activation activity in the yeast assay system. Deletion experiments revealed an active repression domain with 35 amino acids, named NARD (NAC Repression Domain), in the d subdomain of NAC DNA-binding domain. NARD can reduce the transcriptional activation ability of diverse transcription factors when fused to either the amino-terminal or the carboxy-terminal of the transcription factors. NARD-like sequences are also present in other NAC family members and they are functional repression domain when fused to VP16 in plant protoplast assay system. Mutation analysis of conserved amino acid residues in NARD showed that the hydrophobic LVFY motif may partially contribute to the repression function. It is hypothesized that the interactions between the repression domain NARD and the carboxy-terminal activation domain may finally determine the ability of NAC family proteins to regulate downstream gene expressions.

  11. [Brief strategic family therapy: an empirically-validated intervention for reducing adolescent behavior problems].

    Science.gov (United States)

    Robbins, Michael S; Horigian, Viviana E; Szapocznik, José

    2008-01-01

    Brief Strategic Family Therapy (BSFT) is an empirically-supported treatment for children and adolescents with behavior problems and substance use problems. For three decades, the efficacy and effectiveness of BSFT has been established through the results of rigorous clinical trials studies conducted at the University of Miami's Center for Family Studies. BSFT is based on family systems approaches, most notably the work of Salvador Minuchin and Jay Haley, but has been refined to meet the pressing needs of youth with behavior problems. BSFT theory and interventions cover four broad domains: joining with family members and the family system, assessing problematic family interactions, creating a motivational context for change, and restructuring family interactions.

  12. Competitiveness of Family Businesses

    NARCIS (Netherlands)

    M.A.A.M. Leenders (Mark); E. Waarts (Eric)

    2001-01-01

    textabstractThe purpose of this study is to systematically examine the advantages and disadvantages of different types of family businesses. We distinguish four different types of family businesses based on their family and business orientation: (1) House of Business, (2) Family Money Machine, (3) F

  13. Families in Transition .

    Science.gov (United States)

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

    1984-01-01

    Focuses on disrupted families and the role of the school counselor in helping children adjust. Describes characteristics of healthy families, and discusses the transition to the blended family, effects of divorce groups on children's classroom behavior, counseling children in stepfamilies, single-parent families, and parenting strengths of single…

  14. Competitiveness of Family Businesses

    NARCIS (Netherlands)

    M.A.A.M. Leenders (Mark); E. Waarts (Eric)

    2001-01-01

    textabstractThe purpose of this study is to systematically examine the advantages and disadvantages of different types of family businesses. We distinguish four different types of family businesses based on their family and business orientation: (1) House of Business, (2) Family Money Machine, (3) F

  15. Family eating habits, family support and subjective well-being in university students in Chile

    Directory of Open Access Journals (Sweden)

    Berta Schnettler

    Full Text Available Aim: To characterize typologies of university students according to the perception of their families' eating habits. Material and method: A questionnaire was applied to a non-probabilistic sample of 372 students of both genders at the Universidad de La Frontera, Temuco, Chile. The instrument included: the Family Eating Habits Questionnaire (FEHQ, the Satisfaction with Life Scale (SWLS, the Satisfaction with Food-related Life Scale (SWFL and the Family Resources Scale (FRS. Estimated weight and height were asked about as well as sociodemographic variables. Results: Using an exploratory factor analysis (EFA three factors were detected in the FEHQ: importance of eating to family members, cohesiveness of family eating, and pressure to eat. The EFA detected two factors on the FRS: intangible and tangible support. A confirmatory factor analysis (CFA validated the structure of the FEHQ and the FRS with good goodness-of-fit indicators. A cluster analysis distinguished four typologies that differed significantly in the scores of the components on the FEHQ and FRS, scores on the SWLS and SWFL, body mass index, gender and socioeconomic level. Typologies with higher scores in "cohesiveness of family eating" report greater intangible support from their families and higher scores on the SWLS and SWFL. Conclusions: The results show that the frequency and importance assigned to family meals are associated positively with perceived family support, particularly in intangible resources, as well as with the overall satisfaction with life and in the food domain.

  16. Domain Decomposition Solvers for Frequency-Domain Finite Element Equations

    KAUST Repository

    Copeland, Dylan

    2010-10-05

    The paper is devoted to fast iterative solvers for frequency-domain finite element equations approximating linear and nonlinear parabolic initial boundary value problems with time-harmonic excitations. Switching from the time domain to the frequency domain allows us to replace the expensive time-integration procedure by the solution of a simple linear elliptic system for the amplitudes belonging to the sine- and to the cosine-excitation or a large nonlinear elliptic system for the Fourier coefficients in the linear and nonlinear case, respectively. The fast solution of the corresponding linear and nonlinear system of finite element equations is crucial for the competitiveness of this method. © 2011 Springer-Verlag Berlin Heidelberg.

  17. ALOG domains: provenance of plant homeotic and developmental regulators from the DNA-binding domain of a novel class of DIRS1-type retroposons

    Directory of Open Access Journals (Sweden)

    Iyer Lakshminarayan M

    2012-11-01

    Full Text Available Abstract Members of the Arabidopsis LSH1 and Oryza G1 (ALOG family of proteins have been shown to function as key developmental regulators in land plants. However, their precise mode of action remains unclear. Using sensitive sequence and structure analysis, we show that the ALOG domains are a distinct version of the N-terminal DNA-binding domain shared by the XerC/D-like, protelomerase, topoisomerase-IA, and Flp tyrosine recombinases. ALOG domains are distinguished by the insertion of an additional zinc ribbon into this DNA-binding domain. In particular, we show that the ALOG domain is derived from the XerC/D-like recombinases of a novel class of DIRS-1-like retroposons. Copies of this element, which have been recently inactivated, are present in several marine metazoan lineages, whereas the stramenopile Ectocarpus, retains an active copy of the same. Thus, we predict that ALOG domains help establish organ identity and differentiation by binding specific DNA sequences and acting as transcription factors or recruiters of repressive chromatin. They are also found in certain plant defense proteins, where they are predicted to function as DNA sensors. The evolutionary history of the ALOG domain represents a unique instance of a domain, otherwise exclusively found in retroelements, being recruited as a specific transcription factor in the streptophyte lineage of plants. Hence, they add to the growing evidence for derivation of DNA-binding domains of eukaryotic specific TFs from mobile and selfish elements.

  18. Domain organization and crystal structure of the catalytic domain of E.coli RluF, a pseudouridine synthase that acts on 23S rRNA.

    Science.gov (United States)

    Sunita, S; Zhenxing, H; Swaathi, J; Cygler, Miroslaw; Matte, Allan; Sivaraman, J

    2006-06-16

    Pseudouridine synthases catalyze the isomerization of uridine to pseudouridine (Psi) in rRNA and tRNA. The pseudouridine synthase RluF from Escherichia coli (E.C. 4.2.1.70) modifies U2604 in 23S rRNA, and belongs to a large family of pseudouridine synthases present in all kingdoms of life. Here we report the domain architecture and crystal structure of the catalytic domain of E.coli RluF at 2.6A resolution. Limited proteolysis, mass spectrometry and N-terminal sequencing indicate that RluF has a distinct domain architecture, with the catalytic domain flanked at the N and C termini by additional domains connected to it by flexible linkers. The structure of the catalytic domain of RluF is similar to those of RsuA and TruB. RluF is a member of the RsuA sequence family of Psi-synthases, along with RluB and RluE. Structural comparison of RluF with its closest structural homologues, RsuA and TruB, suggests possible functional roles for the N-terminal and C-terminal domains of RluF.

  19. Domain organization and crystal structure of the catalytic domain of E.coli RluF, a pseudouridine synthase that acts on 23S rRNA

    Energy Technology Data Exchange (ETDEWEB)

    Sunita,S.; Zhenxing, H.; Swaathi, J.; Cygler, M.; Matte, A.; Sivaraman, J.

    2006-01-01

    Pseudouridine synthases catalyze the isomerization of uridine to pseudouridine ({psi}) in rRNA and tRNA. The pseudouridine synthase RluF from Escherichia coli (E.C. 4.2.1.70) modifies U2604 in 23S rRNA, and belongs to a large family of pseudouridine synthases present in all kingdoms of life. Here we report the domain architecture and crystal structure of the catalytic domain of E. coli RluF at 2.6 Angstroms resolution. Limited proteolysis, mass spectrometry and N-terminal sequencing indicate that RluF has a distinct domain architecture, with the catalytic domain flanked at the N and C termini by additional domains connected to it by flexible linkers. The structure of the catalytic domain of RluF is similar to those of RsuA and TruB. RluF is a member of the RsuA sequence family of {psi}-synthases, along with RluB and RluE. Structural comparison of RluF with its closest structural homologues, RsuA and TruB, suggests possible functional roles for the N-terminal and C-terminal domains of RluF.

  20. SLAM family receptors in normal immunity and immune pathologies.

    Science.gov (United States)

    Wu, Ning; Veillette, André

    2016-02-01

    The signaling lymphocytic activation molecule (SLAM) family is a group of six receptors restricted to hematopoietic cells. Most of these receptors are self-ligands, and thus are triggered in the context of interactions between hematopoietic cells. By way of their cytoplasmic domain, SLAM-related receptors associate with the SLAM-associated protein (SAP) family of adaptors, which control the signals and functions of SLAM family receptors. Recent findings have provided new insights into the key roles of SLAM family receptors in normal immunity, their involvement in human diseases and their usefulness as drug targets to treat human malignancies. These data are reviewed herein.