The impact of changes in China's family patterns on family pension functions.

PubMed

Su, Zhongxin; Hu, Z; Peng, Xizhe

2017-07-01

Using data from the Chinese census and the China Statistical Yearbook, this paper will analyze the historical changes and future trends of family households in China over the past 30 years and explore the changes of family pension functions and corresponding policies. Our analysis yielded 3 notable results. First, in family size miniaturization and structural simplification, 1- and 2-generation family households are the main body of contemporary China. Second, for family aging and changes in living patterns, which primarily manifest as an increase in; the proportion of elderly households and in middle-aged and elderly people in the family, the elderly model and the "multigenerational model" have become the 2 major residence models for the elderly in China. Third, nontraditional families have emerged in large numbers, such as the exclusively elderly family, empty nest family, grandparents family, Double Income, No Kids (DINK) family, older single family, and single-parent family. We argue that in the process of simplification, China's family structure is increasingly showing characteristics of networking. The change in family patterns entails the restoration of traditional functions and taking on new functions of the family by issuing relevant social policies. Only when these social policies are based on family functions and demands can they provide effective help to social members, particularly regarding the family's responsibilities to parent children and support the elderly. Copyright © 2017 John Wiley & Sons, Ltd.

Functional assignment to JEV proteins using SVM.

PubMed

Sahoo, Ganesh Chandra; Dikhit, Manas Ranjan; Das, Pradeep

2008-01-01

Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP).

Functional assignment to JEV proteins using SVM

PubMed Central

Sahoo, Ganesh Chandra; Dikhit, Manas Ranjan; Das, Pradeep

2008-01-01

Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP). PMID:19052658

Perceived Child Weight Status, Family Structure and Functioning, and Support for Health Behaviors in a Sample of Bariatric Surgery Patients.

PubMed

Pratt, Keeley J; Ferriby, Megan; Noria, Sabrena; Skelton, Joseph; Taylor, Christopher; Needleman, Bradley

2018-01-29

The purpose of this study is to describe the associations between bariatric surgery patients' perspectives of their child's weight status, family support for eating and exercise behavior change, and family structure and functioning. A cross-sectional descriptive design with pre- and postsurgery (N = 224) patients was used. Demographics, perceptions of child weight status, family support for eating habits and exercise, and family functioning were assessed from patients at a University Bariatric Clinic. Patients who perceived their child to be overweight/obese reported more impaired family functioning, less family exercise participation, and more discouragement for eating habit change in the family compared to patients who did not perceive their child to be overweight/obese. Single parents more often perceived their children to be overweight/obese, and had more impaired family functioning, and less support for changing eating habits and family exercise participation. Patients with impaired family functioning reported less support for changing eating habits and family exercise participation. Bariatric patients who perceived their child to be overweight/obese and identified as single parents reported more impaired family functioning and less support for eating habits and family participation in exercise. Assessing pre- and postsurgery measures from parents and children will allow the further identification of relationship variables that can be targeted to promote positive family changes that benefit parents and children long-term. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Studies of the structure-activity relationships of peptides and proteins involved in growth and development based on their three-dimensional structures.

PubMed

Nagata, Koji

2010-01-01

Peptides and proteins with similar amino acid sequences can have different biological functions. Knowledge of their three-dimensional molecular structures is critically important in identifying their functional determinants. In this review, I describe the results of our and other groups' structure-based functional characterization of insect insulin-like peptides, a crustacean hyperglycemic hormone-family peptide, a mammalian epidermal growth factor-family protein, and an intracellular signaling domain that recognizes proline-rich sequence.

Structure of a Trypanosoma Brucei Alpha/Beta--Hydrolase Fold Protein With Unknown Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merritt, E.A.; Holmes, M.; Buckner, F.S.

2009-05-26

The structure of a structural genomics target protein, Tbru020260AAA from Trypanosoma brucei, has been determined to a resolution of 2.2 {angstrom} using multiple-wavelength anomalous diffraction at the Se K edge. This protein belongs to Pfam sequence family PF08538 and is only distantly related to previously studied members of the {alpha}/{beta}-hydrolase fold family. Structural superposition onto representative {alpha}/{beta}-hydrolase fold proteins of known function indicates that a possible catalytic nucleophile, Ser116 in the T. brucei protein, lies at the expected location. However, the present structure and by extension the other trypanosomatid members of this sequence family have neither sequence nor structural similaritymore » at the location of other active-site residues typical for proteins with this fold. Together with the presence of an additional domain between strands {beta}6 and {beta}7 that is conserved in trypanosomatid genomes, this suggests that the function of these homologs has diverged from other members of the fold family.« less

Overview of the family structure in Egypt and its relation to psychiatry.

PubMed

Okasha, Tarek; Elkholy, Hussien; El-Ghamry, Reem

2012-04-01

The family is the basic unit of any society and culture. The concept, structure, and function of the family unit vary considerably across different cultures; however, its role continues to be imperative to the development of individuals and their psychological make-up. All societies have a concept of 'family', its relative importance, structure, and functions; however, this varies according to the particular culture. In the Arabic culture, as well as other collectivistic cultures, the extended family is often regarded as the basic unit. The family is the foundational and basic social unit that fosters the stability, well-being and sustainability of society. The quality of family relationships shapes and influences the social, psychological, and biological development and functioning of its members. This may be especially relevant to individuals with mental health problems. The people of ancient Egypt valued family life highly, and this is the case even now. They treasured children and regarded them as a great blessing. If a couple had no children, they would pray to the gods and goddesses for help. They would also place letters at the tombs of dead relatives asking them to use their influence with the gods. The importance of family has not changed dramatically even though the structures are beginning to. In this paper we highlight changes in family set-up and the state of family therapy in Egypt.

Family Structure and Family Processes in Mexican American Families

PubMed Central

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

2010-01-01

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

Enriching the annotation of Mycobacterium tuberculosis H37Rv proteome using remote homology detection approaches: insights into structure and function.

PubMed

Ramakrishnan, Gayatri; Ochoa-Montaño, Bernardo; Raghavender, Upadhyayula S; Mudgal, Richa; Joshi, Adwait G; Chandra, Nagasuma R; Sowdhamini, Ramanathan; Blundell, Tom L; Srinivasan, Narayanaswamy

2015-01-01

The availability of the genome sequence of Mycobacterium tuberculosis H37Rv has encouraged determination of large numbers of protein structures and detailed definition of the biological information encoded therein; yet, the functions of many proteins in M. tuberculosis remain unknown. The emergence of multidrug resistant strains makes it a priority to exploit recent advances in homology recognition and structure prediction to re-analyse its gene products. Here we report the structural and functional characterization of gene products encoded in the M. tuberculosis genome, with the help of sensitive profile-based remote homology search and fold recognition algorithms resulting in an enhanced annotation of the proteome where 95% of the M. tuberculosis proteins were identified wholly or partly with information on structure or function. New information includes association of 244 proteins with 205 domain families and a separate set of new association of folds to 64 proteins. Extending structural information across uncharacterized protein families represented in the M. tuberculosis proteome, by determining superfamily relationships between families of known and unknown structures, has contributed to an enhancement in the knowledge of structural content. In retrospect, such superfamily relationships have facilitated recognition of probable structure and/or function for several uncharacterized protein families, eventually aiding recognition of probable functions for homologous proteins corresponding to such families. Gene products unique to mycobacteria for which no functions could be identified are 183. Of these 18 were determined to be M. tuberculosis specific. Such pathogen-specific proteins are speculated to harbour virulence factors required for pathogenesis. A re-annotated proteome of M. tuberculosis, with greater completeness of annotated proteins and domain assigned regions, provides a valuable basis for experimental endeavours designed to obtain a better understanding of pathogenesis and to accelerate the process of drug target discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Collagens--structure, function, and biosynthesis.

PubMed

Gelse, K; Pöschl, E; Aigner, T

2003-11-28

The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified so far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. This review focuses on the distribution and function of various collagen types in different tissues. It introduces their basic structural subunits and points out major steps in the biosynthesis and supramolecular processing of fibrillar collagens as prototypical members of this protein family. A final outlook indicates the importance of different collagen types not only for the understanding of collagen-related diseases, but also as a basis for the therapeutical use of members of this protein family discussed in other chapters of this issue.

Assessment of family functioning in Caucasian and Hispanic Americans: reliability, validity, and factor structure of the Family Assessment Device.

PubMed

Aarons, Gregory A; McDonald, Elizabeth J; Connelly, Cynthia D; Newton, Rae R

2007-12-01

The purpose of this study was to examine the factor structure, reliability, and validity of the Family Assessment Device (FAD) among a national sample of Caucasian and Hispanic American families receiving public sector mental health services. A confirmatory factor analysis conducted to test model fit yielded equivocal findings. With few exceptions, indices of model fit, reliability, and validity were poorer for Hispanic Americans compared with Caucasian Americans. Contrary to our expectation, an exploratory factor analysis did not result in a better fitting model of family functioning. Without stronger evidence supporting a reformulation of the FAD, we recommend against such a course of action. Findings highlight the need for additional research on the role of culture in measurement of family functioning.

Divorce, Single Parenthood and Stepfamilies: Structural Implications of These Transactions.

ERIC Educational Resources Information Center

Schulman, Gerda L.

1981-01-01

Focuses on change in the family structure during divorce as well as stages of single parenthood and the reconstituted family. Special characteristics of these families and tasks to be undertaken to enable the new unit to function are discussed. Suggests family therapy is helpful during the crisis stage. (Author)

Recent Advances in Layered Metal Chalcogenides as Superconductors and Thermoelectric Materials: Fe-Based and Bi-Based Chalcogenides.

PubMed

Mizuguchi, Yoshikazu

2016-04-01

Recent advances in layered (Fe-based and Bi-based) chalcogenides as superconductors or functional materials are reviewed. The Fe-chalcogenide (FeCh) family are the simplest Fe-based high-Tc superconductors. The superconductivity in the FeCh family is sensitive to external or chemical pressure, and high Tc is attained when the local structure (anion height) is optimized. The Bi-chalcogenide (BiCh2) family are a new group of layered superconductors with a wide variety of stacking structures. Their physical properties are also sensitive to external or chemical pressure. Recently, we revealed that the emergence of superconductivity and the Tc in this family correlate with the in-plane chemical pressure. Since the flexibility of crystal structure and electronic states are an advantage of the BiCh2 family for designing functionalities, I briefly review recent developments in this family as not only superconductors but also other functional materials. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Family mechanisms of structural ecosystems therapy for HIV-seropositive women in drug recovery.

PubMed

Mitrani, Victoria B; McCabe, Brian E; Burns, Myron J; Feaster, Daniel J

2012-09-01

Examined the effects of Structural Ecosystems Therapy (SET), a family intervention for women living with HIV or AIDS, compared to a psycho-educational health group (HG) intervention, and reciprocal relationships between women and family members. Women (n = 126) and their family members (n = 269) were randomized to one of two conditions and assessed every 4 months for 12 months. Family functioning, drug use, and psychological distress was reported by multiple family members. Multilevel growth curve modeling showed a different family functioning trajectory between SET and HG, B = -0.05, SE = 0.02, p < .01. There was no intervention effect on the trajectory of family-level drug abstinence or psychological distress, but there was a significant difference in the trajectory of psychological distress after controlling for change in family functioning, B = -0.28, SE = 0.13, p < .05. There was an indirect effect from treatment through change in family functioning to change in psychological distress, B = 0.29, SE = 0.12, p < .05. With respect to reciprocal effects, family drug abstinence significantly predicted women's abstinence 4 months later, B = 0.22, SE = 0.06, p < .001. Findings demonstrated the interdependence of family members and the impact of family in relapse prevention and partially supported SET's potential for maintaining family functioning and well-being for women living with HIV or AIDS in drug recovery. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Family Mechanisms of Structural Ecosystems Therapy for HIV-Seropositive Women in Drug Recovery

PubMed Central

Mitrani, Victoria B.; McCabe, Brian E.; Burns, Myron J.; Feaster, Daniel J.

2013-01-01

Objective Examined the effects of Structural Ecosystems Therapy (SET), a family intervention for women living with HIV or AIDS, compared to a psycho-educational health group (HG) intervention, and reciprocal relationships between women and family members. Method Women (n = 126) and their family members (n = 269) were randomized to one of two conditions and assessed every 4 months for 12 months. Family functioning, drug use, and psychological distress was reported by multiple family members. Results Multilevel growth curve modeling showed a different family functioning trajectory between SET and HG, B = −0.05, SE = 0.02, p < .01. There was no intervention effect on the trajectory of family-level drug abstinence or psychological distress, but there was a significant difference in the trajectory of psychological distress after controlling for change in family functioning, B = −0.28, SE = 0.13, p < .05. There was an indirect effect from treatment through change in family functioning to change in psychological distress, B = 0.29, SE = 0.12, p < .05. With respect to reciprocal effects, family drug abstinence significantly predicted women’s abstinence 4 months later, B = 0.22, SE = 0.06, p < .001. Conclusion Findings demonstrated the interdependence of family members and the impact of family in relapse prevention and partially supported SET’s potential for maintaining family functioning and well-being for women living with HIV or AIDS in drug recovery. PMID:22708519

A comparison of family functioning, life and marital satisfaction, and mental health of women in polygamous and monogamous marriages.

PubMed

Al-Krenawi, Alean; Graham, John R

2006-01-01

A considerable body of research concludes that the polygamous family structure has an impact on children's and wives' psychological, social and family functioning. The present study is among the first to consider within the same ethno-racial community such essential factors as family functioning, life satisfaction, marital satisfaction and mental health functioning among women who are in polygamous marriages and women who are in monogamous marriages. A sample of 352 Bedouin-Arab women participated in this study: 235 (67%) were in a monogamous marriage and 117 (33%) were in a polygamous marriage. Findings reveal differences between women in polygamous and monogamous marriages. Women in polygamous marriages showed significantly higher psychological distress, and higher levels of somatisation, phobia and other psychological problems. They also had significantly more problems in family functioning, marital relationships and life satisfaction. The article calls on public policy and social service personnel to increase public awareness of the significance of polygamous family structures for women's wellbeing.

Family Structure and Approval Dependency in College Females

ERIC Educational Resources Information Center

Farley, Frank H.

1975-01-01

Approval dependency in college females was studied as a function of birth order, family size, and sibling sex with control over sib age separation. The results indicated no significant contribution of the family structure variables to approval dependency. (Author)

Relationships between Child Behavior Problems and Family Functioning: A Literature Review.

ERIC Educational Resources Information Center

van As, N. M. C.; Janssens, J. M. A. M.

2002-01-01

Reviews research examining the relationship between family functioning and child behavior problems. Focuses on parenting styles, intergenerational relationships, family structure, and family interaction patterns. Finds that child behavior problems are related to a lack of parental support, an imbalanced parent- child relationship, a lack of…

Structural Determination of Functional Domains in Early B-cell Factor (EBF) Family of Transcription Factors Reveals Similarities to Rel DNA-binding Proteins and a Novel Dimerization Motif*

PubMed Central

Siponen, Marina I.; Wisniewska, Magdalena; Lehtiö, Lari; Johansson, Ida; Svensson, Linda; Raszewski, Grzegorz; Nilsson, Lennart; Sigvardsson, Mikael; Berglund, Helena

2010-01-01

The early B-cell factor (EBF) transcription factors are central regulators of development in several organs and tissues. This protein family shows low sequence similarity to other protein families, which is why structural information for the functional domains of these proteins is crucial to understand their biochemical features. We have used a modular approach to determine the crystal structures of the structured domains in the EBF family. The DNA binding domain reveals a striking resemblance to the DNA binding domains of the Rel homology superfamily of transcription factors but contains a unique zinc binding structure, termed zinc knuckle. Further the EBF proteins contain an IPT/TIG domain and an atypical helix-loop-helix domain with a novel type of dimerization motif. The data presented here provide insights into unique structural features of the EBF proteins and open possibilities for detailed molecular investigations of this important transcription factor family. PMID:20592035

A Thermoacidophile-Specific Protein Family, DUF3211, Functions as a Fatty Acid Carrier with Novel Binding Mode

PubMed Central

Miyakawa, Takuya; Sawano, Yoriko; Miyazono, Ken-ichi; Miyauchi, Yumiko; Hatano, Ken-ichi

2013-01-01

STK_08120 is a member of the thermoacidophile-specific DUF3211 protein family from Sulfolobus tokodaii strain 7. Its molecular function remains obscure, and sequence similarities for obtaining functional remarks are not available. In this study, the crystal structure of STK_08120 was determined at 1.79-Å resolution to predict its probable function using structure similarity searches. The structure adopts an α/β structure of a helix-grip fold, which is found in the START domain proteins with cavities for hydrophobic substrates or ligands. The detailed structural features implied that fatty acids are the primary ligand candidates for STK_08120, and binding assays revealed that the protein bound long-chain saturated fatty acids (>C14) and their trans-unsaturated types with an affinity equal to that for major fatty acid binding proteins in mammals and plants. Moreover, the structure of an STK_08120-myristic acid complex revealed a unique binding mode among fatty acid binding proteins. These results suggest that the thermoacidophile-specific protein family DUF3211 functions as a fatty acid carrier with a novel binding mode. PMID:23836863

Breakfast frequency among adolescents: associations with measures of family functioning.

PubMed

Pedersen, Trine Pagh; Holstein, Bjørn E; Damsgaard, Mogens Trab; Rasmussen, Mette

2016-06-01

To investigate (i) associations between adolescents' frequency of breakfast and family functioning (close relations to parents, quality of family communication and family support) and (ii) if any observed associations between breakfast frequency and family functioning vary by sociodemographic factors. School-based cross-sectional study. Students completed a web-based questionnaire. Associations were estimated by multilevel multivariate logistic regression. Danish arm of the Health Behaviour in School-aged Children study, 2014. Adolescents aged 13 and 15 years (n 3054) from a random sample of forty-one schools. Nearly one-quarter of the adolescents had low breakfast frequency. Low breakfast frequency was associated with low family functioning measured by three dimensions. The OR (95 % CI) of low breakfast frequency was 1·81 (1·40, 2·33) for adolescents who reported no close relations to parents, 2·28 (1·61, 3·22) for adolescents who reported low level of quality of family communication and 2·09 (1·39, 3·15) for adolescents who reported low level of family support. Joint effect analyses suggested that the odds of low breakfast frequency among adolescents with low family functioning compared with high family functioning were highest among adolescents being girls, immigrants and living in other than a traditional family structure. Low breakfast frequency was associated with low family functioning measured by close relations to parents, quality of family communication and family support. Further, analyses suggested that the associations were more pronounced among girls, immigrants and adolescents from other family structure than traditional. The study highlights the importance of the family setting in promoting regular breakfast frequency among adolescents.

New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes.

PubMed

Parker, Brian J; Moltke, Ida; Roth, Adam; Washietl, Stefan; Wen, Jiayu; Kellis, Manolis; Breaker, Ronald; Pedersen, Jakob Skou

2011-11-01

Regulatory RNA structures are often members of families with multiple paralogous instances across the genome. Family members share functional and structural properties, which allow them to be studied as a whole, facilitating both bioinformatic and experimental characterization. We have developed a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein-coding regions comprising 725 individual structures, including 48 families with known structural RNA elements. Known families identified include both noncoding RNAs, e.g., miRNAs and the recently identified MALAT1/MEN β lincRNA family; and cis-regulatory structures, e.g., iron-responsive elements. We also identify tens of new families supported by strong evolutionary evidence and other statistical evidence, such as GO term enrichments. For some of these, detailed analysis has led to the formulation of specific functional hypotheses. Examples include two hypothesized auto-regulatory feedback mechanisms: one involving six long hairpins in the 3'-UTR of MAT2A, a key metabolic gene that produces the primary human methyl donor S-adenosylmethionine; the other involving a tRNA-like structure in the intron of the tRNA maturation gene POP1. We experimentally validate the predicted MAT2A structures. Finally, we identify potential new regulatory networks, including large families of short hairpins enriched in immunity-related genes, e.g., TNF, FOS, and CTLA4, which include known transcript destabilizing elements. Our findings exemplify the diversity of post-transcriptional regulation and provide a resource for further characterization of new regulatory mechanisms and families of noncoding RNAs.

An approach to functionally relevant clustering of the protein universe: Active site profile-based clustering of protein structures and sequences.

PubMed

Knutson, Stacy T; Westwood, Brian M; Leuthaeuser, Janelle B; Turner, Brandon E; Nguyendac, Don; Shea, Gabrielle; Kumar, Kiran; Hayden, Julia D; Harper, Angela F; Brown, Shoshana D; Morris, John H; Ferrin, Thomas E; Babbitt, Patricia C; Fetrow, Jacquelyn S

2017-04-01

Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification-amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two-Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure-Function Linkage Database, SFLD) self-identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self-identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well-curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP-identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F-measure and performance analysis on the enolase search results and comparison to GEMMA and SCI-PHY demonstrate that TuLIP avoids the over-division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

Pathways to Parental Knowledge: The Role of Family Process and Family Structure

ERIC Educational Resources Information Center

Padilla-Walker, Laura M.; Harper, James M.; Bean, Roy A.

2011-01-01

The purpose of the current study was (a) to examine the role of family process on child disclosure, parental solicitation, and parental knowledge and (b) to examine how patterns might differ as a function of family structure. Data for this study were taken from the Flourishing Families Project, which consists of 353 two- and 147 single-parent…

Family structure, family functioning and adolescent well-being: the transcendent influence of parental style.

PubMed

McFarlane, A H; Bellissimo, A; Norman, G R

1995-07-01

This study assessed the association between parental style, family functioning and adolescent well being, contrasting intact families with those of changed configuration. Eight hundred and one grade 10 general level teenagers in 11 high schools of a single educational system were the subjects. Results indicated that the configuration of the family was not the key determinant of effectiveness of family functioning. Instead the style of parenting turned out to be the main determinant of both family functioning and well being of the adolescents. While both "parents" were judged to have contributed to these outcomes cross gender effects were found.

The Ritualization of Family Ties.

ERIC Educational Resources Information Center

Cheal, David

1988-01-01

Examines three theories of family ritual derived from Emile Durkheim's sociology of social order: the structural-functional theory, constructionist theory, and mobilization theory. Concludes that rituals maintain traditional family structures, yet are creative in that they may define new forms of relationships and support emerging possibilities…

An estimated 5% of new protein structures solved today represent a new Pfam family

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mistry, Jaina; Kloppmann, Edda; Rost, Burkhard

2013-11-01

This study uses the Pfam database to show that the sequence redundancy of protein structures deposited in the PDB is increasing. The possible reasons behind this trend are discussed. High-resolution structural knowledge is key to understanding how proteins function at the molecular level. The number of entries in the Protein Data Bank (PDB), the repository of all publicly available protein structures, continues to increase, with more than 8000 structures released in 2012 alone. The authors of this article have studied how structural coverage of the protein-sequence space has changed over time by monitoring the number of Pfam families that acquiredmore » their first representative structure each year from 1976 to 2012. Twenty years ago, for every 100 new PDB entries released, an estimated 20 Pfam families acquired their first structure. By 2012, this decreased to only about five families per 100 structures. The reasons behind the slower pace at which previously uncharacterized families are being structurally covered were investigated. It was found that although more than 50% of current Pfam families are still without a structural representative, this set is enriched in families that are small, functionally uncharacterized or rich in problem features such as intrinsically disordered and transmembrane regions. While these are important constraints, the reasons why it may not yet be time to give up the pursuit of a targeted but more comprehensive structural coverage of the protein-sequence space are discussed.« less

Family Structure and Income during the Stages of Childhood and Subsequent Prosocial Behavior in Young Adulthood

ERIC Educational Resources Information Center

Bandy, Robert; Ottoni-Wilhelm, Mark

2012-01-01

This study investigated whether family structure transition and low income are risk factors in the development of prosocial behavior. Models of young adults' prosocial behavior--charitable giving and volunteering--were estimated as functions of their family structure and income during the stages of childhood. Participants were a representative…

Evaluations of family by youth: do they vary as a function of family structure, gender, and birth order?

PubMed

Parish, T S

1990-01-01

In the present study, 334 youths evaluated their families by responding to the Personal Attribute Inventory for Children. An analysis of variance revealed no significant main effects due to respondents' birth order or gender, but did find a significant main effect due to family structure and a significant two-way interaction effect between respondents' family structure and gender. Specifically, males from divorced remarried families and females from divorced nonremarried families were found to evaluate their respective families significantly more negatively than did their counterparts from other familial configurations. Implications of these findings are discussed.

Structure-Based Phylogenetic Analysis of the Lipocalin Superfamily.

PubMed

Lakshmi, Balasubramanian; Mishra, Madhulika; Srinivasan, Narayanaswamy; Archunan, Govindaraju

2015-01-01

Lipocalins constitute a superfamily of extracellular proteins that are found in all three kingdoms of life. Although very divergent in their sequences and functions, they show remarkable similarity in 3-D structures. Lipocalins bind and transport small hydrophobic molecules. Earlier sequence-based phylogenetic studies of lipocalins highlighted that they have a long evolutionary history. However the molecular and structural basis of their functional diversity is not completely understood. The main objective of the present study is to understand functional diversity of the lipocalins using a structure-based phylogenetic approach. The present study with 39 protein domains from the lipocalin superfamily suggests that the clusters of lipocalins obtained by structure-based phylogeny correspond well with the functional diversity. The detailed analysis on each of the clusters and sub-clusters reveals that the 39 lipocalin domains cluster based on their mode of ligand binding though the clustering was performed on the basis of gross domain structure. The outliers in the phylogenetic tree are often from single member families. Also structure-based phylogenetic approach has provided pointers to assign putative function for the domains of unknown function in lipocalin family. The approach employed in the present study can be used in the future for the functional identification of new lipocalin proteins and may be extended to other protein families where members show poor sequence similarity but high structural similarity.

Structure and transcriptional regulation of the major intrinsic protein gene family in grapevine.

PubMed

Wong, Darren Chern Jan; Zhang, Li; Merlin, Isabelle; Castellarin, Simone D; Gambetta, Gregory A

2018-04-11

The major intrinsic protein (MIP) family is a family of proteins, including aquaporins, which facilitate water and small molecule transport across plasma membranes. In plants, MIPs function in a huge variety of processes including water transport, growth, stress response, and fruit development. In this study, we characterize the structure and transcriptional regulation of the MIP family in grapevine, describing the putative genome duplication events leading to the family structure and characterizing the family's tissue and developmental specific expression patterns across numerous preexisting microarray and RNAseq datasets. Gene co-expression network (GCN) analyses were carried out across these datasets and the promoters of each family member were analyzed for cis-regulatory element structure in order to provide insight into their transcriptional regulation. A total of 29 Vitis vinifera MIP family members (excluding putative pseudogenes) were identified of which all but two were mapped onto Vitis vinifera chromosomes. In this study, segmental duplication events were identified for five plasma membrane intrinsic protein (PIP) and four tonoplast intrinsic protein (TIP) genes, contributing to the expansion of PIPs and TIPs in grapevine. Grapevine MIP family members have distinct tissue and developmental expression patterns and hierarchical clustering revealed two primary groups regardless of the datasets analyzed. Composite microarray and RNA-seq gene co-expression networks (GCNs) highlighted the relationships between MIP genes and functional categories involved in cell wall modification and transport, as well as with other MIPs revealing a strong co-regulation within the family itself. Some duplicated MIP family members have undergone sub-functionalization and exhibit distinct expression patterns and GCNs. Cis-regulatory element (CRE) analyses of the MIP promoters and their associated GCN members revealed enrichment for numerous CREs including AP2/ERFs and NACs. Combining phylogenetic analyses, gene expression profiling, gene co-expression network analyses, and cis-regulatory element enrichment, this study provides a comprehensive overview of the structure and transcriptional regulation of the grapevine MIP family. The study highlights the duplication and sub-functionalization of the family, its strong coordinated expression with genes involved in growth and transport, and the putative classes of TFs responsible for its regulation.

Crystal structure of the YDR533c S. cerevisiae protein, a class II member of the Hsp31 family.

PubMed

Graille, Marc; Quevillon-Cheruel, Sophie; Leulliot, Nicolas; Zhou, Cong-Zhao; Li de la Sierra Gallay, Ines; Jacquamet, Lilian; Ferrer, Jean-Luc; Liger, Dominique; Poupon, Anne; Janin, Joel; van Tilbeurgh, Herman

2004-05-01

The ORF YDR533c from Saccharomyces cerevisiae codes for a 25.5 kDa protein of unknown biochemical function. Transcriptome analysis of yeast has shown that this gene is activated in response to various stress conditions together with proteins belonging to the heat shock family. In order to clarify its biochemical function, we determined the crystal structure of YDR533c to 1.85 A resolution by the single anomalous diffraction method. The protein possesses an alpha/beta hydrolase fold and a putative Cys-His-Glu catalytic triad common to a large enzyme family containing proteases, amidotransferases, lipases, and esterases. The protein has strong structural resemblance with the E. coli Hsp31 protein and the intracellular protease I from Pyrococcus horikoshii, which are considered class I and class III members of the Hsp31 family, respectively. Detailed structural analysis strongly suggests that the YDR533c protein crystal structure is the first one of a class II member of the Hsp31 family.

Recent Changes in the Demographic Structure of Urban and Rural Families. Working Paper No. 7706.

ERIC Educational Resources Information Center

Brown, David L.

Despite pervasive and far-reaching changes in the institution of the family in this century, demographic data suggest not a breakdown of the American family; rather, significant change has occurred in its structure and function. Timing of family formation and childbearing, household size and living arrangements, marital stability (including racial…

A novel TctA citrate transporter from an activated sludge metagenome: structural and mechanistic predictions for the TTT family.

PubMed

Batista-García, Ramón Alberto; Sánchez-Reyes, Ayixon; Millán-Pacheco, César; González-Zuñiga, Víctor Manuel; Juárez, Soledad; Folch-Mallol, Jorge Luis; Pastor, Nina

2014-09-01

We isolated a putative citrate transporter of the tripartite tricarboxylate transporter (TTT) class from a metagenomic library of activated sludge from a sewage treatment plant. The transporter, dubbed TctA_ar, shares ∼50% sequence identity with TctA of Comamonas testosteroni (TctA_ct) and other β-Proteobacteria, and contains two 20-amino acid repeat signature sequences, considered a hallmark of this particular transporter class. The structures for both TctA_ar and TctA_ct were modeled with I-TASSER and two possible structures for this transporter family were proposed. Docking assays with citrate resulted in the corresponding sets of proposed critical residues for function. These models suggest functions for the 20-amino acid repeats in the context of the two different architectures. This constitutes the first attempt at structure modeling of the TTT family, to the best of our knowledge, and could aid functional understanding of this little-studied family. © 2014 Wiley Periodicals, Inc.

A Comparison of Family Adaptations to Having a Child with Cystic Fibrosis.

ERIC Educational Resources Information Center

Johnson, Mark C.; And Others

1985-01-01

Examines effect of cystic fibrosis (CF) on structure and social climate of the family using self-report scales and independent observations of family functioning. Families in which the child with CF was not the firstborn were found to be functioning more healthily than those in which the child was firstborn. (Author/NRB)

Relations between Parent Psychopathology, Family Functioning, and Adolescent Problems in Substance-Abusing Families: Disaggregating the Effects of Parent Gender

ERIC Educational Resources Information Center

Burstein, Marcy; Stanger, Catherine; Dumenci, Levent

2012-01-01

The present study: (1) examined relations between parent psychopathology and adolescent internalizing problems, externalizing problems, and substance use in substance-abusing families; and (2) tested family functioning problems as mediators of these relations. Structural equation modeling was used to estimate the independent effects of parent…

An approach to functionally relevant clustering of the protein universe: Active site profile‐based clustering of protein structures and sequences

PubMed Central

Knutson, Stacy T.; Westwood, Brian M.; Leuthaeuser, Janelle B.; Turner, Brandon E.; Nguyendac, Don; Shea, Gabrielle; Kumar, Kiran; Hayden, Julia D.; Harper, Angela F.; Brown, Shoshana D.; Morris, John H.; Ferrin, Thomas E.; Babbitt, Patricia C.

2017-01-01

Abstract Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification—amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two‐Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure‐Function Linkage Database, SFLD) self‐identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self‐identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well‐curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP‐identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F‐measure and performance analysis on the enolase search results and comparison to GEMMA and SCI‐PHY demonstrate that TuLIP avoids the over‐division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results. PMID:28054422

Functional Classification of Immune Regulatory Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinstein, Rotem; Ramagopal, Udupi A.; Nathenson, Stanley G.

2013-05-01

Members of the immunoglobulin superfamily (IgSF) control innate and adaptive immunity and are prime targets for the treatment of autoimmune diseases, infectious diseases, and malignancies. We describe a computational method, termed the Brotherhood algorithm, which utilizes intermediate sequence information to classify proteins into functionally related families. This approach identifies functional relationships within the IgSF and predicts additional receptor-ligand interactions. As a specific example, we examine the nectin/nectin-like family of cell adhesion and signaling proteins and propose receptor-ligand interactions within this family. We were guided by the Brotherhood approach and present the high-resolution structural characterization of a homophilic interaction involving themore » class-I MHC-restricted T-cell-associated molecule, which we now classify as a nectin-like family member. The Brotherhood algorithm is likely to have a significant impact on structural immunology by identifying those proteins and complexes for which structural characterization will be particularly informative.« less

The history of the CATH structural classification of protein domains.

PubMed

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.

Structure and Function of Na+-Symporters with Inverted Repeats

PubMed Central

Abramson, Jeff; Wright, Ernest M.

2009-01-01

Summary Symporters are membrane proteins that couple energy stored in electrochemical potential gradients to drive the cotransport of molecules and ions into cells. Traditionally, proteins are classified into gene families based on sequence homology and functional properties, e.g. the sodium glucose (SLC5 or Sodium Solute Symporter Family, SSS or SSF) and GABA (SLC6 or Neurotransmitter Sodium Symporter Family, NSS or SNF) symporter families [1-4]. Recently, it has been established that four Na+-symporter proteins with unrelated sequences have a common structural core containing an inverted repeat of 5 transmembrane (TM) helices [5-8]. Analysis of these four structures reveals that they reside in different conformations along the transport cycle providing atomic insight into the mechanism of sodium solute cotransport. PMID:19631523

Functional Evolution of PLP-dependent Enzymes based on Active-Site Structural Similarities

PubMed Central

Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

2014-01-01

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5’-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the Comparison of Protein Active Site Structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. PMID:24920327

Functional evolution of PLP-dependent enzymes based on active-site structural similarities.

PubMed

Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

2014-10-01

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. © 2014 Wiley Periodicals, Inc.

Maternal Parenting Stress and Child Perception of Family Functioning Among Families Affected by HIV.

PubMed

Schulte, Marya T; Armistead, Lisa; Marelich, William D; Payne, Diana L; Goodrum, Nada M; Murphy, Debra A

Mothers living with HIV (MLWH) experience stressors inherent to parenting, often within a context characterized by poverty, stigma, and/or limited social support. Our study assessed the relationship between parenting stress and child perceptions of family functioning in families with MLWH who have healthy school-age children. MLWH and their children (N = 102 pairs) completed measures addressing parenting stress and perceptions of family functioning (i.e., parent-child communication, family routines, and family cohesion). We used covariance structural modeling to evaluate the relationship between these factors, with results showing greater maternal parenting stress associated with poorer family functioning outcomes (reported by both the child and the mother). Findings offer support for the parenting stress-family functioning relationship by providing the child perspective along with the maternal perspective, and point to the need for interventions aimed at minimizing the impact of maternal parenting stress on family functioning. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

[Roles, functions and myths in the family group of the psychotic patient].

PubMed

Gallego Lluesma, O; Pugliese, R

1986-12-01

With the study of two families in treatment we can see the roles that each one gets, and the functions that the psychotic assumes. Because the family has a particular story, a lot of myths appear and the interpretation is the hermeneutic method which serves to explain them. This fact is very important because some of those myths show the pathologic unconscious of the family. Through the myths, the family expresses the values, the credences, the familiar ideology and the ideals, which generally are neither possible, real nor concrete. To consider the clinic material, we start from the description of a pathological family and we continue with the theoretical approximation of Pichon Riviére: the antipsychiatry, the structuralism and the theories about the communication of Palo Alto. Then, we arrive at universal situations about the roles in the psychotic's family: fixation and immobility, stereotypy and aupplementarity, double vinculum situation, the family gives up modifying the structure and the patient who assumes the family pathology is almost permanently disqualified. There is a downfall in the identity of the psychotic mainly because the father's function is perverted (in both families, the father appears as "powerful" and considered in society, but disqualified in the family).

Structural, functional and evolutionary characterization of major drought transcription factors families in maize

NASA Astrophysics Data System (ADS)

Mittal, Shikha; Banduni, Pooja; Mallikarjuna, Mallana G.; Rao, Atmakuri R.; Jain, Prashant A.; Dash, Prasanta K.; Thirunavukkarasu, Nepolean

2018-05-01

Drought is one of the major threats to maize production. In order to improve the production and to breed tolerant hybrids, understanding the genes and regulatory mechanisms during drought stress is important. Transcription factors (TFs) play a major role in gene regulation and many TFs have been identified in response to drought stress. In our experiment, a set of 15 major TF families comprising 1436 genes was structurally and functionally characterized using in-silico tools and a gene expression assay. All 1436 genes were mapped on 10 chromosome of maize. The functional annotation indicated the involvement of these genes in ABA signaling, ROS scavenging, photosynthesis, stomatal regulation, and sucrose metabolism. Duplication was identified as the primary force in divergence and expansion of TF families. Phylogenetic relationship was developed individually for each TF family as well as combined TF families. Phylogenetic analysis grouped the TF family of genes into TF-specific and mixed groups. Phylogenetic analysis of genes belonging to various TF families suggested that the origin of TFs occurred in the lineage of maize evolution. Gene structure analysis revealed that more number of genes were intron-rich as compared to intronless genes. Drought-responsive CRE’s such as ABREA, ABREB, DRE1 and DRECRTCOREAT have been identified. Expression and interaction analyses identified leaf-specific bZIP TF, GRMZM2G140355, as a potential contributor toward drought tolerance in maize. We also analyzed protein-protein interaction network of 269 drought-responsive genes belonging to different drought-related TFs. The information generated on structural and functional characteristics, expression and interaction of the drought-related TF families will be useful to decipher the drought tolerance mechanisms and to derive drought-tolerant genotypes in maize.

Structural Analysis of PTM Hotspots (SAPH-ire) – A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families*

PubMed Central

Dewhurst, Henry M.; Choudhury, Shilpa; Torres, Matthew P.

2015-01-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)—a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits—conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit–N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. PMID:26070665

Structure-based function prediction of the expanding mollusk tyrosinase family

NASA Astrophysics Data System (ADS)

Huang, Ronglian; Li, Li; Zhang, Guofan

2017-11-01

Tyrosinase (Ty) is a common enzyme found in many different animal groups. In our previous study, genome sequencing revealed that the Ty family is expanded in the Pacific oyster ( Crassostrea gigas). Here, we examine the larger number of Ty family members in the Pacific oyster by high-level structure prediction to obtain more information about their function and evolution, especially the unknown role in biomineralization. We verified 12 Ty gene sequences from Crassostrea gigas genome and Pinctada fucata martensii transcriptome. By using phylogenetic analysis of these Tys with functionally known Tys from other molluscan species, eight subgroups were identified (CgTy_s1, CgTy_s2, MolTy_s1, MolTy-s2, MolTy-s3, PinTy-s1, PinTy-s2 and PviTy). Structural data and surface pockets of the dinuclear copper center in the eight subgroups of molluscan Ty were obtained using the latest versions of prediction online servers. Structural comparison with other Ty proteins from the protein databank revealed functionally important residues (HA1, HA2, HA3, HB1, HB2, HB3, Z1-Z9) and their location within these protein structures. The structural and chemical features of these pockets which may related to the substrate binding showed considerable variability among mollusks, which undoubtedly defines Ty substrate binding. Finally, we discuss the potential driving forces of Ty family evolution in mollusks. Based on these observations, we conclude that the Ty family has rapidly evolved as a consequence of substrate adaptation in mollusks.

Family influences on adolescents' birth control and condom use, likelihood of sexually transmitted infections.

PubMed

Kao, Tsui-Sui Annie; Manczak, Melissa

2013-02-01

This study explored the relationships among personal factors, family structure and family function, adolescents' self-efficacy for safe sex, and sexual behaviors among sexually active adolescents. A subset sample from the first three waves of the National Longitudinal Study of Adolescent Health (Add Health) was selected for this exploratory secondary data analysis. Hierarchal and logistic regressions were conducted to explore the relationships among personal factors, family factors, and adolescents' self-reported sexually transmitted infections (STI) over time. Findings suggest that adolescents' racial/ethnic background, parents' disapproving attitudes, and family connectedness are significant predictors for birth control and condom use among adolescents. Although adolescents' personal factor and family structure play a role in their sexual behavior, positive family function significantly protects adolescents from STIs over time. School nurses can provide a vital point of care for at-risk adolescents by finding ways to encourage and incorporate parental and familial influences.

A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase

PubMed Central

Qin, Zhen; Xiao, Yibei; Yang, Xinbin; Mesters, Jeroen R.; Yang, Shaoqing; Jiang, Zhengqiang

2015-01-01

Glycoside hydrolase (GH) family 3 β-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 β-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 Å resolution. The three-dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions — a GH family 3 β-N-acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C-terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non-derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain β-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins. PMID:26669854

A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase.

PubMed

Qin, Zhen; Xiao, Yibei; Yang, Xinbin; Mesters, Jeroen R; Yang, Shaoqing; Jiang, Zhengqiang

2015-12-16

Glycoside hydrolase (GH) family 3 β-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 β-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 Å resolution. The three-dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions--a GH family 3 β-N-acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C-terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non-derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain β-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins.

Using the Rasch Measurement Model in Psychometric Analysis of the Family Effectiveness Measure

PubMed Central

McCreary, Linda L.; Conrad, Karen M.; Conrad, Kendon J.; Scott, Christy K; Funk, Rodney R.; Dennis, Michael L.

2013-01-01

Background Valid assessment of family functioning can play a vital role in optimizing client outcomes. Because family functioning is influenced by family structure, socioeconomic context, and culture, existing measures of family functioning--primarily developed with nuclear, middle class European American families--may not be valid assessments of families in diverse populations. The Family Effectiveness Measure was developed to address this limitation. Objectives To test the Family Effectiveness Measure with data from a primarily low-income African American convenience sample, using the Rasch measurement model. Method A sample of 607 adult women completed the measure. Rasch analysis was used to assess unidimensionality, response category functioning, item fit, person reliability, differential item functioning by race and parental status, and item hierarchy. Criterion-related validity was tested using correlations with five other variables related to family functioning. Results The Family Effectiveness Measure measures two separate constructs: The effective family functioning construct was a psychometrically sound measure of the target construct that was more efficient due to the deletion of 22 items. The ineffective family functioning construct consisted of 16 of those deleted items but was not as strong psychometrically. Items in both constructs evidenced no differential item functioning by race. Criterion-related validity was supported for both. Discussion In contrast to the prevailing conceptualization that family functioning is a single construct, assessed by positively and negatively worded items, use of the Rasch analysis suggested the existence of two constructs. While the effective family functioning is a strong and efficient measure of family functioning, the ineffective family functioning will require additional item development and psychometric testing. PMID:23636342

The Conservation of Structure and Mechanism of Catalytic Action in a Family of Thiamin Pyrophosphate (TPP)-dependent Enzymes

NASA Technical Reports Server (NTRS)

Dominiak, P.; Ciszak, Ewa

2004-01-01

Thiamin pyrophosphate (TPP)-dependent enzymes are a divergent family of TPP and metal ion binding proteins that perform a wide range of functions with the common decarboxylation steps of a -(O=)C-C(OH)- fragment of alpha-ketoacids and alpha- hydroxyaldehydes. To determine how structure and catalytic action are conserved in the context of large sequence differences existing within this family of enzymes, we have carried out an analysis of TPP-dependent enzymes of known structures. The common structure of TPP-dependent enzymes is formed at the interface of four alpha/beta domains from at least two subunits, which provide for two metal and TPP-binding sites. Residues around these catalytic sites are conserved for functional purpose, while those further away from TPP are conserved for structural reasons. Together they provide a network of contacts required for flip-flop catalytic action within TPP-dependent enzymes. Thus our analysis defines a TPP-action motif that is proposed for annotating TPP-dependent enzymes for advancing functional proteomics.

The relation between family adversity and social anxiety among adolescents in Taiwan: effects of family function and self-esteem.

PubMed

Yen, Cheng-Fang; Yang, Pinchen; Wu, Yu-Yu; Cheng, Chung-Ping

2013-11-01

This study aimed to examine the relationship between three indicators of family adversity (domestic violence, family substance use, and broken parental marriage) and the severity of social anxiety among adolescents in Taiwan, as well as the mediating effects of perceived family function and self-esteem on that relationship, using structural equation modeling (SEM). A total of 5607 adolescents completed the social anxiety subscale of the Multidimensional Anxiety Scale for Children; the Family APGAR Index; the Rosenberg Self-Esteem Scale; and a questionnaire for domestic violence, family substance use, and broken parental marriage. The relation between family adversity and social anxiety, as well as the mediating effects of family function and self-esteem, was examined using SEM. SEM analysis revealed that all three indicators of family adversity reduced the level of family function, that decreased family function compromised the level of self-esteem, and that a low level of self-esteem further increased the severity of social anxiety. The results indicated that, along with intervening to change family adversity, evaluating and improving adolescents' self-esteem and family function are also important clinical issues when helping adolescents reduce their social anxiety.

Improving Functioning of the Remarried Family System.

ERIC Educational Resources Information Center

Sager, Clifford J.; And Others

1981-01-01

Presents salient issues for therapists in understanding and treating the remarried (REM, second, blended, reconstituted or step) family. The structure of the remarried family is differentiated from that of the intact family. Specific treatment goals for REM families are elaborated and various treatment modalities advocated. (Author)

A new family of β-helix proteins with similarities to the polysaccharide lyases

DOE PAGES

Close, Devin W.; D'Angelo, Sara; Bradbury, Andrew R. M.

2014-09-27

Microorganisms that degrade biomass produce diverse assortments of carbohydrate-active enzymes and binding modules. Despite tremendous advances in the genomic sequencing of these organisms, many genes do not have an ascribed function owing to low sequence identity to genes that have been annotated. Consequently, biochemical and structural characterization of genes with unknown function is required to complement the rapidly growing pool of genomic sequencing data. A protein with previously unknown function (Cthe_2159) was recently isolated in a genome-wide screen using phage display to identify cellulose-binding protein domains from the biomass-degrading bacterium Clostridium thermocellum. Here, the crystal structure of Cthe_2159 is presentedmore » and it is shown that it is a unique right-handed parallel β-helix protein. Despite very low sequence identity to known β-helix or carbohydrate-active proteins, Cthe_2159 displays structural features that are very similar to those of polysaccharide lyase (PL) families 1, 3, 6 and 9. Cthe_2159 is conserved across bacteria and some archaea and is a member of the domain of unknown function family DUF4353. This suggests that Cthe_2159 is the first representative of a previously unknown family of cellulose and/or acid-sugar binding β-helix proteins that share structural similarities with PLs. More importantly, these results demonstrate how functional annotation by biochemical and structural analysis remains a critical tool in the characterization of new gene products.« less

A new family of β-helix proteins with similarities to the polysaccharide lyases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Close, Devin W.; D'Angelo, Sara; Bradbury, Andrew R. M.

Microorganisms that degrade biomass produce diverse assortments of carbohydrate-active enzymes and binding modules. Despite tremendous advances in the genomic sequencing of these organisms, many genes do not have an ascribed function owing to low sequence identity to genes that have been annotated. Consequently, biochemical and structural characterization of genes with unknown function is required to complement the rapidly growing pool of genomic sequencing data. A protein with previously unknown function (Cthe_2159) was recently isolated in a genome-wide screen using phage display to identify cellulose-binding protein domains from the biomass-degrading bacterium Clostridium thermocellum. Here, the crystal structure of Cthe_2159 is presentedmore » and it is shown that it is a unique right-handed parallel β-helix protein. Despite very low sequence identity to known β-helix or carbohydrate-active proteins, Cthe_2159 displays structural features that are very similar to those of polysaccharide lyase (PL) families 1, 3, 6 and 9. Cthe_2159 is conserved across bacteria and some archaea and is a member of the domain of unknown function family DUF4353. This suggests that Cthe_2159 is the first representative of a previously unknown family of cellulose and/or acid-sugar binding β-helix proteins that share structural similarities with PLs. More importantly, these results demonstrate how functional annotation by biochemical and structural analysis remains a critical tool in the characterization of new gene products.« less

The association between family factors and child behaviour problems using dyadic data.

PubMed

Wang, Y; Pan, J; Zhang, X; Yi, C

2015-11-01

Parental psychopathology and family issues are key influence factors to child behaviour problems. This study aimed to investigate the dyadic impact of maternal and paternal depression and perceived family functioning on child behaviour problems. Both maternal and paternal depression, perceived family functioning and reported child behaviour problems were collected, respectively. Because of the interdependent characteristic of dyadic data, structural equation modelling was used to examine the relationship among all variables and the mutual influence between mother and father. Results showed that father-perceived family functioning mediated the relationship between parental depression and child behaviour problems, but mother-perceived family functioning did not show this mediation effect. Meanwhile, maternal and paternal depression influenced both of their own and their partner's perceived family functioning. The findings indicated that paternal psychopathology and family functioning should not be overlooked in child behaviour development. In addition, this study underscored the importance to investigate the different impact of father and mother on child development within a dyadic unit. © 2014 John Wiley & Sons Ltd.

F-BAR family proteins, emerging regulators for cell membrane dynamic changes-from structure to human diseases.

PubMed

Liu, Suxuan; Xiong, Xinyu; Zhao, Xianxian; Yang, Xiaofeng; Wang, Hong

2015-05-09

Eukaryotic cell membrane dynamics change in curvature during physiological and pathological processes. In the past ten years, a novel protein family, Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain proteins, has been identified to be the most important coordinators in membrane curvature regulation. The F-BAR domain family is a member of the Bin/Amphiphysin/Rvs (BAR) domain superfamily that is associated with dynamic changes in cell membrane. However, the molecular basis in membrane structure regulation and the biological functions of F-BAR protein are unclear. The pathophysiological role of F-BAR protein is unknown. This review summarizes the current understanding of structure and function in the BAR domain superfamily, classifies F-BAR family proteins into nine subfamilies based on domain structure, and characterizes F-BAR protein structure, domain interaction, and functional relevance. In general, F-BAR protein binds to cell membrane via F-BAR domain association with membrane phospholipids and initiates membrane curvature and scission via Src homology-3 (SH3) domain interaction with its partner proteins. This process causes membrane dynamic changes and leads to seven important cellular biological functions, which include endocytosis, phagocytosis, filopodium, lamellipodium, cytokinesis, adhesion, and podosome formation, via distinct signaling pathways determined by specific domain-binding partners. These cellular functions play important roles in many physiological and pathophysiological processes. We further summarize F-BAR protein expression and mutation changes observed in various diseases and developmental disorders. Considering the structure feature and functional implication of F-BAR proteins, we anticipate that F-BAR proteins modulate physiological and pathophysiological processes via transferring extracellular materials, regulating cell trafficking and mobility, presenting antigens, mediating extracellular matrix degradation, and transmitting signaling for cell proliferation.

Associations Between Family Structure, Family Functioning, and Substance Use Among Hispanic/Latino Adolescents

PubMed Central

Wagner, Karla D.; Ritt-Olson, Anamara; Chou, Chih-Ping; Pokhrel, Pallav; Duan, Lei; Baezconde-Garbanati, Lourdes; Soto, Daniel W.; Unger, Jennifer B.

2010-01-01

This study examined the role of family structure and functioning in predicting substance use among Hispanic/Latino adolescents, surveyed in 9th and 10th grade. The sample (N=1433) was half female, mostly of Mexican descent, and the majority was born in the U.S. Living with a single father was associated with less parental monitoring and less family cohesion (γ = −0.07, −0.06, respectively). Living with a single mother was associated with less parental monitoring (γ = −0.10). Living with neither parent was associated with less communication (γ = −0.08), less parental monitoring (γ = −0.09), more family conflict (γ = 0.06), and less family cohesion (γ = −0.06). Less monitoring was associated with substance use at follow-up (β = −0.17). Low rates of parental monitoring appear to mediate the association between parental family structure and substance use. Results suggest that improving basic parenting skills, and offering additional social support and resources to assist parents in monitoring adolescents may help prevent substance use. These interventions may be particularly beneficial for single parents. PMID:20307116

Evolutionary and Functional Relationships in the Truncated Hemoglobin Family.

PubMed

Bustamante, Juan P; Radusky, Leandro; Boechi, Leonardo; Estrin, Darío A; Ten Have, Arjen; Martí, Marcelo A

2016-01-01

Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2 affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends.

Evolutionary and Functional Relationships in the Truncated Hemoglobin Family

PubMed Central

Bustamante, Juan P.; Radusky, Leandro; Boechi, Leonardo; Estrin, Darío A.; ten Have, Arjen; Martí, Marcelo A.

2016-01-01

Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2 affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends. PMID:26788940

The Role of Stress Exposure and Family Functioning in Internalizing Outcomes of Urban Families

PubMed Central

Henry, David B.; Tolan, Patrick H.; Strachan, Martha K.

2013-01-01

Although research suggests that stress exposure and family functioning are associated with internalizing problems in adolescents and caregivers, surprisingly few studies have investigated the mechanisms that underlie this association. To determine whether family functioning buffers the development of internalizing problems in stress-exposed families, we assessed the relation between stress exposure, family functioning, and internalizing symptoms among a large sample of inner-city male youth and their caregivers living in poverty across five waves of data collection. We hypothesized that stress exposure and family functioning would predict development of subsequent youth and caregiver internalizing problems and that family functioning would moderate this relation, with higher functioning families demonstrating greater resiliency to stress exposure. We used a longitudinal, prospective design to evaluate whether family functioning (assessed at waves one through four) activated or buffered the effects of stress exposure (assessed at wave one) on subsequent internalizing symptoms (assessed at waves four and five). Stress from Developmental Transitions and family functioning were significant predictors of depressive symptoms and anxiety in youth; however, family functioning did not moderate the relation. Family functioning mediated the relation between stress from Daily Hassles and internalizing outcomes suggesting that poor parenting practices, low structure, and low emotional cohesion activate depression and anxiety in youth exposed to chronic and frequent everyday stressors. Surprisingly, only family functioning predicted depressive symptoms in caregivers. Results validate the use of a comprehensive, multi-informant assessment of stress when investigating internalizing outcomes in youth and support using family-based interventions in the treatment and prevention of internalizing. PMID:25601821

The Role of Stress Exposure and Family Functioning in Internalizing Outcomes of Urban Families.

PubMed

Sheidow, Ashli J; Henry, David B; Tolan, Patrick H; Strachan, Martha K

2014-11-01

Although research suggests that stress exposure and family functioning are associated with internalizing problems in adolescents and caregivers, surprisingly few studies have investigated the mechanisms that underlie this association. To determine whether family functioning buffers the development of internalizing problems in stress-exposed families, we assessed the relation between stress exposure, family functioning, and internalizing symptoms among a large sample of inner-city male youth and their caregivers living in poverty across five waves of data collection. We hypothesized that stress exposure and family functioning would predict development of subsequent youth and caregiver internalizing problems and that family functioning would moderate this relation, with higher functioning families demonstrating greater resiliency to stress exposure. We used a longitudinal, prospective design to evaluate whether family functioning (assessed at waves one through four) activated or buffered the effects of stress exposure (assessed at wave one) on subsequent internalizing symptoms (assessed at waves four and five). Stress from Developmental Transitions and family functioning were significant predictors of depressive symptoms and anxiety in youth; however, family functioning did not moderate the relation. Family functioning mediated the relation between stress from Daily Hassles and internalizing outcomes suggesting that poor parenting practices, low structure, and low emotional cohesion activate depression and anxiety in youth exposed to chronic and frequent everyday stressors. Surprisingly, only family functioning predicted depressive symptoms in caregivers. Results validate the use of a comprehensive, multi-informant assessment of stress when investigating internalizing outcomes in youth and support using family-based interventions in the treatment and prevention of internalizing.

Genome-Wide Analysis of the NADK Gene Family in Plants

PubMed Central

Li, Wen-Yan; Wang, Xiang; Li, Ri; Li, Wen-Qiang; Chen, Kun-Ming

2014-01-01

Background NAD(H) kinase (NADK) is the key enzyme that catalyzes de novo synthesis of NADP(H) from NAD(H) for NADP(H)-based metabolic pathways. In plants, NADKs form functional subfamilies. Studies of these families in Arabidopsis thaliana indicate that they have undergone considerable evolutionary selection; however, the detailed evolutionary history and functions of the various NADKs in plants are not clearly understood. Principal Findings We performed a comparative genomic analysis that identified 74 NADK gene homologs from 24 species representing the eight major plant lineages within the supergroup Plantae: glaucophytes, rhodophytes, chlorophytes, bryophytes, lycophytes, gymnosperms, monocots and eudicots. Phylogenetic and structural analysis classified these NADK genes into four well-conserved subfamilies with considerable variety in the domain organization and gene structure among subfamily members. In addition to the typical NAD_kinase domain, additional domains, such as adenylate kinase, dual-specificity phosphatase, and protein tyrosine phosphatase catalytic domains, were found in subfamily II. Interestingly, NADKs in subfamily III exhibited low sequence similarity (∼30%) in the kinase domain within the subfamily and with the other subfamilies. These observations suggest that gene fusion and exon shuffling may have occurred after gene duplication, leading to specific domain organization seen in subfamilies II and III, respectively. Further analysis of the exon/intron structures showed that single intron loss and gain had occurred, yielding the diversified gene structures, during the process of structural evolution of NADK family genes. Finally, both available global microarray data analysis and qRT-RCR experiments revealed that the NADK genes in Arabidopsis and Oryza sativa show different expression patterns in different developmental stages and under several different abiotic/biotic stresses and hormone treatments, underscoring the functional diversity and functional divergence of the NADK family in plants. Conclusions These findings will facilitate further studies of the NADK family and provide valuable information for functional validation of this family in plants. PMID:24968225

The Sla2p/HIP1/HIP1R family: similar structure, similar function in endocytosis?

PubMed

Gottfried, Irit; Ehrlich, Marcelo; Ashery, Uri

2010-02-01

HIP1 (huntingtin interacting protein 1) has two close relatives: HIP1R (HIP1-related) and yeast Sla2p. All three members of the family have a conserved domain structure, suggesting a common function. Over the past decade, a number of studies have characterized these proteins using a combination of biochemical, imaging, structural and genetic techniques. These studies provide valuable information on binding partners, structure and dynamics of HIP1/HIP1R/Sla2p. In general, all suggest a role in CME (clathrin-mediated endocytosis) for the three proteins, though some differences have emerged. In this mini-review we summarize the current views on the roles of these proteins, while emphasizing the unique attributes of each family member.

A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters

PubMed Central

Saier, Milton H.

2000-01-01

A comprehensive classification system for transmembrane molecular transporters has been developed and recently approved by the transport panel of the nomenclature committee of the International Union of Biochemistry and Molecular Biology. This system is based on (i) transporter class and subclass (mode of transport and energy coupling mechanism), (ii) protein phylogenetic family and subfamily, and (iii) substrate specificity. Almost all of the more than 250 identified families of transporters include members that function exclusively in transport. Channels (115 families), secondary active transporters (uniporters, symporters, and antiporters) (78 families), primary active transporters (23 families), group translocators (6 families), and transport proteins of ill-defined function or of unknown mechanism (51 families) constitute distinct categories. Transport mode and energy coupling prove to be relatively immutable characteristics and therefore provide primary bases for classification. Phylogenetic grouping reflects structure, function, mechanism, and often substrate specificity and therefore provides a reliable secondary basis for classification. Substrate specificity and polarity of transport prove to be more readily altered during evolutionary history and therefore provide a tertiary basis for classification. With very few exceptions, a phylogenetic family of transporters includes members that function by a single transport mode and energy coupling mechanism, although a variety of substrates may be transported, sometimes with either inwardly or outwardly directed polarity. In this review, I provide cross-referencing of well-characterized constituent transporters according to (i) transport mode, (ii) energy coupling mechanism, (iii) phylogenetic grouping, and (iv) substrates transported. The structural features and distribution of recognized family members throughout the living world are also evaluated. The tabulations should facilitate familial and functional assignments of newly sequenced transport proteins that will result from future genome sequencing projects. PMID:10839820

High-Resolution X-Ray Structures of Two Functionally Distinct Members of the Cyclic Amide Hydrolase Family of Toblerone Fold Enzymes

PubMed Central

Peat, Thomas S.; Balotra, Sahil; Wilding, Matthew; Hartley, Carol J.; Newman, Janet

2017-01-01

ABSTRACT The Toblerone fold was discovered recently when the first structure of the cyclic amide hydrolase, AtzD (a cyanuric acid hydrolase), was elucidated. We surveyed the cyclic amide hydrolase family, finding a strong correlation between phylogenetic distribution and specificity for either cyanuric acid or barbituric acid. One of six classes (IV) could not be tested due to a lack of expression of the proteins from it, and another class (V) had neither cyanuric acid nor barbituric acid hydrolase activity. High-resolution X-ray structures were obtained for a class VI barbituric acid hydrolase (1.7 Å) from a Rhodococcus species and a class V cyclic amide hydrolase (2.4 Å) from a Frankia species for which we were unable to identify a substrate. Both structures were homologous with the tetrameric Toblerone fold enzyme AtzD, demonstrating a high degree of structural conservation within the cyclic amide hydrolase family. The barbituric acid hydrolase structure did not contain zinc, in contrast with early reports of zinc-dependent activity for this enzyme. Instead, each barbituric acid hydrolase monomer contained either Na+ or Mg2+, analogous to the structural metal found in cyanuric acid hydrolase. The Frankia cyclic amide hydrolase contained no metal but instead formed unusual, reversible, intermolecular vicinal disulfide bonds that contributed to the thermal stability of the protein. The active sites were largely conserved between the three enzymes, differing at six positions, which likely determine substrate specificity. IMPORTANCE The Toblerone fold enzymes catalyze an unusual ring-opening hydrolysis with cyclic amide substrates. A survey of these enzymes shows that there is a good correlation between physiological function and phylogenetic distribution within this family of enzymes and provide insights into the evolutionary relationships between the cyanuric acid and barbituric acid hydrolases. This family of enzymes is structurally and mechanistically distinct from other enzyme families; however, to date the structure of just two, physiologically identical, enzymes from this family has been described. We present two new structures: a barbituric acid hydrolase and an enzyme of unknown function. These structures confirm that members of the CyAH family have the unusual Toblerone fold, albeit with some significant differences. PMID:28235873

Functional diversification of ROK-family transcriptional regulators of sugar catabolism in the Thermotogae phylum

PubMed Central

Kazanov, Marat D.; Li, Xiaoqing; Gelfand, Mikhail S.; Osterman, Andrei L.; Rodionov, Dmitry A.

2013-01-01

Large and functionally heterogeneous families of transcription factors have complex evolutionary histories. What shapes specificities toward effectors and DNA sites in paralogous regulators is a fundamental question in biology. Bacteria from the deep-branching lineage Thermotogae possess multiple paralogs of the repressor, open reading frame, kinase (ROK) family regulators that are characterized by carbohydrate-sensing domains shared with sugar kinases. We applied an integrated genomic approach to study functions and specificities of regulators from this family. A comparative analysis of 11 Thermotogae genomes revealed novel mechanisms of transcriptional regulation of the sugar utilization networks, DNA-binding motifs and specific functions. Reconstructed regulons for seven groups of ROK regulators were validated by DNA-binding assays using purified recombinant proteins from the model bacterium Thermotoga maritima. All tested regulators demonstrated specific binding to their predicted cognate DNA sites, and this binding was inhibited by specific effectors, mono- or disaccharides from their respective sugar catabolic pathways. By comparing ligand-binding domains of regulators with structurally characterized kinases from the ROK family, we elucidated signature amino acid residues determining sugar-ligand regulator specificity. Observed correlations between signature residues and the sugar-ligand specificities provide the framework for structure functional classification of the entire ROK family. PMID:23209028

Hegemony in the Roma family.

PubMed

Mrhálek, Tomáš; Lidová, Lenka; Kajanová, Alena

2015-01-01

This article is intended to describe the current hegemonic masculinity within the Roma family structure in the Czech Republic, with regard to changes related to developments in the majority society and the current socioeconomic situation of the Roma. The theoretical context of this article is based on the paradigm of masculine hegemony as it exists and has existed in the Roma families. Data for the study came from semi-structured interviews with 30 Roma females and 30 Roma males living as couples, in three Czech cities. The main finding reveals a dichotomy between the traditional roles of Roma women, i.e. care for the family and the household, and the present functions, i.e. contributing to the family income through social benefits. We observed a decline in the traditional role of Roma men, who were often unemployed. We related the change in the roles of men to the "non-functionality of the men", contributing to the emerging potential for emancipation of Roma women. However, the traditional patriarchal Roma family is structured such that men are given the main decision making powers, which has slowed changes in marginalized Roma families. Additionally, social pressures against women as well as socially conditioned pressures that act to preserve hegemonic masculinity, have largely prevented the realization of the potential for emancipation of Roma women, or if a woman tries to leave her non-functioning husband.

Conserved structural and functional aspects of the tripartite motif gene family point towards therapeutic applications in multiple diseases.

PubMed

Gushchina, Liubov V; Kwiatkowski, Thomas A; Bhattacharya, Sayak; Weisleder, Noah L

2018-05-01

The tripartite motif (TRIM) gene family is a highly conserved group of E3 ubiquitin ligase proteins that can establish substrate specificity for the ubiquitin-proteasome complex and also have proteasome-independent functions. While several family members were studied previously, it is relatively recent that over 80 genes, based on sequence homology, were grouped to establish the TRIM gene family. Functional studies of various TRIM genes linked these proteins to modulation of inflammatory responses showing that they can contribute to a wide variety of disease states including cardiovascular, neurological and musculoskeletal diseases, as well as various forms of cancer. Given the fundamental role of the ubiquitin-proteasome complex in protein turnover and the importance of this regulation in most aspects of cellular physiology, it is not surprising that TRIM proteins display a wide spectrum of functions in a variety of cellular processes. This broad range of function and the highly conserved primary amino acid sequence of family members, particularly in the canonical TRIM E3 ubiquitin ligase domain, complicates the development of therapeutics that specifically target these proteins. A more comprehensive understanding of the structure and function of TRIM proteins will help guide therapeutic development for a number of different diseases. This review summarizes the structural organization of TRIM proteins, their domain architecture, common and unique post-translational modifications within the family, and potential binding partners and targets. Further discussion is provided on efforts to target TRIM proteins as therapeutic agents and how our increasing understanding of the nature of TRIM proteins can guide discovery of other therapeutics in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Family functioning in severe brain injuries: correlations with caregivers' burden, perceived social support and quality of life.

PubMed

Tramonti, Francesco; Bonfiglio, Luca; Di Bernardo, Carolina; Ulivi, Chiara; Virgillito, Alessandra; Rossi, Bruno; Carboncini, Maria Chiara

2015-01-01

Severe brain injuries have long-term consequences on functional status and psychosocial functioning. Family life can be greatly influenced as well, and features of high caregiver burden can emerge. Although the data on caregivers' distress are constantly increasing, less information is available about the role of family functioning. Thirty caregivers of hospitalised patients with severe brain injuries received questionnaires for the evaluation of caregiver burden, family functioning and perceived social support. A semi-structured interview was performed for the evaluation of quality of life. Family cohesion and adaptability positively correlated with caregivers' quality of life and perceived social support. Partner caregivers' scores were significantly higher on the time-dependent burden than those of sons and daughters, whereas the latter scored higher on the emotional burden.

Structure-based analysis of catalysis and substrate definition in the HIT protein family.

PubMed

Lima, C D; Klein, M G; Hendrickson, W A

1997-10-10

The histidine triad (HIT) protein family is among the most ubiquitous and highly conserved in nature, but a biological activity has not yet been identified for any member of the HIT family. Fragile histidine triad protein (FHIT) and protein kinase C interacting protein (PKCI) were used in a structure-based approach to elucidate characteristics of in vivo ligands and reactions. Crystallographic structures of apo, substrate analog, pentacovalent transition-state analog, and product states of both enzymes reveal a catalytic mechanism and define substrate characteristics required for catalysis, thus unifying the HIT family as nucleotidyl hydrolases, transferases, or both. The approach described here may be useful in identifying structure-function relations between protein families identified through genomics.

Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin.

PubMed

Prisilla, A; Prathiviraj, R; Chellapandi, P

2017-04-01

Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 toxin along with botulinum neurotoxins. C2 toxin is belonged to binary toxin A family in bacterial ADP-ribosylation superfamily. A structural and functional diversity of binary toxin A family was inferred from different evolutionary constraints to determine the avirulence state of C2 toxin. Evolutionary genetic analyses revealed evidence of C2 toxin cluster evolution through horizontal gene transfer from the phage or plasmid origins, site-specific insertion by gene divergence, and homologous recombination event. It has also described that residue in conserved NAD-binding core, family-specific domain structure, and functional motifs found to predetermine its virulence state. Any mutational changes in these residues destabilized its structure-function relationship. Avirulent mutants of C2 toxin were screened and selected from a crucial site required for catalytic function of C2I and pore-forming function of C2II. We found coevolved amino acid pairs contributing an essential role in stabilization of its local structural environment. Avirulent toxins selected in this study were evaluated by detecting evolutionary constraints in stability of protein backbone structure, folding and conformational dynamic space, and antigenic peptides. We found 4 avirulent mutants of C2I and 5 mutants of C2II showing more stability in their local structural environment and backbone structure with rapid fold rate, and low conformational flexibility at mutated sites. Since, evolutionary constraints-free mutants with lack of catalytic and pore-forming function suggested as potential immunogenic candidates for treating C. botulinum infected poultry and veterinary animals. Single amino acid substitution in C2 toxin thus provides a major importance to understand its structure-function link, not only of a molecule but also of the pathogenesis.

TRPC Channel Structure and Properties.

PubMed

Feng, Shengjie

2017-01-01

TRPC channels are the first identified members in the TRP family. They function as either homo- or heterotetramers regulating intracellular Ca 2+ concentration in response to numerous physiological or pathological stimuli. TRPC channels are nonselective cation channels permeable to Ca 2+ . The properties and the functional domains of TRPC channels have been identified by electrophysiological and biochemical methods. However, due to the large size, instability, and flexibility of their complexes, the structures of the members in TRPC family remain unrevealed. More efforts should be made on structure analysis and generating good tools, including specific antibodies, agonist, and antagonist.

The crystal structure of Erwinia amylovora AmyR, a member of the YbjN protein family, shows similarity to type III secretion chaperones but suggests different cellular functions

PubMed Central

Bartho, Joseph D.; Bellini, Dom; Wuerges, Jochen; Demitri, Nicola; Toccafondi, Mirco; Schmitt, Armin O.; Zhao, Youfu; Walsh, Martin A.

2017-01-01

AmyR is a stress and virulence associated protein from the plant pathogenic Enterobacteriaceae species Erwinia amylovora, and is a functionally conserved ortholog of YbjN from Escherichia coli. The crystal structure of E. amylovora AmyR reveals a class I type III secretion chaperone-like fold, despite the lack of sequence similarity between these two classes of protein and lacking any evidence of a secretion-associated role. The results indicate that AmyR, and YbjN proteins in general, function through protein-protein interactions without any enzymatic action. The YbjN proteins of Enterobacteriaceae show remarkably low sequence similarity with other members of the YbjN protein family in Eubacteria, yet a high level of structural conservation is observed. Across the YbjN protein family sequence conservation is limited to residues stabilising the protein core and dimerization interface, while interacting regions are only conserved between closely related species. This study presents the first structure of a YbjN protein from Enterobacteriaceae, the most highly divergent and well-studied subgroup of YbjN proteins, and an in-depth sequence and structural analysis of this important but poorly understood protein family. PMID:28426806

The crystal structure of Erwinia amylovora AmyR, a member of the YbjN protein family, shows similarity to type III secretion chaperones but suggests different cellular functions.

PubMed

Bartho, Joseph D; Bellini, Dom; Wuerges, Jochen; Demitri, Nicola; Toccafondi, Mirco; Schmitt, Armin O; Zhao, Youfu; Walsh, Martin A; Benini, Stefano

2017-01-01

AmyR is a stress and virulence associated protein from the plant pathogenic Enterobacteriaceae species Erwinia amylovora, and is a functionally conserved ortholog of YbjN from Escherichia coli. The crystal structure of E. amylovora AmyR reveals a class I type III secretion chaperone-like fold, despite the lack of sequence similarity between these two classes of protein and lacking any evidence of a secretion-associated role. The results indicate that AmyR, and YbjN proteins in general, function through protein-protein interactions without any enzymatic action. The YbjN proteins of Enterobacteriaceae show remarkably low sequence similarity with other members of the YbjN protein family in Eubacteria, yet a high level of structural conservation is observed. Across the YbjN protein family sequence conservation is limited to residues stabilising the protein core and dimerization interface, while interacting regions are only conserved between closely related species. This study presents the first structure of a YbjN protein from Enterobacteriaceae, the most highly divergent and well-studied subgroup of YbjN proteins, and an in-depth sequence and structural analysis of this important but poorly understood protein family.

Strategic Family Therapy: A High-Technology Approach.

ERIC Educational Resources Information Center

Seligman, Linda

Historically, family counseling grew from a focus on the individual to an emphasis on the importance of the entire family as the unit of treatment and the structure of the family as the key ingredient in family functioning. Strategic family therapy (SFT) has evolved from these traditional intervention approaches to the use of a brief, directive,…

Structures of a bi-functional Kunitz-type STI family inhibitor of serine and aspartic proteases: Could the aspartic protease inhibition have evolved from a canonical serine protease-binding loop?

PubMed

Guerra, Yasel; Valiente, Pedro A; Pons, Tirso; Berry, Colin; Rudiño-Piñera, Enrique

2016-08-01

Bi-functional inhibitors from the Kunitz-type soybean trypsin inhibitor (STI) family are glycosylated proteins able to inhibit serine and aspartic proteases. Here we report six crystal structures of the wild-type and a non-glycosylated mutant of the bifunctional inhibitor E3Ad obtained at different pH values and space groups. The crystal structures show that E3Ad adopts the typical β-trefoil fold of the STI family exhibiting some conformational changes due to pH variations and crystal packing. Despite the high sequence identity with a recently reported potato cathepsin D inhibitor (PDI), three-dimensional structures obtained in this work show a significant conformational change in the protease-binding loop proposed for aspartic protease inhibition. The E3Ad binding loop for serine protease inhibition is also proposed, based on structural similarity with a novel non-canonical conformation described for the double-headed inhibitor API-A from the Kunitz-type STI family. In addition, structural and sequence analyses suggest that bifunctional inhibitors of serine and aspartic proteases from the Kunitz-type STI family are more similar to double-headed inhibitor API-A than other inhibitors with a canonical protease-binding loop. Copyright © 2016. Published by Elsevier Inc.

Plant Ion Channels: Gene Families, Physiology, and Functional Genomics Analyses

PubMed Central

Ward, John M.; Mäser, Pascal; Schroeder, Julian I.

2016-01-01

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization-and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide–gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport. PMID:18842100

Plant ion channels: gene families, physiology, and functional genomics analyses.

PubMed

Ward, John M; Mäser, Pascal; Schroeder, Julian I

2009-01-01

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

Structural Analysis of PTM Hotspots (SAPH-ire)--A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families.

PubMed

Dewhurst, Henry M; Choudhury, Shilpa; Torres, Matthew P

2015-08-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)--a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits--conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit-N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Family-Centered Early Intervention for Communication Disorders: Prevention and Treatment. Excellence in Practice Series.

ERIC Educational Resources Information Center

Donahue-Kilburg, Gail

This book is designed to provide a broad range of information on family structure and function in an increasingly multicultural society, family system characteristics and the implications for intervention, communication development in the family context, the nature and delivery of family centered-services, specific requirements of Public Law…

Candida albicans Agglutinin-Like Sequence (Als) Family Vignettes: A Review of Als Protein Structure and Function

PubMed Central

Hoyer, Lois L.; Cota, Ernesto

2016-01-01

Approximately two decades have passed since the description of the first gene in the Candida albicans ALS (agglutinin-like sequence) family. Since that time, much has been learned about the composition of the family and the function of its encoded cell-surface glycoproteins. Solution of the structure of the Als adhesive domain provides the opportunity to evaluate the molecular basis for protein function. This review article is formatted as a series of fundamental questions and explores the diversity of the Als proteins, as well as their role in ligand binding, aggregative effects, and attachment to abiotic surfaces. Interaction of Als proteins with each other, their functional equivalence, and the effects of protein abundance on phenotypic conclusions are also examined. Structural features of Als proteins that may facilitate invasive function are considered. Conclusions that are firmly supported by the literature are presented while highlighting areas that require additional investigation to reveal basic features of the Als proteins, their relatedness to each other, and their roles in C. albicans biology. PMID:27014205

Family Turbulence and Child Internalizing and Externalizing Behaviors: Moderation of Effects by Race.

PubMed

Womack, Sean R; Taraban, Lindsay; Shaw, Daniel S; Wilson, Melvin N; Dishion, Thomas J

2018-06-19

This study examined the impact of residential instability and family structure transitions on the development of internalizing and externalizing problems from age 2 through 10.5. Child's race was examined as a moderator. Caregiver reports of internalizing and externalizing behaviors were obtained on 665 children at ages 5 and 10.5. Early-childhood residential and family structure transitions predicted elevated internalizing and externalizing problems at ages 5 and 10.5, but only for Caucasian children. These findings suggest that residential and family structure instability during early childhood independently contribute to children's later emotional and behavioral development, but vary as a function of the child's race. Community organizations (e.g., Women, Infant, and Children) can connect turbulent families with resources to attenuate effects of residential and family structure instability. © 2018 Society for Research in Child Development.

School Perceptions of Children Raised by Grandparents

ERIC Educational Resources Information Center

Edwards, Oliver W.

2018-01-01

Increasing numbers of children raised by grandparents are students in schools. Their substitute family structure and precursors to the emergence of this family structure have implications for the children's school performance. Research suggests teachers view these children as at risk for difficult school functioning. The aforementioned judgment is…

Global Patterns of Guild Composition and Functional Diversity of Spiders

PubMed Central

Cardoso, Pedro; Pekár, Stano; Jocqué, Rudy; Coddington, Jonathan A.

2011-01-01

The objectives of this work are: (1) to define spider guilds for all extant families worldwide; (2) test if guilds defined at family level are good surrogates of species guilds; (3) compare the taxonomic and guild composition of spider assemblages from different parts of the world; (4) compare the taxonomic and functional diversity of spider assemblages and; (5) relate functional diversity with habitat structure. Data on foraging strategy, prey range, vertical stratification and circadian activity was collected for 108 families. Spider guilds were defined by hierarchical clustering. We searched for inconsistencies between family guild placement and the known guild of each species. Richness and abundance per guild before and after correcting guild placement were compared, as were the proportions of each guild and family between all possible pairs of sites. Functional diversity per site was calculated based on hierarchical clustering. Eight guilds were discriminated: (1) sensing, (2) sheet, (3) space, and (4) orb web weavers; (5) specialists; (6) ambush, (7) ground, and (8) other hunters. Sixteen percent of the species richness corresponding to 11% of all captured individuals was incorrectly attributed to a guild by family surrogacy; however, the correlation of uncorrected vs. corrected guilds was invariably high. The correlation of guild richness or abundances was generally higher than the correlation of family richness or abundances. Functional diversity was not always higher in the tropics than in temperate regions. Families may potentially serve as ecological surrogates for species. Different families may present similar roles in the ecosystems, with replacement of some taxa by other within the same guild. Spiders in tropical regions seem to have higher redundancy of functional roles and/or finer resource partitioning than in temperate regions. Although species and family diversity were higher in the tropics, functional diversity seems to be also influenced by altitude and habitat structure. PMID:21738772

From molecular chemistry to hybrid nanomaterials. Design and functionalization.

PubMed

Mehdi, Ahmad; Reye, Catherine; Corriu, Robert

2011-02-01

This tutorial review reports upon the organisation and functionalization of two families of hybrid organic-inorganic materials. We attempted to show in both cases the best ways permitting the organisation of materials in terms of properties at the nanometric scale. The first family concerns mesoporous hybrid organic-inorganic materials prepared in the presence of a structure-directing agent. We describe the functionalization of the channel pores of ordered mesoporous silica, that of the silica framework, as well as the functionalization of both of them simultaneously. This family is currently one of the best supports for exploring polyfunctional materials, which can provide a route to interactive materials. The second family concerns lamellar hybrid organic-inorganic materials which is a new class of nanostructured materials. These materials were first obtained by self-assembly, as a result of van der Waals interactions of bridged organosilica precursors containing long alkylene chains during the sol-gel process, without any structure directing agent. This methodology has been extended to functional materials. It is also shown that such materials can be obtained from monosilylated precursors.

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP).

PubMed

Rowe, P S; Oudet, C L; Francis, F; Sinding, C; Pannetier, S; Econs, M J; Strom, T M; Meitinger, T; Garabedian, M; David, A; Macher, M A; Questiaux, E; Popowska, E; Pronicka, E; Read, A P; Mokrzycki, A; Glorieux, F H; Drezner, M K; Hanauer, A; Lehrach, H; Goulding, J N; O'Riordan, J L

1997-04-01

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.

Non-Structural Proteins of Arthropod-Borne Bunyaviruses: Roles and Functions

PubMed Central

Eifan, Saleh; Schnettler, Esther; Dietrich, Isabelle; Kohl, Alain; Blomström, Anne-Lie

2013-01-01

Viruses within the Bunyaviridae family are tri-segmented, negative-stranded RNA viruses. The family includes several emerging and re-emerging viruses of humans, animals and plants, such as Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, Schmallenberg virus and tomato spotted wilt virus. Many bunyaviruses are arthropod-borne, so-called arboviruses. Depending on the genus, bunyaviruses encode, in addition to the RNA-dependent RNA polymerase and the different structural proteins, one or several non-structural proteins. These non-structural proteins are not always essential for virus growth and replication but can play an important role in viral pathogenesis through their interaction with the host innate immune system. In this review, we will summarize current knowledge and understanding of insect-borne bunyavirus non-structural protein function(s) in vertebrate, plant and arthropod. PMID:24100888

Childrearing and Child Participation in Jamaican Families

ERIC Educational Resources Information Center

Brown, Janet; Johnson, Sharon

2008-01-01

Existing research in Jamaica on children and families has focused on family structure and function. The recent worldwide focus on the rights of children, particularly young children, has highlighted the absence of research on child rights in Jamaica. This article explores the implementation of protection and participation rights within the family,…

A Training Program for Family Psychology: Evaluation, Prevention and Therapy.

ERIC Educational Resources Information Center

L'Abate, Luciano

1985-01-01

Family psychology stresses theory testing, outcome of interventions, and prevention with functional or at-risk families. An academic curriculum in family psychology, which has been operational for 10 years, is presented. Clinical training follows a gradual approach, starting with relatively simple Structured Enrichment, progressing to more complex…

Predicting functional divergence in protein evolution by site-specific rate shifts

NASA Technical Reports Server (NTRS)

Gaucher, Eric A.; Gu, Xun; Miyamoto, Michael M.; Benner, Steven A.

2002-01-01

Most modern tools that analyze protein evolution allow individual sites to mutate at constant rates over the history of the protein family. However, Walter Fitch observed in the 1970s that, if a protein changes its function, the mutability of individual sites might also change. This observation is captured in the "non-homogeneous gamma model", which extracts functional information from gene families by examining the different rates at which individual sites evolve. This model has recently been coupled with structural and molecular biology to identify sites that are likely to be involved in changing function within the gene family. Applying this to multiple gene families highlights the widespread divergence of functional behavior among proteins to generate paralogs and orthologs.

Structure and stability insights into tumour suppressor p53 evolutionary related proteins.

PubMed

Pagano, Bruno; Jama, Abdullah; Martinez, Pierre; Akanho, Ester; Bui, Tam T T; Drake, Alex F; Fraternali, Franca; Nikolova, Penka V

2013-01-01

The p53 family of genes and their protein products, namely, p53, p63 and p73, have over one billion years of evolutionary history. Advances in computational biology and genomics are enabling studies of the complexities of the molecular evolution of p53 protein family to decipher the underpinnings of key biological conditions spanning from cancer through to various metabolic and developmental disorders and facilitate the design of personalised medicines. However, a complete understanding of the inherent nature of the thermodynamic and structural stability of the p53 protein family is still lacking. This is due, to a degree, to the lack of comprehensive structural information for a large number of homologous proteins and to an incomplete knowledge of the intrinsic factors responsible for their stability and how these might influence function. Here we investigate the thermal stability, secondary structure and folding properties of the DNA-binding domains (DBDs) of a range of proteins from the p53 family using biophysical methods. While the N- and the C-terminal domains of the p53 family show sequence diversity and are normally targets for post-translational modifications and alternative splicing, the central DBD is highly conserved. Together with data obtained from Molecular Dynamics simulations in solution and with structure based homology modelling, our results provide further insights into the molecular properties of evolutionary related p53 proteins. We identify some marked structural differences within the p53 family, which could account for the divergence in biological functions as well as the subtleties manifested in the oligomerization properties of this family.

The X-ray Crystallographic Structure and Activity Analysis of a Pseudomonas-Specific Subfamily of the HAD Enzyme Superfamily Evidences a Novel Biochemical Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peisach,E.; Wang, L.; Burroughs, A.

2008-01-01

The haloacid dehalogenase (HAD) superfamily is a large family of proteins dominated by phosphotransferases. Thirty-three sequence families within the HAD superfamily (HADSF) have been identified to assist in function assignment. One such family includes the enzyme phosphoacetaldehyde hydrolase (phosphonatase). Phosphonatase possesses the conserved Rossmanniod core domain and a C1-type cap domain. Other members of this family do not possess a cap domain and because the cap domain of phosphonatase plays an important role in active site desolvation and catalysis, the function of the capless family members must be unique. A representative of the capless subfamily, PSPTO{_}2114, from the plant pathogenmore » Pseudomonas syringae, was targeted for catalytic activity and structure analyses. The X-ray structure of PSPTO{_}2114 reveals a capless homodimer that conserves some but not all of the intersubunit contacts contributed by the core domains of the phosphonatase homodimer. The region of the PSPTO{_}2114 that corresponds to the catalytic scaffold of phosphonatase (and other HAD phosphotransfereases) positions amino acid residues that are ill suited for Mg+2 cofactor binding and mediation of phosphoryl group transfer between donor and acceptor substrates. The absence of phosphotransferase activity in PSPTO{_}2114 was confirmed by kinetic assays. To explore PSPTO{_}2114 function, the conservation of sequence motifs extending outside of the HADSF catalytic scaffold was examined. The stringently conserved residues among PSPTO{_}2114 homologs were mapped onto the PSPTO{_}2114 three-dimensional structure to identify a surface region unique to the family members that do not possess a cap domain. The hypothesis that this region is used in protein-protein recognition is explored to define, for the first time, HADSF proteins which have acquired a function other than that of a catalyst. Proteins 2008.« less

First Hand Lessons in an Information Age: Single Parent Working Women Speak for Themselves.

ERIC Educational Resources Information Center

Quinn, Peggy; Allen, Katherine

The female-headed, single parent family is a family structure that presents challenges to family life educators, family counselors, and policy makers. For effective delivery of services, accurate information on the functioning of these families is needed. This study used a phenomenological perspective to examine the various challenges faced by…

The association of family functioning and psychosis proneness in five countries that differ in cultural values and family structures.

PubMed

Wüsten, Caroline; Lincoln, Tania M

2017-07-01

For decades, researchers have attributed the better prognosis of psychosis in developing countries to a host of socio-cultural factors, including family functioning. Nevertheless, it is unknown whether family functioning and its association with symptoms differ across countries. This study assessed family functioning (support, satisfaction with family relations, and criticism) and psychosis proneness in community samples from Chile (n =399), Colombia (n=486), Indonesia (n=115), Germany (n=174) and the USA (n=143). Family functioning was compared between prototypical developing countries (Chile, Columbia, Indonesia) and highly industrialized countries (Germany, USA). Hierarchical regression analysis was used to test for the moderating effect of country on the associations between family functioning and psychosis proneness. Participants from developing countries perceived more support and felt more satisfied. However, they also perceived more criticism than participants from highly industrialized countries. Criticism and family satisfaction were significantly associated with psychosis proneness. Moreover, the relationship between criticism and psychosis proneness was significantly stronger in developing countries compared to highly industrialized countries. Generally, family satisfaction and criticism appear to be more relevant to psychosis proneness than the quantity of family support. Moreover, criticism seems to be more closely related to psychosis proneness in developing countries. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Intergenerational Transmission of Neuropsychological Executive Functioning

ERIC Educational Resources Information Center

Jester, Jennifer M.; Nigg, Joel T.; Puttler, Leon I.; Long, Jeffrey C.; Fitzgerald, Hiram E.; Zucker, Robert A.

2009-01-01

Relationships between parent and child executive functioning were examined, controlling for the critical potential confound of IQ, in a family study involving 434 children (130 girls and 304 boys) and 376 parents from 204 community recruited families at high risk for the development of substance use disorder. Structural equation modeling found…

Cholinesterase Confabs and Cousins: Approaching Forty Years

PubMed Central

Taylor, Palmer; De Jaco, Antonella; Comoletti, Davide; Miller, Meghan; Camp, Shelley

2013-01-01

In the past four decades of cholinesterase (ChE) research, we have seen substantive evolution of the field from one centered around substrate and inhibitor kinetic profiles and compound characterizations to the analysis of ChE structure, first through the gene families and then by x-ray crystallographic determinations of the free enzymes and their complexes and conjugates. Indeed, these endeavors have been facilitated by recombinant DNA technologies, structure determinations and parallel studies in related proteins in the α/β-hydrolase fold family. This approach has not only contributed to a fundamental understanding of structure and function of a large family of hydrolase-like proteins possessing functions other than catalysis, but also has been used to develop new practical strategies for scavenging and antidotal activity in cases of organophosphate insecticide or nerve agent exposure. PMID:23085121

Domain organization, genomic structure, evolution, and regulation of expression of the aggrecan gene family.

PubMed

Schwartz, N B; Pirok, E W; Mensch, J R; Domowicz, M S

1999-01-01

Proteoglycans are complex macromolecules, consisting of a polypeptide backbone to which are covalently attached one or more glycosaminoglycan chains. Molecular cloning has allowed identification of the genes encoding the core proteins of various proteoglycans, leading to a better understanding of the diversity of proteoglycan structure and function, as well as to the evolution of a classification of proteoglycans on the basis of emerging gene families that encode the different core proteins. One such family includes several proteoglycans that have been grouped with aggrecan, the large aggregating chondroitin sulfate proteoglycan of cartilage, based on a high number of sequence similarities within the N- and C-terminal domains. Thus far these proteoglycans include versican, neurocan, and brevican. It is now apparent that these proteins, as a group, are truly a gene family with shared structural motifs on the protein and nucleotide (mRNA) levels, and with nearly identical genomic organizations. Clearly a common ancestral origin is indicated for the members of the aggrecan family of proteoglycans. However, differing patterns of amplification and divergence have also occurred within certain exons across species and family members, leading to the class-characteristic protein motifs in the central carbohydrate-rich region exclusively. Thus the overall domain organization strongly suggests that sequence conservation in the terminal globular domains underlies common functions, whereas differences in the central portions of the genes account for functional specialization among the members of this gene family.

The Origins and Evolution of the p53 Family of Genes

PubMed Central

Belyi, Vladimir A.; Ak, Prashanth; Markert, Elke; Wang, Haijian; Hu, Wenwei; Puzio-Kuter, Anna; Levine, Arnold J.

2010-01-01

A common ancestor to the three p53 family members of human genes p53, p63, and p73 is first detected in the evolution of modern‐day sea anemones, in which both structurally and functionally it acts to protect the germ line from genomic instabilities in response to stresses. This p63/p73 common ancestor gene is found in almost all invertebrates and first duplicates to produce a p53 gene and a p63/p73 ancestor in cartilaginous fish. Bony fish contain all three genes, p53, p63, and p73, and the functions of these three transcription factors diversify in the higher vertebrates. Thus, this gene family has preserved its structural features and functional activities for over one billion years of evolution. PMID:20516129

Exploration of Uncharted Regions of the Protein Universe

PubMed Central

Jaroszewski, Lukasz; Li, Zhanwen; Krishna, S. Sri; Bakolitsa, Constantina; Wooley, John; Deacon, Ashley M.; Wilson, Ian A.; Godzik, Adam

2009-01-01

The genome projects have unearthed an enormous diversity of genes of unknown function that are still awaiting biological and biochemical characterization. These genes, as most others, can be grouped into families based on sequence similarity. The PFAM database currently contains over 2,200 such families, referred to as domains of unknown function (DUF). In a coordinated effort, the four large-scale centers of the NIH Protein Structure Initiative have determined the first three-dimensional structures for more than 250 of these DUF families. Analysis of the first 248 reveals that about two thirds of the DUF families likely represent very divergent branches of already known and well-characterized families, which allows hypotheses to be formulated about their biological function. The remainder can be formally categorized as new folds, although about one third of these show significant substructure similarity to previously characterized folds. These results infer that, despite the enormous increase in the number and the diversity of new genes being uncovered, the fold space of the proteins they encode is gradually becoming saturated. The previously unexplored sectors of the protein universe appear to be primarily shaped by extreme diversification of known protein families, which then enables organisms to evolve new functions and adapt to particular niches and habitats. Notwithstanding, these DUF families still constitute the richest source for discovery of the remaining protein folds and topologies. PMID:19787035

Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life

PubMed Central

2011-01-01

Background The inorganic (Pi) phosphate transporter (PiT) family comprises known and putative Na+- or H+-dependent Pi-transporting proteins with representatives from all kingdoms. The mammalian members are placed in the outer cell membranes and suggested to supply cells with Pi to maintain house-keeping functions. Alignment of protein sequences representing PiT family members from all kingdoms reveals the presence of conserved amino acids and that bacterial phosphate permeases and putative phosphate permeases from archaea lack substantial parts of the protein sequence when compared to the mammalian PiT family members. Besides being Na+-dependent Pi (NaPi) transporters, the mammalian PiT paralogs, PiT1 and PiT2, also are receptors for gamma-retroviruses. We have here exploited the dual-function of PiT1 and PiT2 to study the structure-function relationship of PiT proteins. Results We show that the human PiT2 histidine, H502, and the human PiT1 glutamate, E70, - both conserved in eukaryotic PiT family members - are critical for Pi transport function. Noticeably, human PiT2 H502 is located in the C-terminal PiT family signature sequence, and human PiT1 E70 is located in ProDom domains characteristic for all PiT family members. A human PiT2 truncation mutant, which consists of the predicted 10 transmembrane (TM) domain backbone without a large intracellular domain (human PiT2ΔR254-V483), was found to be a fully functional Pi transporter. Further truncation of the human PiT2 protein by additional removal of two predicted TM domains together with the large intracellular domain created a mutant that resembles a bacterial phosphate permease and an archaeal putative phosphate permease. This human PiT2 truncation mutant (human PiT2ΔL183-V483) did also support Pi transport albeit at very low levels. Conclusions The results suggest that the overall structure of the Pi-transporting unit of the PiT family proteins has remained unchanged during evolution. Moreover, in combination, our studies of the gene structure of the human PiT1 and PiT2 genes (SLC20A1 and SLC20A2, respectively) and alignment of protein sequences of PiT family members from all kingdoms, along with the studies of the dual functions of the human PiT paralogs show that these proteins are excellent as models for studying the evolution of a protein's structure-function relationship. PMID:21586110

Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life.

PubMed

Bøttger, Pernille; Pedersen, Lene

2011-05-17

The inorganic (Pi) phosphate transporter (PiT) family comprises known and putative Na(+)- or H(+)-dependent Pi-transporting proteins with representatives from all kingdoms. The mammalian members are placed in the outer cell membranes and suggested to supply cells with Pi to maintain house-keeping functions. Alignment of protein sequences representing PiT family members from all kingdoms reveals the presence of conserved amino acids and that bacterial phosphate permeases and putative phosphate permeases from archaea lack substantial parts of the protein sequence when compared to the mammalian PiT family members. Besides being Na(+)-dependent P(i) (NaP(i)) transporters, the mammalian PiT paralogs, PiT1 and PiT2, also are receptors for gamma-retroviruses. We have here exploited the dual-function of PiT1 and PiT2 to study the structure-function relationship of PiT proteins. We show that the human PiT2 histidine, H(502), and the human PiT1 glutamate, E(70),--both conserved in eukaryotic PiT family members--are critical for P(i) transport function. Noticeably, human PiT2 H(502) is located in the C-terminal PiT family signature sequence, and human PiT1 E(70) is located in ProDom domains characteristic for all PiT family members.A human PiT2 truncation mutant, which consists of the predicted 10 transmembrane (TM) domain backbone without a large intracellular domain (human PiT2ΔR(254)-V(483)), was found to be a fully functional P(i) transporter. Further truncation of the human PiT2 protein by additional removal of two predicted TM domains together with the large intracellular domain created a mutant that resembles a bacterial phosphate permease and an archaeal putative phosphate permease. This human PiT2 truncation mutant (human PiT2ΔL(183)-V(483)) did also support P(i) transport albeit at very low levels. The results suggest that the overall structure of the P(i)-transporting unit of the PiT family proteins has remained unchanged during evolution. Moreover, in combination, our studies of the gene structure of the human PiT1 and PiT2 genes (SLC20A1 and SLC20A2, respectively) and alignment of protein sequences of PiT family members from all kingdoms, along with the studies of the dual functions of the human PiT paralogs show that these proteins are excellent as models for studying the evolution of a protein's structure-function relationship. © 2011 Bøttger and Pedersen; licensee BioMed Central Ltd.

Family Structure and Income During the Stages of Childhood and Subsequent Prosocial Behavior in Young Adulthood

PubMed Central

Bandy, Robert; Ottoni-Wilhelm, Mark

2012-01-01

This study investigated whether family structure transition and low income are risk factors in the development of prosocial behavior. Models of young adults’ prosocial behavior – charitable giving and volunteering – were estimated as functions of their family structure and income during the stages of childhood. Participants were a representative sample of 1,011 American young adults. In the full sample, family structure transition during adolescence was negatively associated with subsequent charitable giving in young adulthood. Low income during adolescence was negatively associated with both giving and volunteering in young adulthood. European-American young men also exhibited a negative association between family structure transition during adolescence and subsequent volunteering. The results did not seem to describe African-American young adults. Keeping this qualification in mind, the results suggest that adolescence is a sensitive stage in the development of charitable giving and volunteering. PMID:22414561

An overview of the structures of protein-DNA complexes

PubMed Central

Luscombe, Nicholas M; Austin, Susan E; Berman , Helen M; Thornton, Janet M

2000-01-01

On the basis of a structural analysis of 240 protein-DNA complexes contained in the Protein Data Bank (PDB), we have classified the DNA-binding proteins involved into eight different structural/functional groups, which are further classified into 54 structural families. Here we present this classification and review the functions, structures and binding interactions of these protein-DNA complexes. PMID:11104519

Describing the Elephant: Structure and Function in Multivariate Data.

ERIC Educational Resources Information Center

McDonald, Roderick P.

1986-01-01

There is a unity underlying the diversity of models for the analysis of multivariate data. Essentially, they constitute a family of models, most generally nonlinear, for structural/functional relations between variables drawn from a behavior domain. (Author)

Premarital Sexual Behavior and Attitudes Toward Marriage and Divorce among Young Women as a Function of Their Mothers' Marital Status.

ERIC Educational Resources Information Center

Kinnaird, Keri L.; Gerrard, Meg

1986-01-01

Investigated attitudes and sexual activity of young unmarried women from different family structures. Intact family respondents reported most positive attitudes toward marriage; reconstituted family respondents reported most accepting attitudes toward divorce. Divorced and reconstituted family subjects reported significantly more sexual experience…

Development and testing of the Survey of Family Environment (SFE): a novel instrument to measure family functioning and needs for family support.

PubMed

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.

Review of the GAS3 Family of Proteins and their Relevance to Cancer

PubMed Central

Ashki, Negin; Gordon, Lynn; Wadehra, Madhuri

2017-01-01

The GAS3 family of tetraspan proteins has recently been implicated in the progression of cancer. Currently, six members of the GAS3 family have been identified in humans and mice, and while their expressions in disease vary, data suggest that they play a role in epithelial cell structure and function. In this review, we highlight the studies implicating four of the members in disease pathogenesis as well as probe the structural similarities between the family members. Finally, the impact of targeting select members of the family such as PMP22 and EMP2 is discussed. PMID:27279240

Review of the GAS3 Family of Proteins and their Relevance to Cancer.

PubMed

Ashki, Negin; Gordon, Lynn; Wadehra, Madhuri

2015-01-01

The GAS3 family of tetraspan proteins has recently been implicated in the progression of cancer. Currently, six members of the GAS3 family have been identified in humans and mice, and while their expressions in disease vary, data suggest that they play a role in epithelial cell structure and function. In this review, we highlight the studies implicating four of the members in disease pathogenesis as well as probe the structural similarities between the family members. Finally, the impact of targeting select members of the family such as PMP22 and EMP2 is discussed.

AlloRep: A Repository of Sequence, Structural and Mutagenesis Data for the LacI/GalR Transcription Regulators.

PubMed

Sousa, Filipa L; Parente, Daniel J; Shis, David L; Hessman, Jacob A; Chazelle, Allen; Bennett, Matthew R; Teichmann, Sarah A; Swint-Kruse, Liskin

2016-02-22

Protein families evolve functional variation by accumulating point mutations at functionally important amino acid positions. Homologs in the LacI/GalR family of transcription regulators have evolved to bind diverse DNA sequences and allosteric regulatory molecules. In addition to playing key roles in bacterial metabolism, these proteins have been widely used as a model family for benchmarking structural and functional prediction algorithms. We have collected manually curated sequence alignments for >3000 sequences, in vivo phenotypic and biochemical data for >5750 LacI/GalR mutational variants, and noncovalent residue contact networks for 65 LacI/GalR homolog structures. Using this rich data resource, we compared the noncovalent residue contact networks of the LacI/GalR subfamilies to design and experimentally validate an allosteric mutant of a synthetic LacI/GalR repressor for use in biotechnology. The AlloRep database (freely available at www.AlloRep.org) is a key resource for future evolutionary studies of LacI/GalR homologs and for benchmarking computational predictions of functional change. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular evolution of the crustacean hyperglycemic hormone family in ecdysozoans

PubMed Central

2010-01-01

Background Crustacean Hyperglycemic Hormone (CHH) family peptides are neurohormones known to regulate several important functions in decapod crustaceans such as ionic and energetic metabolism, molting and reproduction. The structural conservation of these peptides, together with the variety of functions they display, led us to investigate their evolutionary history. CHH family peptides exist in insects (Ion Transport Peptides) and may be present in all ecdysozoans as well. In order to extend the evolutionary study to the entire family, CHH family peptides were thus searched in taxa outside decapods, where they have been, to date, poorly investigated. Results CHH family peptides were characterized by molecular cloning in a branchiopod crustacean, Daphnia magna, and in a collembolan, Folsomia candida. Genes encoding such peptides were also rebuilt in silico from genomic sequences of another branchiopod, a chelicerate and two nematodes. These sequences were included in updated datasets to build phylogenies of the CHH family in pancrustaceans. These phylogenies suggest that peptides found in Branchiopoda and Collembola are more closely related to insect ITPs than to crustacean CHHs. Datasets were also used to support a phylogenetic hypothesis about pancrustacean relationships, which, in addition to gene structures, allowed us to propose two evolutionary scenarios of this multigenic family in ecdysozoans. Conclusions Evolutionary scenarios suggest that CHH family genes of ecdysozoans originate from an ancestral two-exon gene, and genes of arthropods from a three-exon one. In malacostracans, the evolution of the CHH family has involved several duplication, insertion or deletion events, leading to neuropeptides with a wide variety of functions, as observed in decapods. This family could thus constitute a promising model to investigate the links between gene duplications and functional divergence. PMID:20184761

The role of acculturation and family functioning in predicting HIV risk behaviors among Hispanic delinquent youth.

PubMed

Farrelly, Colleen; Cordova, David; Huang, Shi; Estrada, Yannine; Prado, Guillermo

2013-06-01

The present study examined the relationship between Berry's acculturation typology and HIV risk behaviors and whether family functioning mediated any such effects. A total of 235 high risk Hispanic adolescents were categorized into one of Berry's four acculturation typologies through the use of cut-off scores on measures of Hispanicism and Americanism. Structural equation modeling was used to examine the effects of acculturation typology on HIV risk behaviors and the indirect effects of acculturation typology on HIV risk behaviors through family functioning. Acculturation typology was related to HIV risk behaviors. Family functioning partially mediated the effects of acculturation typology on the HIV risk behavior outcomes. These findings suggest that both Americanism and Hispanicism play an important role in the etiology of HIV risk behaviors among Hispanic youth and that both, along with family functioning, are important to consider when designing preventive interventions for this population.

The Role of Acculturation and Family Functioning in Predicting HIV Risk Behaviors Among Hispanic Delinquent Youth

PubMed Central

Farrelly, Colleen; Cordova, David; Huang, Shi; Estrada, Yannine

2012-01-01

The present study examined the relationship between Berry’s acculturation typology and HIV risk behaviors and whether family functioning mediated any such effects. A total of 235 high risk Hispanic adolescents were categorized into one of Berry’s four acculturation typologies through the use of cut-off scores on measures of Hispanicism and Americanism. Structural equation modeling was used to examine the effects of acculturation typology on HIV risk behaviors and the indirect effects of acculturation typology on HIV risk behaviors through family functioning. Acculturation typology was related to HIV risk behaviors. Family functioning partially mediated the effects of acculturation typology on the HIV risk behavior outcomes. These findings suggest that both Americanism and Hispanicism play an important role in the etiology of HIV risk behaviors among Hispanic youth and that both, along with family functioning, are important to consider when designing preventive interventions for this population. PMID:22532299

Role Diffusion and Role Reversal: Structural Variations in Divorced Families and Children's Functioning.

ERIC Educational Resources Information Center

Johnston, Janet R.

1990-01-01

Tested model of family structure and process using 133 children where both divorced parents remained in children's lives about 3 years after separation. Found role diffusion, lack of coparental alliance, parental boundary problems, parent-child rejection associated with reduced social competence and behavioral difficulties (especially in boys and…

A Review on Structures and Functions of Bcl-2 Family Proteins from Homo sapiens.

PubMed

Sivakumar, Dakshinamurthy; Sivaraman, Thirunavukkarasu

2016-01-01

Cancer cells evade apoptosis, which is regulated by proteins of Bcl-2 family in the intrinsic pathways. Numerous experimental three-dimensional (3D) structures of the apoptotic proteins and the proteins bound with small chemical molecules/peptides/proteins have been reported in the literature. In this review article, the 3D structures of the Bcl-2 family proteins from Homo sapiens and as well complex structures of the anti-apoptotic proteins bound with small molecular inhibitors reported in the literature to date have been comprehensively listed out and described in detail. Moreover, the molecular mechanisms by which the Bcl-2 family proteins modulate the apoptotic processes and strategies for designing antagonists to anti-apoptotic proteins have been concisely discussed.

Characterization of macular structure and function in two Swedish families with genetically identified autosomal dominant retinitis pigmentosa

PubMed Central

Abdulridha-Aboud, Wissam; Kjellström, Ulrika; Andréasson, Sten

2016-01-01

Purpose To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions These two families demonstrate the extreme inter- and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype. PMID:27212874

Cartilage acidic protein 1, a new member of the beta-propeller protein family with amyloid propensity.

PubMed

Anjos, Liliana; Morgado, Isabel; Guerreiro, Marta; Cardoso, João C R; Melo, Eduardo P; Power, Deborah M

2017-02-01

Cartilage acidic protein1 (CRTAC1) is an extracellular matrix protein of chondrogenic tissue in humans and its presence in bacteria indicate it is of ancient origin. Structural modeling of piscine CRTAC1 reveals it belongs to the large family of beta-propeller proteins that in mammals have been associated with diseases, including amyloid diseases such as Alzheimer's. In order to characterize the structure/function evolution of this new member of the beta-propeller family we exploited the unique characteristics of piscine duplicate genes Crtac1a and Crtac1b and compared their structural and biochemical modifications with human recombinant CRTAC1. We demonstrate that CRTAC1 has a beta-propeller structure that has been conserved during evolution and easily forms high molecular weight thermo-stable aggregates. We reveal for the first time the propensity of CRTAC1 to form amyloid-like structures, and hypothesize that the aggregating property of CRTAC1 may be related to its disease-association. We further contribute to the general understating of CRTAC1's and beta-propeller family evolution and function. Proteins 2017; 85:242-255. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Structural and functional analysis of PucM, a hydrolase in the ureide pathway and a member of the transthyretin-related protein family

PubMed Central

Jung, Du-Kyo; Lee, Youra; Park, Sung Goo; Park, Byoung Chul; Kim, Ghyung-Hwa; Rhee, Sangkee

2006-01-01

The ureide pathway, which produces ureides from uric acid, is an essential purine catabolic process for storing and transporting the nitrogen fixed in leguminous plants and some bacteria. PucM from Bacillus subtilis was recently characterized and found to catalyze the second reaction of the pathway, hydrolyzing 5-hydroxyisourate (HIU), a product of uricase in the first step. PucM has 121 amino acid residues and shows high sequence similarity to the functionally unrelated protein transthyretin (TTR), a thyroid hormone-binding protein. Therefore, PucM belongs to the TTR-related proteins (TRP) family. The crystal structures of PucM at 2.0 Å and its complexes with the substrate analogs 8-azaxanthine and 5,6-diaminouracil reveal that even with their overall structure similarity, homotetrameric PucM and TTR are completely different, both in their electrostatic potential and in the size of the active sites located at the dimeric interface. Nevertheless, the absolutely conserved residues across the TRP family, including His-14, Arg-49, His-105, and the C-terminal Tyr-118–Arg-119–Gly-120–Ser-121, indeed form the active site of PucM. Based on the results of site-directed mutagenesis of these residues, we propose a possible mechanism for HIU hydrolysis. The PucM structure determined for the TRP family leads to the conclusion that diverse members of the TRP family would function similarly to PucM as HIU hydrolase. PMID:16782815

Analysis of Family Functioning and Parent-Child Relationship between Adolescents with Depression and their Parents.

PubMed

Chen, Qing; DU, Wenyong; Gao, Yan; Ma, Changlin; Ban, Chunxia; Meng, Fu

2017-12-25

Drug therapy combined with family therapy is currently the best treatment for adolescent depression. Nevertheless, family therapy requires an exploration of unresolved problems in the family system, which in practice presents certain difficulties. Previous studies have found that the perceptual differences of family function between parents and children reflect the problems in the family system. To explore the characteristics and role of family functioning and parent-child relationship between adolescents with depressive disorder and their parents. The general information and clinical data of the 93 adolescents with depression were collected. The Family Functioning Assessment Scale and Parent-child Relationship Scale were used to assess adolescents with depressive disorder and their parents. a) The dimensions of family functioning in adolescents with depressive disorder were more negative in communication, emotional response, emotional involvement, roles, and overall functioning than their parents. The differences were statistically significant. Parent-child relationship dimensions: the closeness and parent-child total scores were more negative compared with the parents and the differences were statistically significant. b) All dimensions of parent-child relationship and family functioning in adolescents with depression except the time spent together were negatively correlated or significantly negatively correlated. c) The results of multivariate regression analysis showed: the characteristics of family functioning, emotional involvement, emotional response, family structure, and income of the adolescents with depressive disorder mainly affected the parent-child relationship. There were perceptual differences in partial family functioning and parent-child relationship between adolescents with depressive disorder and their parents. Unclear roles between family members, mutual entanglement, too much or too little emotional investment, negligence of inner feelings, parental divorce, and low average monthly family income were the main factors causing adverse parent-child relationship. These perceptual differences have a relatively good predictive effect on family problems, and can be used as an important guide for exploring the family relationship in family therapy.

Analysis of Family Functioning and Parent-Child Relationship between Adolescents with Depression and their Parents

PubMed Central

CHEN, Qing; DU, Wenyong; GAO, Yan; MA, Changlin; BAN, Chunxia; MENG, Fu

2017-01-01

Background Drug therapy combined with family therapy is currently the best treatment for adolescent depression. Nevertheless, family therapy requires an exploration of unresolved problems in the family system, which in practice presents certain difficulties. Previous studies have found that the perceptual differences of family function between parents and children reflect the problems in the family system. Aims To explore the characteristics and role of family functioning and parent-child relationship between adolescents with depressive disorder and their parents. Methods The general information and clinical data of the 93 adolescents with depression were collected. The Family Functioning Assessment Scale and Parent-child Relationship Scale were used to assess adolescents with depressive disorder and their parents. Results a) The dimensions of family functioning in adolescents with depressive disorder were more negative in communication, emotional response, emotional involvement, roles, and overall functioning than their parents. The differences were statistically significant. Parent-child relationship dimensions: the closeness and parent-child total scores were more negative compared with the parents and the differences were statistically significant. b) All dimensions of parent-child relationship and family functioning in adolescents with depression except the time spent together were negatively correlated or significantly negatively correlated. c) The results of multivariate regression analysis showed: the characteristics of family functioning, emotional involvement, emotional response, family structure, and income of the adolescents with depressive disorder mainly affected the parent-child relationship. Conclusions There were perceptual differences in partial family functioning and parent-child relationship between adolescents with depressive disorder and their parents. Unclear roles between family members, mutual entanglement, too much or too little emotional investment, negligence of inner feelings, parental divorce, and low average monthly family income were the main factors causing adverse parent-child relationship. These perceptual differences have a relatively good predictive effect on family problems, and can be used as an important guide for exploring the family relationship in family therapy. PMID:29719348

Family breakup and adolescents' psychosocial maladjustment: public health implications of family disruptions.

PubMed

Roustit, Christelle; Chaix, Basile; Chauvin, Pierre

2007-10-01

Recent changes in family structure are associated with an increase in psychosocial maladjustment in adolescents. We examined, from a public health intervention perspective, the association between family breakup and psychosocial maladjustment in adolescents and assessed the mediating role of family-functioning variables. We analyzed data from the Social and Health Survey of Children and Adolescents in Quebec, Montreal, Canada, which was conducted in 1999. Sample-weighted logistic regression analyses were performed to determine the risk of internalizing disorders, externalizing disorders, substance abuse, and alcohol consumption in relation to family breakups and family-functioning variables, after adjusting for socioeconomic factors. All 4 of the indicators of psychosocial maladjustment were significantly associated with family breakup. The association between family breakups and internalizing disorders was mediated by parental psychological distress and low paternal emotional support. Independently, the witnessing of interparental violence was also strongly associated with internalizing disorders. For the other 3 outcomes, that is, externalizing disorders, substance abuse, and alcohol consumption, family breakup and family-functioning variables had independent effects. Family-based interventions and social approaches are complementary support modalities for adolescents experiencing family disruptions.

Multifunctionality and diversity of GDSL esterase/lipase gene family in rice (Oryza sativa L. japonica) genome: new insights from bioinformatics analysis

PubMed Central

2012-01-01

Background GDSL esterases/lipases are a newly discovered subclass of lipolytic enzymes that are very important and attractive research subjects because of their multifunctional properties, such as broad substrate specificity and regiospecificity. Compared with the current knowledge regarding these enzymes in bacteria, our understanding of the plant GDSL enzymes is very limited, although the GDSL gene family in plant species include numerous members in many fully sequenced plant genomes. Only two genes from a large rice GDSL esterase/lipase gene family were previously characterised, and the majority of the members remain unknown. In the present study, we describe the rice OsGELP (Oryza sativa GDSL esterase/lipase protein) gene family at the genomic and proteomic levels, and use this knowledge to provide insights into the multifunctionality of the rice OsGELP enzymes. Results In this study, an extensive bioinformatics analysis identified 114 genes in the rice OsGELP gene family. A complete overview of this family in rice is presented, including the chromosome locations, gene structures, phylogeny, and protein motifs. Among the OsGELPs and the plant GDSL esterase/lipase proteins of known functions, 41 motifs were found that represent the core secondary structure elements or appear specifically in different phylogenetic subclades. The specification and distribution of identified putative conserved clade-common and -specific peptide motifs, and their location on the predicted protein three dimensional structure may possibly signify their functional roles. Potentially important regions for substrate specificity are highlighted, in accordance with protein three-dimensional model and location of the phylogenetic specific conserved motifs. The differential expression of some representative genes were confirmed by quantitative real-time PCR. The phylogenetic analysis, together with protein motif architectures, and the expression profiling were analysed to predict the possible biological functions of the rice OsGELP genes. Conclusions Our current genomic analysis, for the first time, presents fundamental information on the organization of the rice OsGELP gene family. With combination of the genomic, phylogenetic, microarray expression, protein motif distribution, and protein structure analyses, we were able to create supported basis for the functional prediction of many members in the rice GDSL esterase/lipase family. The present study provides a platform for the selection of candidate genes for further detailed functional study. PMID:22793791

Structure-function relationships of family GH70 glucansucrase and 4,6-α-glucanotransferase enzymes, and their evolutionary relationships with family GH13 enzymes.

PubMed

Meng, Xiangfeng; Gangoiti, Joana; Bai, Yuxiang; Pijning, Tjaard; Van Leeuwen, Sander S; Dijkhuizen, Lubbert

2016-07-01

Lactic acid bacteria (LAB) are known to produce large amounts of α-glucan exopolysaccharides. Family GH70 glucansucrase (GS) enzymes catalyze the synthesis of these α-glucans from sucrose. The elucidation of the crystal structures of representative GS enzymes has advanced our understanding of their reaction mechanism, especially structural features determining their linkage specificity. In addition, with the increase of genome sequencing, more and more GS enzymes are identified and characterized. Together, such knowledge may promote the synthesis of α-glucans with desired structures and properties from sucrose. In the meantime, two new GH70 subfamilies (GTFB- and GTFC-like) have been identified as 4,6-α-glucanotransferases (4,6-α-GTs) that represent novel evolutionary intermediates between the family GH13 and "classical GH70 enzymes". These enzymes are not active on sucrose; instead, they use (α1 → 4) glucans (i.e. malto-oligosaccharides and starch) as substrates to synthesize novel α-glucans by introducing linear chains of (α1 → 6) linkages. All these GH70 enzymes are very interesting biocatalysts and hold strong potential for applications in the food, medicine and cosmetic industries. In this review, we summarize the microbiological distribution and the structure-function relationships of family GH70 enzymes, introduce the two newly identified GH70 subfamilies, and discuss evolutionary relationships between family GH70 and GH13 enzymes.

Long-term impact of family arguments and physical violence on adult functioning at age 30 years: findings from the simmons longitudinal study.

PubMed

Paradis, Angela D; Reinherz, Helen Z; Giaconia, Rose M; Beardslee, William R; Ward, Kirsten; Fitzmaurice, Garrett M

2009-03-01

To prospectively examine the extent to which an increase in family arguments by age 15 years and the occurrence of family physical violence by age 18 years are related to deficits in key domains of adult functioning at age 30 years. The 346 participants were part of a single-age cohort from a predominately white working-class community whose psychosocial development has been traced since age 5 years. Family arguments and violence were assessed through self-reports during adolescence. Developmentally relevant areas of current adult functioning were measured by self-reports, structured diagnostic interviews, and clinical interviewer ratings. Both family arguments and physical violence were significantly related to compromised functioning across multiple areas of adult functioning. Although many associations were somewhat attenuated after controlling for sex, other early family adversities, and family history of disorder, most relations retained statistical significance. Both risk factors were linked with later mental health problems and deficits in psychological and occupational/career functioning. Family violence was also linked to poorer physical health at age 30 years. Findings underscore the potential long-term impact of troubled family interactions and highlight the critical importance of early intervention programs for youths experiencing either verbal conflict or physical violence in the home.

Caribbean Families: Diversity among Ethnic Groups. Advances in Applied Developmental Psychology, Volume 14.

ERIC Educational Resources Information Center

Roopnarine, Jaipaul L., Ed.; Brown, Janet, Ed.

Little is known about the development and function of families in major Caribbean communities, an area composed of diverse ethnic and political groups, the majority of whom live on the edge of poverty. This edited book provides an interdisciplinary examination of Caribbean families, each chapter detailing studies dealing with family structures and…

Family Support Network for Adolescent Cannabis Users, Cannabis Youth Treatment (CYT) Series, Volume 3.

ERIC Educational Resources Information Center

Hamilton, Nancy L.; Brantley, Laura Bunch; Tims, Frank M.; Angelovich, Nancy; McDougall, Barbara

Substance-abusing adolescents experiencing inadequate family structure and functioning will be at a serious disadvantage with regard to recovery. The family support network (FSN) intervention seeks to extend the focus of treatment beyond the world of the adolescent by engaging the family, a major system in his or her life. Designed to increase…

A Family Therapist's Reaction to "The Influences of the Family of Origin on Career Development: A Review and Analysis." Reactions

ERIC Educational Resources Information Center

Alderfer, Charleen

2004-01-01

This reaction to Whiston and Keller is that of a family therapist with great respect for the amount of work the article represents. Two theories of family therapy, structural and Bowenian, are discussed with particular attention to the contributions each can make in understanding the influences of families on career choices. The functional and…

Family boundary structures and child adjustment: the indirect role of emotional reactivity.

PubMed

Lindahl, Kristin M; Bregman, Hallie R; Malik, Neena M

2012-12-01

Structural and system theories propose that disruptions in family subsystem functioning increase risk for youth maladjustment. While there is growing evidence to support this proposition, studies that specifically focus on the larger family system remain relatively rare. Furthermore, the pathways that connect problems in family subsystem alliances to externalizing or internalizing problems in youth are as yet largely unexplored. This study examined youth emotional reactivity (anger and sadness) to family conflict as an indirect pathway of the association between family boundary disturbances and youth adjustment in a sample of two-parent families (N = 270). Observational coding was used to group families into Balanced, Dyadic, or Disengaged family alliance structures and to assess youth emotional reactivity, and parent-report was used to assess youth psychopathology. Structural equation modeling indicated both anger and sadness served as indirect pathways through which family boundary disturbances are linked with youth adjustment. In addition, gender was tested as a moderator and important gender differences were found. Specifically, boys were directly impacted by dyadic disturbances while girls were directly impacted by family disengagement. The findings help target goals for intervention and indicate that worthwhile objectives may include realigning family subsystem boundaries, changing family communication patterns, and improving affective coping skills for youth. PsycINFO Database Record (c) 2012 APA, all rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, Hsiu-Ju; Bakolitsa, Constantina; Skerra, Arne

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

Family Environments and Children's Executive Function: The Mediating Role of Children's Affective State and Stress.

PubMed

He, Zhong-Hua; Yin, Wen-Gang

2016-09-01

There is increasing evidence that inadequate family environments (family material environment and family psychosocial environment) are not only social problems but also factors contributing to adverse neurocognitive outcomes. In the present study, the authors investigated the relationship among family environments, children's naturalistic affective state, self-reported stress, and executive functions in a sample of 157 Chinese families. These findings revealed that in inadequate family material environments, reduced children's cognitive flexibility is associated with increased naturalistic negative affectivity and self-reported stress. In addition, naturalistic negative affectivity mediated the association between family expressiveness and children's cognitive flexibility. The authors used a structural equation model to examine the mediation model hypothesis, and the results confirmed the mediating roles of naturalistic negative affectivity and self-reported stress between family environments and the cognitive flexibility of Chinese children. These findings indicate the importance of reducing stress and negative emotional state for improving cognitive functions in children of low socioeconomic status.

Convergence of Domain Architecture, Structure, and Ligand Affinity in Animal and Plant RNA-Binding Proteins.

PubMed

Dias, Raquel; Manny, Austin; Kolaczkowski, Oralia; Kolaczkowski, Bryan

2017-06-01

Reconstruction of ancestral protein sequences using phylogenetic methods is a powerful technique for directly examining the evolution of molecular function. Although ancestral sequence reconstruction (ASR) is itself very efficient, downstream functional, and structural studies necessary to characterize when and how changes in molecular function occurred are often costly and time-consuming, currently limiting ASR studies to examining a relatively small number of discrete functional shifts. As a result, we have very little direct information about how molecular function evolves across large protein families. Here we develop an approach combining ASR with structure and function prediction to efficiently examine the evolution of ligand affinity across a large family of double-stranded RNA binding proteins (DRBs) spanning animals and plants. We find that the characteristic domain architecture of DRBs-consisting of 2-3 tandem double-stranded RNA binding motifs (dsrms)-arose independently in early animal and plant lineages. The affinity with which individual dsrms bind double-stranded RNA appears to have increased and decreased often across both animal and plant phylogenies, primarily through convergent structural mechanisms involving RNA-contact residues within the β1-β2 loop and a small region of α2. These studies provide some of the first direct information about how protein function evolves across large gene families and suggest that changes in molecular function may occur often and unassociated with major phylogenetic events, such as gene or domain duplications. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Sex differences in physical and mental functioning of Japanese civil servants: explanations from work and family characteristics.

PubMed

Sekine, Michikazu; Chandola, Tarani; Martikainen, Pekka; Marmot, Michael; Kagamimori, Sadanobu

2010-12-01

Poor physical and mental functioning are more common among women than men and those with disadvantaged work and family characteristics. This study aims to clarify whether sex differences in health functioning can be explained by sex differences in work and family characteristics. The subjects were 3787 civil servants (2525 men and 1262 women), aged 20-65, working in a local government on the west coast of Japan. A questionnaire survey was conducted in January 2003. Low employment grade, high demands, long work hours, shift work, being unmarried, having no young children, high family-to-work conflict and high work-to-family conflict were more common among women than men and were independently associated with poor physical and mental functioning. The age-adjusted odds ratios (ORs) of women for poor health functioning were 1.80 for poor physical functioning and 1.77 for poor mental functioning. When adjusted for employment grade and work characteristics (control, demand, support, work hours, and shift work), the sex differences in health functioning attenuated. When adjusted for family characteristics (family structure and work-family conflicts), the sex differences in health functioning further attenuated and were no longer statistically significant. Sex differences in family characteristics contributed more to sex difference in mental functioning than sex differences in work characteristics. Japan belongs to conservative welfare regimes. In such countries, men are able to concentrate on their work with relative freedom from their family tasks and responsibilities, whereas women feel difficulties in maintaining their work-life balances. Such sex differences in work- and family-related stresses may contribute to sex difference in health. Longitudinal research is necessary to clarify the causal nature of these associations. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comprehensive comparison of two protein family of P-ATPases (13A1 and 13A3) in insects.

PubMed

Seddigh, Samin

2017-06-01

The P-type ATPases (P-ATPases) are present in all living cells where they mediate ion transport across membranes on the expense of ATP hydrolysis. Different ions which are transported by these pumps are protons like calcium, sodium, potassium, and heavy metals such as manganese, iron, copper, and zinc. Maintenance of the proper gradients for essential ions across cellular membranes makes P-ATPases crucial for cell survival. In this study, characterization of two families of P-ATPases including P-ATPase 13A1 and P-ATPase 13A3 protein was compared in two different insect species from different orders. According to the conserved motifs found with MEME, nine motifs were shared by insects of 13A1 family but eight in 13A3 family. Seven different insect species from 13A1 and five samples from 13A3 family were selected as the representative samples for functional and structural analyses. The structural and functional analyses were performed with ProtParam, SOPMA, SignalP 4.1, TMHMM 2.0, ProtScale and ProDom tools in the ExPASy database. The tertiary structure of Bombus terrestris as a sample of each family of insects were predicted by the Phyre2 and TM-score servers and their similarities were verified by SuperPose server. The tertiary structures were predicted via the "c3b9bA" model (PDB Accession Code: 3B9B) in P-ATPase 13A1 family and "c2zxeA" model (PDB Accession Code: 2ZXE) in P-ATPase 13A3 family. A phylogenetic tree was constructed with MEGA 6.06 software using the Neighbor-joining method. According to the results, there was a high identity of P-ATPase families so that they should be derived from a common ancestor however they belonged to separate groups. In protein-protein interaction analysis by STRING 10.0, six common enriched pathways of KEGG were identified in B. terrestris in both families. The obtained data provide a background for bioinformatic studies of the function and evolution of other insects and organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exponential Family Functional data analysis via a low-rank model.

PubMed

Li, Gen; Huang, Jianhua Z; Shen, Haipeng

2018-05-08

In many applications, non-Gaussian data such as binary or count are observed over a continuous domain and there exists a smooth underlying structure for describing such data. We develop a new functional data method to deal with this kind of data when the data are regularly spaced on the continuous domain. Our method, referred to as Exponential Family Functional Principal Component Analysis (EFPCA), assumes the data are generated from an exponential family distribution, and the matrix of the canonical parameters has a low-rank structure. The proposed method flexibly accommodates not only the standard one-way functional data, but also two-way (or bivariate) functional data. In addition, we introduce a new cross validation method for estimating the latent rank of a generalized data matrix. We demonstrate the efficacy of the proposed methods using a comprehensive simulation study. The proposed method is also applied to a real application of the UK mortality study, where data are binomially distributed and two-way functional across age groups and calendar years. The results offer novel insights into the underlying mortality pattern. © 2018, The International Biometric Society.

Relations Between Parent Psychopathology, Family Functioning, and Adolescent Problems In Substance-Abusing Families: Disaggregating the Effects of Parent Gender

PubMed Central

Burstein, Marcy; Stanger, Catherine; Dumenci, Levent

2015-01-01

The present study: (1) examined relations between parent psychopathology and adolescent internalizing problems, externalizing problems, and substance use in substanceabusing families; and (2) tested family functioning problems as mediators of these relations. Structural equation modeling was used to estimate the independent effects of parent psychopathology and family functioning problems by parent gender. Participants included 242 parents in treatment for substance abuse and/or dependence and 59 of their coparents (16.9% in treatment for substance-abuse/dependence) from middle income households (SES: M = 4.7; SD = 2.1). Ratings were obtained for 325 adolescents (48% female; 27.8% non-Caucasian) between the ages of 10 and 18 years (M = 13.5 years; SD = 2.5 years). Parent psychopathology, family functioning problems, and adolescent problems were assessed with parent and coparent ratings on the Symptom Checklist (SCL-90)/Brief Symptom Inventory (BSI), the Family Relationship Measure, and the Child Behavior Checklist, respectively. Results indicated that maternal psychopathology was directly related to adolescent internalizing problems and substance use, but maternal perceptions of family functioning problems failed to mediate relations between maternal psychopathology and adolescent problems. By contrast, paternal perceptions of family functioning problems uniquely mediated relations between paternal psychopathology and adolescent externalizing problems. Findings underscore the importance of examining how mothers and fathers may differentially impact adolescent problems in substance-abusing families. PMID:22392413

The Nature of Family Engagement in Interventions for Children With Chronic Conditions.

PubMed

Knafl, Kathleen A; Havill, Nancy L; Leeman, Jennifer; Fleming, Louise; Crandell, Jamie L; Sandelowski, Margarete

2017-05-01

Recognizing the bi-directional relationship between family functioning and child well-being in the context of childhood chronic conditions, researchers have tested family-focused interventions aimed at promoting both child and family well-being through improving the family's condition management capacity. Based on a sample of 70 interventions for families in which there was a child with a chronic physical condition, this analysis examined the nature of family engagement in the interventions. Data were extracted from the intervention reports using a standardized template; conventional content analysis was used to describe family engagement. Interventions varied in focus, structure, and level of family engagement. Investigators most often sought to improve condition control or management, with parent engagement focused on improving capacity to manage the treatment regimen. Few investigators addressed capacity building in the context of family functioning. Recommendations are made for reporting standards for family-focused interventions and for enhancing the family systems grounding of interventions.

Professional Support for Families in Difficult Life Situations

ERIC Educational Resources Information Center

Zakirova, Venera G.; Gaysina, Guzel I.; Raykova, Elena

2016-01-01

Relevance of the problem stated in the article is determined by the presence of a significant number of families in difficult life situations who need in professional support and socio-psychological assistance. The article aims to substantiate the effectiveness of the structural-functional model of professional supporting for families in difficult…

Rebelling for a Reason: Protein Structural “Outliers”

PubMed Central

Arumugam, Gandhimathi; Nair, Anu G.; Hariharaputran, Sridhar; Ramanathan, Sowdhamini

2013-01-01

Analysis of structural variation in domain superfamilies can reveal constraints in protein evolution which aids protein structure prediction and classification. Structure-based sequence alignment of distantly related proteins, organized in PASS2 database, provides clues about structurally conserved regions among different functional families. Some superfamily members show large structural differences which are functionally relevant. This paper analyses the impact of structural divergence on function for multi-member superfamilies, selected from the PASS2 superfamily alignment database. Functional annotations within superfamilies, with structural outliers or ‘rebels’, are discussed in the context of structural variations. Overall, these data reinforce the idea that functional similarities cannot be extrapolated from mere structural conservation. The implication for fold-function prediction is that the functional annotations can only be inherited with very careful consideration, especially at low sequence identities. PMID:24073209

RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential

PubMed Central

Findeisen, Maria; Rathmann, Daniel; Beck-Sickinger, Annette G.

2011-01-01

Different neuropeptides, all containing a common carboxy-terminal RFamide sequence, have been characterized as ligands of the RFamide peptide receptor family. Currently, five subgroups have been characterized with respect to their N-terminal sequence and hence cover a wide pattern of biological functions, like important neuroendocrine, behavioral, sensory and automatic functions. The RFamide peptide receptor family represents a multiligand/multireceptor system, as many ligands are recognized by several GPCR subtypes within one family. Multireceptor systems are often susceptible to cross-reactions, as their numerous ligands are frequently closely related. In this review we focus on recent results in the field of structure-activity studies as well as mutational exploration of crucial positions within this GPCR system. The review summarizes the reported peptide analogs and recently developed small molecule ligands (agonists and antagonists) to highlight the current understanding of the pharmacophoric elements, required for affinity and activity at the receptor family. Furthermore, we address the biological functions of the ligands and give an overview on their involvement in physiological processes. We provide insights in the knowledge for the design of highly selective ligands for single receptor subtypes to minimize cross-talk and to eliminate effects from interactions within the GPCR system. This will support the drug development of members of the RFamide family.

Slice regular functions of several Clifford variables

NASA Astrophysics Data System (ADS)

Ghiloni, R.; Perotti, A.

2012-11-01

We introduce a class of slice regular functions of several Clifford variables. Our approach to the definition of slice functions is based on the concept of stem functions of several variables and on the introduction on real Clifford algebras of a family of commuting complex structures. The class of slice regular functions include, in particular, the family of (ordered) polynomials in several Clifford variables. We prove some basic properties of slice and slice regular functions and give examples to illustrate this function theory. In particular, we give integral representation formulas for slice regular functions and a Hartogs type extension result.

Isoforms, structures, and functions of versatile spectraplakin MACF1.

PubMed

Hu, Lifang; Su, Peihong; Li, Runzhi; Yin, Chong; Zhang, Yan; Shang, Peng; Yang, Tuanmin; Qian, Airong

2016-01-01

Spectraplakins are crucially important communicators, linking cytoskeletal components to each other and cellular junctions. Microtubule actin crosslinking factor 1 (MACF1), also known as actin crosslinking family 7 (ACF7), is a member of the spectraplakin family. It is expressed in numerous tissues and cells as one extensively studied spectraplakin. MACF1 has several isoforms with unique structures and well-known function to be able to crosslink F-actin and microtubules. MACF1 is one versatile spectraplakin with various functions in cell processes, embryo development, tissue-specific functions, and human diseases. The importance of MACF1 has become more apparent in recent years. Here, we summarize the current knowledge on the presence and function of MACF1 and provide perspectives on future research of MACF1 based on our studies and others.

Structural, functional and evolutionary relationships between homing endonucleases and proteins from their host organisms

PubMed Central

Taylor, Gregory K.; Stoddard, Barry L.

2012-01-01

Homing endonucleases (HEs) are highly specific DNA-cleaving enzymes that are encoded by invasive DNA elements (usually mobile introns or inteins) within the genomes of phage, bacteria, archea, protista and eukaryotic organelles. Six unique structural HE families, that collectively span four distinct nuclease catalytic motifs, have been characterized to date. Members of each family display structural homology and functional relationships to a wide variety of proteins from various organisms. The biological functions of those proteins are highly disparate and include non-specific DNA-degradation enzymes, restriction endonucleases, DNA-repair enzymes, resolvases, intron splicing factors and transcription factors. These relationships suggest that modern day HEs share common ancestors with proteins involved in genome fidelity, maintenance and gene expression. This review summarizes the results of structural studies of HEs and corresponding proteins from host organisms that have illustrated the manner in which these factors are related. PMID:22406833

Eukaryotic expression, purification and structure/function analysis of native, recombinant CRISP3 from human and mouse

NASA Astrophysics Data System (ADS)

Volpert, Marianna; Mangum, Jonathan E.; Jamsai, Duangporn; D'Sylva, Rebecca; O'Bryan, Moira K.; McIntyre, Peter

2014-02-01

While the Cysteine-Rich Secretory Proteins (CRISPs) have been broadly proposed as regulators of reproduction and immunity, physiological roles have yet to be established for individual members of this family. Past efforts to investigate their functions have been limited by the difficulty of purifying correctly folded CRISPs from bacterial expression systems, which yield low quantities of correctly folded protein containing the eight disulfide bonds that define the CRISP family. Here we report the expression and purification of native, glycosylated CRISP3 from human and mouse, expressed in HEK 293 cells and isolated using ion exchange and size exclusion chromatography. Functional authenticity was verified by substrate-affinity, native glycosylation characteristics and quaternary structure (monomer in solution). Validated protein was used in comparative structure/function studies to characterise sites and patterns of N-glycosylation in CRISP3, revealing interesting inter-species differences.

Deciphering the molecular and functional basis of Dbl family proteins: a novel systematic approach toward classification of selective activation of the Rho family proteins.

PubMed

Jaiswal, Mamta; Dvorsky, Radovan; Ahmadian, Mohammad Reza

2013-02-08

The diffuse B-cell lymphoma (Dbl) family of the guanine nucleotide exchange factors is a direct activator of the Rho family proteins. The Rho family proteins are involved in almost every cellular process that ranges from fundamental (e.g. the establishment of cell polarity) to highly specialized processes (e.g. the contraction of vascular smooth muscle cells). Abnormal activation of the Rho proteins is known to play a crucial role in cancer, infectious and cognitive disorders, and cardiovascular diseases. However, the existence of 74 Dbl proteins and 25 Rho-related proteins in humans, which are largely uncharacterized, has led to increasing complexity in identifying specific upstream pathways. Thus, we comprehensively investigated sequence-structure-function-property relationships of 21 representatives of the Dbl protein family regarding their specificities and activities toward 12 Rho family proteins. The meta-analysis approach provides an unprecedented opportunity to broadly profile functional properties of Dbl family proteins, including catalytic efficiency, substrate selectivity, and signaling specificity. Our analysis has provided novel insights into the following: (i) understanding of the relative differences of various Rho protein members in nucleotide exchange; (ii) comparing and defining individual and overall guanine nucleotide exchange factor activities of a large representative set of the Dbl proteins toward 12 Rho proteins; (iii) grouping the Dbl family into functionally distinct categories based on both their catalytic efficiencies and their sequence-structural relationships; (iv) identifying conserved amino acids as fingerprints of the Dbl and Rho protein interaction; and (v) defining amino acid sequences conserved within, but not between, Dbl subfamilies. Therefore, the characteristics of such specificity-determining residues identified the regions or clusters conserved within the Dbl subfamilies.

A Hamilton-Jacobi theory for implicit differential systems

NASA Astrophysics Data System (ADS)

Esen, Oǧul; de León, Manuel; Sardón, Cristina

2018-02-01

In this paper, we propose a geometric Hamilton-Jacobi theory for systems of implicit differential equations. In particular, we are interested in implicit Hamiltonian systems, described in terms of Lagrangian submanifolds of TT*Q generated by Morse families. The implicit character implies the nonexistence of a Hamiltonian function describing the dynamics. This fact is here amended by a generating family of Morse functions which plays the role of a Hamiltonian. A Hamilton-Jacobi equation is obtained with the aid of this generating family of functions. To conclude, we apply our results to singular Lagrangians by employing the construction of special symplectic structures.

Functional modulation of a protein folding landscape via side-chain distortion

PubMed Central

Kelch, Brian A.; Salimi, Neema L.; Agard, David A.

2012-01-01

Ultrahigh-resolution (< 1.0 Å) structures have revealed unprecedented and unexpected details of molecular geometry, such as the deformation of aromatic rings from planarity. However, the functional utility of such energetically costly strain is unknown. The 0.83 Å structure of α-lytic protease (αLP) indicated that residues surrounding a conserved Phe side-chain dictate a rotamer which results in a ∼6° distortion along the side-chain, estimated to cost 4 kcal/mol. By contrast, in the closely related protease Streptomyces griseus Protease B (SGPB), the equivalent Phe adopts a different rotamer and is undistorted. Here, we report that the αLP Phe side-chain distortion is both functional and conserved in proteases with large pro regions. Sequence analysis of the αLP serine protease family reveals a bifurcation separating those sequences expected to induce distortion and those that would not, which correlates with the extent of kinetic stability. Structural and folding kinetics analyses of family members suggest that distortion of this side-chain plays a role in increasing kinetic stability within the αLP family members that use a large Pro region. Additionally, structural and kinetic folding studies of mutants demonstrate that strain alters the folding free energy landscape by destabilizing the transition state (TS) relative to the native state (N). Although side-chain distortion comes at a cost of foldability, it suppresses the rate of unfolding, thereby enhancing kinetic stability and increasing protein longevity under harsh extracellular conditions. This ability of a structural distortion to enhance function is unlikely to be unique to αLP family members and may be relevant in other proteins exhibiting side-chain distortions. PMID:22635267

Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution.

PubMed

Kaur, Gurmeet; Subramanian, Srikrishna

2016-08-26

Treble clef (TC) zinc fingers constitute a large fold-group of structural zinc-binding protein domains that mediate numerous cellular functions. We have analysed the sequence, structure, and function relationships among all TCs in the Protein Data Bank. This led to the identification of novel TCs, such as lsr2, YggX and TFIIIC τ 60 kDa subunit, and prediction of a nuclease-like function for the DUF1364 family. The structural malleability of TCs is evident from the many examples with variations to the core structural elements of the fold. We observe domains wherein the structural core of the TC fold is circularly permuted, and also some examples where the overall fold resembles both the TC motif and another unrelated fold. All extant TC families do not share a monophyletic origin, as several TC proteins are known to have been present in the last universal common ancestor and the last eukaryotic common ancestor. We identify several TCs where the zinc-chelating site and residues are not merely responsible for structure stabilization but also perform other functions, such as being redox active in C1B domain of protein kinase C, a nucleophilic acceptor in Ada and catalytic in organomercurial lyase, MerB.

Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution

NASA Astrophysics Data System (ADS)

Kaur, Gurmeet; Subramanian, Srikrishna

2016-08-01

Treble clef (TC) zinc fingers constitute a large fold-group of structural zinc-binding protein domains that mediate numerous cellular functions. We have analysed the sequence, structure, and function relationships among all TCs in the Protein Data Bank. This led to the identification of novel TCs, such as lsr2, YggX and TFIIIC τ 60 kDa subunit, and prediction of a nuclease-like function for the DUF1364 family. The structural malleability of TCs is evident from the many examples with variations to the core structural elements of the fold. We observe domains wherein the structural core of the TC fold is circularly permuted, and also some examples where the overall fold resembles both the TC motif and another unrelated fold. All extant TC families do not share a monophyletic origin, as several TC proteins are known to have been present in the last universal common ancestor and the last eukaryotic common ancestor. We identify several TCs where the zinc-chelating site and residues are not merely responsible for structure stabilization but also perform other functions, such as being redox active in C1B domain of protein kinase C, a nucleophilic acceptor in Ada and catalytic in organomercurial lyase, MerB.

Familial Predictors of Sibling and Romantic-Partner Conflict Resolution: Comparing Late Adolescents from Intact and Divorced Families

ERIC Educational Resources Information Center

Reese-Weber, M.; Kahn, J.H.

2005-01-01

The present study examined whether predictors of romantic-partner conflict may vary as a function of family structure. Using a cross-sectional design, we tested a mediation model of conflict resolution behaviours among late adolescents from intact (n=185) and divorced (n=87) families. Adolescents rated conflict resolution behaviours in five dyadic…

The family in Romania: cultural and economic context and implications for treatment.

PubMed

Mihai, Adriana; Butiu, Otilia

2012-04-01

The study of family structures, functioning, roles and values is fundamental in family therapist's activities for better understanding the psychological, cultural and social specificity of different clients and interventions. In this paper we describe the Romanian family and the family therapies which are available in Romania. We illustrate basic needs using demographic data and research available from Romania. The nuclear family remains dominant instead of other alternatives, the age of marriage is earlier than in western European countries and celibate and consensual living are exceptions or only for the transitional period before marriage. The role of marriage and childbirth within the marital setting is still important. The model of a single child appears increasingly common due to an improvement in financial resources and better living conditions. Relations with family of origin remain close. The difficulties for children with parents working in different countries raise problems and have implications for the extended family, educators and psychotherapists as well as mental health service providers. Family therapists should keep in mind the structure, function, role and values of the Romanian family for better understanding the issues and resources and use these accordingly in therapy. Policy-makers should be aware of the difficulties concerning availability and access to this therapeutic approach.

Intergenerational Transmission of Neuropsychological Executive Functioning

PubMed Central

Jester, Jennifer M.; Nigg, Joel T.; Puttler, Leon I.; Long, Jeffrey C.; Fitzgerald, Hiram E.; Zucker, Robert A.

2009-01-01

Relationships between parent and child executive functioning were examined, controlling for the critical potential confound of IQ, in a family study involving 434 children (130 girls, 304 boys) and 376 parents from 204 community recruited families at high risk for the development of substance use disorder. Structural equation modeling found evidence of separate executive functioning and intelligence (IQ) latent variables. Mother’s and father’s executive functioning were associated with child’s executive functioning (beta = 0.34 for father-child, 0.51 for mother-child), independently of parental IQ, which as expected was associated with child’s IQ (beta = 0.52 for father-child, 0.54 for mother-child). Familial correlations also showed a significant relationship of executive functioning between parents and offspring. These findings clarify that key elements of the executive functioning construct are reliably differentiable from IQ, and are transmitted in families. This work supports the utility of the construct of executive function in further study of the mechanisms and etiology of externalizing psychopathologies. PMID:19243871

The relationship between neurobehavioural problems of severe traumatic brain injury (TBI), family functioning and the psychological well-being of the spouse/caregiver: path model analysis.

PubMed

Anderson, Malcolm I; Parmenter, Trevor R; Mok, Magdalena

2002-09-01

This study used a modern theory of stress as a framework to strengthen the understanding of the relationship between neurobehavioural problems of TBI, family functioning and psychological distress in spouse/caregivers. The research was an ex post facto design utilising a cross-sectional methodology. Path analysis was used to determine the structural effect of neurobehavioural problems on family functioning and psychological distress. Forty-seven female and 17 male spouse/caregivers of partners with severe TBI were recruited. Spouse/caregivers who reported partners with TBI as having high levels of behavioural and cognitive problems experienced high levels of unhealthy family functioning. High levels of unhealthy family functioning were related to high levels of distress in spouse/caregivers, as family functioning had a moderate influence on psychological distress. Furthermore, indirect effects of behavioural and cognitive problems operating through family functioning intensified the level of psychological distress experienced by spouse/caregivers. Additionally, spouse/caregivers who reported high levels of behavioural, communication and social problems in their partners also experienced high levels of psychological distress. This study was significant because the impact of TBI on the spouse/caregiver from a multidimensional perspective is an important and under-researched area in the brain injury and disability field.

Unzippers, Resolvers and Sensors: A Structural and Functional Biochemistry Tale of RNA Helicases

PubMed Central

Leitão, Ana Lúcia; Costa, Marina C.; Enguita, Francisco J.

2015-01-01

The centrality of RNA within the biological world is an irrefutable fact that currently attracts increasing attention from the scientific community. The panoply of functional RNAs requires the existence of specific biological caretakers, RNA helicases, devoted to maintain the proper folding of those molecules, resolving unstable structures. However, evolution has taken advantage of the specific position and characteristics of RNA helicases to develop new functions for these proteins, which are at the interface of the basic processes for transference of information from DNA to proteins. RNA helicases are involved in many biologically relevant processes, not only as RNA chaperones, but also as signal transducers, scaffolds of molecular complexes, and regulatory elements. Structural biology studies during the last decade, founded in X-ray crystallography, have characterized in detail several RNA-helicases. This comprehensive review summarizes the structural knowledge accumulated in the last two decades within this family of proteins, with special emphasis on the structure-function relationships of the most widely-studied families of RNA helicases: the DEAD-box, RIG-I-like and viral NS3 classes. PMID:25622248

Antimicrobial Peptides from Plants

PubMed Central

Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

2015-01-01

Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

The relationship between family functioning and caregiving appraisal of dementia family caregivers: caregiving self-efficacy as a mediator.

PubMed

Liu, Hsin-Yi; Huang, Lian-Hua

2018-04-01

The aim of this study was to explore caregiving self-efficacy as a mediator for the association between family functioning and caregiving appraisal of dementia family caregivers in Taiwan. This study adopted a cross-sectional correlational design. Purposive sampling was used to recruit 115 dyads of dementia patients and family caregivers from the outpatient neurological clinics of two hospitals in northern Taiwan. Data were gathered through interviews with a structured questionnaire, which included demographic characteristics for caregivers and patients, family functioning, caregiving self-efficacy, as well as positive and negative aspects of caregiving appraisal. Family functioning, patients' activities of daily living score, Neuropsychiatric Inventory caregiver distress, and three domains of self-efficacy were significantly associated with caregiver burden. Hierarchical multiple regression analyses indicated that self-efficacy for obtaining respite (SE-OR) significantly explained 20.5% of the variance in caregiver esteem. Caregiver perceived worsened health status, family functioning, and SE-OR significantly explained 59% of the variance in caregiver burden. The mediation test only supported the partially mediating role of SE-OR on the relationship between family functioning and caregiver burden, while the mediating effect of self-efficacy for responding to disruptive behaviours and controlling upsetting thoughts were insignificant. Our findings provided preliminary evidence for health professionals recommending that future studies should assess the family dynamic and health problems of caregivers, and develop appropriate family-centred interventions that focus on strengthening interfamily support and respite services to alleviate caregiver burden.

De novo discovery of structural motifs in RNA 3D structures through clustering.

PubMed

Ge, Ping; Islam, Shahidul; Zhong, Cuncong; Zhang, Shaojie

2018-05-18

As functional components in three-dimensional (3D) conformation of an RNA, the RNA structural motifs provide an easy way to associate the molecular architectures with their biological mechanisms. In the past years, many computational tools have been developed to search motif instances by using the existing knowledge of well-studied families. Recently, with the rapidly increasing number of resolved RNA 3D structures, there is an urgent need to discover novel motifs with the newly presented information. In this work, we classify all the loops in non-redundant RNA 3D structures to detect plausible RNA structural motif families by using a clustering pipeline. Compared with other clustering approaches, our method has two benefits: first, the underlying alignment algorithm is tolerant to the variations in 3D structures. Second, sophisticated downstream analysis has been performed to ensure the clusters are valid and easily applied to further research. The final clustering results contain many interesting new variants of known motif families, such as GNAA tetraloop, kink-turn, sarcin-ricin and T-loop. We have also discovered potential novel functional motifs conserved in ribosomal RNA, sgRNA, SRP RNA, riboswitch and ribozyme.

Zebra: a web server for bioinformatic analysis of diverse protein families.

PubMed

Suplatov, Dmitry; Kirilin, Evgeny; Takhaveev, Vakil; Svedas, Vytas

2014-01-01

During evolution of proteins from a common ancestor, one functional property can be preserved while others can vary leading to functional diversity. A systematic study of the corresponding adaptive mutations provides a key to one of the most challenging problems of modern structural biology - understanding the impact of amino acid substitutions on protein function. The subfamily-specific positions (SSPs) are conserved within functional subfamilies but are different between them and, therefore, seem to be responsible for functional diversity in protein superfamilies. Consequently, a corresponding method to perform the bioinformatic analysis of sequence and structural data has to be implemented in the common laboratory practice to study the structure-function relationship in proteins and develop novel protein engineering strategies. This paper describes Zebra web server - a powerful remote platform that implements a novel bioinformatic analysis algorithm to study diverse protein families. It is the first application that provides specificity determinants at different levels of functional classification, therefore addressing complex functional diversity of large superfamilies. Statistical analysis is implemented to automatically select a set of highly significant SSPs to be used as hotspots for directed evolution or rational design experiments and analyzed studying the structure-function relationship. Zebra results are provided in two ways - (1) as a single all-in-one parsable text file and (2) as PyMol sessions with structural representation of SSPs. Zebra web server is available at http://biokinet.belozersky.msu.ru/zebra .

Common and Distant Structural Characteristics of Feruloyl Esterase Families from Aspergillus oryzae

PubMed Central

Udatha, D. B. R. K. Gupta; Mapelli, Valeria; Panagiotou, Gianni; Olsson, Lisbeth

2012-01-01

Background Feruloyl esterases (FAEs) are important biomass degrading accessory enzymes due to their capability of cleaving the ester links between hemicellulose and pectin to aromatic compounds of lignin, thus enhancing the accessibility of plant tissues to cellulolytic and hemicellulolytic enzymes. FAEs have gained increased attention in the area of biocatalytic transformations for the synthesis of value added compounds with medicinal and nutritional applications. Following the increasing attention on these enzymes, a novel descriptor based classification system has been proposed for FAEs resulting into 12 distinct families and pharmacophore models for three FAE sub-families have been developed. Methodology/Principal Findings The feruloylome of Aspergillus oryzae contains 13 predicted FAEs belonging to six sub-families based on our recently developed descriptor-based classification system. The three-dimensional structures of the 13 FAEs were modeled for structural analysis of the feruloylome. The three genes coding for three enzymes, viz., A.O.2, A.O.8 and A.O.10 from the feruloylome of A. oryzae, representing sub-families with unknown functional features, were heterologously expressed in Pichia pastoris, characterized for substrate specificity and structural characterization through CD spectroscopy. Common feature-based pharamacophore models were developed according to substrate specificity characteristics of the three enzymes. The active site residues were identified for the three expressed FAEs by determining the titration curves of amino acid residues as a function of the pH by applying molecular simulations. Conclusions/Significance Our findings on the structure-function relationships and substrate specificity of the FAEs of A. oryzae will be instrumental for further understanding of the FAE families in the novel classification system. The developed pharmacophore models could be applied for virtual screening of compound databases for short listing the putative substrates prior to docking studies or for post-processing docking results to remove false positives. Our study exemplifies how computational predictions can complement to the information obtained through experimental methods. PMID:22745763

Common and distant structural characteristics of feruloyl esterase families from Aspergillus oryzae.

PubMed

Udatha, D B R K Gupta; Mapelli, Valeria; Panagiotou, Gianni; Olsson, Lisbeth

2012-01-01

Feruloyl esterases (FAEs) are important biomass degrading accessory enzymes due to their capability of cleaving the ester links between hemicellulose and pectin to aromatic compounds of lignin, thus enhancing the accessibility of plant tissues to cellulolytic and hemicellulolytic enzymes. FAEs have gained increased attention in the area of biocatalytic transformations for the synthesis of value added compounds with medicinal and nutritional applications. Following the increasing attention on these enzymes, a novel descriptor based classification system has been proposed for FAEs resulting into 12 distinct families and pharmacophore models for three FAE sub-families have been developed. The feruloylome of Aspergillus oryzae contains 13 predicted FAEs belonging to six sub-families based on our recently developed descriptor-based classification system. The three-dimensional structures of the 13 FAEs were modeled for structural analysis of the feruloylome. The three genes coding for three enzymes, viz., A.O.2, A.O.8 and A.O.10 from the feruloylome of A. oryzae, representing sub-families with unknown functional features, were heterologously expressed in Pichia pastoris, characterized for substrate specificity and structural characterization through CD spectroscopy. Common feature-based pharamacophore models were developed according to substrate specificity characteristics of the three enzymes. The active site residues were identified for the three expressed FAEs by determining the titration curves of amino acid residues as a function of the pH by applying molecular simulations. Our findings on the structure-function relationships and substrate specificity of the FAEs of A. oryzae will be instrumental for further understanding of the FAE families in the novel classification system. The developed pharmacophore models could be applied for virtual screening of compound databases for short listing the putative substrates prior to docking studies or for post-processing docking results to remove false positives. Our study exemplifies how computational predictions can complement to the information obtained through experimental methods.

Natural diversity of glycoside hydrolase family 48 exoglucanases: insights from structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brunecky, Roman; Alahuhta, Markus; Sammond, Deanne W.

Glycoside hydrolase (GH) family 48 is an understudied and increasingly important exoglucanase family found in the majority of bacterial cellulase systems. Moreover, many thermophilic enzyme systems contain GH48 enzymes. Deletion of GH48 enzymes in these microorganisms results in drastic reduction in biomass deconstruction. Surprisingly, given their importance for these microorganisms, GH48s have intrinsically low cellulolytic activity but even in low ratios synergize greatly with GH9 endoglucanases. In this study, we explore the structural and enzymatic diversity of these enzymes across a wide range of temperature optima. We have crystallized one new GH48 module from Bacillus pumilus in a complex withmore » cellobiose and cellohexaose (BpumGH48). We compare this structure to other known GH48 enzymes in an attempt to understand GH48 structure/function relationships and draw general rules correlating amino acid sequences and secondary structures to thermostability in this GH family.« less

Natural diversity of glycoside hydrolase family 48 exoglucanases: insights from structure

DOE PAGES

Brunecky, Roman; Alahuhta, Markus; Sammond, Deanne W.; ...

2017-11-30

Glycoside hydrolase (GH) family 48 is an understudied and increasingly important exoglucanase family found in the majority of bacterial cellulase systems. Moreover, many thermophilic enzyme systems contain GH48 enzymes. Deletion of GH48 enzymes in these microorganisms results in drastic reduction in biomass deconstruction. Surprisingly, given their importance for these microorganisms, GH48s have intrinsically low cellulolytic activity but even in low ratios synergize greatly with GH9 endoglucanases. In this study, we explore the structural and enzymatic diversity of these enzymes across a wide range of temperature optima. We have crystallized one new GH48 module from Bacillus pumilus in a complex withmore » cellobiose and cellohexaose (BpumGH48). We compare this structure to other known GH48 enzymes in an attempt to understand GH48 structure/function relationships and draw general rules correlating amino acid sequences and secondary structures to thermostability in this GH family.« less

Parental Knowledge and Its Sources: Examining the Moderating Roles of Family Structure and Race

ERIC Educational Resources Information Center

Bumpus, Matthew F.; Rodgers, Kathleen Boyce

2009-01-01

This study aims to examine patterns of parental knowledge and its sources (adolescent reports of disclosure, parental solicitation, and parental trust) among adolescents who differ as a function of family structure and race. Data are drawn from adolescents (N = 2,374, M = 14 years, SD = 1.68) participating in a school-based study. Adolescent…

WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes.

PubMed

Jia, Da; Gomez, Timothy S; Metlagel, Zoltan; Umetani, Junko; Otwinowski, Zbyszek; Rosen, Michael K; Billadeau, Daniel D

2010-06-08

We recently showed that the Wiskott-Aldrich syndrome protein (WASP) family member, WASH, localizes to endosomal subdomains and regulates endocytic vesicle scission in an Arp2/3-dependent manner. Mechanisms regulating WASH activity are unknown. Here we show that WASH functions in cells within a 500 kDa core complex containing Strumpellin, FAM21, KIAA1033 (SWIP), and CCDC53. Although recombinant WASH is constitutively active toward the Arp2/3 complex, the reconstituted core assembly is inhibited, suggesting that it functions in cells to regulate actin dynamics through WASH. FAM21 interacts directly with CAPZ and inhibits its actin-capping activity. Four of the five core components show distant (approximately 15% amino acid sequence identify) but significant structural homology to components of a complex that negatively regulates the WASP family member, WAVE. Moreover, biochemical and electron microscopic analyses show that the WASH and WAVE complexes are structurally similar. Thus, these two distantly related WASP family members are controlled by analogous structurally related mechanisms. Strumpellin is mutated in the human disease hereditary spastic paraplegia, and its link to WASH suggests that misregulation of actin dynamics on endosomes may play a role in this disorder.

The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition.

PubMed

Sullivan, Lucy C; Clements, Craig S; Beddoe, Travis; Johnson, Darryl; Hoare, Hilary L; Lin, Jie; Huyton, Trevor; Hopkins, Emma J; Reid, Hugh H; Wilce, Matthew C J; Kabat, Juraj; Borrego, Francisco; Coligan, John E; Rossjohn, Jamie; Brooks, Andrew G

2007-12-01

The CD94-NKG2 receptor family that regulates NK and T cells is unique among the lectin-like receptors encoded within the natural killer cell complex. The function of the CD94-NKG2 receptors is dictated by the pairing of the invariant CD94 polypeptide with specific NKG2 isoforms to form a family of functionally distinct heterodimeric receptors. However, the structural basis for this selective pairing and how they interact with their ligand, HLA-E, is unknown. We describe the 2.5 A resolution crystal structure of CD94-NKG2A in which the mode of dimerization contrasts with that of other homodimeric NK receptors. Despite structural homology between the CD94 and NKG2A subunits, the dimer interface is asymmetric, thereby providing a structural basis for the preferred heterodimeric assembly. Structure-based sequence comparisons of other CD94-NKG2 family members, combined with extensive mutagenesis studies on HLA-E and CD94-NKG2A, allows a model of the interaction between CD94-NKG2A and HLA-E to be established, in which the invariant CD94 chain plays a more dominant role in interacting with HLA-E in comparison to the variable NKG2 chain.

Resolving protein structure-function-binding site relationships from a binding site similarity network perspective.

PubMed

Mudgal, Richa; Srinivasan, Narayanaswamy; Chandra, Nagasuma

2017-07-01

Functional annotation is seldom straightforward with complexities arising due to functional divergence in protein families or functional convergence between non-homologous protein families, leading to mis-annotations. An enzyme may contain multiple domains and not all domains may be involved in a given function, adding to the complexity in function annotation. To address this, we use binding site information from bound cognate ligands and catalytic residues, since it can help in resolving fold-function relationships at a finer level and with higher confidence. A comprehensive database of 2,020 fold-function-binding site relationships has been systematically generated. A network-based approach is employed to capture the complexity in these relationships, from which different types of associations are deciphered, that identify versatile protein folds performing diverse functions, same function associated with multiple folds and one-to-one relationships. Binding site similarity networks integrated with fold, function, and ligand similarity information are generated to understand the depth of these relationships. Apart from the observed continuity in the functional site space, network properties of these revealed versatile families with topologically different or dissimilar binding sites and structural families that perform very similar functions. As a case study, subtle changes in the active site of a set of evolutionarily related superfamilies are studied using these networks. Tracing of such similarities in evolutionarily related proteins provide clues into the transition and evolution of protein functions. Insights from this study will be helpful in accurate and reliable functional annotations of uncharacterized proteins, poly-pharmacology, and designing enzymes with new functional capabilities. Proteins 2017; 85:1319-1335. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Controlled Comparison of Family Cognitive Behavioral Therapy and Psychoeducation/Relaxation Training for Child Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Piacentini, John; Bergman, R. Lindsey; Chang, Susanna; Langley, Audra; Peris, Tara; Wood, Jeffrey J.; McCracken, James

2011-01-01

Objective: To examine the efficacy of exposure-based cognitive-behavioral therapy (CBT) plus a structured family intervention (FCBT) versus psychoeducation plus relaxation training (PRT) for reducing symptom severity, functional impairment, and family accommodation in youths with obsessive-compulsive disorder (OCD). Method: A total of 71…

Family Influences on Adolescents’ Birth Control and Condom Use, Likelihood of Sexually Transmitted Infections

ERIC Educational Resources Information Center

Kao, Tsui-Sui Annie; Manczak, Melissa

2013-01-01

This study explored the relationships among personal factors, family structure and family function, adolescents’ self-efficacy for safe sex, and sexual behaviors among sexually active adolescents. A subset sample from the first three waves of the National Longitudinal Study of Adolescent Health (Add Health) was selected for this exploratory…

Impact of Adolescents' Filial Self-Efficacy on Quality of Family Functioning and Satisfaction

ERIC Educational Resources Information Center

Caprara, Gian Vittorio; Pastorelli, Concetta; Regalia, Camillo; Scabini, Eugenia; Bandura, Albert

2005-01-01

In this prospective study, we tested a structural model in which adolescents' perceived self-efficacy to manage parental relationships affected their satisfaction with family life both directly, and indirectly, through its impact on family practices. Findings based on 380 Italian adolescents showed that perceived filial self-efficacy was linked…

STRIPAK complexes: structure, biological function, and involvement in human diseases.

PubMed

Hwang, Juyeon; Pallas, David C

2014-02-01

The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear autoantigen, and zinedin. Striatin family members have no intrinsic catalytic activity, but rather function as scaffolding proteins. Remarkably, they organize multiple diverse, large signaling complexes that participate in a variety of cellular processes. Moreover, they appear to be regulatory/targeting subunits for the major eukaryotic serine/threonine protein phosphatase 2A. In addition, striatin family members associate with germinal center kinase III kinases as well as other novel components, earning these assemblies the name striatin-interacting phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great increase in functional and mechanistic studies aimed at identifying and understanding the roles of STRIPAK and STRIPAK-like complexes in cellular processes of multiple organisms. These studies have identified novel STRIPAK and STRIPAK-like complexes and have explored their roles in specific signaling pathways. Together, the results of these studies have sparked increased interest in striatin family complexes because they have revealed roles in signaling, cell cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity, cell migration, neural and vascular development, and cardiac function. Moreover, STRIPAK complexes have been connected to clinical conditions, including cardiac disease, diabetes, autism, and cerebral cavernous malformation. In this review, we discuss the expression, localization, and protein domain structure of striatin family members. Then we consider the diverse complexes these proteins and their homologs form in various organisms, emphasizing what is known regarding function and regulation. Finally, we explore possible roles of striatin family complexes in disease, especially cerebral cavernous malformation. Copyright © 2013 Elsevier Ltd. All rights reserved.

FK506-Binding Proteins and Their Diverse Functions.

PubMed

Tong, Mingming; Jiang, Yu

2015-01-01

FK506 binding proteins (FKBPs) are a family of highly conserved proteins in eukaryotes. The prototype of this protein family, FKBP12, is the binding partner for immunosuppressive drugs FK506 and rapamycin. FKBP12 functions as a cis/trans peptidyl prolyl isomerase (PPIase) that catalyzes interconversion between prolyl cis/trans conformations. Members of the FKBP family contain one or several PPIase domains, which do not always exhibit PPIase activity yet are all essential for their function. FKBPs are involved in diverse cellular functions including protein folding, cellular signaling, apoptosis and transcription. They elicit their function through direct binding and altering conformation of their target proteins, hence acting as molecular switches. In this review, we provide a general summary for the structures and diverse functions of FKBPs found in mammalian cells.

Protein sectors: evolutionary units of three-dimensional structure

PubMed Central

Halabi, Najeeb; Rivoire, Olivier; Leibler, Stanislas; Ranganathan, Rama

2011-01-01

Proteins display a hierarchy of structural features at primary, secondary, tertiary, and higher-order levels, an organization that guides our current understanding of their biological properties and evolutionary origins. Here, we reveal a structural organization distinct from this traditional hierarchy by statistical analysis of correlated evolution between amino acids. Applied to the S1A serine proteases, the analysis indicates a decomposition of the protein into three quasi-independent groups of correlated amino acids that we term “protein sectors”. Each sector is physically connected in the tertiary structure, has a distinct functional role, and constitutes an independent mode of sequence divergence in the protein family. Functionally relevant sectors are evident in other protein families as well, suggesting that they may be general features of proteins. We propose that sectors represent a structural organization of proteins that reflects their evolutionary histories. PMID:19703402

The Child's Eye View of Family Life: A Report to Respondents in a Study Conducted in Victoria in Late 1982 and Early 1983.

ERIC Educational Resources Information Center

Ochiltree, Gay; Amato, Paul

Marriage and the family traditionally have been structured around the key functions of the nurturing and socialization of children. This report looks closely at how effectively and competently various family types manage these tasks. Containing a brief overview of the "Australian Children in Families Study," this report concentrates on…

TMEM16 proteins: unknown structure and confusing functions.

PubMed

Picollo, Alessandra; Malvezzi, Mattia; Accardi, Alessio

2015-01-16

The TMEM16 family of membrane proteins, also known as anoctamins, plays key roles in a variety of physiological functions that range from ion transport to phospholipid scrambling and to regulating other ion channels. The first two family members to be functionally characterized, TMEM16A (ANO1) and TMEM16B (ANO2), form Ca(2+)-activated Cl(-) channels and are important for transepithelial ion transport, olfaction, phototransduction, smooth muscle contraction, nociception, cell proliferation and control of neuronal excitability. The roles of other family members, such as TMEM16C (ANO3), TMEM16D (ANO4), TMEM16F (ANO6), TMEM16G (ANO7) and TMEM16J (ANO9), remain poorly understood and controversial. These homologues were reported to be phospholipid scramblases, ion channels, to have both functions or to be regulatory subunits of other channels. Mutations in TMEM16F cause Scott syndrome, a bleeding disorder caused by impaired Ca(2+)-dependent externalization of phosphatidylserine in activated platelets, suggesting that this homologue might be a scramblase. However, overexpression of TMEM16F has also been associated with a remarkable number of different ion channel types, raising the possibility that this protein might be involved in both ion and lipid transports. The recent identification of an ancestral TMEM16 homologue with intrinsic channel and scramblase activities supports this hypothesis. Thus, the TMEM16 family might have diverged in two or three different subclasses, channels, scramblases and dual-function channel/scramblases. The structural bases and functional implication of such a functional diversity within a single protein family remain to be elucidated and the links between TMEM16 functions and human physiology and pathologies need to be investigated. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Classification of Protein Domains.

PubMed

Dawson, Natalie; Sillitoe, Ian; Marsden, Russell L; Orengo, Christine A

2017-01-01

The significant expansion in protein sequence and structure data that we are now witnessing brings with it a pressing need to bring order to the protein world. Such order enables us to gain insights into the evolution of proteins, their function and the extent to which the functional repertoire can vary across the three kingdoms of life. This has lead to the creation of a wide range of protein family classifications that aim to group proteins based upon their evolutionary relationships.In this chapter we discuss the approaches and methods that are frequently used in the classification of proteins, with a specific emphasis on the classification of protein domains. The construction of both domain sequence and domain structure databases is considered and we show how the use of domain family annotations to assign structural and functional information is enhancing our understanding of genomes.

Psychological health of military children: Longitudinal evaluation of a family-centered prevention program to enhance family resilience

PubMed Central

Lester, Patricia; Stein, Judith A.; Saltzman, William; Woodward, Kirsten; MacDermid, Shelley W.; Milburn, Norweeta; Mogil, Catherine; Beardslee, William

2014-01-01

Family-centered preventive interventions have been proposed as relevant to mitigating psychological health risk and promoting resilience in military families facing wartime deployment and reintegration. This study evaluates the impact of a family-centered prevention program, Families OverComing Under Stress Family Resilience Training (FOCUS), on the psychological adjustment of military children. Two primary goals include: 1) Understanding the relationships of distress among family members using a longitudinal path model to assess relations at the child and family level, and 2) Determining pathways of program impact on child adjustment. Multilevel data analysis using structural equation modeling was conducted with de-identified service delivery data from 280 families (505 children ages 3-17) in two follow-up assessments. Standardized measures included Service Member and Civilian parental distress (Brief Symptom Inventory, PTSD Checklist – Military), child adjustment (Strengths and Difficulties Questionnaire), and family functioning (McMaster Family Assessment Device). Distress was significantly related among the service member parent, civilian parent and children. FOCUS improved family functioning, which in turn significantly reduced child distress at follow-up. Salient components of improved family functioning in reducing child distress mirrored resilience processes targeted by FOCUS. These findings underscore the public health potential of family-centered prevention for military families, and suggest areas for future research. PMID:23929043

Pathways between profiles of family functioning, child security in the interparental subsystem, and child psychological problems.

PubMed

Davies, Patrick T; Cummings, E Mark; Winter, Marcia A

2004-01-01

This study was designed to delineate pathways between systems profiles of family functioning, children's emotional insecurity in the interparental relationship, and their psychological adjustment in a sample of 221 children and their parents. Consistent with family systems theory, cluster analyses conducted with assessments of marital, coparental, and parent-child functioning indicated that families fit into one of four profiles: (a) cohesive families, characterized by warmth, affection, and flexible well-defined boundaries in family relationships; (b) disengaged families, reflected in high levels of adversity and low levels of support across family subsystems; (c) enmeshed families, evidenced by high levels of discord and weak maintenance of relationship boundaries in the family unit; and (d) adequate families, defined by elevated parental psychological control within a larger family context of low discord and high warmth. In comparison to children in cohesive families, children in enmeshed and disengaged families exhibited greater signs of insecurity in the interparental relationship concurrently and internalizing and externalizing symptoms both concurrently and 1 year later. Structural equation models revealed that a latent, multimethod measure of insecurity in the interparental relationship partially mediated associations between family enmeshment and disengagement and children's psychological symptoms 1 year later. Results are discussed in relation to how they inform and refine a family-wide model of the emotional security hypothesis.

Multivariate sequence analysis reveals additional function impacting residues in the SDR superfamily.

PubMed

Tiwari, Pratibha; Singh, Noopur; Dixit, Aparna; Choudhury, Devapriya

2014-10-01

The "extended" type of short chain dehydrogenases/reductases (SDR), share a remarkable similarity in their tertiary structures inspite of being highly divergent in their functions and sequences. We have carried out principal component analysis (PCA) on structurally equivalent residue positions of 10 SDR families using information theoretic measures like Jensen-Shannon divergence and average shannon entropy as variables. The results classify residue positions in the SDR fold into six groups, one of which is characterized by low Shannon entropies but high Jensen-Shannon divergence against the reference family SDR1E, suggesting that these positions are responsible for the specific functional identities of individual SDR families, distinguishing them from the reference family SDR1E. Site directed mutagenesis of three residues from this group in the enzyme UDP-Galactose 4-epimerase belonging to SDR1E shows that the mutants promote the formation of NADH containing abortive complexes. Finally, molecular dynamics simulations have been used to suggest a mechanism by which the mutants interfere with the re-oxidation of NADH leading to the formation of abortive complexes. © 2014 Wiley Periodicals, Inc.

Isoforms, structures, and functions of versatile spectraplakin MACF1

PubMed Central

Hu, Lifang; Su, Peihong; Li, Runzhi; Yin, Chong; Zhang, Yan; Shang, Peng; Yang, Tuanmin; Qian, Airong

2016-01-01

Spectraplakins are crucially important communicators, linking cytoskeletal components to each other and cellular junctions. Microtubule actin crosslinking factor 1 (MACF1), also known as actin crosslinking family 7 (ACF7), is a member of the spectraplakin family. It is expressed in numerous tissues and cells as one extensively studied spectraplakin. MACF1 has several isoforms with unique structures and well-known function to be able to crosslink F-actin and microtubules. MACF1 is one versatile spectraplakin with various functions in cell processes, embryo development, tissue-specific functions, and human diseases. The importance of MACF1 has become more apparent in recent years. Here, we summarize the current knowledge on the presence and function of MACF1 and provide perspectives on future research of MACF1 based on our studies and others. [BMB Reports 2016; 49(1): 37-44] PMID:26521939

Family-Based Processes Associated with Adolescent Distress, Substance Use and Risky Sexual Behavior in Families Affected by Maternal HIV

PubMed Central

Lester, Patricia; Stein, Judith A.; Bursch, Brenda; Rice, Eric; Green, Sara; Penniman, Typhanye; Rotheram-Borus, Mary Jane

2014-01-01

The present study investigated how maternal HIV and mediating family processes are associated with adolescent distress, substance use, and risky sexual behavior. Mother–adolescent (ages 12–21) dyads (N=264) were recruited from neighborhoods where the HIV-affected families resided (161 had mothers with HIV). Mediating family processes were youth aggressive conflict style, maternal bonding, maternal role reversal expectations, and overall family functioning. Results of structural equation modeling indicated that youth aggressive conflict resolution style was strongly associated with adolescent distress, substance use, and risky sexual behavior. In HIV-affected families, youth less frequently reported using an aggressive conflict resolution style and more frequently reported positive maternal bonds; their mothers reported less positive family functioning than control families. Finally, maternal distress indirectly affected adolescent distress and risk behavior via youth aggressive conflict resolution style. PMID:20419574

Family-based processes associated with adolescent distress, substance use and risky sexual behavior in families affected by maternal HIV.

PubMed

Lester, Patricia; Stein, Judith A; Bursch, Brenda; Rice, Eric; Green, Sara; Penniman, Typhanye; Rotheram-Borus, Mary Jane

2010-01-01

The present study investigated how maternal HIV and mediating family processes are associated with adolescent distress, substance use, and risky sexual behavior. Mother-adolescent (ages 12-21) dyads (N = 264) were recruited from neighborhoods where the HIV-affected families resided (161 had mothers with HIV). Mediating family processes were youth aggressive conflict style, maternal bonding, maternal role reversal expectations, and overall family functioning. Results of structural equation modeling indicated that youth aggressive conflict resolution style was strongly associated with adolescent distress, substance use, and risky sexual behavior. In HIV-affected families, youth less frequently reported using an aggressive conflict resolution style and more frequently reported positive maternal bonds; their mothers reported less positive family functioning than control families. Finally, maternal distress indirectly affected adolescent distress and risk behavior via youth aggressive conflict resolution style.

Structure of a PL17 Family Alginate Lyase Demonstrates Functional Similarities among Exotype Depolymerases

PubMed Central

Park, David; Jagtap, Sujit; Nair, Satish K.

2014-01-01

Brown macroalgae represent an ideal source for complex polysaccharides that can be utilized as precursors for cellulosic biofuels. The lack of recalcitrant lignin components in macroalgae polysaccharide reserves provides a facile route for depolymerization of constituent polysaccharides into simple monosaccharides. The most abundant sugars in macroalgae are alginate, mannitol, and glucan, and although several classes of enzymes that can catabolize the latter two have been characterized, studies of alginate-depolymerizing enzymes have lagged. Here, we present several crystal structures of Alg17c from marine bacterium Saccharophagus degradans along with structure-function characterization of active site residues that are suggested to be involved in the exolytic mechanism of alginate depolymerization. This represents the first structural and biochemical characterization of a family 17 polysaccharide lyase enzyme. Despite the lack of appreciable sequence conservation, the structure and β-elimination mechanism for glycolytic bond cleavage by Alg17c are similar to those observed for family 15 polysaccharide lyases and other lyases. This work illuminates the evolutionary relationships among enzymes within this unexplored class of polysaccharide lyases and reinforces the notion of a structure-based hierarchy in the classification of these enzymes. PMID:24478312

Cellulase Linkers Are Optimized Based on Domain Type and Function: Insights from Sequence Analysis, Biophysical Measurements, and Molecular Simulation

PubMed Central

Sammond, Deanne W.; Payne, Christina M.; Brunecky, Roman; Himmel, Michael E.; Crowley, Michael F.; Beckham, Gregg T.

2012-01-01

Cellulase enzymes deconstruct cellulose to glucose, and are often comprised of glycosylated linkers connecting glycoside hydrolases (GHs) to carbohydrate-binding modules (CBMs). Although linker modifications can alter cellulase activity, the functional role of linkers beyond domain connectivity remains unknown. Here we investigate cellulase linkers connecting GH Family 6 or 7 catalytic domains to Family 1 or 2 CBMs, from both bacterial and eukaryotic cellulases to identify conserved characteristics potentially related to function. Sequence analysis suggests that the linker lengths between structured domains are optimized based on the GH domain and CBM type, such that linker length may be important for activity. Longer linkers are observed in eukaryotic GH Family 6 cellulases compared to GH Family 7 cellulases. Bacterial GH Family 6 cellulases are found with structured domains in either N to C terminal order, and similar linker lengths suggest there is no effect of domain order on length. O-glycosylation is uniformly distributed across linkers, suggesting that glycans are required along entire linker lengths for proteolysis protection and, as suggested by simulation, for extension. Sequence comparisons show that proline content for bacterial linkers is more than double that observed in eukaryotic linkers, but with fewer putative O-glycan sites, suggesting alternative methods for extension. Conversely, near linker termini where linkers connect to structured domains, O-glycosylation sites are observed less frequently, whereas glycines are more prevalent, suggesting the need for flexibility to achieve proper domain orientations. Putative N-glycosylation sites are quite rare in cellulase linkers, while an N-P motif, which strongly disfavors the attachment of N-glycans, is commonly observed. These results suggest that linkers exhibit features that are likely tailored for optimal function, despite possessing low sequence identity. This study suggests that cellulase linkers may exhibit function in enzyme action, and highlights the need for additional studies to elucidate cellulase linker functions. PMID:23139804

Thioesterases: A new perspective based on their primary and tertiary structures

PubMed Central

Cantu, David C; Chen, Yingfei; Reilly, Peter J

2010-01-01

Thioesterases (TEs) are classified into EC 3.1.2.1 through EC 3.1.2.27 based on their activities on different substrates, with many remaining unclassified (EC 3.1.2.–). Analysis of primary and tertiary structures of known TEs casts a new light on this enzyme group. We used strong primary sequence conservation based on experimentally proved proteins as the main criterion, followed by verification with tertiary structure superpositions, mechanisms, and catalytic residue positions, to accurately define TE families. At present, TEs fall into 23 families almost completely unrelated to each other by primary structure. It is assumed that all members of the same family have essentially the same tertiary structure; however, TEs in different families can have markedly different folds and mechanisms. Conversely, the latter sometimes have very similar tertiary structures and catalytic mechanisms despite being only slightly or not at all related by primary structure, indicating that they have common distant ancestors and can be grouped into clans. At present, four clans encompass 12 TE families. The new constantly updated ThYme (Thioester-active enzYmes) database contains TE primary and tertiary structures, classified into families and clans that are different from those currently found in the literature or in other databases. We review all types of TEs, including those cleaving CoA, ACP, glutathione, and other protein molecules, and we discuss their structures, functions, and mechanisms. PMID:20506386

Insights into the structure and function of fungal β-mannosidases from glycoside hydrolase family 2 based on multiple crystal structures of the Trichoderma harzianum enzyme.

PubMed

Nascimento, Alessandro S; Muniz, Joao Renato C; Aparício, Ricardo; Golubev, Alexander M; Polikarpov, Igor

2014-09-01

Hemicellulose is an important part of the plant cell wall biomass, and is relevant to cellulosic ethanol technologies. β-Mannosidases are enzymes capable of cleaving nonreducing residues of β-d-mannose from β-d-mannosides and hemicellulose mannose-containing polysaccharides, such as mannans and galactomannans. β-Mannosidases are distributed between glycoside hydrolase (GH) families 1, 2, and 5, and only a handful of the enzymes have been structurally characterized to date. The only published X-ray structure of a GH family 2 mannosidase is that of the bacterial Bacteroides thetaiotaomicron enzyme. No structures of eukaryotic mannosidases of this family are currently available. To fill this gap, we set out to solve the structure of Trichoderma harzianum GH family 2 β-mannosidase and to refine it to 1.9-Å resolution. Structural comparisons of the T. harzianum GH2 β-mannosidase highlight similarities in its structural architecture with other members of GH family 2, reveal the molecular mechanism of β-mannoside binding and recognition, and shed light on its putative galactomannan-binding site. Coordinates and observed structure factor amplitudes have been deposited with the Protein Data Bank (4CVU and 4UOJ). The T. harzianum β-mannosidase 2A nucleotide sequence has GenBank accession number BankIt1712036 GeneMark.hmm KJ624918. © 2014 FEBS.

From structure to function - a family portrait of plant subtilases.

PubMed

Schaller, Andreas; Stintzi, Annick; Rivas, Susana; Serrano, Irene; Chichkova, Nina V; Vartapetian, Andrey B; Martínez, Dana; Guiamét, Juan J; Sueldo, Daniela J; van der Hoorn, Renier A L; Ramírez, Vicente; Vera, Pablo

2018-05-01

Contents Summary 901 I. Introduction 901 II. Biochemistry and structure of plant SBTs 902 III. Phylogeny of plant SBTs and family organization 903 IV. Physiological roles of plant SBTs 905 V. Conclusions and outlook 911 Acknowledgements 912 References 912 SUMMARY: Subtilases (SBTs) are serine peptidases that are found in all three domains of life. As compared with homologs in other Eucarya, plant SBTs are more closely related to archaeal and bacterial SBTs, with which they share many biochemical and structural features. However, in the course of evolution, functional diversification led to the acquisition of novel, plant-specific functions, resulting in the present-day complexity of the plant SBT family. SBTs are much more numerous in plants than in any other organism, and include enzymes involved in general proteolysis as well as highly specific processing proteases. Most SBTs are targeted to the cell wall, where they contribute to the control of growth and development by regulating the properties of the cell wall and the activity of extracellular signaling molecules. Plant SBTs affect all stages of the life cycle as they contribute to embryogenesis, seed development and germination, cuticle formation and epidermal patterning, vascular development, programmed cell death, organ abscission, senescence, and plant responses to their biotic and abiotic environments. In this article we provide a comprehensive picture of SBT structure and function in plants. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Expanding Diversity in Molecular Structures and Functions of the IL-6/IL-12 Heterodimeric Cytokine Family

PubMed Central

Hasegawa, Hideaki; Mizoguchi, Izuru; Chiba, Yukino; Ohashi, Mio; Xu, Mingli; Yoshimoto, Takayuki

2016-01-01

The interleukin (IL)-6/IL-12 family cytokines have pleiotropic functions and play critical roles in multiple immune responses. This cytokine family has very unique characteristics in that they comprise two distinct subunits forming a heterodimer and each cytokine and receptor subunit shares with each other. The members of this cytokine family are increasing; currently, there are more than six cytokines, including the tentatively named cytokines IL-Y (p28/p40), IL-12 (p35/p40), IL-23 (p19/p40), IL-27 [p28/Epstein–Barr virus-induced protein 3 (EBI3)], IL-35 (p35/EBI3), and IL-39 (p19/EBI3). This family of cytokines covers a very broad range of immune responses, including pro-inflammatory responses, such as helper T (Th)1, Th2, and Th17, to anti-inflammatory responses, such as regulatory T (Treg) cells and IL-10-producing Treg cells. IL-12 is the first member of this family, and IL-12, IL-23, and IL-27 are mainly produced by activated antigen-presenting cells, such as dendritic cells and macrophages. IL-12 plays a critical role in the promotion of Th1 immune responses by inducing interferon-γ production to combat pathogens and malignant tumors. IL-23 induces IL-17 production and is necessary to maintain pathogenic Th17 cells that cause inflammatory and autoimmune diseases. IL-27 was initially reported to play a critical role in promotion of Th1 differentiation; however, subsequent studies revealed that IL-27 has broader stimulatory and inhibitory roles by inducing IL-10-producing Treg cells. IL-35 is produced by forkhead box P3+ Treg cells and activated B cells and has immunosuppressive functions to maintain immune tolerance. The most recently identified cytokine, IL-39, is produced by activated B cells and has pro-inflammatory functions. The cytokine tentatively named IL-Y seems to have anti-inflammatory functions by inhibiting Th1 and Th17 differentiation. In addition, individual cytokine subunits were also shown to have self-standing activities. Thus, promiscuity within the IL-6/IL-12 family cytokines complicates structural and functional clarification and assignment of individual cytokines. A better understanding of the recent advances and expanding diversity in molecular structures and functions of the IL-6/IL-12 family cytokines could allow the creation of novel therapeutic strategies by using them as tools and targeted molecules. PMID:27867385

Quality Indicators for Multidisciplinary Team Functioning in Community-Based Children’s Mental Health Services

PubMed Central

Kutash, Krista; Acri, Mary; Pollock, Michele; Armusewicz, Kelsey; Hoagwood, Kimberly Eaton

2014-01-01

The current study examined the organizational social context in 21 community-based programs serving youth at-risk for out-of-home care due to emotional or behavioral disorders and their families and program performance on five quality indicators of team functioning in teams that included a family support specialist. Results indicate that programs with higher performance on structures to facilitate teamwork, informal communication mechanisms among team members, and the ability to integrate family support specialists as equal members of the team showed more positive organizational functioning. Implications for the role of quality indicators in health care reform efforts are discussed. PMID:23873037

Social Service Utilization, Sense of Community, Family Functioning and the Mental Health of New Immigrant Women in Hong Kong

PubMed Central

Wu, Qiaobing; Chow, Julian Chun-Chung

2013-01-01

Drawing upon a sample of 296 new immigrant women in Hong Kong, this study investigated how social service utilization, family functioning, and sense of community influenced the depressive symptoms of new immigrant women. Results of the structural equation modeling suggested that family functioning and sense of community were both significantly and negatively associated with the depression of new immigrant women. Utilization of community services also influenced the depression of immigrant women indirectly through the mediating effect of sense of community. Implications of the research findings for mental health intervention were discussed. PMID:23629592

Crystal Structures of Phd-Doc, HigA, and YeeU Establish Multiple Evolutionary Links between Microbial Growth-Regulating Toxin-Antitoxin Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arbing, Mark A.; Handelman, Samuel K.; Kuzin, Alexandre P.

2010-09-27

Bacterial toxin-antitoxin (TA) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. Sequence analyses suggest that TA families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E. coli K12 and Shigella flexneri confirm this inference and reveal additional, unanticipated structural relationships. The growth-regulating Doc toxin exhibits structural similarity to secreted virulence factors that are toxic for eukaryotic target cells. The Phdmore » antitoxin possesses the same fold as both the YefM and NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an antitoxin-like activity that represses toxin expression, is structurally similar to the ribosome-interacting toxins YoeB and RelE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution.« less

Does parental sexual orientation matter? A longitudinal follow-up of adoptive families with school-age children.

PubMed

Farr, Rachel H

2017-02-01

Controversy continues to surround parenting by lesbian and gay (LG) adults and outcomes for their children. As sexual minority parents increasingly adopt children, longitudinal research about child development, parenting, and family relationships is crucial for informing such debates. In the psychological literature, family systems theory contends that children's healthy development depends upon healthy family functioning more so than family structure. From the framework of family stress theory, it was expected that longitudinal outcomes for school-age children adopted in infancy could be distinct among those with same-sex versus other-sex parents (N = 96 families). Similar findings were hypothesized in terms of parent adjustment, couple relationships, and family functioning in comparing same-sex and other-sex parent families. Results indicated that adjustment among children, parents, and couples, as well as family functioning, were not different on the basis of parental sexual orientation (lesbian, gay, or heterosexual) when children were school-age. Rather, children's behavior problems and family functioning during middle childhood were predicted by earlier child adjustment issues and parenting stress. These findings are consistent with and extend previous literature about families headed by LG parents, particularly those that have adopted children. The results have implications for advancing supportive policies, practices, and laws related to adoption and parenting by sexual minority adults. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Maps on statistical manifolds exactly reduced from the Perron-Frobenius equations for solvable chaotic maps

NASA Astrophysics Data System (ADS)

Goto, Shin-itiro; Umeno, Ken

2018-03-01

Maps on a parameter space for expressing distribution functions are exactly derived from the Perron-Frobenius equations for a generalized Boole transform family. Here the generalized Boole transform family is a one-parameter family of maps, where it is defined on a subset of the real line and its probability distribution function is the Cauchy distribution with some parameters. With this reduction, some relations between the statistical picture and the orbital one are shown. From the viewpoint of information geometry, the parameter space can be identified with a statistical manifold, and then it is shown that the derived maps can be characterized. Also, with an induced symplectic structure from a statistical structure, symplectic and information geometric aspects of the derived maps are discussed.

Structure of Gremlin-2 in Complex with GDF5 Gives Insight into DAN-Family-Mediated BMP Antagonism.

PubMed

Nolan, Kristof; Kattamuri, Chandramohan; Rankin, Scott A; Read, Randy J; Zorn, Aaron M; Thompson, Thomas B

2016-08-23

The DAN family, including Gremlin-1 and Gremlin-2 (Grem1 and Grem2), represents a large family of secreted BMP (bone morphogenetic protein) antagonists. However, how DAN proteins specifically inhibit BMP signaling has remained elusive. Here, we report the structure of Grem2 bound to GDF5 at 2.9-Å resolution. The structure reveals two Grem2 dimers binding perpendicularly to each GDF5 monomer, resembling an H-like structure. Comparison to the unbound Grem2 structure reveals a dynamic N terminus that undergoes significant transition upon complex formation, leading to simultaneous interaction with the type I and type II receptor motifs on GDF5. Binding studies show that DAN-family members can interact with BMP-type I receptor complexes, whereas Noggin outcompetes the type I receptor for ligand binding. Interestingly, Grem2-GDF5 forms a stable aggregate-like structure in vitro that is not clearly observed for other antagonists, including Noggin and Follistatin. These findings exemplify the structural and functional diversity across the various BMP antagonist families. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Impact of Ego-resilience and Family Function on Quality of Life in Childhood Leukemia Survivors

PubMed Central

CHO, Ok-Hee; YOO, Yang-Sook; HWANG, Kyung-Hye

2016-01-01

Background: This study aimed to examine the impact of ego-resilience and family function on quality of life in childhood leukemia survivors. Methods: This study targeted 100 pediatric leukemia survivors, who visited the Pediatric Hemato-Oncology Center in South Korea from Aug to Dec 2011. A structured questionnaire of ego-resilience, family function and quality of life used to collect data through direct interview with the pediatric patients and their parents. The correlation between the study variables analyzed using the Pearson’s correlation coefficient, and the impact on quality of life analyzed using a stepwise multiple regression. Results: Ego-resilience (r = 0.69, P<0.001) and family function (r =0.46, P< 0.001) had a positive correlation with quality of life and all the sub-categories of quality of life. Ego-resilience was a major factor affecting quality of life in childhood leukemia survivors, with an explanatory power of 48%. The explanatory power for quality of life increased to 53% when age and family function were included. Conclusion: Ego-resilience, age, and family function affect quality of life in childhood leukemia survivors. Hence, strategies are required to construct age-matched programs to improve quality of life, in order to help restore the necessary ego-resilience and to strengthen family function in childhood leukemia survivors. PMID:28032062

Psychometric Properties of the Chinese Family Assessment Instrument in Chinese Adolescents in Hong Kong

ERIC Educational Resources Information Center

Siu, Andrew M. H.; Shek, Daniel T. L.

2005-01-01

This paper reports evidence on the factor structure, reliability, and validity of the Chinese Family Assessment Instrument (C-FAI), an instrument developed to assess family functioning in Chinese populations. A convenience sample of 1,462 adolescents from junior secondary schools completed the C-FAI and measures of parent-adolescent conflict.…

Glycemic control, cognitive function, and family support among middle-aged and older Hispanics with diabetes: The Hispanic Community Health Study/Study of Latinos.

PubMed

Strizich, Garrett; Kaplan, Robert C; González, Hector M; Daviglus, Martha L; Giachello, Aida L; Teng, Yanping; Lipton, Richard B; Grober, Ellen

2016-07-01

To examine among Hispanics in the U.S., a population with increased reliance on informal healthcare support structures, (1) the association between cognitive function and control of diabetes; and (2) whether this association is modified by family support. The Digit Symbol Substitution Test (DSST), word fluency, and learning and delayed recall components of the Spanish English Verbal Learning Test were administered to 1794 Hispanic adults aged 45-76years with diagnosed diabetes. An executive function index and global cognitive function index (GCFI) were derived. Uncontrolled diabetes (HbA1c⩾7% [53mmol/mol]) was compared across quartiles of cognitive function using multivariable logit models with interaction terms for cognitive function and family support. After adjustment, lower DSST scores were associated with uncontrolled diabetes (P=0.03). Family support modified the relationship between other measures of cognition and diabetes control (Pinteraction: 0.002, 0.09). Among individuals with low family support, as cognitive function declined, the odds of uncontrolled diabetes increased (P-trend across quartiles of the GCFI, 0.015). Among those with low family support, persons in the lowest quartile of global cognitive function were more than twice as likely to have uncontrolled diabetes as those in the highest performing quartile (OR=2.31; 95% CI: 1.17, 4.55). There was no similar effect among those with high family support. Family support may buffer the negative association between low cognitive functioning and diabetes control in US Hispanics/Latinos. Educational programs targeted at family members of middle-age and older persons with diabetes regardless of neurocognitive status may help improve population-level glycemic control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Family function and depression in relatives of earthquake victims: a survey conducted one year after China's Wenchuan Earthquake].

PubMed

Hu, Xiao-Lin; Li, Xiao-Lin; Jiang, Xiao-Lian; Li, Rong; Dou, Xin-Man

2012-10-01

The Wenchuan Earthquake that hit Sichuan, China in 2008 not only caused huge losses in terms of human life and economic damage. It also caused psychological trauma in survivors, especially those who had lost relatives and close friends (bereaved). In the aftermath of earthquakes, bereaved individuals require family and spiritual renewal in addition to material assistance. This study investigated the status of and relationship between family function and depression in bereaved individuals living in areas devastated by the Wenchuan Earthquake. Results provide baseline information for post-disaster family reconstruction. This cross-sectional study surveyed 264 qualified bereaved individuals who lived in an area hard hit by the Wenchuan Earthquake. Face-to-face interviews were administered based on the family APGAR(adaptation, partnership, growth, affection, resolve) index and Hamilton depression (HAMD) scale. The mean family function score for participants was 6.52 ± 2.65. Results for half (50.0%) of participants indicated "good" family function. Results indicated marital status, family structure and status of having another baby as factors that significantly influence family function (p < .05). Participants' mean depression score was 40.41 ± 9.35, with all (100%) of participants demonstrating symptoms of depression. The 5 most prevalent depressive symptoms were: depressed mood, decreased interest in work, mental anxiety, diminished capacity and agitation. Results showed marital status, leisure frequency, economic status, and having another baby as factors that significantly influenced family function (p < .05). A Pearson's correlation analysis indicated no significant relationship between level of depression and family function (p >.05). Family functions of the bereaved living in areas hard hit by the Wenchuan Earthquake were all undermined to varying degrees. Although participants all exhibited depressive symptoms, this study found no affect of such symptoms on family functions. Interventions delivered in the months and years after an earthquake should be tailored to address each individual's depression status. Interventions should also help these individuals learn to improve and enhance family functions to effectively reduce negative behaviors and reactions in order to better promote physical and mental health.

Phylogenetic analysis and protein structure modelling identifies distinct Ca(2+)/Cation antiporters and conservation of gene family structure within Arabidopsis and rice species.

PubMed

Pittman, Jon K; Hirschi, Kendal D

2016-12-01

The Ca(2+)/Cation Antiporter (CaCA) superfamily is an ancient and widespread family of ion-coupled cation transporters found in nearly all kingdoms of life. In animals, K(+)-dependent and K(+)-indendent Na(+)/Ca(2+) exchangers (NCKX and NCX) are important CaCA members. Recently it was proposed that all rice and Arabidopsis CaCA proteins should be classified as NCX proteins. Here we performed phylogenetic analysis of CaCA genes and protein structure homology modelling to further characterise members of this transporter superfamily. Phylogenetic analysis of rice and Arabidopsis CaCAs in comparison with selected CaCA members from non-plant species demonstrated that these genes form clearly distinct families, with the H(+)/Cation exchanger (CAX) and cation/Ca(2+) exchanger (CCX) families dominant in higher plants but the NCKX and NCX families absent. NCX-related Mg(2+)/H(+) exchanger (MHX) and CAX-related Na(+)/Ca(2+) exchanger-like (NCL) proteins are instead present. Analysis of genomes of ten closely-related rice species and four Arabidopsis-related species found that CaCA gene family structures are highly conserved within related plants, apart from minor variation. Protein structures were modelled for OsCAX1a and OsMHX1. Despite exhibiting broad structural conservation, there are clear structural differences observed between the different CaCA types. Members of the CaCA superfamily form clearly distinct families with different phylogenetic, structural and functional characteristics, and therefore should not be simply classified as NCX proteins, which should remain as a separate gene family.

Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakai, A.; Fedorov, A; Fedorov, E

2009-01-01

The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature's strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the a-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the e-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologous MLEs that catalyzes anti-cycloisomerization has been identified.more » Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, gi 70731221; anti, Mycobacterium smegmatis, gi 118470554) document that the conserved Lys at the end of the second e-strand in the (e/a)7e-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of 'pseudoconvergent' evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction.« less

Structural Basis of Merlin Tumor Suppressor Functions in Neurofibromatosis-2

DTIC Science & Technology

2013-10-01

Neurofibromatosis -2 PRINCIPAL INVESTIGATOR: Tina Izard CONTRACTING ORGANIZATION: The Scripps Research Institute La Jolla, CA 92037-1000...30September2012-29September2013 4. TITLE AND SUBTITLE Structural Basis of Merlin Tumor Suppressor Functions in Neurofibromatosis -2 5a. CONTRACT...14. ABSTRACT Loss-of-function mutations in the neurofibromatosis -2 (NF2) gene lead to familial and sporadic neurological malignancies in man

Parental Problem Drinking and Adolescent Externalizing Behaviors: The Mediating Role of Family Functioning

PubMed Central

Schulz, Jessica; Gordon, Mellissa S.; Ohannessian, Christine McCauley

2015-01-01

This study explored relationships among parental problem drinking, family functioning, and adolescent externalizing behaviors. The unique effects of maternal and paternal drinking were examined separately for girls and boys. The sample included 14-19 year old U.S. adolescents (Mage=16.15; SD=.75; 52.5% female) and their parents. Participants completed surveys in the spring of 2007 and 2008. Structural equation modelling was used to conduct path analysis models. Results showed the distinctive and adverse effects of parental problem drinking on adolescent alcohol use, drug use, rule breaking, and aggressive behavior over time. Findings also highlighted the indirect and mediating roles of family functioning. For both girls and boys, family cohesion mediated the relationship between parental problem drinking and adolescent externalizing behaviors. For girls, adolescent-father communication predicted increased externalizing behaviors over time. These findings draw attention to the importance of exploring adolescent and parent gender when examining parental problem drinking, family functioning, and externalizing behaviors. PMID:26073673

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

PubMed

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

2017-01-04

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. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Decisional Conflict: Relationships Between and Among Family Context Variables in Cancer Survivors.

PubMed

Lim, Jung-Won; Shon, En-Jung

2016-07-01

To investigate the relationships among life stress, family functioning, family coping, reliance on formal and informal resources, and decisional conflict in cancer survivors. 
. Cross-sectional.
. Participants were recruited from the California Cancer Surveillance Program, hospital registries, and community agencies in southern California and Cleveland, Ohio. 
. 243 European American, African American, Chinese American, and Korean American cancer survivors diagnosed with breast, colorectal, or prostate cancer.
. The merged data from an ethnically diverse cohort of cancer survivors participating in the two survey studies were used. Standardized measures were used to identify family context variables and decisional conflict. 
. Life stress, family functioning, family coping, reliance on formal and informal resources, and decisional conflict.
. Structural equation modeling demonstrated that life stress was significantly associated with decisional conflict. Family functioning significantly mediated the impact of life stress on decisional conflict through family coping. Reliance on formal and informal resources moderated the relationships among the study variables. 
. The role of the family context, which includes family functioning and coping, on decisional conflict is important in the adjustment process to make high-quality decisions in cancer survivorship care. 
. Findings present nursing practice and research implications that highlight the need for efforts to encourage and support family involvement in the decision-making process and to enhance cancer survivors' adjustment process.

[Family. Public health workshop of the Centro de Investigaciones en Psicologia Social].

PubMed

Sanchez Maria Felix, B; Leon, M J

1993-04-01

An abbreviated primer on the sociology of the family is presented. The work defines family, describes different types of family structure, outlines the family life cycle, and discusses the functioning of families. Human beings in all societies require membership in a family of some type for reproduction and socialization. One of the most basic human needs is for a mother who will feed, protect, and instruct her offspring. Families have always changed in response to societal changes. The functions of a family are devoted to two different sets of objectives, the internal ones of psychosocial protection of the members and the external ones of accommodation to and transmission of a culture. Families in all cultures provide their members with a sense of identity. Families must respond to internal and external changes and should be capable of transforming themselves to adjust to new circumstances without losing continuity. Family systems differentiate themselves to carry out their functions through their subsystems. Individuals and dyads such as maternal-child or husband-wife are the subsystems. The family life cycle entails a series of stages: courtship, marriage, the birth and growth of children, separation of the children, retirement, old age. Each stage has its own pitfalls and challenges. Each family has a hierarchy of status and power, although in some cases the proper hierarchies are inverted, and the children carry out functions that should be completed by the parents. A series of explicit and implicit, rigid and flexible rules guide the functioning of the family. Various roles are carried out, including parental, marital, and sibling roles, as well as roles of authority, administration, and messenger.

Processing of Cholinesterase-like α/β-Hydrolase Fold Proteins: Alterations Associated with Congenital Disorders

PubMed Central

De Jaco, Antonella; Comoletti, Davide; Dubi, Noga; Camp, Shelley; Taylor, Palmer

2016-01-01

The α/β hydrolase fold family is perhaps the largest group of proteins presenting significant structural homology with divergent functions, ranging from catalytic hydrolysis to heterophilic cell adhesive interactions to chaperones in hormone production. All the proteins of the family share a common three-dimensional core structure containing the α/β-hydrolase fold domain that is crucial for proper protein function. Several mutations associated with congenital diseases or disorders have been reported in conserved residues within the α/β-hydrolase fold domain of cholinesterase-like proteins, neuroligins, butyrylcholinesterase and thyroglobulin. These mutations are known to disrupt the architecture of the common structural domain either globally or locally. Characterization of the natural mutations affecting the α/β-hydrolase fold domain in these proteins has shown that they mainly impair processing and trafficking along the secretory pathway causing retention of the mutant protein in the endoplasmic reticulum. Studying the processing of α/β-hydrolase fold mutant proteins should uncover new functions for this domain, that in some cases require structural integrity for both export of the protein from the ER and for facilitating subunit dimerization. A comparative study of homologous mutations in proteins that are closely related family members, along with the definition of new three-dimensional crystal structures, will identify critical residues for the assembly of the α/β-hydrolase fold. PMID:21933121

Calpain chronicle--an enzyme family under multidisciplinary characterization.

PubMed

Sorimachi, Hiroyuki; Hata, Shoji; Ono, Yasuko

2011-01-01

Calpain is an intracellular Ca2+-dependent cysteine protease (EC 3.4.22.17; Clan CA, family C02) discovered in 1964. It was also called CANP (Ca2+-activated neutral protease) as well as CASF, CDP, KAF, etc. until 1990. Calpains are found in almost all eukaryotes and a few bacteria, but not in archaebacteria. Calpains have a limited proteolytic activity, and function to transform or modulate their substrates' structures and activities; they are therefore called, "modulator proteases." In the human genome, 15 genes--CAPN1, CAPN2, etc.--encode a calpain-like protease domain. Their products are calpain homologs with divergent structures and various combinations of functional domains, including Ca2+-binding and microtubule-interaction domains. Genetic studies have linked calpain deficiencies to a variety of defects in many different organisms, including lethality, muscular dystrophies, gastropathy, and diabetes. This review of the study of calpains focuses especially on recent findings about their structure-function relationships. These discoveries have been greatly aided by the development of 3D structural studies and genetic models.

When galectins recognize glycans: from biochemistry to physiology and back again.

PubMed

Di Lella, Santiago; Sundblad, Victoria; Cerliani, Juan P; Guardia, Carlos M; Estrin, Dario A; Vasta, Gerardo R; Rabinovich, Gabriel A

2011-09-20

In the past decade, increasing efforts have been devoted to the study of galectins, a family of evolutionarily conserved glycan-binding proteins with multifunctional properties. Galectins function, either intracellularly or extracellularly, as key biological mediators capable of monitoring changes occurring on the cell surface during fundamental biological processes such as cellular communication, inflammation, development, and differentiation. Their highly conserved structures, exquisite carbohydrate specificity, and ability to modulate a broad spectrum of biological processes have captivated a wide range of scientists from a wide spectrum of disciplines, including biochemistry, biophysics, cell biology, and physiology. However, in spite of enormous efforts to dissect the functions and properties of these glycan-binding proteins, limited information about how structural and biochemical aspects of these proteins can influence biological functions is available. In this review, we aim to integrate structural, biochemical, and functional aspects of this bewildering and ancient family of glycan-binding proteins and discuss their implications in physiologic and pathologic settings. © 2011 American Chemical Society

[Structural empowerment and work-family fit in nurses].

PubMed

Orłowska, Agnieszka; Łaguna, Mariola

2016-12-22

The goal of the study was to investigate the relationship between structural empowerment and work-family fit in Polish nurses. Structural empowerment is a strategy for managing by providing the employees with opportunities, information, support and resources essential for the effective performance of work duties. Work-family fit takes 2 forms of relationships between these 2 spheres: conflict (functioning in one role is more difficult because of participation in the other role) and facilitation (fulfilling the duties associated with one role enriches filling up the other role). A total of 159 nurses employed in hospitals took part in the study. The Polish versions of the Conditions of Work Effectiveness Questionnaire and the Work-Family Fit Questionnaire were used. Hierarchical linear regression analysis was applied for data analysis. The results show statistically signifficant relationships between structural empowerment and work-family fit in nurses. In the hospital environment, characterized by a high degree of empowerment, nurses experience a lower level of work-family conflict and a higher level of facilitation in both directions. Hospital management strategy based on structural empowerment of nurses favors reconciliation of professional and family roles. Therefore, it is important for hospitals to create appropriate working conditions that allow nurses to effectively deal with demands arising from work and family spheres. Med Pr 2016;67(6):787-800. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Structure/function relationships in serotonin transporter: new insights from the structure of a bacterial transporter.

PubMed

Rudnick, G

2006-01-01

Serotonin transporter (SERT) serves the important function of taking up serotonin (5-HT) released during serotonergic neurotransmission. It is the target for important therapeutic drugs and psychostimulants. SERT catalyzes the influx of 5-HT together with Na+ and Cl- in a 1:1:1 stoichiometry. In the same catalytic cycle, there is coupled efflux of one K+ ion. SERT is one member of a large family of amino acid and amine transporters that is believed to utilize similar mechanisms of transport. A bacterial member of this family was recently crystallized, revealing the structural basis of these transporters. In light of the new structure, previous results with SERT have been re-interpreted, providing new insight into the substrate binding site, the permeation pathway, and the conformational changes that occur during the transport cycle.

Depression and resilience mediates the effect of family function on quality of life of the elderly.

PubMed

Lu, Canjie; Yuan, Lexin; Lin, Weiquan; Zhou, Ying; Pan, Shengmao

2017-07-01

Family function, which improves individual resilience and strongly link to quality of life (QOL) among the elderly, increases the risk of depression. Because of these demonstrated relationships, it can be hypothesized that both depression and resilience are mediators of the association between family function and QOL. To test this hypothesis, the structural equation model (SEM) constructed by Amos 21.0 was employed to assess the indirect effect of depression (Geriatric Depression Scale, GDS) and resilience (Connor-Davidson Resilience Scale, CD-RISC) on the relationship between family function (Family APGAR Score, APGAR) and QOL (12-item Short Form health survey, SF-12) in 474 elderly adults from three communities in Guangzhou, China. Correlation matrix showed that depression is significantly negatively correlated with family functioning (r=-0.54, P<0.01), resilience (r=-0.46, P<0.01) and QOL (r=-0.63, P<0.01), while resilience is significantly positively correlated with family functioning (r=0.35, P<0.01) and QOL (r=0.40, P<0.01). SEM indicated that Family functioning appeared to have significant indirect effects through resilience (β=0.089) and depression (β=0.307; combined β=0.056) on QOL (R 2 =0.55). The model fit indices showed a good fit of the model of the data (χ 2 /df=1.362, P>0.05, SRMR=0.023, RMSEA=0.028, GFI=0.985, NFI=0.987, TLI=0.993, CFI=0.996). The finding supports the assumption that depression and resilience are consistent intermediary factors of the relationship between family function and QOL among the elderly. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a family functioning scale for major depressive disorder.

PubMed

DiBenedetti, Dana Britt; Danchenko, Natalya; François, Clement; Lewis, Sandra; Davis, Kimberly H; Fehnel, Sheri E

2012-03-01

To better understand depression's impact on family functioning from the perspectives of patients with major depressive disorder (MDD) and their partners; to develop and test patient and partner versions of a new self-reported measure, the Depression and Family Functioning Scale (DFFS), for use in clinical trials. Concept elicitation interviews were conducted with 32 adults with clinician-diagnosed moderate-to-severe MDD and their respective partners. Twenty-six items were drafted to address relevant aspects of family functioning and were then tested and refined through two iterative sets of cognitive debriefing interviews, each conducted by the same pair of highly experienced researchers, including a licensed clinical psychologist. Depression negatively affects family functioning through poorer communication, increased conflicts, decreased family interaction, and decreased intimacy. No existing instrument measured all domains of interest, or had been rigorously developed and psychometrically validated in the target populations. The draft DFFS items generally tested well and only minor modifications were made to the items after the second set of interviews. Both patients and partners indicated that the final set of 15 DFFS items addresses all concepts of importance. The DFFS evaluates the impact of depression on family functioning and has the potential to provide important information that can facilitate a more comprehensive evaluation of new treatments in clinical trial settings. Although MDD severity was not confirmed with a standardized interview, in clinical practice in the US, MDD is generally not diagnosed with the use of a structured clinical interview or clinician-administered tool. In the current study, depression severity had little (if any) impact on the specific concepts elicited as being important to family functioning. In fact, patients with milder depression had more insight and were able to better articulate changes in family functioning with treatment.

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

PubMed

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

2014-01-01

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

The importance of melanoma inhibitory activity gene family in the tumor progression of oral cancer.

PubMed

Sasahira, Tomonori; Bosserhoff, Anja Katrin; Kirita, Tadaaki

2018-05-01

Oral squamous cell carcinoma has a high potential for locoregional invasion and nodal metastasis. Consequently, early detection of such malignancies is of immense importance. The melanoma inhibitory activity (MIA) gene family comprises MIA, MIA2, transport and Golgi organization protein 1 (TANGO), and otoraplin (OTOR). These members of the MIA gene family have a highly conserved Src homology 3 (SH3)-like structure. Although the molecules of this family share 34-45% amino acid homology and 47-59% cDNA sequence homology, those members, excluding OTOR, play different tumor-associated functions. MIA has a pivotal role in the progression and metastasis of melanoma; MIA2 and TANGO have been suggested to possess tumor-suppressive functions; and OTOR is uniquely expressed in cochlea of the inner ear. Therefore, the definite functions of the MIA gene family in cancer cells remain unclear. Since the members of the MIA gene family are secreted proteins, these molecules might be useful tumor markers that can be detected in the body fluids, including serum and saliva. In this review, we described the molecular biological functions of the MIA gene family in oral cancer. © 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Psychological health of military children: longitudinal evaluation of a family-centered prevention program to enhance family resilience.

PubMed

Lester, Patricia; Stein, Judith A; Saltzman, William; Woodward, Kirsten; MacDermid, Shelley W; Milburn, Norweeta; Mogil, Catherine; Beardslee, William

2013-08-01

Family-centered preventive interventions have been proposed as relevant to mitigating psychological health risk and promoting resilience in military families facing wartime deployment and reintegration. This study evaluates the impact of a family-centered prevention program, Families OverComing Under Stress Family Resilience Training (FOCUS), on the psychological adjustment of military children. Two primary goals include (1) understanding the relationships of distress among family members using a longitudinal path model to assess relations at the child and family level and (2) determining pathways of program impact on child adjustment. Multilevel data analysis using structural equation modeling was conducted with deidentified service delivery data from 280 families (505 children aged 3-17) in two follow-up assessments. Standardized measures included service member and civilian parental distress (Brief Symptom Inventory, PTSD Checklist-Military), child adjustment (Strengths and Difficulties Questionnaire), and family functioning (McMaster Family Assessment Device). Distress was significantly related among the service member parent, civilian parent, and children. FOCUS improved family functioning, which in turn significantly reduced child distress at follow-up. Salient components of improved family functioning in reducing child distress mirrored resilience processes targeted by FOCUS. These findings underscore the public health potential of family-centered prevention for military families and suggest areas for future research. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

Genome-wide analysis of the homeodomain-leucine zipper (HD-ZIP) gene family in peach (Prunus persica).

PubMed

Zhang, C H; Ma, R J; Shen, Z J; Sun, X; Korir, N K; Yu, M L

2014-04-08

In this study, 33 homeodomain-leucine zipper (HD-ZIP) genes were identified in peach using the HD-ZIP amino acid sequences of Arabidopsis thaliana as a probe. Based on the phylogenetic analysis and the individual gene or protein characteristics, the HD-ZIP gene family in peach can be classified into 4 subfamilies, HD-ZIP I, II, III, and IV, containing 14, 7, 4, and 8 members, respectively. The most closely related peach HD-ZIP members within the same subfamilies shared very similar gene structure in terms of either intron/exon numbers or lengths. Almost all members of the same subfamily shared common motif compositions, thereby implying that the HD-ZIP proteins within the same subfamily may have functional similarity. The 33 peach HD-ZIP genes were distributed across scaffolds 1 to 7. Although the primary structure varied among HD-ZIP family proteins, their tertiary structures were similar. The results from this study will be useful in selecting candidate genes from specific subfamilies for functional analysis.

Insights into the Shc Family of Adaptor Proteins

PubMed Central

Prigent, Sally A.

2017-01-01

The Shc family of adaptor proteins is a group of proteins that lacks intrinsic enzymatic activity. Instead, Shc proteins possess various domains that allow them to recruit different signalling molecules. Shc proteins help to transduce an extracellular signal into an intracellular signal, which is then translated into a biological response. The Shc family of adaptor proteins share the same structural topography, CH2-PTB-CH1-SH2, which is more than an isoform of Shc family proteins; this structure, which includes multiple domains, allows for the posttranslational modification of Shc proteins and increases the functional diversity of Shc proteins. The deregulation of Shc proteins has been linked to different disease conditions, including cancer and Alzheimer’s, which indicates their key roles in cellular functions. Accordingly, a question might arise as to whether Shc proteins could be targeted therapeutically to correct their disturbance. To answer this question, thorough knowledge must be acquired; herein, we aim to shed light on the Shc family of adaptor proteins to understand their intracellular role in normal and disease states, which later might be applied to connote mechanisms to reverse the disease state.

Influence and adaptability in families with deaf parents and hearing children.

PubMed

Rienzi, B M

1990-12-01

This study assessed the influence of individual family members in functional families, primarily to determine whether hearing children of deaf parents have more influence than do hearing children of hearing parents. Eight families with deaf parents and a hearing child and eight all hearing families were videotaped while planning a family meal together. It was found that deaf-parented families share many traits with hearing families. However, there were some differences. The hearing children of deaf parents had a greater number and percentage of their ideas accepted than did the hearing children of hearing parents. Differences were also noted between the deaf fathers and the hearing fathers. The deaf-parented families were more adaptable, as measured by the Family Adaptability and Cohesion Evaluation Scale. The observed difference in child influence, in and of itself, is neither good nor bad. Deafness of one family member, in an auditory dependent environment, may require a more flexible family power structure. Professionals assessing deaf-parented families should be sensitive to the special adaptive needs required for healthy functioning of the family.

Automated extraction of family history information from clinical notes.

PubMed

Bill, Robert; Pakhomov, Serguei; Chen, Elizabeth S; Winden, Tamara J; Carter, Elizabeth W; Melton, Genevieve B

2014-01-01

Despite increased functionality for obtaining family history in a structured format within electronic health record systems, clinical notes often still contain this information. We developed and evaluated an Unstructured Information Management Application (UIMA)-based natural language processing (NLP) module for automated extraction of family history information with functionality for identifying statements, observations (e.g., disease or procedure), relative or side of family with attributes (i.e., vital status, age of diagnosis, certainty, and negation), and predication ("indicator phrases"), the latter of which was used to establish relationships between observations and family member. The family history NLP system demonstrated F-scores of 66.9, 92.4, 82.9, 57.3, 97.7, and 61.9 for detection of family history statements, family member identification, observation identification, negation identification, vital status, and overall extraction of the predications between family members and observations, respectively. While the system performed well for detection of family history statements and predication constituents, further work is needed to improve extraction of certainty and temporal modifications.

Automated Extraction of Family History Information from Clinical Notes

PubMed Central

Bill, Robert; Pakhomov, Serguei; Chen, Elizabeth S.; Winden, Tamara J.; Carter, Elizabeth W.; Melton, Genevieve B.

2014-01-01

Despite increased functionality for obtaining family history in a structured format within electronic health record systems, clinical notes often still contain this information. We developed and evaluated an Unstructured Information Management Application (UIMA)-based natural language processing (NLP) module for automated extraction of family history information with functionality for identifying statements, observations (e.g., disease or procedure), relative or side of family with attributes (i.e., vital status, age of diagnosis, certainty, and negation), and predication (“indicator phrases”), the latter of which was used to establish relationships between observations and family member. The family history NLP system demonstrated F-scores of 66.9, 92.4, 82.9, 57.3, 97.7, and 61.9 for detection of family history statements, family member identification, observation identification, negation identification, vital status, and overall extraction of the predications between family members and observations, respectively. While the system performed well for detection of family history statements and predication constituents, further work is needed to improve extraction of certainty and temporal modifications. PMID:25954443

[Study on the relationship of family functioning and subjective well-being of junior-high school students].

PubMed

Hu, Fang; Ma, Ying-hua; Hu, Li-ming; Deng, Xin-long; Mei, Jin-feng

2010-06-18

To describe the status of subjective well-being among junior high school students in a city of Jiangxi Province and to explore the relationship between family functioning and subjective well-being. To explore the relationship between growth environment and subjective well-being among junior high school students in the perspective of family functioning and to provide basis and data for the mental health education among junior high school students. 630 students in a junior high school in Jiangxi Province were sampled by stratified cluster sampling, and 103 junior high school students from 18 villages were sampled by household survey. They were investigated by subjective well-being scale for adolescents and Family Assessment Device. (1)The overall subjective well-being of junior high school students was in the lower-middle level. Regarding all the dimensions of subjective well-being, they had the highest satisfaction on family and friendship, lowest academic satisfaction, low positive as well as passive emotion. (2)Girls had higher satisfaction on friendship and freedom than that of boys; children from families with more than one kids had more negative emotion than that of single child; boarding students had higher satisfaction on family, academics and freedom than that of non-boarding students; family residence and structure affected the satisfaction on family; grade and learning achievement affected some dimensions of subjective well-being among junior high school students. (3)Pearson correlation analysis and multiple linear regression analysis showed that some dimensions of family functioning were related to certain dimensions of subjective well-being among junior school students, and family functioning could predict the level of subjective well-being. The overall subjective well-being of junior high school students is in the lower-middle level, and further improving is needed. Family functioning has a great influence on junior school students' subjective well-being. Junior high school students who have healthy family functioning are more likely to have higher life satisfaction, and tend to experience higher subjective well-being.

A confirmative clinimetric analysis of the 36-item Family Assessment Device.

PubMed

Timmerby, Nina; Cosci, Fiammetta; Watson, Maggie; Csillag, Claudio; Schmitt, Florence; Steck, Barbara; Bech, Per; Thastum, Mikael

2018-02-07

The Family Assessment Device (FAD) is a 60-item questionnaire widely used to evaluate self-reported family functioning. However, the factor structure as well as the number of items has been questioned. A shorter and more user-friendly version of the original FAD-scale, the 36-item FAD, has therefore previously been proposed, based on findings in a nonclinical population of adults. We aimed in this study to evaluate the brief 36-item version of the FAD in a clinical population. Data from a European multinational study, examining factors associated with levels of family functioning in adult cancer patients' families, were used. Both healthy and ill parents completed the 60-item version FAD. The psychometric analyses conducted were Principal Component Analysis and Mokken-analysis. A total of 564 participants were included. Based on the psychometric analysis we confirmed that the 36-item version of the FAD has robust psychometric properties and can be used in clinical populations. The present analysis confirmed that the 36-item version of the FAD (18 items assessing 'well-being' and 18 items assessing 'dysfunctional' family function) is a brief scale where the summed total score is a valid measure of the dimensions of family functioning. This shorter version of the FAD is, in accordance with the concept of 'measurement-based care', an easy to use scale that could be considered when the aim is to evaluate self-reported family functioning.

Family functioning and child asthma severity: A bio-behavioral approach.

PubMed

Al Ghriwati, Nour; Winter, Marcia A; Everhart, Robin S; Fiese, Barbara H

2017-12-01

Family factors are directly associated with the psychosocial adjustment of children with chronic illnesses such as asthma (Kaugars, Klinnert, & Bender, 2004). Research indicates that negative family factors may also contribute to child disease severity via bio-behavioral mechanisms of effect. For instance, children from more conflicted families often experience greater internalizing symptoms that subsequently impact their asthma severity (Wood et al., 2006). These pathways have yet to be examined with a comprehensive focus on strength-based family factors. This study examined whether factors such as family cohesion, problem-solving abilities, and communication influence asthma severity via their effects on child depression and anxiety symptoms. Participants were 215 children (136 males and 79 females), ages 5 to 12 years old, and their families. Primary caregiver, child, and teacher ratings of child and family functioning in addition to objective measures of parent-child interactions and asthma severity were collected. Using structural equation modeling, the authors identified significant indirect associations between family factors and child asthma severity via child depressive symptoms; however, these associations were not present in models with child anxiety symptoms. Results suggest an indirect effect of family functioning on children's lung function, with differential roles of anxiety and depression in these pathways. This article also highlights the importance of incorporating multirater multimethod measures to understand children's experiences in pediatric asthma. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A structural-alphabet-based strategy for finding structural motifs across protein families

PubMed Central

Wu, Chih Yuan; Chen, Yao Chi; Lim, Carmay

2010-01-01

Proteins with insignificant sequence and overall structure similarity may still share locally conserved contiguous structural segments; i.e. structural/3D motifs. Most methods for finding 3D motifs require a known motif to search for other similar structures or functionally/structurally crucial residues. Here, without requiring a query motif or essential residues, a fully automated method for discovering 3D motifs of various sizes across protein families with different folds based on a 16-letter structural alphabet is presented. It was applied to structurally non-redundant proteins bound to DNA, RNA, obligate/non-obligate proteins as well as free DNA-binding proteins (DBPs) and proteins with known structures but unknown function. Its usefulness was illustrated by analyzing the 3D motifs found in DBPs. A non-specific motif was found with a ‘corner’ architecture that confers a stable scaffold and enables diverse interactions, making it suitable for binding not only DNA but also RNA and proteins. Furthermore, DNA-specific motifs present ‘only’ in DBPs were discovered. The motifs found can provide useful guidelines in detecting binding sites and computational protein redesign. PMID:20525797

Structural analysis of the Quaking homodimerization interface

PubMed Central

Beuck, Christine; Qu, Song; Fagg, W. Samuel; Ares, Manuel; Williamson, James R.

2012-01-01

Quaking is a prototypical member of the STAR protein family, which plays key roles in posttranscriptional gene regulation by controlling mRNA translation, stability and splicing. QkI-5 has been shown to regulate mRNA expression in the central nervous system, but little is known about its roles in other tissues. STAR proteins function as dimers and bind to bipartite RNA sequences, however, the structural and functional roles of homo- and hetero-dimerization are still unclear. Here, we present the crystal structure of the QkI dimerization domain, which adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 and Sam68, but differs by an additional helix inserted in the dimer interface. Variability of the dimer interface residues likely ensures selective homodimerization by preventing association with non-cognate STAR family proteins in the cell. Mutations that inhibit dimerization also significantly impair RNA binding in vitro, alter QkI-5 protein levels, and impair QkI function in a splicing assay in vivo. Together our results indicate that a functional Qua1 homodimerization domain is required for QkI-5 function in mammalian cells. PMID:22982292

Genome-wide analysis of TCP family in tobacco.

PubMed

Chen, L; Chen, Y Q; Ding, A M; Chen, H; Xia, F; Wang, W F; Sun, Y H

2016-05-23

The TCP family is a transcription factor family, members of which are extensively involved in plant growth and development as well as in signal transduction in the response against many physiological and biochemical stimuli. In the present study, 61 TCP genes were identified in tobacco (Nicotiana tabacum) genome. Bioinformatic methods were employed for predicting and analyzing the gene structure, gene expression, phylogenetic analysis, and conserved domains of TCP proteins in tobacco. The 61 NtTCP genes were divided into three diverse groups, based on the division of TCP genes in tomato and Arabidopsis, and the results of the conserved domain and sequence analyses further confirmed the classification of the NtTCP genes. The expression pattern of NtTCP also demonstrated that majority of these genes play important roles in all the tissues, while some special genes exercise their functions only in specific tissues. In brief, the comprehensive and thorough study of the TCP family in other plants provides sufficient resources for studying the structure and functions of TCPs in tobacco.

Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system.

PubMed

Jia, Xuanyan; Yao, Jianyun; Gao, Zengqiang; Liu, Guangfeng; Dong, Yu-Hui; Wang, Xiaoxue; Zhang, Heng

2018-05-04

Toxin-antitoxin (TA) loci in bacteria are small genetic modules that regulate various cellular activities, including cell growth and death. The two-gene module encoding a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and a cognate MNT (minimal nucleotidyltransferase) domain have been predicted to represent a novel type II TA system prevalent in archaea and bacteria. However, the neutralization mechanism and cellular targets of the TA family remain unclear. The toxin SO_3166 having a HEPN domain and its cognate antitoxin SO_3165 with an MNT domain constitute a typical type II TA system that regulates cell motility and confers plasmid stability in the bacterium Shewanella oneidensis Here, we report the crystal structure and solution conformation of the SO_3166-SO_3165 pair, representing the first complex structures in this TA family. The structures revealed that SO_3165 and SO_3166 form a tight heterooctamer (at a 2:6 ratio), an organization that is very rare in other TA systems. We also observed that SO_3166 dimerization enables the formation of a deep cleft at the HEPN-domain interface harboring a composite R X 4-6H active site that functions as an RNA-cleaving RNase. SO_3165 bound SO_3166 mainly through its two α-helices (α2 and α4), functioning as molecular recognition elements. Moreover, their insertion into the SO_3166 cleft sterically blocked the R X 4-6H site or narrowed the cleft to inhibit RNA substrate binding. Structure-based mutagenesis confirmed the important roles of these α-helices in SO_3166 binding and inhibition. Our structure-function analysis provides first insights into the neutralization mechanism of the HEPN-MNT TA family. © 2018 Jia et al.

Integrating protein structural dynamics and evolutionary analysis with Bio3D.

PubMed

Skjærven, Lars; Yao, Xin-Qiu; Scarabelli, Guido; Grant, Barry J

2014-12-10

Popular bioinformatics approaches for studying protein functional dynamics include comparisons of crystallographic structures, molecular dynamics simulations and normal mode analysis. However, determining how observed displacements and predicted motions from these traditionally separate analyses relate to each other, as well as to the evolution of sequence, structure and function within large protein families, remains a considerable challenge. This is in part due to the general lack of tools that integrate information of molecular structure, dynamics and evolution. Here, we describe the integration of new methodologies for evolutionary sequence, structure and simulation analysis into the Bio3D package. This major update includes unique high-throughput normal mode analysis for examining and contrasting the dynamics of related proteins with non-identical sequences and structures, as well as new methods for quantifying dynamical couplings and their residue-wise dissection from correlation network analysis. These new methodologies are integrated with major biomolecular databases as well as established methods for evolutionary sequence and comparative structural analysis. New functionality for directly comparing results derived from normal modes, molecular dynamics and principal component analysis of heterogeneous experimental structure distributions is also included. We demonstrate these integrated capabilities with example applications to dihydrofolate reductase and heterotrimeric G-protein families along with a discussion of the mechanistic insight provided in each case. The integration of structural dynamics and evolutionary analysis in Bio3D enables researchers to go beyond a prediction of single protein dynamics to investigate dynamical features across large protein families. The Bio3D package is distributed with full source code and extensive documentation as a platform independent R package under a GPL2 license from http://thegrantlab.org/bio3d/ .

Electronic structure contributions to reactivity in xanthine oxidase family enzymes.

PubMed

Stein, Benjamin W; Kirk, Martin L

2015-03-01

We review the xanthine oxidase (XO) family of pyranopterin molybdenum enzymes with a specific emphasis on electronic structure contributions to reactivity. In addition to xanthine and aldehyde oxidoreductases, which catalyze the two-electron oxidation of aromatic heterocycles and aldehyde substrates, this mini-review highlights recent work on the closely related carbon monoxide dehydrogenase (CODH) that catalyzes the oxidation of CO using a unique Mo-Cu heterobimetallic active site. A primary focus of this mini-review relates to how spectroscopy and computational methods have been used to develop an understanding of critical relationships between geometric structure, electronic structure, and catalytic function.

Phylogenomics and sequence-structure-function relationships in the GmrSD family of Type IV restriction enzymes.

PubMed

Machnicka, Magdalena A; Kaminska, Katarzyna H; Dunin-Horkawicz, Stanislaw; Bujnicki, Janusz M

2015-10-23

GmrSD is a modification-dependent restriction endonuclease that specifically targets and cleaves glucosylated hydroxymethylcytosine (glc-HMC) modified DNA. It is encoded either as two separate single-domain GmrS and GmrD proteins or as a single protein carrying both domains. Previous studies suggested that GmrS acts as endonuclease and NTPase whereas GmrD binds DNA. In this work we applied homology detection, sequence conservation analysis, fold recognition and homology modeling methods to study sequence-structure-function relationships in the GmrSD restriction endonucleases family. We also analyzed the phylogeny and genomic context of the family members. Results of our comparative genomics study show that GmrS exhibits similarity to proteins from the ParB/Srx fold which can have both NTPase and nuclease activity. In contrast to the previous studies though, we attribute the nuclease activity also to GmrD as we found it to contain the HNH endonuclease motif. We revealed residues potentially important for structure and function in both domains. Moreover, we found that GmrSD systems exist predominantly as a fused, double-domain form rather than as a heterodimer and that their homologs are often encoded in regions enriched in defense and gene mobility-related elements. Finally, phylogenetic reconstructions of GmrS and GmrD domains revealed that they coevolved and only few GmrSD systems appear to be assembled from distantly related GmrS and GmrD components. Our study provides insight into sequence-structure-function relationships in the yet poorly characterized family of Type IV restriction enzymes. Comparative genomics allowed to propose possible role of GmrD domain in the function of the GmrSD enzyme and possible active sites of both GmrS and GmrD domains. Presented results can guide further experimental characterization of these enzymes.

Pore-forming activity and structural autoinhibition of the gasdermin family.

PubMed

Ding, Jingjin; Wang, Kun; Liu, Wang; She, Yang; Sun, Qi; Shi, Jianjin; Sun, Hanzi; Wang, Da-Cheng; Shao, Feng

2016-07-07

Inflammatory caspases cleave the gasdermin D (GSDMD) protein to trigger pyroptosis, a lytic form of cell death that is crucial for immune defences and diseases. GSDMD contains a functionally important gasdermin-N domain that is shared in the gasdermin family. The functional mechanism of action of gasdermin proteins is unknown. Here we show that the gasdermin-N domains of the gasdermin proteins GSDMD, GSDMA3 and GSDMA can bind membrane lipids, phosphoinositides and cardiolipin, and exhibit membrane-disrupting cytotoxicity in mammalian cells and artificially transformed bacteria. Gasdermin-N moved to the plasma membrane during pyroptosis. Purified gasdermin-N efficiently lysed phosphoinositide/cardiolipin-containing liposomes and formed pores on membranes made of artificial or natural phospholipid mixtures. Most gasdermin pores had an inner diameter of 10–14 nm and contained 16 symmetric protomers. The crystal structure of GSDMA3 showed an autoinhibited two-domain architecture that is conserved in the gasdermin family. Structure-guided mutagenesis demonstrated that the liposome-leakage and pore-forming activities of the gasdermin-N domain are required for pyroptosis. These findings reveal the mechanism for pyroptosis and provide insights into the roles of the gasdermin family in necrosis, immunity and diseases.

Eisenstein type series for Calabi-Yau varieties

NASA Astrophysics Data System (ADS)

Movasati, Hossein

2011-06-01

In this article we introduce an ordinary differential equation associated to the one parameter family of Calabi-Yau varieties which is mirror dual to the universal family of smooth quintic three folds. It is satisfied by seven functions written in the q-expansion form and the Yukawa coupling turns out to be rational in these functions. We prove that these functions are algebraically independent over the field of complex numbers, and hence, the algebra generated by such functions can be interpreted as the theory of (quasi) modular forms attached to the one parameter family of Calabi-Yau varieties. Our result is a reformulation and realization of a problem of Griffiths around seventies on the existence of automorphic functions for the moduli of polarized Hodge structures. It is a generalization of the Ramanujan differential equation satisfied by three Eisenstein series.

Soluble expression, purification and characterization of the full length IS2 Transposase.

PubMed

Lewis, Leslie A; Astatke, Mekbib; Umekubo, Peter T; Alvi, Shaheen; Saby, Robert; Afrose, Jehan

2011-10-27

The two-step transposition pathway of insertion sequences of the IS3 family, and several other families, involves first the formation of a branched figure-of-eight (F-8) structure by an asymmetric single strand cleavage at one optional donor end and joining to the flanking host DNA near the target end. Its conversion to a double stranded minicircle precedes the second insertional step, where both ends function as donors. In IS2, the left end which lacks donor function in Step I acquires it in Step II. The assembly of two intrinsically different protein-DNA complexes in these F-8 generating elements has been intuitively proposed, but a barrier to testing this hypothesis has been the difficulty of isolating a full length, soluble and active transposase that creates fully formed synaptic complexes in vitro with protein bound to both binding and catalytic domains of the ends. We address here a solution to expressing, purifying and structurally analyzing such a protein. A soluble and active IS2 transposase derivative with GFP fused to its C-terminus functions as efficiently as the native protein in in vivo transposition assays. In vitro electrophoretic mobility shift assay data show that the partially purified protein prepared under native conditions binds very efficiently to cognate DNA, utilizing both N- and C-terminal residues. As a precursor to biophysical analyses of these complexes, a fluorescence-based random mutagenesis protocol was developed that enabled a structure-function analysis of the protein with good resolution at the secondary structure level. The results extend previous structure-function work on IS3 family transposases, identifying the binding domain as a three helix H + HTH bundle and explaining the function of an atypical leucine zipper-like motif in IS2. In addition gain- and loss-of-function mutations in the catalytic active site define its role in regional and global binding and identify functional signatures that are common to the three dimensional catalytic core motif of the retroviral integrase superfamily. Intractably insoluble transposases, such as the IS2 transposase, prepared by solubilization protocols are often refractory to whole protein structure-function studies. The results described here have validated the use of GFP-tagging and fluorescence-based random mutagenesis in overcoming this limitation at the secondary structure level.

Soluble expression, purification and characterization of the full length IS2 Transposase

PubMed Central

2011-01-01

Background The two-step transposition pathway of insertion sequences of the IS3 family, and several other families, involves first the formation of a branched figure-of-eight (F-8) structure by an asymmetric single strand cleavage at one optional donor end and joining to the flanking host DNA near the target end. Its conversion to a double stranded minicircle precedes the second insertional step, where both ends function as donors. In IS2, the left end which lacks donor function in Step I acquires it in Step II. The assembly of two intrinsically different protein-DNA complexes in these F-8 generating elements has been intuitively proposed, but a barrier to testing this hypothesis has been the difficulty of isolating a full length, soluble and active transposase that creates fully formed synaptic complexes in vitro with protein bound to both binding and catalytic domains of the ends. We address here a solution to expressing, purifying and structurally analyzing such a protein. Results A soluble and active IS2 transposase derivative with GFP fused to its C-terminus functions as efficiently as the native protein in in vivo transposition assays. In vitro electrophoretic mobility shift assay data show that the partially purified protein prepared under native conditions binds very efficiently to cognate DNA, utilizing both N- and C-terminal residues. As a precursor to biophysical analyses of these complexes, a fluorescence-based random mutagenesis protocol was developed that enabled a structure-function analysis of the protein with good resolution at the secondary structure level. The results extend previous structure-function work on IS3 family transposases, identifying the binding domain as a three helix H + HTH bundle and explaining the function of an atypical leucine zipper-like motif in IS2. In addition gain- and loss-of-function mutations in the catalytic active site define its role in regional and global binding and identify functional signatures that are common to the three dimensional catalytic core motif of the retroviral integrase superfamily. Conclusions Intractably insoluble transposases, such as the IS2 transposase, prepared by solubilization protocols are often refractory to whole protein structure-function studies. The results described here have validated the use of GFP-tagging and fluorescence-based random mutagenesis in overcoming this limitation at the secondary structure level. PMID:22032517

Perceived family functioning, adolescent psychopathology and quality of life in the general population: a 6-month follow-up study.

PubMed

Jozefiak, Thomas; Wallander, Jan L

2016-04-01

The aim of the study was to investigate whether perceived family functioning of adolescent is moderating or mediating the longitudinal association of adolescent internalizing and externalizing psychopathology with quality of life (QoL) after 6 months in the general population. Using a cluster sampling technique in one Norwegian county 1331, 10- to 16-year-old students were included in the study (51 % girls). Parents completed the Child Behavior Checklist for the assessment of adolescent psychopathology at Time 1. The students completed the General Functioning Scale of the McMaster Family Assessment Device and the Inventory of Life Quality in Children and Adolescents at time 2 6 months later. Psychopathology, family functioning and QoL were treated as latent variables in a structural equation model adjusted for sex, age and parent education. The regression coefficients for paths from psychopathology decreased (β = .199 for the internalizing and β = .102 for the externalizing model) in each case when including the indirect path via family functioning compared with the direct path from psychopathology to QoL. The sum of indirect effects on QoL via family functioning was significant for internalizing β = 0.093 (95 % CI 0.054-0.133) and externalizing β = 0.119 (95 % CI 0.076-0.162) psychopathology. Family functioning significantly mediated the longitudinal association between psychopathology and QoL. Because the family remains an important social domain for adolescents, it must be an important consideration when attempting to reduce or alleviate psychopathology in youth and improve the quality of their life experience throughout this period.

Functional classification of skeletal muscle networks. I. Normal physiology

PubMed Central

Wang, Yu; Winters, Jack

2012-01-01

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca2+ fluxes to bind Ca2+ to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling. PMID:23085959

Evolution of structural diversity of trichothecene mycotoxins

USDA-ARS?s Scientific Manuscript database

Fungal secondary metabolites (SMs) are diverse in structure and biological activity. Most can be divided into families of analogs that share a core structure but vary in patterns of functional groups (substituents) attached to the core. Typically, fungal genes responsible for synthesis of the same S...

Longitudinal Impact of a Randomized Clinical Trial to Improve Family Function, Reduce Maternal Stress and Improve Child Outcomes in Families of Children with ADHD.

PubMed

Churchill, Shervin S; Leo, Michael C; Brennan, Eileen M; Sellmaier, Claudia; Kendall, Judy; Houck, Gail M

2018-02-23

Objective Evaluate the efficacy of a 12 month nursing case-management intervention over a period of 18 months, 6 months after the end of intervention, for families of children attention deficit hyperactivity disorder (ADHD). Methods Mother and child dyads were enrolled to participate in a randomized controlled clinical trial. Children were 4-18 years old. Data were collected at baseline, 6, 12, and 18 months or 6 months after the termination of direct intervention. Longitudinal analyses, using generalized estimating equations, were conducted to assess change in study outcomes relating to family function, maternal stress, and child behavior over the 18 month period. Results Compared to control families, some family function outcomes were moderately improved in the intervention group. In particular, intervention families demonstrated substantial improvement in implementing family behavior controls (p value = 0.038) and improvement in family satisfaction (not statistically significant p = 0.062). Although there was improvement in the overall family function measure there was not a statistically significant difference between groups. Maternal stress and child behavior outcomes were not significantly different between control and intervention groups by the end of the intervention. Conclusions for Practice Addressing ADHD is complex and requires the assessment of comorbidities that might exacerbate negative behavior. Our findings support the latest American Academy of Pediatrics guidelines to use behavioral therapy as the first line of treatment in young children. Nursing case-management interventions that provide direct family education and improve family function, especially with respect to providing structure and behavior control, may complement and facilitate behavioral therapy for treatment of ADHD and improving child behavior.

Child functional characteristics explain child and family outcomes better than diagnosis: Population-based study of children with autism or other neurodevelopmental disorders/disabilities.

PubMed

Miller, Anton; Shen, Jane; Mâsse, Louise C

2016-06-15

Allocation of resources for services and supports for children with neurodevelopmental disorders/disabilities (NDD/D) is often based on the presence of specific health conditions. This study investigated the relative roles of a child's diagnosed health condition and neurodevelopmental and related functional characteristics in explaining child and family health and well-being. The data on children with NDD/D (ages 5 to 14; weighted n = 120,700) are from the 2006 Participation and Activity Limitation Survey (PALS), a population-based Canadian survey of parents of children with functional limitations/disabilities. Direct and indirect effects of child diagnosis status-autism spectrum disorder (ASD)/not ASD-and functional characteristics (particularly, ASD-related impairments in speech, cognition, and emotion and behaviour) on child participation and family health and well-being were investigated in a series of structural equation models, while controlling for covariates. All models adequately fitted the data. Child ASD diagnosis was significantly associated with child participation and family health and well-being. When ASD-related child functional characteristics were added to the model, all direct effects from child diagnosis on child and family outcomes disappeared; the effect of child diagnosis on child and family outcomes was fully mediated via ASD-related child functional characteristics. Children's neurodevelopmental functional characteristics are integral to understanding the child and family health-related impact of neurodevelopmental disorders such as ASD. These findings have implications for the relative weighting given to functional versus diagnosis-specific factors in considering needs for services and supports.

Differentiating the Effects of Familial Risk for Alcohol Dependence and Prenatal Exposure to Alcohol on Offspring Brain Morphology.

PubMed

Sharma, Vinod K; Hill, Shirley Y

2017-02-01

Offspring with a family history of alcohol dependence (AD) have been shown to have altered structural and functional integrity of corticolimbic brain structures. Similarly, prenatal exposure to alcohol is associated with a variety of structural and functional brain changes. The goal of this study was to differentiate the brain gray matter volumetric differences associated with familial risk and prenatal exposure to alcohol among offspring while controlling for lifetime personal exposures to alcohol and drugs. A total of 52 high-risk (HR) offspring from maternal multiplex families with a high proportion of AD were studied along with 55 low-risk (LR) offspring. Voxel-based morphometric analysis was performed using statistical parametric mapping (SPM8) software using 3T structural images from these offspring to identify gray matter volume differences associated with familial risk and prenatal exposure. Significant familial risk group differences were seen with HR males showing reduced volume of the left inferior temporal, left fusiform, and left and right insula regions relative to LR males, controlling for prenatal exposure to alcohol drugs and cigarettes. HR females showed a reduction in the right fusiform but also showed a reduction in volume in portions of the cerebellum (left crus I and left lobe 8). Prenatal alcohol exposure effects, assessed within the familial HR group, was associated with reduced right middle cingulum and left middle temporal volume. Even low exposure resulting from mothers drinking in amounts less than the median of those who drank (53 drinks or less over the course of the pregnancy) showed a reduction in volume in the right anterior cingulum and in the left cerebellum (lobes 4 and 5). Familial risk for AD and prenatal exposure to alcohol and other drugs show independent effects on brain morphology. Copyright © 2017 by the Research Society on Alcoholism.

Crystal Structure of a Plant Multidrug and Toxic Compound Extrusion Family Protein.

PubMed

Tanaka, Yoshiki; Iwaki, Shigehiro; Tsukazaki, Tomoya

2017-09-05

The multidrug and toxic compound extrusion (MATE) family of proteins consists of transporters responsible for multidrug resistance in prokaryotes. In plants, a number of MATE proteins were identified by recent genomic and functional studies, which imply that the proteins have substrate-specific transport functions instead of multidrug extrusion. The three-dimensional structure of eukaryotic MATE proteins, including those of plants, has not been reported, preventing a better understanding of the molecular mechanism of these proteins. Here, we describe the crystal structure of a MATE protein from the plant Camelina sativa at 2.9 Å resolution. Two sets of six transmembrane α helices, assembled pseudo-symmetrically, possess a negatively charged internal pocket with an outward-facing shape. The crystal structure provides insight into the diversity of plant MATE proteins and their substrate recognition and transport through the membrane. Copyright © 2017 Elsevier Ltd. All rights reserved.

CATH-Gene3D: Generation of the Resource and Its Use in Obtaining Structural and Functional Annotations for Protein Sequences.

PubMed

Dawson, Natalie L; Sillitoe, Ian; Lees, Jonathan G; Lam, Su Datt; Orengo, Christine A

2017-01-01

This chapter describes the generation of the data in the CATH-Gene3D online resource and how it can be used to study protein domains and their evolutionary relationships. Methods will be presented for: comparing protein structures, recognizing homologs, predicting domain structures within protein sequences, and subclassifying superfamilies into functionally pure families, together with a guide on using the webpages.

Genealogy of an ancient protein family: the Sirtuins, a family of disordered members.

PubMed

Costantini, Susan; Sharma, Ankush; Raucci, Raffaele; Costantini, Maria; Autiero, Ida; Colonna, Giovanni

2013-03-05

Sirtuins genes are widely distributed by evolution and have been found in eubacteria, archaea and eukaryotes. While prokaryotic and archeal species usually have one or two sirtuin homologs, in humans as well as in eukaryotes we found multiple versions and in mammals this family is comprised of seven different homologous proteins being all NAD-dependent de-acylases. 3D structures of human SIRT2, SIRT3, and SIRT5 revealed the overall conformation of the conserved core domain but they were unable to give a structural information about the presence of very flexible and dynamically disordered regions, the role of which is still structurally and functionally unclear. Recently, we modeled the 3D-structure of human SIRT1, the most studied member of this family, that unexpectedly emerged as a member of the intrinsically disordered proteins with its long disordered terminal arms. Despite clear similarities in catalytic cores between the human sirtuins little is known of the general structural characteristics of these proteins. The presence of disorder in human SIRT1 and the propensity of these proteins in promoting molecular interactions make it important to understand the underlying mechanisms of molecular recognition that reasonably should involve terminal segments. The mechanism of recognition, in turn, is a prerequisite for the understanding of any functional activity. Aim of this work is to understand what structural properties are shared among members of this family in humans as well as in other organisms. We have studied the distribution of the structural features of N- and C-terminal segments of sirtuins in all known organisms to draw their evolutionary histories by taking into account average length of terminal segments, amino acid composition, intrinsic disorder, presence of charged stretches, presence of putative phosphorylation sites, flexibility, and GC content of genes. Finally, we have carried out a comprehensive analysis of the putative phosphorylation sites in human sirtuins confirming those sites already known experimentally for human SIRT1 and 2 as well as extending their topology to all the family to get feedback of their physiological functions and cellular localization. Our results highlight that the terminal segments of the majority of sirtuins possess a number of structural features and chemical and physical properties that strongly support their involvement in activities of recognition and interaction with other protein molecules. We also suggest how a multisite phosphorylation provides a possible mechanism by which flexible and intrinsically disordered segments of a sirtuin supported by the presence of positively or negatively charged stretches might enhance the strength and specificity of interaction with a particular molecular partner.

Ascidian and amphioxus Adh genes correlate functional and molecular features of the ADH family expansion during vertebrate evolution.

PubMed

Cañestro, Cristian; Albalat, Ricard; Hjelmqvist, Lars; Godoy, Laura; Jörnvall, Hans; Gonzàlez-Duarte, Roser

2002-01-01

The alcohol dehydrogenase (ADH) family has evolved into at least eight ADH classes during vertebrate evolution. We have characterized three prevertebrate forms of the parent enzyme of this family, including one from an urochordate (Ciona intestinalis) and two from cephalochordates (Branchiostoma floridae and Branchiostoma lanceolatum). An evolutionary analysis of the family was performed gathering data from protein and gene structures, exon-intron distribution, and functional features through chordate lines. Our data strongly support that the ADH family expansion occurred 500 million years ago, after the cephalochordate/vertebrate split, probably in the gnathostome subphylum line of the vertebrates. Evolutionary rates differ between the ancestral, ADH3 (glutathione-dependent formaldehyde dehydrogenase), and the emerging forms, including the classical alcohol dehydrogenase, ADH1, which has an evolutionary rate 3.6-fold that of the ADH3 form. Phylogenetic analysis and chromosomal mapping of the vertebrate Adh gene cluster suggest that family expansion took place by tandem duplications, probably concurrent with the extensive isoform burst observed before the fish/tetrapode split, rather than through the large-scale genome duplications also postulated in early vertebrate evolution. The absence of multifunctionality in lower chordate ADHs and the structures compared argue in favor of the acquisition of new functions in vertebrate ADH classes. Finally, comparison between B. floridae and B. lanceolatum Adhs provides the first estimate for a cephalochordate speciation, 190 million years ago, probably concomitant with the beginning of the drifting of major land masses from the Pangea.

Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors

PubMed Central

2013-01-01

Background The widespread protozoan parasite Toxoplasma gondii interferes with host cell functions by exporting the contents of a unique apical organelle, the rhoptry. Among the mix of secreted proteins are an expanded, lineage-specific family of protein kinases termed rhoptry kinases (ROPKs), several of which have been shown to be key virulence factors, including the pseudokinase ROP5. The extent and details of the diversification of this protein family are poorly understood. Results In this study, we comprehensively catalogued the ROPK family in the genomes of Toxoplasma gondii, Neospora caninum and Eimeria tenella, as well as portions of the unfinished genome of Sarcocystis neurona, and classified the identified genes into 42 distinct subfamilies. We systematically compared the rhoptry kinase protein sequences and structures to each other and to the broader superfamily of eukaryotic protein kinases to study the patterns of diversification and neofunctionalization in the ROPK family and its subfamilies. We identified three ROPK sub-clades of particular interest: those bearing a structurally conserved N-terminal extension to the kinase domain (NTE), an E. tenella-specific expansion, and a basal cluster including ROP35 and BPK1 that we term ROPKL. Structural analysis in light of the solved structures ROP2, ROP5, ROP8 and in comparison to typical eukaryotic protein kinases revealed ROPK-specific conservation patterns in two key regions of the kinase domain, surrounding a ROPK-conserved insert in the kinase hinge region and a disulfide bridge in the kinase substrate-binding lobe. We also examined conservation patterns specific to the NTE-bearing clade. We discuss the possible functional consequences of each. Conclusions Our work sheds light on several important but previously unrecognized features shared among rhoptry kinases, as well as the essential differences between active and degenerate protein kinases. We identify the most distinctive ROPK-specific features conserved across both active kinases and pseudokinases, and discuss these in terms of sequence motifs, evolutionary context, structural impact and potential functional relevance. By characterizing the proteins that enable these parasites to invade the host cell and co-opt its signaling mechanisms, we provide guidance on potential therapeutic targets for the diseases caused by coccidian parasites. PMID:23742205

Functional characterization of a prokaryotic Kir channel.

PubMed

Enkvetchakul, Decha; Bhattacharyya, Jaya; Jeliazkova, Iana; Groesbeck, Darcy K; Cukras, Catherine A; Nichols, Colin G

2004-11-05

The Kir gene family encodes inward rectifying K+ (Kir) channels that are widespread and critical regulators of excitability in eukaryotic cells. A related gene family (KirBac) has recently been identified in prokaryotes. While a crystal structure of one member, Kir-Bac1.1, has been solved, there has been no functional characterization of any KirBac gene products. Here we present functional characterization of KirBac1.1 reconstituted in liposomes. Utilizing a 86Rb+ uptake assay, we demonstrate that KirBac1.1 generates a K+ -selective permeation path that is inhibited by extraliposomal Ba2+ and Ca2+ ions. In contrast to KcsA (an acid-activated bacterial potassium channel), KirBac1.1 is inhibited by extraliposomal acid (pKa approximately 6). This characterization of KirBac1.1 activity now paves the way for further correlation of structure and function in this model Kir channel.

Identification and expression profiling analysis of TCP family genes involved in growth and development in maize.

PubMed

Chai, Wenbo; Jiang, Pengfei; Huang, Guoyu; Jiang, Haiyang; Li, Xiaoyu

2017-10-01

The TCP family is a group of plant-specific transcription factors. TCP genes encode proteins harboring bHLH structure, which is implicated in DNA binding and protein-protein interactions and known as the TCP domain. TCP genes play important roles in plant development and have been evolutionarily and functionally elaborated in various plants, however, no overall phylogenetic analysis or expression profiling of TCP genes in Zea mays has been reported. In the present study, a systematic analysis of molecular evolution and functional prediction of TCP family genes in maize ( Z . mays L.) has been conducted. We performed a genome-wide survey of TCP genes in maize, revealing the gene structure, chromosomal location and phylogenetic relationship of family members. Microsynteny between grass species and tissue-specific expression profiles were also investigated. In total, 29 TCP genes were identified in the maize genome, unevenly distributed on the 10 maize chromosomes. Additionally, ZmTCP genes were categorized into nine classes based on phylogeny and purifying selection may largely be responsible for maintaining the functions of maize TCP genes. What's more, microsynteny analysis suggested that TCP genes have been conserved during evolution. Finally, expression analysis revealed that most TCP genes are expressed in the stem and ear, which suggests that ZmTCP genes influence stem and ear growth. This result is consistent with the previous finding that maize TCP genes represses the growth of axillary organs and enables the formation of female inflorescences. Altogether, this study presents a thorough overview of TCP family in maize and provides a new perspective on the evolution of this gene family. The results also indicate that TCP family genes may be involved in development stage in plant growing conditions. Additionally, our results will be useful for further functional analysis of the TCP gene family in maize.

Structural basis for the substrate specificity of PepA from Streptococcus pneumoniae, a dodecameric tetrahedral protease.

PubMed

Kim, Doyoun; San, Boi Hoa; Moh, Sang Hyun; Park, Hyejin; Kim, Dong Young; Lee, Sangho; Kim, Kyeong Kyu

2010-01-01

Regulated cytosolic proteolysis is one of the key cellular processes ensuring proper functioning of a cell. M42 family proteases show a broad spectrum of substrate specificities, but the structural basis for such diversity of the substrate specificities is lagging behind biochemical data. Here we report the crystal structure of PepA from Streptococcus pneumoniae, a glutamyl aminopeptidase belonging to M42 family (SpPepA). We found that Arg-257 in the substrate binding pocket is strategically positioned so that Arg-257 can make electrostatic interactions with the acidic residue of a substrate at its N-terminus. Structural comparison of the substrate binding pocket of the M42 family proteases, along with the structure-based multiple sequence alignment, argues that the appropriate electrostatic interactions contribute to the selective substrate specificity of SpPepA. Copyright 2009 Elsevier Inc. All rights reserved.

Extended kin and children's behavioral functioning: Family structure and parental immigrant status.

PubMed

Kang, Jeehye; Cohen, Philip N

2017-08-01

Using the Los Angeles Family and Neighborhood Survey (L.A. FANS), this paper examines the association between the presence of co-resident extended kin and children's internalizing and externalizing behaviors. The paper demonstrates the differential role of extended kin by family structure, as well as across parental immigrant status - specifically, nativity and documentation status. Children in the sample were found to be disadvantaged in extended family households, especially with regard to internalizing behaviors. This disadvantageous association was found mostly among married-parent extended family households, whereas there was no association between the presence of extended kin and behavior problems in children from single-parent families. This pattern emerged more clearly among children of documented immigrants, compared to those with native-born parents and those whose parents were unauthorized immigrants. These findings suggest a need to modify previous theories on extended family living arrangements; they also provide policy implications for immigrant families. Copyright © 2017 Elsevier Ltd. All rights reserved.

Youth Experiences of Family Violence and Teen Dating Violence Perpetration: Cognitive and Emotional Mediators

ERIC Educational Resources Information Center

Jouriles, Ernest N.; McDonald, Renee; Mueller, Victoria; Grych, John H.

2012-01-01

This article describes a conceptual model of cognitive and emotional processes proposed to mediate the relation between youth exposure to family violence and teen dating violence perpetration. Explicit beliefs about violence, internal knowledge structures, and executive functioning are hypothesized as cognitive mediators, and their potential…

Autonomy and Relatedness in Inner-City Families of Substance Abusing Adolescents

ERIC Educational Resources Information Center

Samuolis, Jessica; Hogue, Aaron; Dauber, Sarah; Liddle, Howard A.

2006-01-01

This study examined parent-adolescent autonomous-relatedness functioning in inner-city, ethnic minority families of adolescents exhibiting drug abuse and related problem behaviors. Seventy-four parent-adolescent dyads completed a structured interaction task prior to the start of treatment that was coded using an established autonomous-relatedness…

Family Worlds: Couple Satisfaction, Parenting Style, and Mothers' and Fathers' Speech to Young Children.

ERIC Educational Resources Information Center

Pratt, Michael W.; And Others

1992-01-01

Investigated relations between certain family context variables and the conversational behavior of 36 parents who were playing with their 3 year olds. Transcripts were coded for types of conversational functions and structure of parent speech. Marital satisfaction was associated with aspects of parent speech. (LB)

Structure of Full-length Drosophila Cryptochrome

PubMed Central

Zoltowski, Brian D.; Vaidya, Anand T.; Top, Deniz; Widom, Joanne; Young, Michael W.; Crane, Brian R.

2011-01-01

The Cryptochrome/Photolyase (CRY/PL) family of photoreceptors mediates adaptive responses to UV and blue light exposure in all kingdoms of life 1; 2; 3; 4; 5. Whereas PLs function predominantly in DNA repair of cyclobutane pyrimidine dimers (CPDs)and 6-4 photolesions caused by UV radiation, CRYs transduce signals important for growth, development, magnetosensitivity and circadian clocks1; 2; 3; 4; 5. Despite these diverse functions, PLs/CRYs preserve a common structural fold, a dependence on flavin adenine dinucleotide (FAD) and an internal photoactivation mechanism3; 6. However, members of the CRY/PL family differ in the substrates recognized (protein or DNA), photochemical reactions catalyzed and involvement of an antenna cofactor. It is largely unknown how the animal CRYs that regulate circadian rhythms act on their substrates. CRYs contain a variable C-terminal tail that appends the conserved PL homology domain (PHD) and is important for function 7; 8; 9; 10; 11; 12. Herein, we report a 2.3 Å resolution crystal structure of Drosophila CRY with an intact C-terminus. The C-terminal helix docks in the analogous groove that binds DNA substrates in PLs. Conserved Trp536 juts into the CRY catalytic center to mimic PL recognition of DNA photolesions. The FAD anionic semiquinone found in the crystals assumes a conformation to facilitate restructuring of the tail helix. These results help reconcile the diverse functions of the CRY/PL family by demonstrating how conserved protein architecture, and photochemistry can be elaborated into a range of light-driven functions. PMID:22080955

Apo And Calcium-Bound Crystal Structures of Alpha-11 Giardin, An Unusual Annexin From 'Giardia Lamblia'

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pathuri, P.; Nguyen, E.T.; Svard, S.G.

2007-07-12

Alpha-11 giardin is a member of the multi-gene alpha-giardin family in the intestinal protozoan, Giardia lamblia. This gene family shares an ancestry with the annexin super family, whose common characteristic is calcium-dependent binding to membranes that contain acidic phospholipids. Several alpha giardins are highly expressed during parasite-induced diarrhea in humans. Despite being a member of a large family of proteins, little is known about the function and cellular localization of alpha-11 giardin, although giardins are often associated with the cytoskeleton. It has been shown that Giardia exhibits high levels of alpha-11 giardin mRNA transcript throughout its life cycle; however, constitutivemore » over-expression of this protein is lethal to the parasite. Determining the three-dimensional structure of an alpha-giardin is essential to identifying functional domains shared in the alpha-giardin family. Here we report the crystal structures of the apo and Ca{sup 2+}-bound forms of alpha-11 giardin, the first alpha giardin to be characterized structurally. Crystals of apo and Ca{sup 2+}-bound alpha-11 giardin diffracted to 1.1 angstroms and 2.93 angstroms, respectively. The crystal structure of selenium-substituted apo alpha-11 giardin reveals a planar array of four tandem repeats of predominantly {alpha}-helical domains, reminiscent of previously determined annexin structures, making this the highest-resolution structure of an annexin to date. The apo alpha-11 giardin structure also reveals a hydrophobic core formed between repeats I/IV and II/III, a region typically hydrophilic in other annexins. Surprisingly, the Ca{sup 2+}-bound structure contains only a single calcium ion, located in the DE loop of repeat I and coordinated differently from the two types of calcium sites observed in previous annexin structures. The apo and Ca{sup 2+}-bound alpha-11 giardin structures assume overall similar conformations; however, Ca2+-bound alpha-11 giardin crystallized in a lower-symmetry space group with four molecules in the asymmetric unit. Vesicle-binding studies suggest that alpha-11 giardin, unlike most other annexins, does not bind to vesicles composed of acidic phospholipids in a calcium-dependent manner.« less

A comparative study of family-specific protein-ligand complex affinity prediction based on random forest approach

NASA Astrophysics Data System (ADS)

Wang, Yu; Guo, Yanzhi; Kuang, Qifan; Pu, Xuemei; Ji, Yue; Zhang, Zhihang; Li, Menglong

2015-04-01

The assessment of binding affinity between ligands and the target proteins plays an essential role in drug discovery and design process. As an alternative to widely used scoring approaches, machine learning methods have also been proposed for fast prediction of the binding affinity with promising results, but most of them were developed as all-purpose models despite of the specific functions of different protein families, since proteins from different function families always have different structures and physicochemical features. In this study, we proposed a random forest method to predict the protein-ligand binding affinity based on a comprehensive feature set covering protein sequence, binding pocket, ligand structure and intermolecular interaction. Feature processing and compression was respectively implemented for different protein family datasets, which indicates that different features contribute to different models, so individual representation for each protein family is necessary. Three family-specific models were constructed for three important protein target families of HIV-1 protease, trypsin and carbonic anhydrase respectively. As a comparison, two generic models including diverse protein families were also built. The evaluation results show that models on family-specific datasets have the superior performance to those on the generic datasets and the Pearson and Spearman correlation coefficients ( R p and Rs) on the test sets are 0.740, 0.874, 0.735 and 0.697, 0.853, 0.723 for HIV-1 protease, trypsin and carbonic anhydrase respectively. Comparisons with the other methods further demonstrate that individual representation and model construction for each protein family is a more reasonable way in predicting the affinity of one particular protein family.

Family and housing instability: Longitudinal impact on adolescent emotional and behavioral well-being.

PubMed

Fowler, Patrick J; Henry, David B; Marcal, Katherine E

2015-09-01

This study investigated the longitudinal effects of family structure changes and housing instability in adolescence on functioning in the transition to adulthood. A model examined the influence of household composition changes and mobility in context of ethnic differences and sociodemographic risks. Data from the National Longitudinal Study of Adolescent Health measured household and residential changes over a 12-month period among a nationally representative sample of adolescents. Assessments in young adulthood measured rates of depression, criminal activity, and smoking. Findings suggested housing mobility in adolescence predicted poorer functioning across outcomes in young adulthood, and youth living in multigenerational homes exhibited greater likelihood to be arrested than adolescents in single-generation homes. However, neither family structure changes nor its interaction with residential instability or ethnicity related to young adult outcomes. Findings emphasized the unique influence of housing mobility in the context of dynamic household compositions. Copyright © 2015 Elsevier Inc. All rights reserved.

Von Bertalanffy's dynamics under a polynomial correction: Allee effect and big bang bifurcation

NASA Astrophysics Data System (ADS)

Leonel Rocha, J.; Taha, A. K.; Fournier-Prunaret, D.

2016-02-01

In this work we consider new one-dimensional populational discrete dynamical systems in which the growth of the population is described by a family of von Bertalanffy's functions, as a dynamical approach to von Bertalanffy's growth equation. The purpose of introducing Allee effect in those models is satisfied under a correction factor of polynomial type. We study classes of von Bertalanffy's functions with different types of Allee effect: strong and weak Allee's functions. Dependent on the variation of four parameters, von Bertalanffy's functions also includes another class of important functions: functions with no Allee effect. The complex bifurcation structures of these von Bertalanffy's functions is investigated in detail. We verified that this family of functions has particular bifurcation structures: the big bang bifurcation of the so-called “box-within-a-box” type. The big bang bifurcation is associated to the asymptotic weight or carrying capacity. This work is a contribution to the study of the big bang bifurcation analysis for continuous maps and their relationship with explosion birth and extinction phenomena.

The role of family and maternal factors in childhood obesity.

PubMed

Gibson, Lisa Y; Byrne, Susan M; Davis, Elizabeth A; Blair, Eve; Jacoby, Peter; Zubrick, Stephen R

2007-06-04

To investigate the relationship between a child's weight and a broad range of family and maternal factors. Cross-sectional data from a population-based prospective study, collected between January 2004 and December 2005, for 329 children aged 6-13 years (192 healthy weight, 97 overweight and 40 obese) and their mothers (n=265) recruited from a paediatric hospital endocrinology department and eight randomly selected primary schools in Perth, Western Australia. Height, weight and body mass index (BMI) of children and mothers; demographic information; maternal depression, anxiety, stress and self-esteem; general family functioning; parenting style; and negative life events. In a multilevel model, maternal BMI and family structure (single-parent v two-parent families) were the only significant predictors of child BMI z scores. Childhood obesity is not associated with adverse maternal or family characteristics such as maternal depression, negative life events, poor general family functioning or ineffective parenting style. However, having an overweight mother and a single-parent (single-mother) family increases the likelihood of a child being overweight or obese.

Exploring the post-deployment reintegration experiences of veterans with PTSD and their significant others.

PubMed

Freytes, I Magaly; LeLaurin, Jennifer H; Zickmund, Susan L; Resende, Rosana D; Uphold, Constance R

2017-01-01

Veterans with family support have better functional recovery and reintegration outcomes. However, families' ability to support the veteran with PTSD's rehabilitation and reintegration oftentimes is hindered by interpersonal challenges. We report findings of a qualitative study that examined OEF/OIF veterans with PTSD/TBI and their significant others' (SOs') perceptions of family functioning. We conducted 24 in-depth interviews with 12 veteran/SO dyads using an adapted version of the Family Assessment Device Structured Interview. Descriptive qualitative analytic methods were used to analyze the data. Data show that the impact of deployment and the resulting changes in the individuals and the family dynamics lingered years after the veterans returned home and had a lasting influence on veterans' and SOs' perceptions of family functioning. Most couples acknowledged growth in their relationships several years postdeployment. However, many continued to struggle with disruptions generated by deployment. Four themes emerged from the data: individual changes, coping strategies, relationship changes, and a "new normal." Postdeployment family functioning was influenced by a dynamic interplay of individual and relationship factors and the development of coping strategies and a new normal. This study contributes to the understanding of the prolonged postdeployment family reintegration experiences of veterans and their SOs. Findings underscore the importance of continuing to advance the current knowledge base about the long-term impact of deployment on veterans and their families, especially factors that contribute to positive postdeployment family functioning. Additional empirical studies are needed to provide more in-depth understanding of the long-term postdeployment reintegration experiences of veterans and their families. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Independent Evolution of Six Families of Halogenating Enzymes.

PubMed

Xu, Gangming; Wang, Bin-Gui

2016-01-01

Halogenated natural products are widespread in the environment, and the halogen atoms are typically vital to their bioactivities. Thus far, six families of halogenating enzymes have been identified: cofactor-free haloperoxidases (HPO), vanadium-dependent haloperoxidases (V-HPO), heme iron-dependent haloperoxidases (HI-HPO), non-heme iron-dependent halogenases (NI-HG), flavin-dependent halogenases (F-HG), and S-adenosyl-L-methionine (SAM)-dependent halogenases (S-HG). However, these halogenating enzymes with similar biological functions but distinct structures might have evolved independently. Phylogenetic and structural analyses suggest that the HPO, V-HPO, HI-HPO, NI-HG, F-HG, and S-HG enzyme families may have evolutionary relationships to the α/β hydrolases, acid phosphatases, peroxidases, chemotaxis phosphatases, oxidoreductases, and SAM hydroxide adenosyltransferases, respectively. These halogenating enzymes have established sequence homology, structural conservation, and mechanistic features within each family. Understanding the distinct evolutionary history of these halogenating enzymes will provide further insights into the study of their catalytic mechanisms and halogenation specificity.

Structural and mechanistic basis of proton-coupled metal ion transport in the SLC11/NRAMP family

PubMed Central

Ehrnstorfer, Ines A.; Manatschal, Cristina; Arnold, Fabian M.; Laederach, Juerg; Dutzler, Raimund

2017-01-01

Secondary active transporters of the SLC11/NRAMP family catalyse the uptake of iron and manganese into cells. These proteins are highly conserved across all kingdoms of life and thus likely share a common transport mechanism. Here we describe the structural and functional properties of the prokaryotic SLC11 transporter EcoDMT. Its crystal structure reveals a previously unknown outward-facing state of the protein family. In proteoliposomes EcoDMT mediates proton-coupled uptake of manganese at low micromolar concentrations. Mutants of residues in the transition-metal ion-binding site severely affect transport, whereas a mutation of a conserved histidine located near this site results in metal ion transport that appears uncoupled to proton transport. Combined with previous results, our study defines the conformational changes underlying transition-metal ion transport in the SLC11 family and it provides molecular insight to its coupling to protons. PMID:28059071

Profile of Your Geriatric Patient

PubMed Central

Longhurst, Mark F.; Slade, Debra

1990-01-01

The family doctor cares for many geriatric patients. Many of these patients enter the family practice for the first time, having either recently moved to the area or to a nearby long-term care facility. Obtaining a meaningful patient profile is essential to the physicians' care, allowing future medical decisions to be made in the best interest of that person. Patients' beliefs motivate their functioning in a system. Any system has its own history, structure, and function. PMID:21234029

[Family medicine and functional somatic syndromes].

PubMed

Nago, Naoki

2009-09-01

Between psychosomatic medicine and psychiatry, FSS (functional somatic syndromes) patients are often visiting a family doctor. For FSS, the role of family physicians is large, but the family physicians are not required for the role of diagnosis and treatment of FSS. Rather, appropriate referral to a specialist to exclude organic disease is important and a role as the coordinator is large to the patient to refuse a psychiatric consultation. To serve as a role for such coordination, a family physician has to response the patient's emotional side and focus on the construction of the doctor-patient relationship and response. I also think of structuralism medicine approach to describe disease from the meta-level as a new procedure to the patient. This approach consists of 4 components, 'entity', 'phenomenon', 'words', and 'I'. This may be a useful approach to family physicians who coordinate the overall for FSS patients' management.

Assessment of the psychometric properties of the Family Management Measure.

PubMed

Knafl, Kathleen; Deatrick, Janet A; Gallo, Agatha; Dixon, Jane; Grey, Margaret; Knafl, George; O'Malley, Jean

2011-06-01

This paper reports development of the Family Management Measure (FaMM) of parental perceptions of family management of chronic conditions. By telephone interview, 579 parents of children age 3 to 19 with a chronic condition (349 partnered mothers, 165 partners, 65 single mothers) completed the FaMM and measures of child functional status and behavioral problems and family functioning. Analyses addressed reliability, factor structure, and construct validity. Exploratory factor analysis yielded six scales: Child's Daily Life, Condition Management Ability, Condition Management Effort, Family Life Difficulty, Parental Mutuality, and View of Condition Impact. Internal consistency reliability ranged from .72 to .91, and test-retest reliability from .71 to .94. Construct validity was supported by significant correlations in hypothesized directions between FaMM scales and established measures. Results support FaMM's; reliability and validity, indicating it performs in a theoretically meaningful way and taps distinct aspects of family response to childhood chronic conditions.

The Assessment of Family Functions, Dyadic Adjustment, and Parental Attitude in Adolescents with Substance Use Disorder.

PubMed

Öngel Atar, Ayça; Yalçin, Özhan; Uygun, Ersin; Çiftçi Demirci, Arzu; Erdoğan, Ayten

2016-03-01

Family structure and family attitudes have been reported to be important factors in the development of substance use disorders. In this study, we aimed to assess the relationship between substance use and family functions, parental attitude, and parental dyadic adjustment of adolescents with substance use disorder. The study was conducted on 50 patients, comprising 9 female and 41 male adolescents between the ages of 14 and 18 years, treated at Bakırköy Mental Health Hospital, Substance Abuse Research, Treatment and Education Center for Children Adolescents (ÇEMATEM), Turkey, with the diagnosis of substance use disorder according to DSM-5 and their parents and a control group comprising 50 healthy adolescents without any psychopathology or substance use disorder and their parents. The study was designed as a matched case-control study for age and gender. Sociodemographic Data Form (SDF), Parental Attitude Scale (PAS), Dyadic Adjustment Scale (DAS), and Family Assessment Device (FAD) were applied to both groups. When the study and control groups were compared with regard to the PAS, the study group scores determined for "involvement-acceptance," "psychological autonomy," and "control-supervision" dimensions were significantly lower than the control group scores. Compared with the control group, dyadic adjustment was lower in terms of "dyadic cohesion," "dyadic consensus," and "affectional expression." Living with biological parents and the togetherness of parents were lower in the study group. "Problem solving," "communication," "roles," "affective responsiveness," "affective involvement," "behavior control," and "general functioning" dimension scores according to FAD were also significantly higher in the study group. Compared with togetherness of the controls, the dyadic adjustment of their parents was lower and family functions as perceived by the parents and adolescents were unhealthier in the adolescents using substances. These findings indicate that the family functions, dyadic adjustment, and parental attitude styles need to be assessed in the risk groups to determine familial risk factors and to structure protective measures. These assessments may guide clinicians and policy-makers toward good clinical practice and help build protective measures.

Basic Helix-Loop-Helix Transcription Factor Gene Family Phylogenetics and Nomenclature

PubMed Central

Skinner, Michael K.; Rawls, Alan; Wilson-Rawls, Jeanne; Roalson, Eric H.

2010-01-01

A phylogenetic analysis of the basic helix-loop-helix (bHLH) gene superfamily was performed using seven different species (human, mouse, rat, worm, fly, yeast, and plant Arabidopsis) and involving over 600 bHLH genes [1]. All bHLH genes were identified in the genomes of the various species, including expressed sequence tags, and the entire coding sequence was used in the analysis. Nearly 15% of the gene family has been updated or added since the original publication. A super-tree involving six clades and all structural relationships was established and is now presented for four of the species. The wealth of functional data available for members of the bHLH gene superfamily provides us with the opportunity to use this exhaustive phylogenetic tree to predict potential functions of uncharacterized members of the family. This phylogenetic and genomic analysis of the bHLH gene family has revealed unique elements of the evolution and functional relationships of the different genes in the bHLH gene family. PMID:20219281

Functional, structural and phylogenetic analysis of domains underlying the Al sensitivity of the aluminum-activated malate/anion transporter, TaALMT1.

PubMed

Ligaba, Ayalew; Dreyer, Ingo; Margaryan, Armine; Schneider, David J; Kochian, Leon; Piñeros, Miguel

2013-12-01

Triticum aestivum aluminum-activated malate transporter (TaALMT1) is the founding member of a unique gene family of anion transporters (ALMTs) that mediate the efflux of organic acids. A small sub-group of root-localized ALMTs, including TaALMT1, is physiologically associated with in planta aluminum (Al) resistance. TaALMT1 exhibits significant enhancement of transport activity in response to extracellular Al. In this study, we integrated structure-function analyses of structurally altered TaALMT1 proteins expressed in Xenopus oocytes with phylogenic analyses of the ALMT family. Our aim is to re-examine the role of protein domains in terms of their potential involvement in the Al-dependent enhancement (i.e. Al-responsiveness) of TaALMT1 transport activity, as well as the roles of all its 43 negatively charged amino acid residues. Our results indicate that the N-domain, which is predicted to form the conductive pathway, mediates ion transport even in the absence of the C-domain. However, segments in both domains are involved in Al(3+) sensing. We identified two regions, one at the N-terminus and a hydrophobic region at the C-terminus, that jointly contribute to the Al-response phenotype. Interestingly, the characteristic motif at the N-terminus appears to be specific for Al-responsive ALMTs. Our study highlights the need to include a comprehensive phylogenetic analysis when drawing inferences from structure-function analyses, as a significant proportion of the functional changes observed for TaALMT1 are most likely the result of alterations in the overall structural integrity of ALMT family proteins rather than modifications of specific sites involved in Al(3+) sensing. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

StructRNAfinder: an automated pipeline and web server for RNA families prediction.

PubMed

Arias-Carrasco, Raúl; Vásquez-Morán, Yessenia; Nakaya, Helder I; Maracaja-Coutinho, Vinicius

2018-02-17

The function of many noncoding RNAs (ncRNAs) depend upon their secondary structures. Over the last decades, several methodologies have been developed to predict such structures or to use them to functionally annotate RNAs into RNA families. However, to fully perform this analysis, researchers should utilize multiple tools, which require the constant parsing and processing of several intermediate files. This makes the large-scale prediction and annotation of RNAs a daunting task even to researchers with good computational or bioinformatics skills. We present an automated pipeline named StructRNAfinder that predicts and annotates RNA families in transcript or genome sequences. This single tool not only displays the sequence/structural consensus alignments for each RNA family, according to Rfam database but also provides a taxonomic overview for each assigned functional RNA. Moreover, we implemented a user-friendly web service that allows researchers to upload their own nucleotide sequences in order to perform the whole analysis. Finally, we provided a stand-alone version of StructRNAfinder to be used in large-scale projects. The tool was developed under GNU General Public License (GPLv3) and is freely available at http://structrnafinder.integrativebioinformatics.me . The main advantage of StructRNAfinder relies on the large-scale processing and integrating the data obtained by each tool and database employed along the workflow, of which several files are generated and displayed in user-friendly reports, useful for downstream analyses and data exploration.

Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases: Poxvirus Uracil-DNA Glycosylase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schormann, Norbert; Zhukovskaya, Natalia; Bedwell, Gregory

We report that uracil-DNA glycosylases are ubiquitous enzymes, which play a key role repairing damages in DNA and in maintaining genomic integrity by catalyzing the first step in the base excision repair pathway. Within the superfamily of uracil-DNA glycosylases family I enzymes or UNGs are specific for recognizing and removing uracil from DNA. These enzymes feature conserved structural folds, active site residues and use common motifs for DNA binding, uracil recognition and catalysis. Within this family the enzymes of poxviruses are unique and most remarkable in terms of amino acid sequences, characteristic motifs and more importantly for their novel non-enzymaticmore » function in DNA replication. UNG of vaccinia virus, also known as D4, is the most extensively characterized UNG of the poxvirus family. D4 forms an unusual heterodimeric processivity factor by attaching to a poxvirus-specific protein A20, which also binds to the DNA polymerase E9 and recruits other proteins necessary for replication. D4 is thus integrated in the DNA polymerase complex, and its DNA-binding and DNA scanning abilities couple DNA processivity and DNA base excision repair at the replication fork. In conclusion, the adaptations necessary for taking on the new function are reflected in the amino acid sequence and the three-dimensional structure of D4. We provide an overview of the current state of the knowledge on the structure-function relationship of D4.« less

Structural and functional characterizations of SsgB, a conserved activator of developmental cell division in morphologically complex actinomycetes.

PubMed

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

2009-09-11

SsgA-like proteins (SALPs) are a family of homologous cell division-related proteins that occur exclusively in morphologically complex actinomycetes. We show that SsgB, a subfamily of SALPs, is the archetypal SALP that is functionally conserved in all sporulating actinomycetes. Sporulation-specific cell division of Streptomyces coelicolor ssgB mutants is restored by introduction of distant ssgB orthologues from other actinomycetes. Interestingly, the number of septa (and spores) of the complemented null mutants is dictated by the specific ssgB orthologue that is expressed. The crystal structure of the SsgB from Thermobifida fusca was determined at 2.6 A resolution and represents the first structure for this family. The structure revealed similarities to a class of eukaryotic "whirly" single-stranded DNA/RNA-binding proteins. However, the electro-negative surface of the SALPs suggests that neither SsgB nor any of the other SALPs are likely to interact with nucleotide substrates. Instead, we show that a conserved hydrophobic surface is likely to be important for SALP function and suggest that proteins are the likely binding partners.

Social support, family functioning and parenting competence in adolescent parents.

PubMed

Angley, Meghan; Divney, Anna; Magriples, Urania; Kershaw, Trace

2015-01-01

Depression is known to mediate the association between low social support and parenting competence in adult mothers, but this relationship is rarely assessed in adolescent mothers and fathers. The primary aim of this study was to identify the association between social support, family functioning and social capital on parenting competence, including self-efficacy and satisfaction in adolescent mothers and their partners. Secondary aims included identifying potential partner effects (e.g. whether a partner's social support influenced the respondent's parenting efficacy). Data was obtained from a subset of participants from a longitudinal study of pregnant adolescent females and their partners. Couples completed individual structured interviews via audio computer-assisted self-interview during pregnancy and at 6 months postpartum. To measure the influence of support on parenting outcomes, multi-level modeling was used to assess the Actor-Partner Interdependence model, which examines responses from both members of a dyad in a single analysis. Greater social support was associated with increased parenting self-efficacy (B = 0.062, p = 0.006) and parenting satisfaction (B = 0.111, p < 0.001). Higher family functioning was also associated with greater parenting satisfaction (B = 0.05, p = 0.035). Greater partner family functioning was associated with higher parenting satisfaction (B = 0.047, p = 0.026). This study found the importance of a strong support structure during pregnancy on perceived parenting competence in the early postpartum period for young mothers and fathers. Both social support and family functioning during pregnancy were associated with a greater sense of parenting competence, and these associations were mediated by parental depression. The results of this study underscore the importance of providing social support for young expectant fathers as well as mothers.

Electronic Structure Contributions to Reactivity in Xanthine Oxidase Family Enzymes

PubMed Central

Stein, Benjamin W.; Kirk, Martin L.

2016-01-01

We review the xanthine oxidase (XO) family of pyranopterin molybdenum enzymes with a specific emphasis on electronic structure contributions to reactivity. In addition to xanthine and aldehyde oxidoreductases, which catalyze the 2-electron oxidation of aromatic heterocycles and aldehyde substrates, this mini-review highlights recent work on the closely related carbon monoxide dehydrogenase (CODH) that catalyzes the oxidation of CO using a unique Mo-Cu heterobimetallic active site. A primary focus of this mini-review relates to how spectroscopy and computational methods have been used to develop an understanding of critical relationships between geometric structure, electronic structure, and catalytic function. PMID:25425163

Social relationships and health: the relative roles of family functioning and social support.

PubMed

Franks, P; Campbell, T L; Shields, C G

1992-04-01

The associations between social relationships and health have been examined using two major research traditions. Using a social epidemiological approach, much research has shown the beneficial effect of social supports on health and health behaviors. Family interaction research, which has grown out of a more clinical tradition, has shown the complex effects of family functioning on health, particularly mental health. No studies have examined the relative power of these two approaches in explicating the connections between social relationships and health. We hypothesized that social relationships (social support and family functioning) would exert direct and indirect (through depressive symptoms) effects on health behaviors. We also hypothesized that the effects of social relationships on health would be more powerfully explicated by family functioning than by social support. We mailed a pilot survey to a random sample of patients attending a family practice center, including questions on depressive symptoms, cardiovascular health behaviors, demographics, social support using the ISEL scale, and family functioning using the FEICS scale. FEICS is a self-report questionnaire designed to assess family emotional involvement and criticism, the media elements of family expressed emotion. Eighty-three useable responses were obtained. Regression analyses and structural modelling showed both direct and indirect statistically significant paths from social relationships to health behaviors. Family criticism was directly associated (standardized coefficient = 0.29) with depressive symptoms, and family emotional involvement was directly associated with both depressive symptoms (coefficient = 0.35) and healthy cardiovascular behaviors (coefficient = 0.32). The results support the primacy of family functioning factors in understanding the associations among social relationships, mental health, and health behaviors. The contrasting relationships between emotional involvement and depressive symptoms on the one hand and emotional involvement and health behaviors on the other suggest the need for a more complex model to understand the connections between social relationships and health.

New Cyt-like δ-endotoxins from Dickeya dadantii: structure and aphicidal activity.

PubMed

Loth, Karine; Costechareyre, Denis; Effantin, Géraldine; Rahbé, Yvan; Condemine, Guy; Landon, Céline; da Silva, Pedro

2015-03-05

In the track of new biopesticides, four genes namely cytA, cytB, cytC and cytD encoding proteins homologous to Bacillus thuringiensis (Bt) Cyt toxins have been identified in the plant pathogenic bacteria Dickeya dadantii genome. Here we show that three Cyt-like δ-endotoxins from D. dadantii (CytA, CytB and CytC) are toxic to the pathogen of the pea aphid Acyrthosiphon pisum in terms of both mortality and growth rate. The phylogenetic analysis of the comprehensive set of Cyt toxins available in genomic databases shows that the whole family is of limited taxonomic occurrence, though in quite diverse microbial taxa. From a structure-function perspective the 3D structure of CytC and its backbone dynamics in solution have been determined by NMR. CytC adopts a cytolysin fold, structurally classified as a Cyt2-like protein. Moreover, the identification of a putative lipid binding pocket in CytC structure, which has been probably maintained in most members of the Cyt-toxin family, could support the importance of this lipid binding cavity for the mechanism of action of the whole family. This integrative approach provided significant insights into the evolutionary and functional history of D. dadantii Cyt toxins, which appears to be interesting leads for biopesticides.

Metagenomics and the protein universe

PubMed Central

Godzik, Adam

2011-01-01

Metagenomics sequencing projects have dramatically increased our knowledge of the protein universe and provided over one-half of currently known protein sequences; they have also introduced a much broader phylogenetic diversity into the protein databases. The full analysis of metagenomic datasets is only beginning, but it has already led to the discovery of thousands of new protein families, likely representing novel functions specific to given environments. At the same time, a deeper analysis of such novel families, including experimental structure determination of some representatives, suggests that most of them represent distant homologs of already characterized protein families, and thus most of the protein diversity present in the new environments are due to functional divergence of the known protein families rather than the emergence of new ones. PMID:21497084

Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease.

PubMed

Itoh, Nobuyuki; Ornitz, David M

2011-02-01

Fibroblast growth factors (FGFs) are a family of structurally related polypeptides that are essential for embryonic development and that function postnatally as homoeostatic factors, in the response to injury, in the regulation of electrical excitability of cells and as hormones that regulate metabolism. In humans, FGF signalling is involved in developmental, neoplastic, metabolic and neurological diseases. Fgfs have been identified in metazoans but not in unicellular organisms. In vertebrates, FGFs can be classified as having intracrine, paracrine and endocrine functions. Paracrine and endocrine FGFs act via cell-surface FGF receptors (FGFRs); while, intracrine FGFs act independent of FGFRs. The evolutionary history of the Fgf family indicates that an intracrine Fgf is the likely ancestor of the Fgf family. During metazoan evolution, the Fgf family expanded in two phases, after the separation of protostomes and deuterostomes and in the evolution of early vertebrates. These expansions enabled FGFs to acquire diverse actions and functions.

Organization and evolution of highly repeated satellite DNA sequences in plant chromosomes.

PubMed

Sharma, S; Raina, S N

2005-01-01

A major component of the plant nuclear genome is constituted by different classes of repetitive DNA sequences. The structural, functional and evolutionary aspects of the satellite repetitive DNA families, and their organization in the chromosomes is reviewed. The tandem satellite DNA sequences exhibit characteristic chromosomal locations, usually at subtelomeric and centromeric regions. The repetitive DNA family(ies) may be widely distributed in a taxonomic family or a genus, or may be specific for a species, genome or even a chromosome. They may acquire large-scale variations in their sequence and copy number over an evolutionary time-scale. These features have formed the basis of extensive utilization of repetitive sequences for taxonomic and phylogenetic studies. Hybrid polyploids have especially proven to be excellent models for studying the evolution of repetitive DNA sequences. Recent studies explicitly show that some repetitive DNA families localized at the telomeres and centromeres have acquired important structural and functional significance. The repetitive elements are under different evolutionary constraints as compared to the genes. Satellite DNA families are thought to arise de novo as a consequence of molecular mechanisms such as unequal crossing over, rolling circle amplification, replication slippage and mutation that constitute "molecular drive". Copyright 2005 S. Karger AG, Basel.

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

PubMed Central

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

2012-01-01

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

Comparative and evolutionary analysis of the HES/HEY gene family reveal exon/intron loss and teleost specific duplication events.

PubMed

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

2012-01-01

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

Multiple conformations of the cytidine repressor DNA-binding domain coalesce to one upon recognition of a specific DNA surface.

PubMed

Moody, Colleen L; Tretyachenko-Ladokhina, Vira; Laue, Thomas M; Senear, Donald F; Cocco, Melanie J

2011-08-09

The cytidine repressor (CytR) is a member of the LacR family of bacterial repressors with distinct functional features. The Escherichia coli CytR regulon comprises nine operons whose palindromic operators vary in both sequence and, most significantly, spacing between the recognition half-sites. This suggests a strong likelihood that protein folding would be coupled to DNA binding as a mechanism to accommodate the variety of different operator architectures to which CytR is targeted. Such coupling is a common feature of sequence-specific DNA-binding proteins, including the LacR family repressors; however, there are no significant structural rearrangements upon DNA binding within the three-helix DNA-binding domains (DBDs) studied to date. We used nuclear magnetic resonance (NMR) spectroscopy to characterize the CytR DBD free in solution and to determine the high-resolution structure of a CytR DBD monomer bound specifically to one DNA half-site of the uridine phosphorylase (udp) operator. We find that the free DBD populates multiple distinct conformations distinguished by up to four sets of NMR peaks per residue. This structural heterogeneity is previously unknown in the LacR family. These stable structures coalesce into a single, more stable udp-bound form that features a three-helix bundle containing a canonical helix-turn-helix motif. However, this structure differs from all other LacR family members whose structures are known with regard to the packing of the helices and consequently their relative orientations. Aspects of CytR activity are unique among repressors; we identify here structural properties that are also distinct and that might underlie the different functional properties. © 2011 American Chemical Society

Acculturation, enculturation, and symptoms of depression in Hispanic youth: the roles of gender, Hispanic cultural values, and family functioning.

PubMed

Lorenzo-Blanco, Elma I; Unger, Jennifer B; Baezconde-Garbanati, Lourdes; Ritt-Olson, Anamara; Soto, Daniel

2012-10-01

The risk for depression increases as Hispanic youth acculturate to U.S. society. This association is stronger for Hispanic girls than boys. To better understand the influence of culture and family on depressive symptoms, we tested a process-oriented model of acculturation, cultural values, and family functioning. The data came from Project RED, which included 1,922 Hispanic students (53 % girls; 86 % were 14 years old; and 84 % were U.S. born) from Southern California. We used data from 9th to 11th grade to test the influence of acculturation-related experiences on depressive symptoms over time. Multi-group structural equation analysis suggested that both family conflict and cohesion were linked with depressive symptoms. Hispanic cultural values were associated with family cohesion and conflict but the strength and direction of these relationships varied across cultural values and gender. For girls and boys, familismo and respeto were associated with higher family cohesion and lower family conflict. Moreover, gender roles were linked with higher family cohesion in girls but not in boys. These results indicate that improving family functioning will be beneficial for boys' and girls' psychological well-being. This may be achieved by promoting familismo and respeto for boys and girls and by promoting traditional gender roles for girls.

Acculturation, Enculturation, and Symptoms of Depression in Hispanic Youth: The Roles of Gender, Hispanic Cultural Values, and Family Functioning

PubMed Central

Unger, Jennifer B.; Baezconde-Garbanati, Lourdes; Ritt-Olson, Anamara; Soto, Daniel

2015-01-01

The risk for depression increases as Hispanic youth acculturate to U.S. society. This association is stronger for Hispanic girls than boys. To better understand the influence of culture and family on depressive symptoms, we tested a process-oriented model of acculturation, cultural values, and family functioning. The data came from Project RED, which included 1,922 Hispanic students (53 % girls; 86 % were 14 years old; and 84 % were U.S. born) from Southern California. We used data from 9th to 11th grade to test the influence of acculturation-related experiences on depressive symptoms over time. Multi-group structural equation analysis suggested that both family conflict and cohesion were linked with depressive symptoms. Hispanic cultural values were associated with family cohesion and conflict but the strength and direction of these relationships varied across cultural values and gender. For girls and boys, familismo and respeto were associated with higher family cohesion and lower family conflict. Moreover, gender roles were linked with higher family cohesion in girls but not in boys. These results indicate that improving family functioning will be beneficial for boys’ and girls’ psychological well-being. This may be achieved by promoting familismo and respeto for boys and girls and by promoting traditional gender roles for girls. PMID:22627624

Comprehensive Genomic Analysis and Expression Profiling of the NOX Gene Families under Abiotic Stresses and Hormones in Plants.

PubMed

Chang, Yan-Li; Li, Wen-Yan; Miao, Hai; Yang, Shuai-Qi; Li, Ri; Wang, Xiang; Li, Wen-Qiang; Chen, Kun-Ming

2016-02-23

Plasma membrane NADPH oxidases (NOXs) are key producers of reactive oxygen species under both normal and stress conditions in plants and they form functional subfamilies. Studies of these subfamilies indicated that they show considerable evolutionary selection. We performed a comparative genomic analysis that identified 50 ferric reduction oxidases (FRO) and 77 NOX gene homologs from 20 species representing the eight major plant lineages within the supergroup Plantae: glaucophytes, rhodophytes, chlorophytes, bryophytes, lycophytes, gymnosperms, monocots, and eudicots. Phylogenetic and structural analysis classified these FRO and NOX genes into four well-conserved groups represented as NOX, FRO I, FRO II, and FRO III. Further analysis of NOXs of phylogenetic and exon/intron structures showed that single intron loss and gain had occurred, yielding the diversified gene structures during the evolution of NOXs family genes and which were classified into four conserved subfamilies which are represented as Sub.I, Sub.II, Sub.III, and Sub.IV. Additionally, both available global microarray data analysis and quantitative real-time PCR experiments revealed that the NOX genes in Arabidopsis and rice (Oryza sativa) have different expression patterns in different developmental stages, various abiotic stresses and hormone treatments. Finally, coexpression network analysis of NOX genes in Arabidopsis and rice revealed that NOXs have significantly correlated expression profiles with genes which are involved in plants metabolic and resistance progresses. All these results suggest that NOX family underscores the functional diversity and divergence in plants. This finding will facilitate further studies of the NOX family and provide valuable information for functional validation of this family in plants. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Psychosocial issues in children and adolescents with HIV infection evaluated with a World Health Organization age-specific descriptor system.

PubMed

Giannattasio, Antonietta; Officioso, Annunziata; Continisio, Grazia Isabella; Griso, Giovanna; Storace, Cinzia; Coppini, Simonetta; Longhi, Daniela; Mango, Carmela; Guarino, Alfredo; Badolato, Raffaele; Pisacane, Alfredo

2011-01-01

After active antiretroviral therapy, children with HIV are clinically well, whereas psychosocial issues continue to influence their quality of life. The International Classification of Functioning, Disability and Health (ICF) of the World Health Organization evaluates health status and environmental and social factors associated with health. We investigated the efficacy of the ICF to describe the health status and needs of a cohort of children and adolescents with HIV seen at a reference center for pediatric AIDS in Europe. A quantitative analysis of structured interviews was performed. Caregivers of children and adolescents with HIV infection in follow-up at 2 reference centers for pediatric AIDS were enrolled. Four major areas included in the ICF instrument were investigated: impairments of body structures; impairments of body functions; environmental factors; and activity limitations and restrictions to social life. Forty-one families of children with HIV were enrolled. Body structures and functions were marginally impaired, whereas environmental factors and psychosocial issues had a relevant impact on quality of life. Most families considered environmental factors to be "barriers"; these were poverty, unemployment, and single-parent family structure. Activity limitations and social restrictions were also reported in a few cases. Almost all parents reported problems in disclosing their child's HIV status because of the fear of social stigma. Psychosocial issues are part of the well-being of children with HIV. The ICF is a standard tool to evaluate the clinical and psychosocial status of children and adolescents with HIV infection and to measure the impact of therapeutic interventions and strategies on psychosocial functioning.

Molecular evolution of miraculin-like proteins in soybean Kunitz super-family.

PubMed

Selvakumar, Purushotham; Gahloth, Deepankar; Tomar, Prabhat Pratap Singh; Sharma, Nidhi; Sharma, Ashwani Kumar

2011-12-01

Miraculin-like proteins (MLPs) belong to soybean Kunitz super-family and have been characterized from many plant families like Rutaceae, Solanaceae, Rubiaceae, etc. Many of them possess trypsin inhibitory activity and are involved in plant defense. MLPs exhibit significant sequence identity (~30-95%) to native miraculin protein, also belonging to Kunitz super-family compared with a typical Kunitz family member (~30%). The sequence and structure-function comparison of MLPs with that of a classical Kunitz inhibitor have demonstrated that MLPs have evolved to form a distinct group within Kunitz super-family. Sequence analysis of new genes along with available MLP sequences in the literature revealed three major groups for these proteins. A significant feature of Rutaceae MLP type 2 sequences is the presence of phosphorylation motif. Subtle changes are seen in putative reactive loop residues among different MLPs suggesting altered specificities to specific proteases. In phylogenetic analysis, Rutaceae MLP type 1 and type 2 proteins clustered together on separate branches, whereas native miraculin along with other MLPs formed distinct clusters. Site-specific positive Darwinian selection was observed at many sites in both the groups of Rutaceae MLP sequences with most of the residues undergoing positive selection located in loop regions. The results demonstrate the sequence and thereby the structure-function divergence of MLPs as a distinct group within soybean Kunitz super-family due to biotic and abiotic stresses of local environment.

A single mothers' group for mothers of children attending an outpatient psychiatric clinic: preliminary results.

PubMed

McNamee, J E; Lipman, E L; Hicks, F

1995-09-01

To provide a preliminary report of data from 2 support groups for single mothers, all of whom were mothers of children attending a child outpatient psychiatric clinic. The groups' 2 purposes were: 1. to assess the feasibility of adding structured evaluation to a common clinical intervention; 2. to improve single mothers' parenting skills through raised levels of self-esteem, increased capacity for family functioning and reduced levels of depression. Three structured evaluation instruments were used to measure the domains of self-esteem, family functioning and depression. These instruments were given to both groups of women on 3 occasions: 1. before the group; 2. after the group; 3. at a follow-up session 4 months after group termination. Open-ended questions were also asked at group termination. The questionnaire response rate was 100%; overall response rate for the 3 open-ended questions was 89%. Comparisons of pre-group and post-group scores showed that there was a significant increase in self-esteem (p < 0.01) and significant improvements in family functioning (p < 0.05) and depression (p < 0.01). It is possible to introduce a structured evaluation component into a common clinical intervention, and this support group seemed to assist single mothers' parenting skills. Methodologic concerns and future directions are discussed.

A functional Kv1.2-hERG chimaeric channel expressed in Pichia pastoris

PubMed Central

Dhillon, Mandeep S.; Cockcroft, Christopher J.; Munsey, Tim; Smith, Kathrine J.; Powell, Andrew J.; Carter, Paul; Wrighton, David C.; Rong, Hong-lin; Yusaf, Shahnaz P.; Sivaprasadarao, Asipu

2014-01-01

Members of the six-transmembrane segment family of ion channels share a common structural design. However, there are sequence differences between the members that confer distinct biophysical properties on individual channels. Currently, we do not have 3D structures for all members of the family to help explain the molecular basis for the differences in their biophysical properties and pharmacology. This is due to low-level expression of many members in native or heterologous systems. One exception is rat Kv1.2 which has been overexpressed in Pichia pastoris and crystallised. Here, we tested chimaeras of rat Kv1.2 with the hERG channel for function in Xenopus oocytes and for overexpression in Pichia. Chimaera containing the S1–S6 transmembrane region of HERG showed functional and pharmacological properties similar to hERG and could be overexpressed and purified from Pichia. Our results demonstrate that rat Kv1.2 could serve as a surrogate to express difficult-to-overexpress members of the six-transmembrane segment channel family. PMID:24569544

Saturation scanning of ubiquitin variants reveals a common hot spot for binding to USP2 and USP21.

PubMed

Leung, Isabel; Dekel, Ayelet; Shifman, Julia M; Sidhu, Sachdev S

2016-08-02

A detailed understanding of the molecular mechanisms whereby ubiquitin (Ub) recognizes enzymes in the Ub proteasome system is crucial for understanding the biological function of Ub. Many structures of Ub complexes have been solved and, in most cases, reveal a large structural epitope on a common face of the Ub molecule. However, owing to the generally weak nature of these interactions, it has been difficult to map in detail the functional contributions of individual Ub side chains to affinity and specificity. Here we took advantage of Ub variants (Ubvs) that bind tightly to particular Ub-specific proteases (USPs) and used phage display and saturation scanning mutagenesis to comprehensively map functional epitopes within the structural epitopes. We found that Ubvs that bind to USP2 or USP21 contain a remarkably similar core functional epitope, or "hot spot," consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences. The Ubv core functional epitope contacts residues that are conserved in the human USP family, and thus it is likely important for the interactions of Ub across many family members.

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease.

PubMed

Torres, Matthew P; Dewhurst, Henry; Sundararaman, Niveda

2016-11-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable body of potential regulatory elements that impact hundreds of different biological processes important in eukaryotic biology and human health. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease*

PubMed Central

Dewhurst, Henry; Sundararaman, Niveda

2016-01-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable body of potential regulatory elements that impact hundreds of different biological processes important in eukaryotic biology and human health. PMID:27697855

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

PubMed

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. Copyright © 2014 John Wiley & Sons, Ltd.

The evolution of function within the Nudix homology clan

PubMed Central

Srouji, John R.; Xu, Anting; Park, Annsea; Kirsch, Jack F.

2017-01-01

ABSTRACT The Nudix homology clan encompasses over 80,000 protein domains from all three domains of life, defined by homology to each other. Proteins with a domain from this clan fall into four general functional classes: pyrophosphohydrolases, isopentenyl diphosphate isomerases (IDIs), adenine/guanine mismatch‐specific adenine glycosylases (A/G‐specific adenine glycosylases), and nonenzymatic activities such as protein/protein interaction and transcriptional regulation. The largest group, pyrophosphohydrolases, encompasses more than 100 distinct hydrolase specificities. To understand the evolution of this vast number of activities, we assembled and analyzed experimental and structural data for 205 Nudix proteins collected from the literature. We corrected erroneous functions or provided more appropriate descriptions for 53 annotations described in the Gene Ontology Annotation database in this family, and propose 275 new experimentally‐based annotations. We manually constructed a structure‐guided sequence alignment of 78 Nudix proteins. Using the structural alignment as a seed, we then made an alignment of 347 “select” Nudix homology domains, curated from structurally determined, functionally characterized, or phylogenetically important Nudix domains. Based on our review of Nudix pyrophosphohydrolase structures and specificities, we further analyzed a loop region downstream of the Nudix hydrolase motif previously shown to contact the substrate molecule and possess known functional motifs. This loop region provides a potential structural basis for the functional radiation and evolution of substrate specificity within the hydrolase family. Finally, phylogenetic analyses of the 347 select protein domains and of the complete Nudix homology clan revealed general monophyly with regard to function and a few instances of probable homoplasy. Proteins 2017; 85:775–811. © 2016 Wiley Periodicals, Inc. PMID:27936487

Functional and Structural Insights of the Zinc-Finger HIT protein family members Involved in Box C/D snoRNP Biogenesis.

PubMed

Bragantini, Benoit; Tiotiu, Decebal; Rothé, Benjamin; Saliou, Jean-Michel; Marty, Hélène; Cianférani, Sarah; Charpentier, Bruno; Quinternet, Marc; Manival, Xavier

2016-06-05

Zf–HIT family members share the zf–HIT domain (ZHD), which is characterized by a fold in “treble-clef” through interleaved CCCC and CCHC ZnF motifs that both bind a zinc atom. Six proteins containing ZHD are present in human and three in yeast proteome, all belonging to multimodular RNA/protein complexes involved in gene regulation, chromatin remodeling, and snoRNP assembly. An interesting characteristic of the cellular complexes that ensure these functions is the presence of the RuvBL1/2/Rvb1/2 ATPases closely linked with zf–HIT proteins. Human ZNHIT6/BCD1 and its counterpart in yeast Bcd1p were previously characterized as assembly factors of the box C/D snoRNPs. Our data reveal that the ZHD of Bcd1p is necessary but not sufficient for yeast growth and that the motif has no direct RNA-binding capacity but helps Bcd1p maintain the box C/D snoRNAs level in steady state. However, we demonstrated that Bcd1p interacts nonspecifically with RNAs depending on their length. Interestingly, the ZHD of Bcd1p is functionally interchangeable with that of Hit1p, another box C/D snoRNP assembly factor belonging to the zf–HIT family. This prompted us to use NMR to solve the 3D structures of ZHD from yeast Bcd1p and Hit1p to highlight the structural similarity in the zf–HIT family. We identified structural features associated with the requirement of Hit1p and Bcd1p ZHD for cell growth and box C/D snoRNA stability under heat stress. Altogether, our data suggest an important role of ZHD could be to maintain functional folding to the rest of the protein, especially under heat stress conditions.

Occurrence, structure, and function of the nitrogen-fixing microsymbiont Frankia from nodules of Arizona alder [Abstract

Treesearch

J. O. Dawson; G. J. Gottfried; D. Hahn

2005-01-01

Actinorhizal plants are nodulated by the symbiotic, nitrogen-fixing actinomycete Frankia. The genus Alnus in the family Betulaceae is one of the 25 genera in 8 families of angiospermous plants that are actinorhizal. Arizona alder (Alnus oblongifolia Torr.) occurs in isolated populations associated with the...

The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle.

PubMed

Arredondo, Silvia A; Kappe, Stefan H I

2017-06-01

During their life cycle Plasmodium parasites rely upon an arsenal of proteins that establish key interactions with the host and vector, and between the parasite sexual stages, with the purpose of ensuring infection, reproduction and proliferation. Among these is a group of secreted or membrane-anchored proteins known as the six-cysteine (6-cys) family. This is a small but important family with only 14 members thus far identified, each stage-specifically expressed during the parasite life cycle. 6-cys proteins often localise at the parasite surface or interface with the host and vector, and are conserved in different Plasmodium species. The unifying feature of the family is the s48/45 domain, presumably involved in adhesion and structurally related to Ephrins, the ligands of Eph receptors. The most prominent s48/45 members are currently under functional investigation and are being pursued as vaccine candidates. In this review, we examine what is known about the 6-cys family, their structure and function, and discuss future research directions. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Functional evolution and structural conservation in chimeric cytochromes p450: calibrating a structure-guided approach.

PubMed

Otey, Christopher R; Silberg, Jonathan J; Voigt, Christopher A; Endelman, Jeffrey B; Bandara, Geethani; Arnold, Frances H

2004-03-01

Recombination generates chimeric proteins whose ability to fold depends on minimizing structural perturbations that result when portions of the sequence are inherited from different parents. These chimeric sequences can display functional properties characteristic of the parents or acquire entirely new functions. Seventeen chimeras were generated from two CYP102 members of the functionally diverse cytochrome p450 family. Chimeras predicted to have limited structural disruption, as defined by the SCHEMA algorithm, displayed CO binding spectra characteristic of folded p450s. Even this small population exhibited significant functional diversity: chimeras displayed altered substrate specificities, a wide range in thermostabilities, up to a 40-fold increase in peroxidase activity, and ability to hydroxylate a substrate toward which neither parent heme domain shows detectable activity. These results suggest that SCHEMA-guided recombination can be used to generate diverse p450s for exploring function evolution within the p450 structural framework.

Structural Characterization of the Predominant Family of Histidine Kinase Sensor Domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Z.; Hendrickson, W

2010-01-01

Histidine kinase (HK) receptors are used ubiquitously by bacteria to monitor environmental changes, and they are also prevalent in plants, fungi, and other protists. Typical HK receptors have an extracellular sensor portion that detects a signal, usually a chemical ligand, and an intracellular transmitter portion that includes both the kinase domain itself and the site for histidine phosphorylation. While kinase domains are highly conserved, sensor domains are diverse. HK receptors function as dimers, but the molecular mechanism for signal transduction across cell membranes remains obscure. In this study, eight crystal structures were determined from five sensor domains representative of themore » most populated family, family HK1, found in a bioinformatic analysis of predicted sensor domains from transmembrane HKs. Each structure contains an inserted repeat of PhoQ/DcuS/CitA (PDC) domains, and similarity between sequence and structure is correlated across these and other double-PDC sensor proteins. Three of the five sensors crystallize as dimers that appear to be physiologically relevant, and comparisons between ligated structures and apo-state structures provide insights into signal transmission. Some HK1 family proteins prove to be sensors for chemotaxis proteins or diguanylate cyclase receptors, implying a combinatorial molecular evolution.« less

Healthy family functioning: a cross-cultural appraisal*

PubMed Central

David, Henry P.

1978-01-01

It is increasingly recognized that rapid cultural, social, economic, and technological changes are imposing increasing stress on family structures, traditional values, and the ability to adapt to new environments in different societies. For the purposes of this paper, ”healthy family functioning” is defined in terms of a family unit (however it is conceived in any given culture) effectively coping with cultural, environmental, psychosocial, and socioeconomic stresses throughout the family life cycle. While a review of international literature in the behavioural and biomedical sciences yields little data on comparative studies, there is growing awareness of the need for cooperative international research on family coping mechanisms and determinants of self-reliant communal coping behaviour, as well as more efficient utilization of already available knowledge. After consideration of methodological pitfalls of assessment procedures, there is a presentation of an evolving theory of healthy family functioning with the suggestion that studies of young married couples constitute a particularly promising vehicle for developing needed cooperative cross-cultural research. PMID:308401

A FRMD7 variant in a Japanese family causes congenital nystagmus.

PubMed

Kohmoto, Tomohiro; Okamoto, Nana; Satomura, Shigeko; Naruto, Takuya; Komori, Takahide; Hashimoto, Toshiaki; Imoto, Issei

2015-01-01

Idiopathic congenital nystagmus (ICN) is a genetically heterogeneous eye movement disorder that causes a large proportion of childhood visual impairment. Here we describe a missense variant (p.L292P) within a mutation-rich region of FRMD7 detected in three affected male siblings in a Japanese family with X-linked ICN. Combining sequence analysis and results from structural and functional predictions, we report p.L292P as a variant potentially disrupting FRMD7 function associated with X-linked ICN.

A FRMD7 variant in a Japanese family causes congenital nystagmus

PubMed Central

Kohmoto, Tomohiro; Okamoto, Nana; Satomura, Shigeko; Naruto, Takuya; Komori, Takahide; Hashimoto, Toshiaki; Imoto, Issei

2015-01-01

Idiopathic congenital nystagmus (ICN) is a genetically heterogeneous eye movement disorder that causes a large proportion of childhood visual impairment. Here we describe a missense variant (p.L292P) within a mutation-rich region of FRMD7 detected in three affected male siblings in a Japanese family with X-linked ICN. Combining sequence analysis and results from structural and functional predictions, we report p.L292P as a variant potentially disrupting FRMD7 function associated with X-linked ICN. PMID:27081518

The Leu-Arg-Glu (LRE) adhesion motif in proteins of the neuromuscular junction with special reference to proteins of the carboxylesterase/cholinesterase family.

PubMed

Johnson, Glynis; Moore, Samuel W

2013-09-01

Short linear motifs confer evolutionary flexibility on proteins as they can be added with relative ease allowing the acquisition of new functions. Such motifs may mediate a variety of signalling functions. The adhesion-mediating Leu-Arg-Glu (LRE) motif is enriched in laminin beta 2, and has been observed in other proteins, including members of the carboxylesterase/cholinesterase family. It acts as a stop signal for growing axons in the developing neuromuscular junction, binding to the voltage-gated calcium channel. In this bioinformatic analysis, we have investigated the presence of the motif in proteins of the neuromuscular junction, and have also examined its structural position and potential for ligand interaction, as well as phylogenetic conservation, in the carboxylesterase/cholinesterase family. The motif was observed to occur with a significantly higher frequency than expected in the UniProt/Swiss-Prot database, as well as in four individual species (human, mouse, Caenorhabditis elegans and Drosophila melanogaster). Examination of its presence in neuromuscular junction proteins showed it to be enriched in certain proteins of the synaptic basement membrane, including laminin, agrin, acetylcholinesterase and tenascin. A highly significant enrichment was observed in cytoskeletal proteins, particularly intermediate filament proteins and members of the spectrin family. In the carboxylesterase/cholinesterase family, the motif was observed in four conserved positions in the protein structure. It is present in the majority of mammalian acetylcholinesterases, as well as acetylcholinesterases from electric fish and a number of invertebrates. In insects, it is present in the ace-2, rather than in the synaptic ace-1, enzyme. It is also observed in the cholinesterase-like adhesion molecules (neuroligins, neurotactin and glutactin). It is never seen in butyrylcholinesterases, which do not mediate cell adhesion. In conclusion, the significant enrichment of the motif in certain classes of protein, as well as its conserved presence and structural positioning in one protein family, suggests that it has specific functions both in cell adhesion in the neuromuscular junction and in maintaining the structural integrity of the cytoskeleton. Copyright © 2013 Elsevier Inc. All rights reserved.

The catalytic mechanism of dye-decolorizing peroxidase DyP may require the swinging movement of an aspartic acid residue.

PubMed

Yoshida, Toru; Tsuge, Hideaki; Konno, Hiroki; Hisabori, Toru; Sugano, Yasushi

2011-07-01

The dye-decolorizing peroxidase (DyP)-type peroxidase family is a unique heme peroxidase family. The primary and tertiary structures of this family are obviously different from those of other heme peroxidases. However, the details of the structure-function relationships of this family remain poorly understood. We show four high-resolution structures of DyP (EC1.11.1.19), which is representative of this family: the native DyP (1.40 Å), the D171N mutant DyP (1.42 Å), the native DyP complexed with cyanide (1.45 Å), and the D171N mutant DyP associated with cyanide (1.40 Å). These structures contain four amino acids forming the binding pocket for hydrogen peroxide, and they are remarkably conserved in this family. Moreover, these structures show that OD2 of Asp171 accepts a proton from hydrogen peroxide in compound I formation, and that OD2 can swing to the appropriate position in response to the ligand for heme iron. On the basis of these results, we propose a swing mechanism in compound I formation. When DyP reacts with hydrogen peroxide, OD2 swings towards an optimal position to accept the proton from hydrogen peroxide bound to the heme iron. © 2011 The Authors Journal compilation © 2011 FEBS.

Comparative genome analysis of PHB gene family reveals deep evolutionary origins and diverse gene function.

PubMed

Di, Chao; Xu, Wenying; Su, Zhen; Yuan, Joshua S

2010-10-07

PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence, defence, and others. Despite the importance of the PHB gene family, no comprehensive gene family analysis has been carried to evaluate the relatedness of PHB genes across different species. In order to better guide the gene function analysis and understand the evolution of the PHB gene family, we therefore carried out the comparative genome analysis of the PHB genes across different kingdoms. The relatedness, motif distribution, and intron/exon distribution all indicated that PHB genes is a relatively conserved gene family. The PHB genes can be classified into 5 classes and each class have a very deep evolutionary origin. The PHB genes within the class maintained the same motif patterns during the evolution. With Arabidopsis as the model species, we found that PHB gene intron/exon structure and domains are also conserved during the evolution. Despite being a conserved gene family, various gene duplication events led to the expansion of the PHB genes. Both segmental and tandem gene duplication were involved in Arabidopsis PHB gene family expansion. However, segmental duplication is predominant in Arabidopsis. Moreover, most of the duplicated genes experienced neofunctionalization. The results highlighted that PHB genes might be involved in important functions so that the duplicated genes are under the evolutionary pressure to derive new function. PHB gene family is a conserved gene family and accounts for diverse but important biological functions based on the similar molecular mechanisms. The highly diverse biological function indicated that more research needs to be carried out to dissect the PHB gene function. The conserved gene evolution indicated that the study in the model species can be translated to human and mammalian studies.

Evolution and functional divergence of the anoctamin family of membrane proteins

PubMed Central

2010-01-01

Background The anoctamin family of transmembrane proteins are found in all eukaryotes and consists of 10 members in vertebrates. Ano1 and ano2 were observed to have Ca2+ activated Cl- channel activity. Recent findings however have revealed that ano6, and ano7 can also produce chloride currents, although with different properties. In contrast, ano9 and ano10 suppress baseline Cl- conductance when co-expressed with ano1 thus suggesting that different anoctamins can interfere with each other. In order to elucidate intrinsic functional diversity, and underlying evolutionary mechanism among anoctamins, we performed comprehensive bioinformatics analysis of anoctamin gene family. Results Our results show that anoctamin protein paralogs evolved from several gene duplication events followed by functional divergence of vertebrate anoctamins. Most of the amino acid replacements responsible for the functional divergence were fixed by adaptive evolution and this seem to be a common pattern in anoctamin gene family evolution. Strong purifying selection and the loss of many gene duplication products indicate rigid structure-function relationships among anoctamins. Conclusions Our study suggests that anoctamins have evolved by series of duplication events, and that they are constrained by purifying selection. In addition we identified a number of protein domains, and amino acid residues which contribute to predicted functional divergence. Hopefully, this work will facilitate future functional characterization of the anoctamin membrane protein family. PMID:20964844

Antecedents of basic psychological need satisfaction of pharmacy students: The role of peers, family, lecturers and workload.

PubMed

Basson, Mariëtta J; Rothmann, Sebastiaan

2018-04-01

Self-determination theory (SDT) provides a model to improve pharmacy students' well-being or functioning in their study context. According to SDT, students need a context that satisfies their needs for autonomy, relatedness and competence in order to function optimally. Contextual factors that could have an impact on a student's functioning are lecturers, family, peers and workload. To investigate whether there is a difference between the contributions family, lecturers, peers and workload make towards the satisfaction of pharmacy students' basic psychological needs within a university context. An electronic survey was administered amongst students registered with the North-West University's School of Pharmacy. Registered pharmacy students, 779, completed said electronic survey comprised of a questionnaire on demographics, BMPN (Balanced Measure of Psychological Needs) and self-developed ANPNS (Antecedents of Psychological Need-satisfaction Scale). Data derived from the afore-going was analysed with the aid of structural equation modelling (SEM). Structural equation modelling explained 46%, 25% and 30% respectively of the total group's variances in autonomy, competence and relatedness satisfaction, and 26% of the variance in psychological need frustration. Peers and family played a significant role in the satisfaction of students' need for autonomy, relatedness and competence, whilst workload seemingly hampered satisfaction with regards to relatedness and autonomy. Workload contributed towards frustration with regards to psychological need satisfaction. The role played by lecturers in satisfying pharmacy students' need for autonomy, relatedness and competence will also be highlighted. This study added to the body of knowledge regarding contextual factors and the impact those factors have on pharmacy students' need satisfaction by illustrating that not all factors (family, lecturers, peers and workload) can be considered equal. Lecturers ought to recognise the important role family and peers play in the emotional and mental wellbeing of students and utilise those factors in their teaching. The mechanism of basic psychological need satisfaction as described in Self-determination theory provide insight into pharmacy students' optimal functioning. Hence the influence of contextual factors, (lecturers, peers, family and workload) on the need satisfaction was investigated by means of a survey. The structural model explained 46%, 25% and 30% of the variances in autonomy, competence and relatedness satisfaction and 26% of the variance in psychological need frustration. Family and Peer support contributed the most to the variance explained of the variables. Lecturers should acknowledge this important role of family and peers and utilise this premise when they design learning encounters. Copyright © 2017 Elsevier Inc. All rights reserved.

Distinct families of cis-acting RNA replication elements epsilon from hepatitis B viruses

PubMed Central

Chen, Augustine; Brown, Chris

2012-01-01

The hepadnavirus encapsidation signal, epsilon (ε), is an RNA structure located at the 5′ end of the viral pregenomic RNA. It is essential for viral replication and functions in polymerase protein binding and priming. This structure could also have potential regulatory roles in controlling the expression of viral replicative proteins. In addition to its structure, the primary sequence of this RNA element has crucial functional roles in the viral lifecycle. Although the ε elements in hepadnaviruses share common critical functions, there are some significant differences in mammalian and avian hepadnaviruses, which include both sequence and structural variations.   Here we present several covariance models for ε elements from the Hepadnaviridae. The model building included experimentally determined data from previous studies using chemical probing and NMR analysis. These models have sufficient similarity to comprise a clan. The clan has in common a highly conserved overall structure consisting of a lower-stem, bulge, upper-stem and apical-loop. The models differ in functionally critical regions—notably the two types of avian ε elements have a tetra-loop (UGUU) including a non-canonical UU base pair, while the hepatitis B virus (HBV) epsilon has a tri-loop (UGU). The avian epsilon elements have a less stable dynamic structure in the upper stem. Comparisons between these models and all other Rfam models, and searches of genomes, showed these structures are specific to the Hepadnaviridae. Two family models and the clan are available from the Rfam database. PMID:22418844

Four signature motifs define the first class of structurally related large coiled-coil proteins in plants.

PubMed Central

Gindullis, Frank; Rose, Annkatrin; Patel, Shalaka; Meier, Iris

2002-01-01

Background Animal and yeast proteins containing long coiled-coil domains are involved in attaching other proteins to the large, solid-state components of the cell. One subgroup of long coiled-coil proteins are the nuclear lamins, which are involved in attaching chromatin to the nuclear envelope and have recently been implicated in inherited human diseases. In contrast to other eukaryotes, long coiled-coil proteins have been barely investigated in plants. Results We have searched the completed Arabidopsis genome and have identified a family of structurally related long coiled-coil proteins. Filament-like plant proteins (FPP) were identified by sequence similarity to a tomato cDNA that encodes a coiled-coil protein which interacts with the nuclear envelope-associated protein, MAF1. The FPP family is defined by four novel unique sequence motifs and by two clusters of long coiled-coil domains separated by a non-coiled-coil linker. All family members are expressed in a variety of Arabidopsis tissues. A homolog sharing the structural features was identified in the monocot rice, indicating conservation among angiosperms. Conclusion Except for myosins, this is the first characterization of a family of long coiled-coil proteins in plants. The tomato homolog of the FPP family binds in a yeast two-hybrid assay to a nuclear envelope-associated protein. This might suggest that FPP family members function in nuclear envelope biology. Because the full Arabidopsis genome does not appear to contain genes for lamins, it is of interest to investigate other long coiled-coil proteins, which might functionally replace lamins in the plant kingdom. PMID:11972898

The impact of HIV/AIDS on the family and other significant relationships: the African clan revisited.

PubMed

Ankrah, E M

1993-01-01

Although changing in size, structure and function, the African family has persistently maintained its place as the central human social unit. Beyond the traditional African family--whether in the nuclear or the extended form--is a network of people, most of whom are connected by kin or blood relationships, termed the clanship system. Patterns of family treatment and care are deeply embedded in this wider kinship system. The AIDS epidemic has caused adverse psychosocial and economic consequences leading to change in the family structure, and thus disturbed the capacity of the nuclear and extended family to respond to the needs of members afflicted by HIV and AIDS. Hence, the clanship system could become the locus of AIDS activity designed to ensure the well-being and continuity of the family where its leadership undertakes to sustain, to reorganize, or to create wholly new families or structures among populations being devastated by AIDS. New associations based on common emotional bonds of caring beyond kinship ties will be necessary to support some vulnerable members. However, for such to prove durable in the troubled socio-economic context of Sub-Saharan Africa, these will need strong links to or derive their legitimacy from the resilient traditional social network, the African kinship system.

SACCHARIS: an automated pipeline to streamline discovery of carbohydrate active enzyme activities within polyspecific families and de novo sequence datasets.

PubMed

Jones, Darryl R; Thomas, Dallas; Alger, Nicholas; Ghavidel, Ata; Inglis, G Douglas; Abbott, D Wade

2018-01-01

Deposition of new genetic sequences in online databases is expanding at an unprecedented rate. As a result, sequence identification continues to outpace functional characterization of carbohydrate active enzymes (CAZymes). In this paradigm, the discovery of enzymes with novel functions is often hindered by high volumes of uncharacterized sequences particularly when the enzyme sequence belongs to a family that exhibits diverse functional specificities (i.e., polyspecificity). Therefore, to direct sequence-based discovery and characterization of new enzyme activities we have developed an automated in silico pipeline entitled: Sequence Analysis and Clustering of CarboHydrate Active enzymes for Rapid Informed prediction of Specificity (SACCHARIS). This pipeline streamlines the selection of uncharacterized sequences for discovery of new CAZyme or CBM specificity from families currently maintained on the CAZy website or within user-defined datasets. SACCHARIS was used to generate a phylogenetic tree of a GH43, a CAZyme family with defined subfamily designations. This analysis confirmed that large datasets can be organized into sequence clusters of manageable sizes that possess related functions. Seeding this tree with a GH43 sequence from Bacteroides dorei DSM 17855 (BdGH43b, revealed it partitioned as a single sequence within the tree. This pattern was consistent with it possessing a unique enzyme activity for GH43 as BdGH43b is the first described α-glucanase described for this family. The capacity of SACCHARIS to extract and cluster characterized carbohydrate binding module sequences was demonstrated using family 6 CBMs (i.e., CBM6s). This CBM family displays a polyspecific ligand binding profile and contains many structurally determined members. Using SACCHARIS to identify a cluster of divergent sequences, a CBM6 sequence from a unique clade was demonstrated to bind yeast mannan, which represents the first description of an α-mannan binding CBM. Additionally, we have performed a CAZome analysis of an in-house sequenced bacterial genome and a comparative analysis of B. thetaiotaomicron VPI-5482 and B. thetaiotaomicron 7330, to demonstrate that SACCHARIS can generate "CAZome fingerprints", which differentiate between the saccharolytic potential of two related strains in silico. Establishing sequence-function and sequence-structure relationships in polyspecific CAZyme families are promising approaches for streamlining enzyme discovery. SACCHARIS facilitates this process by embedding CAZyme and CBM family trees generated from biochemically to structurally characterized sequences, with protein sequences that have unknown functions. In addition, these trees can be integrated with user-defined datasets (e.g., genomics, metagenomics, and transcriptomics) to inform experimental characterization of new CAZymes or CBMs not currently curated, and for researchers to compare differential sequence patterns between entire CAZomes. In this light, SACCHARIS provides an in silico tool that can be tailored for enzyme bioprospecting in datasets of increasing complexity and for diverse applications in glycobiotechnology.

Identification of GH15 Family Thermophilic Archaeal Trehalases That Function within a Narrow Acidic-pH Range.

PubMed

Sakaguchi, Masayoshi; Shimodaira, Satoru; Ishida, Shin-Nosuke; Amemiya, Miko; Honda, Shotaro; Sugahara, Yasusato; Oyama, Fumitaka; Kawakita, Masao

2015-08-01

Two glucoamylase-like genes, TVN1315 and Ta0286, from the archaea Thermoplasma volcanium and T. acidophilum, respectively, were expressed in Escherichia coli. The gene products, TVN1315 and Ta0286, were identified as archaeal trehalases. These trehalases belong to the CAZy database family GH15, although they have putative (α/α)6 barrel catalytic domain structures similar to those of GH37 and GH65 family trehalases from other organisms. These newly identified trehalases function within a narrow range of acidic pH values (pH 3.2 to 4.0) and at high temperatures (50 to 60°C), and these enzymes display Km values for trehalose higher than those observed for typical trehalases. These enzymes were inhibited by validamycin A; however, the inhibition constants (Ki) were higher than those of other trehalases. Three TVN1315 mutants, corresponding to E408Q, E571Q, and E408Q/E571Q mutations, showed reduced activity, suggesting that these two glutamic acid residues are involved in trehalase catalysis in a manner similar to that of glucoamylase. To date, TVN1315 and Ta0286 are the first archaeal trehalases to be identified, and this is the first report of the heterologous expression of GH15 family trehalases. The identification of these trehalases could extend our understanding of the relationships between the structure and function of GH15 family enzymes as well as glycoside hydrolase family enzymes; additionally, these enzymes provide insight into archaeal trehalose metabolism. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Structure and Function of the Intracellular Region of the Plexin-B1 Transmembrane Receptor*

PubMed Central

Tong, Yufeng; Hota, Prasanta K.; Penachioni, Junia Y.; Hamaneh, Mehdi B.; Kim, SoonJeung; Alviani, Rebecca S.; Shen, Limin; He, Hao; Tempel, Wolfram; Tamagnone, Luca; Park, Hee-Won; Buck, Matthias

2009-01-01

Members of the plexin family are unique transmembrane receptors in that they interact directly with Rho family small GTPases; moreover, they contain a GTPase-activating protein (GAP) domain for R-Ras, which is crucial for plexin-mediated regulation of cell motility. However, the functional role and structural basis of the interactions between the different intracellular domains of plexins remained unclear. Here we present the 2.4 Å crystal structure of the complete intracellular region of human plexin-B1. The structure is monomeric and reveals that the GAP domain is folded into one structure from two segments, separated by the Rho GTPase binding domain (RBD). The RBD is not dimerized, as observed previously. Instead, binding of a conserved loop region appears to compete with dimerization and anchors the RBD to the GAP domain. Cell-based assays on mutant proteins confirm the functional importance of this coupling loop. Molecular modeling based on structural homology to p120GAP·H-Ras suggests that Ras GTPases can bind to the plexin GAP region. Experimentally, we show that the monomeric intracellular plexin-B1 binds R-Ras but not H-Ras. These findings suggest that the monomeric form of the intracellular region is primed for GAP activity and extend a model for plexin activation. PMID:19843518

Structure–Function Studies of DNA Polymerase λ

PubMed Central

2015-01-01

DNA polymerase λ (pol λ) functions in DNA repair with its main roles considered to be filling short gaps during repair of double-strand breaks by nonhomologous end joining and during base excision repair. As indicated by structural and biochemical studies over the past 10 years, pol λ shares many common properties with other family X siblings (pol β, pol μ, and terminal deoxynucleotidyl transferase) but also has unique structural features that determine its specific functions. In this review, we consider how structural studies over the past decade furthered our understanding of the behavior and biological roles of pol λ. PMID:24716527

Predicting condom use attitudes, norms, and control beliefs in Hispanic problem behavior youth: the effects of family functioning and parent-adolescent communication about sex on condom use.

PubMed

Malcolm, Shandey; Huang, Shi; Cordova, David; Freitas, Derek; Arzon, Margaret; Jimenez, Giselle Leon; Pantin, Hilda; Prado, Guillermo

2013-08-01

Hispanic problem behavior youth are at an increased risk of engaging in HIV risk behaviors, including low condom use. However, relatively little research has examined factors that affect condom use in this population. Although research indicates that family processes, such as higher levels of family functioning and open parent-adolescent communication about sex, and condom use attitudes, norms, and control beliefs as depicted by the theory of planned behavior have an effect on condom use behaviors, the combination of the two factors has received minimal attention. The purpose of this study was to examine the effect of family functioning on condom use intentions and behaviors through communication about sex and condom use attitudes, parental norms, and control beliefs. A cross-sectional study of 171 predominately male (73.1%) sexually active Hispanic problem behavior adolescents (mean age = 14.88 years) was conducted. Structural equation modeling was used to test the study hypothesis. Findings largely support the overall model and suggest that family functioning had an indirect effect on condom use intention and behavior through communication about sex, condom use attitudes, and control beliefs. Family functioning, however, did not have an indirect effect on condom use intention and behavior through communication about sex and parental norms. Implications for prevention science and future research are discussed.

Maternal Emotion Regulation and Adolescent Behaviors: The Mediating Role of Family Functioning and Parenting.

PubMed

Crandall, AliceAnn; Ghazarian, Sharon R; Day, Randal D; Riley, Anne W

2016-11-01

Prior research links poor maternal emotion regulation to maladaptive parenting and child behaviors, but little research is available on these relationships during the adolescent period. We use structural equation modeling to assess the influence of poor maternal emotion regulation, measured as emotional reactivity and distancing, on adolescent behaviors (measured as aggression and prosocial behaviors) among 478 adolescents (53 % female; baseline age 10-13 years) and their mothers over a 5 year period. We also tested the possible mediating roles of family functioning and parenting behaviors between maternal emotion regulation and adolescent behaviors. Results indicated that higher baseline maternal emotional distancing and reactivity were not directly predictive of adolescents' behaviors, but they were indirectly related through family functioning and parenting. Specifically, indulgent parenting mediated the relationship between maternal emotional reactivity and adolescent aggression. Maternal-reported family functioning significantly mediated the relationship between maternal emotional distancing and adolescent aggression. Family functioning also mediated the relationship between emotional distancing and regulation parenting. The results imply that poor maternal emotion regulation during their child's early adolescence leads to more maladaptive parenting and problematic behaviors during the later adolescent period. However, healthy family processes may ameliorate the negative impact of low maternal emotion regulation on parenting and adolescent behavioral outcomes. The implications for future research and interventions to improve parenting and adolescent outcomes are discussed.

3D RNA and functional interactions from evolutionary couplings

PubMed Central

Weinreb, Caleb; Riesselman, Adam; Ingraham, John B.; Gross, Torsten; Sander, Chris; Marks, Debora S.

2016-01-01

Summary Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces research on their structure and functional interactions. We mine the evolutionary sequence record to derive precise information about function and structure of RNAs and RNA-protein complexes. As in protein structure prediction, we use maximum entropy global probability models of sequence co-variation to infer evolutionarily constrained nucleotide-nucleotide interactions within RNA molecules, and nucleotide-amino acid interactions in RNA-protein complexes. The predicted contacts allow all-atom blinded 3D structure prediction at good accuracy for several known RNA structures and RNA-protein complexes. For unknown structures, we predict contacts in 160 non-coding RNA families. Beyond 3D structure prediction, evolutionary couplings help identify important functional interactions, e.g., at switch points in riboswitches and at a complex nucleation site in HIV. Aided by accelerating sequence accumulation, evolutionary coupling analysis can accelerate the discovery of functional interactions and 3D structures involving RNA. PMID:27087444

Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins.

PubMed

Aouacheria, Abdel; Baghdiguian, Stephen; Lamb, Heather M; Huska, Jason D; Pineda, Fernando J; Hardwick, J Marie

2017-10-01

The morphology of a population of mitochondria is the result of several interacting dynamical phenomena, including fission, fusion, movement, elimination and biogenesis. Each of these phenomena is controlled by underlying molecular machinery, and when defective can cause disease. New understanding of the relationships between form and function of mitochondria in health and disease is beginning to be unraveled on several fronts. Studies in mammals and model organisms have revealed that mitochondrial morphology, dynamics and function appear to be subject to regulation by the same proteins that regulate apoptotic cell death. One protein family that influences mitochondrial dynamics in both healthy and dying cells is the Bcl-2 protein family. Connecting mitochondrial dynamics with life-death pathway forks may arise from the intersection of Bcl-2 family proteins with the proteins and lipids that determine mitochondrial shape and function. Bcl-2 family proteins also have multifaceted influences on cells and mitochondria, including calcium handling, autophagy and energetics, as well as the subcellular localization of mitochondrial organelles to neuronal synapses. The remarkable range of physical or functional interactions by Bcl-2 family proteins is challenging to assimilate into a cohesive understanding. Most of their effects may be distinct from their direct roles in apoptotic cell death and are particularly apparent in the nervous system. Dual roles in mitochondrial dynamics and cell death extend beyond BCL-2 family proteins. In this review, we discuss many processes that govern mitochondrial structure and function in health and disease, and how Bcl-2 family proteins integrate into some of these processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Expression, Purification, and Structural Insights for the Human Uric Acid Transporter, GLUT9, Using the Xenopus laevis Oocytes System

PubMed Central

Clémençon, Benjamin; Lüscher, Benjamin P.; Fine, Michael; Baumann, Marc U.; Surbek, Daniel V.; Bonny, Olivier; Hediger, Matthias A.

2014-01-01

The urate transporter, GLUT9, is responsible for the basolateral transport of urate in the proximal tubule of human kidneys and in the placenta, playing a central role in uric acid homeostasis. GLUT9 shares the least homology with other members of the glucose transporter family, especially with the glucose transporting members GLUT1-4 and is the only member of the GLUT family to transport urate. The recently published high-resolution structure of XylE, a bacterial D-xylose transporting homologue, yields new insights into the structural foundation of this GLUT family of proteins. While this represents a huge milestone, it is unclear if human GLUT9 can benefit from this advancement through subsequent structural based targeting and mutagenesis. Little progress has been made toward understanding the mechanism of GLUT9 since its discovery in 2000. Before work can begin on resolving the mechanisms of urate transport we must determine methods to express, purify and analyze hGLUT9 using a model system adept in expressing human membrane proteins. Here, we describe the surface expression, purification and isolation of monomeric protein, and functional analysis of recombinant hGLUT9 using the Xenopus laevis oocyte system. In addition, we generated a new homology-based high-resolution model of hGLUT9 from the XylE crystal structure and utilized our purified protein to generate a low-resolution single particle reconstruction. Interestingly, we demonstrate that the functional protein extracted from the Xenopus system fits well with the homology-based model allowing us to generate the predicted urate-binding pocket and pave a path for subsequent mutagenesis and structure-function studies. PMID:25286413

Structural genomics analysis of uncharacterized protein families overrepresented in human gut bacteria identifies a novel glycoside hydrolase

PubMed Central

2014-01-01

Background Bacteroides spp. form a significant part of our gut microbiome and are well known for optimized metabolism of diverse polysaccharides. Initial analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172 glycosyl hydrolases and a large number of uncharacterized proteins associated with polysaccharide metabolism. Results BT_1012 from Bacteroides thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a large protein family consisting entirely of uncharacterized proteins. Initial sequence analysis predicted that this protein has two domains, one on the N- and one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90 half size homologs consisting only of the N-terminal domain. The experimentally determined three-dimensional structure of the BT_1012 protein confirms its two-domain architecture and structural analysis of both domains suggests their specific functions. The N-terminal domain is a putative catalytic domain with significant similarity to known glycoside hydrolases, the C-terminal domain has a beta-sandwich fold typically found in C-terminal domains of other glycosyl hydrolases, however these domains are typically involved in substrate binding. We describe the structure of the BT_1012 protein and discuss its sequence-structure relationship and their possible functional implications. Conclusions Structural and sequence analyses of the BT_1012 protein identifies it as a glycosyl hydrolase, expanding an already impressive catalog of enzymes involved in polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the Pfam families representing the two domains found in the BT_1012 protein, PF13204 and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C-terminal domain respectively. PMID:24742328

Cavin Family: New Players in the Biology of Caveolae.

PubMed

Nassar, Zeyad D; Parat, Marie-Odile

2015-01-01

Caveolae are specialized small plasma-membrane invaginations that play crucial cellular functions. Two essential protein families are required for caveola formation: membrane caveolin proteins and cytoplasmic cavin proteins. Each family includes members with specific tissue distribution, and their expression is altered under physiological and pathological conditions, implying highly specialized functions. Cavins not only stabilize caveolae, but modulate their morphology and functions as well. Before association with the plasma membrane, cavins form homo- and hetero-oligomers with strikingly strict stoichiometry in the cytosol. At the plasma membrane, they provide an outer peripheral cytosolic layer, necessary for caveola stability. Interestingly, upon stimulation, cavins can be released from caveolae into the cytoplasm in distinct subcomplexes, providing a rapid dynamic link between caveolae and cellular organelles including the nucleus. In this review, we detail the biology of cavins, their structural and functional roles, and their implication in pathophysiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuroglobin and cytoglobin: two new members of globin family

PubMed Central

Tosqui, Priscilla; Colombo, Marcio Francisco

2011-01-01

The globin family has long been defined by myoglobin and hemoglobin, proteins with the functions of oxygen storage and transportation, respectively. Recently, two new members of this family were discovered: neuroglobin present in neurons and retinal cells and cytoglobin found in various types of tissue. The increased expression of these proteins in hypoxic conditions first suggested a role in oxygen supply. However structural and functional differences, such as the hexacoordinated heme, a high autoxidation rate and different concentrations between different cellular types, have dismissed this hypothesis. The protective role of these globins has already been established. In vitro and in vivo studies have demonstrated increased survival of neurons under stress in the presence of neuroglobin and increased resistance to neurodegenerative diseases. However the mechanism remains unknown. Functions, including detoxification of nitric oxide, free radical scavenging and as an antioxidant and signaling of apoptosis, have also been suggested for neuroglobin and an antifibrotic function for cytoglobin. PMID:23049323

Structure and DNA-Binding Sites of the SWI1 AT-rich Interaction Domain (ARID) Suggest Determinants for Sequence-Specific DNA Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Suhkmann; Zhang, Ziming; Upchurch, Sean

2004-04-16

2 ARID is a homologous family of DNA-binding domains that occur in DNA binding proteins from a wide variety of species, ranging from yeast to nematodes, insects, mammals and plants. SWI1, a member of the SWI/SNF protein complex that is involved in chromatin remodeling during transcription, contains the ARID motif. The ARID domain of human SWI1 (also known as p270) does not select for a specific DNA sequence from a random sequence pool. The lack of sequence specificity shown by the SWI1 ARID domain stands in contrast to the other characterized ARID domains, which recognize specific AT-rich sequences. We havemore » solved the three-dimensional structure of human SWI1 ARID using solution NMR methods. In addition, we have characterized non-specific DNA-binding by the SWI1 ARID domain. Results from this study indicate that a flexible long internal loop in ARID motif is likely to be important for sequence specific DNA-recognition. The structure of human SWI1 ARID domain also represents a distinct structural subfamily. Studies of ARID indicate that boundary of the DNA binding structural and functional domains can extend beyond the sequence homologous region in a homologous family of proteins. Structural studies of homologous domains such as ARID family of DNA-binding domains should provide information to better predict the boundary of structural and functional domains in structural genomic studies. Key Words: ARID, SWI1, NMR, structural genomics, protein-DNA interaction.« less

Complete Reversible Refolding of a G-Protein Coupled Receptor on a Solid Support

PubMed Central

Di Bartolo, Natalie; Compton, Emma L. R.; Warne, Tony; Edwards, Patricia C.; Tate, Christopher G.; Schertler, Gebhard F. X.; Booth, Paula J.

2016-01-01

The factors defining the correct folding and stability of integral membrane proteins are poorly understood. Folding of only a few select membrane proteins has been scrutinised, leaving considerable deficiencies in knowledge for large protein families, such as G protein coupled receptors (GPCRs). Complete reversible folding, which is problematic for any membrane protein, has eluded this dominant receptor family. Moreover, attempts to recover receptors from denatured states are inefficient, yielding at best 40–70% functional protein. We present a method for the reversible unfolding of an archetypal family member, the β1-adrenergic receptor, and attain 100% recovery of the folded, functional state, in terms of ligand binding, compared to receptor which has not been subject to any unfolding and retains its original, folded structure. We exploit refolding on a solid support, which could avoid unwanted interactions and aggregation that occur in bulk solution. We determine the changes in structure and function upon unfolding and refolding. Additionally, we employ a method that is relatively new to membrane protein folding; pulse proteolysis. Complete refolding of β1-adrenergic receptor occurs in n-decyl-β-D-maltoside (DM) micelles from a urea-denatured state, as shown by regain of its original helical structure, ligand binding and protein fluorescence. The successful refolding strategy on a solid support offers a defined method for the controlled refolding and recovery of functional GPCRs and other membrane proteins that suffer from instability and irreversible denaturation once isolated from their native membranes. PMID:26982879

Structural and interpersonal characteristics of family meals: associations with adolescent body mass index and dietary patterns.

PubMed

Berge, Jerica M; Jin, Seok Won; Hannan, Peter; Neumark-Sztainer, Dianne

2013-06-01

The last decade of research has suggested that family meals play an important role in promoting healthful dietary intake in youth. However, little is known about the structural characteristics and interpersonal dynamics of family meals that might help to inform why family meals are protective for youth. The current mixed methods, cross-sectional study conducted in 2010-2011 includes adolescents and parents who participated in two linked population-based studies. Participants included 40 parents (91.5% female) and adolescents (57.5% female) from the Minneapolis/St Paul, MN, area participating in EAT (Eating and Activity Among Teens) 2010 and F-EAT (Families and Eating and Activity Among Teens). The structural (eg, length of the meal, types of foods served) and interpersonal characteristics (eg, communication, emotion/affect management) of family meals were described, and associations between interpersonal dynamics at family meals and adolescent body mass index and dietary intake were examined via direct observational methods. Families were videorecorded during two mealtimes in their homes. Results indicated that family meals were approximately 20 minutes in length, included multiple family members, were typically served family style (70%), and occurred in the kitchen 62% of the time and 38% of the time in another room (eg, family room, office). In addition, significant associations were found between positive interpersonal dynamics (ie, communication, affect management, interpersonal involvement, overall family functioning) at family meals and lower adolescent body mass index and higher vegetable intake. These findings add to the growing body of literature on family meals by providing a better understanding of what is happening at family meals in order to inform obesity-prevention studies and recommendations for providers working with families of youth. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Structural diversity in the dandelion (Taraxacum officinale) polyphenol oxidase family results in different responses to model substrates.

PubMed

Dirks-Hofmeister, Mareike E; Singh, Ratna; Leufken, Christine M; Inlow, Jennifer K; Moerschbacher, Bruno M

2014-01-01

Polyphenol oxidases (PPOs) are ubiquitous type-3 copper enzymes that catalyze the oxygen-dependent conversion of o-diphenols to the corresponding quinones. In most plants, PPOs are present as multiple isoenzymes that probably serve distinct functions, although the precise relationship between sequence, structure and function has not been addressed in detail. We therefore compared the characteristics and activities of recombinant dandelion PPOs to gain insight into the structure-function relationships within the plant PPO family. Phylogenetic analysis resolved the 11 isoenzymes of dandelion into two evolutionary groups. More detailed in silico and in vitro analyses of four representative PPOs covering both phylogenetic groups were performed. Molecular modeling and docking predicted differences in enzyme-substrate interactions, providing a structure-based explanation for grouping. One amino acid side chain positioned at the entrance to the active site (position HB2+1) potentially acts as a "selector" for substrate binding. In vitro activity measurements with the recombinant, purified enzymes also revealed group-specific differences in kinetic parameters when the selected PPOs were presented with five model substrates. The combination of our enzyme kinetic measurements and the in silico docking studies therefore indicate that the physiological functions of individual PPOs might be defined by their specific interactions with different natural substrates.

pocketZebra: a web-server for automated selection and classification of subfamily-specific binding sites by bioinformatic analysis of diverse protein families.

PubMed

Suplatov, Dmitry; Kirilin, Eugeny; Arbatsky, Mikhail; Takhaveev, Vakil; Svedas, Vytas

2014-07-01

The new web-server pocketZebra implements the power of bioinformatics and geometry-based structural approaches to identify and rank subfamily-specific binding sites in proteins by functional significance, and select particular positions in the structure that determine selective accommodation of ligands. A new scoring function has been developed to annotate binding sites by the presence of the subfamily-specific positions in diverse protein families. pocketZebra web-server has multiple input modes to meet the needs of users with different experience in bioinformatics. The server provides on-site visualization of the results as well as off-line version of the output in annotated text format and as PyMol sessions ready for structural analysis. pocketZebra can be used to study structure-function relationship and regulation in large protein superfamilies, classify functionally important binding sites and annotate proteins with unknown function. The server can be used to engineer ligand-binding sites and allosteric regulation of enzymes, or implemented in a drug discovery process to search for potential molecular targets and novel selective inhibitors/effectors. The server, documentation and examples are freely available at http://biokinet.belozersky.msu.ru/pocketzebra and there are no login requirements. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structural and enzymatic characterization of a host-specificity determinant from Salmonella

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohler, Amanda C.; Spanò, Stefania; Galán, Jorge E.

The Salmonella effector protein GtgE functions as a cysteine protease to cleave a subset of the Rab-family GTPases and to prevent delivery of antimicrobial agents to the Salmonella-containing vacuole. GtgE is an effector protein from Salmonella Typhimurium that modulates trafficking of the Salmonella-containing vacuole. It exerts its function by cleaving the Rab-family GTPases Rab29, Rab32 and Rab38, thereby preventing the delivery of antimicrobial factors to the bacteria-containing vacuole. Here, the crystal structure of GtgE at 1.65 Å resolution is presented, and structure-based mutagenesis and in vivo infection assays are used to identify its catalytic triad. A panel of cysteine proteasemore » inhibitors were examined and it was determined that N-ethylmaleimide, antipain and chymostatin inhibit GtgE activity in vitro. These findings provide the basis for the development of novel therapeutic strategies to combat Salmonella infections.« less

Amino acid sequence analysis of the annexin super-gene family of proteins.

PubMed

Barton, G J; Newman, R H; Freemont, P S; Crumpton, M J

1991-06-15

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of the predictions and shows the power of techniques for the determination of tertiary structural information from the amino acid sequences of an aligned protein family.

Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps

DOE PAGES

Su, Chih -Chia; Bolla, Jani  Reddy; Kumar, Nitin; ...

2015-04-01

Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein that belongs to the AbgT family of transporters for which no structural information is available. Here, we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm tomore » halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump mediating bacterial resistance to sulfonamide antimetabolite drugs.« less

Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps

PubMed Central

Su, Chih-Chia; Bolla, Jani Reddy; Kumar, Nitin; Radhakrishnan, Abhijith; Long, Feng; Delmar, Jared A.; Chou, Tsung-Han; Rajashankar, Kanagalaghatta R.; Shafer, William M.; Yu, Edward W.

2015-01-01

SUMMARY Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually-transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein, which belongs to the AbgT family of transporters for which no structural information is available. Here we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump, mediating bacterial resistance to sulfonamide antimetabolite drugs. PMID:25818299

The Extended Granin Family: Structure, Function, and Biomedical Implications

PubMed Central

Bartolomucci, Alessandro; Possenti, Roberta; Mahata, Sushil K.; Fischer-Colbrie, Reiner; Loh, Y. Peng

2011-01-01

The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers. PMID:21862681

The extended granin family: structure, function, and biomedical implications.

PubMed

Bartolomucci, Alessandro; Possenti, Roberta; Mahata, Sushil K; Fischer-Colbrie, Reiner; Loh, Y Peng; Salton, Stephen R J

2011-12-01

The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers. Copyright © 2011 by The Endocrine Society

Family Functions and Children's Post-Divorce Adjustment.

ERIC Educational Resources Information Center

Portes, Pedro R.; And Others

Divorce is common phenomenon in the lives of many persons today. It changes the structure of the family and, in so doing, changes the lives of the couples involved and presents the children of divorce with their own set of adjustment issues. This study examined the literature on children's overall adjustment to divorce. Subjects (N=102) were…

Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides.

PubMed

Boonen, Jente; Bronselaer, Antoon; Nielandt, Joachim; Veryser, Lieselotte; De Tré, Guy; De Spiegeleer, Bart

2012-08-01

N-Alkylamides (NAAs) are a promising group of bioactive compounds, which are anticipated to act as important lead compounds for plant protection and biocidal products, functional food, cosmeceuticals and drugs in the next decennia. These molecules, currently found in more than 25 plant families and with a wide structural diversity, exert a variety of biological-pharmacological effects and are of high ethnopharmacological importance. However, information is scattered in literature, with different, often unstandardized, pharmacological methodologies being used. Therefore, a comprehensive NAA database (acronym: Alkamid) was constructed to collect the available structural and functional NAA data, linked to their occurrence in plants (family, tribe, species, genus). For loading information in the database, literature data was gathered over the period 1950-2010, by using several search engines. In order to represent the collected information about NAAs, the plants in which they occur and the functionalities for which they have been examined, a relational database is constructed and implemented on a MySQL back-end. The database is supported by describing the NAA plant-, functional- and chemical-space. The chemical space includes a NAA classification, according to their fatty acid and amine structures. The Alkamid database (publicly available on the website http://alkamid.ugent.be/) is not only a central information point, but can also function as a useful tool to prioritize the NAA choice in the evaluation of their functionality, to perform data mining leading to quantitative structure-property relationships (QSPRs), functionality comparisons, clustering, plant biochemistry and taxonomic evaluations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Is family functioning and communication associated with health-related quality of life for Chinese- and Korean-American breast cancer survivors?

PubMed

Lim, Jung-won; Ashing-Giwa, Kimlin T

2013-08-01

This study aims to investigate direct and indirect pathways of family flexibility, social support, and family communication on health-related quality of life (HRQOL) for Chinese- and Korean-American breast cancer survivors (BCS). A total of 157 Chinese (n = 86)- and Korean-American (n = 71) BCS were recruited from the California Cancer Surveillance Program and area hospitals in Los Angeles County. The present study was guided by the Resiliency Model of Family Stress, Adjustment, and Adaptation. Structural equation modeling demonstrated that (1) family communication was directly associated with HRQOL for both groups; (2) family flexibility was indirectly associated with HRQOL through family communication for Korean-Americans only; (3) social support mediated the relationship between family flexibility and family communication for Chinese-Americans only; and (4) acculturation was directly related to social support for both groups. Multigroup analysis demonstrated that the structural paths were equivalent between Chinese- and Korean-American BCS, although statistical differences in baseline parameters were noted. Our findings suggest that family communication impacts HRQOL among Asian-American BCS. Our results show that while there are commonalities in family characteristics among Asian-Americans, specific ethnic variations also exist. Therefore, specific cultural and familial contexts should be assessed to better inform interventions to enhance family communication strategies and improve HRQOL.

Unique Structural and Nucleotide Exchange Features of the Rho1 GTPase of Entamoeba histolytica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosch, Dustin E.; Wittchen, Erika S.; Qiu, Connie

The single-celled human parasite Entamoeba histolytica possesses a dynamic actin cytoskeleton vital for its intestinal and systemic pathogenicity. The E. histolytica genome encodes several Rho family GTPases known to regulate cytoskeletal dynamics. EhRho1, the first family member identified, was reported to be insensitive to the Rho GTPase-specific Clostridium botulinum C3 exoenzyme, raising the possibility that it may be a misclassified Ras family member. Here, we report the crystal structures of EhRho1 in both active and inactive states. EhRho1 is activated by a conserved switch mechanism, but diverges from mammalian Rho GTPases in lacking a signature Rho insert helix. EhRho1 engagesmore » a homolog of mDia, EhFormin1, suggesting a role in mediating serum-stimulated actin reorganization and microtubule formation during mitosis. EhRho1, but not a constitutively active mutant, interacts with a newly identified EhRhoGDI in a prenylation-dependent manner. Furthermore, constitutively active EhRho1 induces actin stress fiber formation in mammalian fibroblasts, thereby identifying it as a functional Rho family GTPase. EhRho1 exhibits a fast rate of nucleotide exchange relative to mammalian Rho GTPases due to a distinctive switch one isoleucine residue reminiscent of the constitutively active F28L mutation in human Cdc42, which for the latter protein, is sufficient for cellular transformation. Nonconserved, nucleotide-interacting residues within EhRho1, revealed by the crystal structure models, were observed to contribute a moderating influence on fast spontaneous nucleotide exchange. Collectively, these observations indicate that EhRho1 is a bona fide member of the Rho GTPase family, albeit with unique structural and functional aspects compared with mammalian Rho GTPases.« less

Structural and Interpersonal Characteristics of Family Meals: Associations with Adolescent BMI and Dietary Patterns

PubMed Central

Berge, Jerica M.; Jin, Seok Won; Hannan, Peter; Neumark-Sztainer, Dianne

2013-01-01

The last decade of research has suggested that family meals play an important role in promoting healthful dietary intake in youth. However, little is known about the structural characteristics and interpersonal dynamics of family meals that may help to inform why family meals are protective for youth. The current mixed methods, cross-sectional study conducted in 2010–2011 includes adolescents and parents who participated in two linked population-based studies. Participants included 40 parents (91.5% female) and adolescents (57.5% female) from the Minneapolis/St. Paul area participating in EAT 2010 and F-EAT. The structural (e.g. length of the meal, types of foods served) and interpersonal characteristics (e.g., communication, emotion/affect management) of family meals were described and associations between interpersonal dynamics at family meals and adolescent body mass index (BMI) and dietary intake were examined via direct observational methods. Families were video-recorded during two mealtimes in their homes. Results indicated that family meals were approximately 20 minutes in length, included multiple family members, were typically served family style (70%) and occurred in the kitchen 62% of the time and 38% of the time in another room (e.g., family room, office). Additionally, significant associations were found between positive interpersonal dynamics (i.e., communication, affect management, interpersonal involvement, overall family functioning) at family meals and lower adolescent BMI and higher vegetable intake. These findings add to the growing body of literature on family meals by providing a better understanding of what is happening at family meals in order to inform obesity prevention studies and recommendations for providers working with families of youth. PMID:23567247

Abnormal swelling of the peritrophic membrane in Eri silkworm gut caused by MLX56 family defense proteins with chitin-binding and extensin domains.

PubMed

Konno, Kotaro; Shimura, Sachiko; Ueno, Chihiro; Arakawa, Toru; Nakamura, Masatoshi

2018-03-01

MLX56 family defense proteins, MLX56 and its close homolog LA-b, are chitin-binding defense proteins found in mulberry latex that show strong growth-inhibitions against caterpillars when fed at concentrations as low as 0.01%. MLX56 family proteins contain a unique structure with an extensin domain surrounded by two hevein-like chitin-binding domains, but their defensive modes of action remain unclear. Here, we analyzed the effects of MLX56 family proteins on the peritrophic membrane (PM), a thin and soft membrane consisting of chitin that lines the midgut lumen of insects. We observed an abnormally thick (>1/5 the diameter of midgut) hard gel-like membrane consisted of chitin and MLX56 family proteins, MLX56 and LA-b, in the midgut of the Eri silkworms, Samia ricini, fed a diet containing MLX56 family proteins, MLX56 and LA-b. When polyoxin AL, a chitin-synthesis-inhibitor, was added to the diet containing MLX56 family proteins, the toxicity of MLX56 family proteins disappeared and PM became thinner and fragmented. These results suggest that MLX56 family proteins, through their chitin-binding domains, bind to the chitin framework of PM, then through their extensin-domain (gum arabic-like structure), which functions as swelling agent, expands PM into an abnormally thick membrane that inhibits the growth of insects. This study shows that MLX56 family proteins are plant defense lectins with a totally unique mode of action, and reveals the functions of extensin domains and arabinogalactan proteins as swelling (gel-forming) agents of plants. Copyright © 2018 Elsevier Ltd. All rights reserved.

GeneFarm, structural and functional annotation of Arabidopsis gene and protein families by a network of experts

PubMed Central

Aubourg, Sébastien; Brunaud, Véronique; Bruyère, Clémence; Cock, Mark; Cooke, Richard; Cottet, Annick; Couloux, Arnaud; Déhais, Patrice; Deléage, Gilbert; Duclert, Aymeric; Echeverria, Manuel; Eschbach, Aimée; Falconet, Denis; Filippi, Ghislain; Gaspin, Christine; Geourjon, Christophe; Grienenberger, Jean-Michel; Houlné, Guy; Jamet, Elisabeth; Lechauve, Frédéric; Leleu, Olivier; Leroy, Philippe; Mache, Régis; Meyer, Christian; Nedjari, Hafed; Negrutiu, Ioan; Orsini, Valérie; Peyretaillade, Eric; Pommier, Cyril; Raes, Jeroen; Risler, Jean-Loup; Rivière, Stéphane; Rombauts, Stéphane; Rouzé, Pierre; Schneider, Michel; Schwob, Philippe; Small, Ian; Soumayet-Kampetenga, Ghislain; Stankovski, Darko; Toffano, Claire; Tognolli, Michael; Caboche, Michel; Lecharny, Alain

2005-01-01

Genomic projects heavily depend on genome annotations and are limited by the current deficiencies in the published predictions of gene structure and function. It follows that, improved annotation will allow better data mining of genomes, and more secure planning and design of experiments. The purpose of the GeneFarm project is to obtain homogeneous, reliable, documented and traceable annotations for Arabidopsis nuclear genes and gene products, and to enter them into an added-value database. This re-annotation project is being performed exhaustively on every member of each gene family. Performing a family-wide annotation makes the task easier and more efficient than a gene-by-gene approach since many features obtained for one gene can be extrapolated to some or all the other genes of a family. A complete annotation procedure based on the most efficient prediction tools available is being used by 16 partner laboratories, each contributing annotated families from its field of expertise. A database, named GeneFarm, and an associated user-friendly interface to query the annotations have been developed. More than 3000 genes distributed over 300 families have been annotated and are available at http://genoplante-info.infobiogen.fr/Genefarm/. Furthermore, collaboration with the Swiss Institute of Bioinformatics is underway to integrate the GeneFarm data into the protein knowledgebase Swiss-Prot. PMID:15608279

Structural classification of small, disulfide-rich protein domains.

PubMed

Cheek, Sara; Krishna, S Sri; Grishin, Nick V

2006-05-26

Disulfide-rich domains are small protein domains whose global folds are stabilized primarily by the formation of disulfide bonds and, to a much lesser extent, by secondary structure and hydrophobic interactions. Disulfide-rich domains perform a wide variety of roles functioning as growth factors, toxins, enzyme inhibitors, hormones, pheromones, allergens, etc. These domains are commonly found both as independent (single-domain) proteins and as domains within larger polypeptides. Here, we present a comprehensive structural classification of approximately 3000 small, disulfide-rich protein domains. We find that these domains can be arranged into 41 fold groups on the basis of structural similarity. Our fold groups, which describe broader structural relationships than existing groupings of these domains, bring together representatives with previously unacknowledged similarities; 18 of the 41 fold groups include domains from several SCOP folds. Within the fold groups, the domains are assembled into families of homologs. We define 98 families of disulfide-rich domains, some of which include newly detected homologs, particularly among knottin-like domains. On the basis of this classification, we have examined cases of convergent and divergent evolution of functions performed by disulfide-rich proteins. Disulfide bonding patterns in these domains are also evaluated. Reducible disulfide bonding patterns are much less frequent, while symmetric disulfide bonding patterns are more common than expected from random considerations. Examples of variations in disulfide bonding patterns found within families and fold groups are discussed.

Evolutionary divergence and functions of the human interleukin (IL) gene family

PubMed Central

2010-01-01

Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term 'interleukin' (IL) has been used to describe a group of cytokines with complex immunomodulatory functions -- including cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host's immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating cell type. Determining evolutionary relationships between ILs therefore can be confusing. More recently, crystallographic data and the identification of common structural motifs have led to a more accurate classification system. To date, the known ILs can be divided into four major groups based on distinguishing structural features. These groups include the genes encoding the IL1-like cytokines, the class I helical cytokines (IL4-like, γ-chain and IL6/12-like), the class II helical cytokines (IL10-like and IL28-like) and the IL17-like cytokines. In addition, there are a number of ILs that do not fit into any of the above groups, due either to their unique structural features or lack of structural information. This suggests that the gene family organisation may be subject to further change in the near future. PMID:21106488

TAM Receptor Tyrosine Kinases: Biologic Functions, Signaling, and Potential Therapeutic Targeting in Human Cancer

PubMed Central

Linger, Rachel M. A.; Keating, Amy K.; Earp, H. Shelton; Graham, Douglas K.

2011-01-01

Tyro-3, Axl, and Mer constitute the TAM family of receptor tyrosine kinases (RTKs) characterized by a conserved sequence within the kinase domain and adhesion molecule-like extracellular domains. This small family of RTKs regulates an intriguing mix of processes, including cell proliferation/survival, cell adhesion and migration, blood clot stabilization, and regulation of inflammatory cytokine release. Genetic or experimental alteration of TAM receptor function can contribute to a number of disease states, including coagulopathy, autoimmune disease, retinitis pigmentosa, and cancer. In this chapter, we first provide a comprehensive review of the structure, regulation, biologic functions, and down-stream signaling pathways of these receptors. In addition, we discuss recent evidence which suggests a role for TAM receptors in oncogenic mechanisms as family members are over-expressed in a spectrum of human cancers and have prognostic significance in some. Possible strategies for targeted inhibition of the TAM family in the treatment of human cancer are described. Further research will be necessary to evaluate the full clinical implications of TAM family expression and activation in cancer. PMID:18620092

Computational Approaches for Revealing the Structure of Membrane Transporters: Case Study on Bilitranslocase.

PubMed

Venko, Katja; Roy Choudhury, A; Novič, Marjana

2017-01-01

The structural and functional details of transmembrane proteins are vastly underexplored, mostly due to experimental difficulties regarding their solubility and stability. Currently, the majority of transmembrane protein structures are still unknown and this present a huge experimental and computational challenge. Nowadays, thanks to X-ray crystallography or NMR spectroscopy over 3000 structures of membrane proteins have been solved, among them only a few hundred unique ones. Due to the vast biological and pharmaceutical interest in the elucidation of the structure and the functional mechanisms of transmembrane proteins, several computational methods have been developed to overcome the experimental gap. If combined with experimental data the computational information enables rapid, low cost and successful predictions of the molecular structure of unsolved proteins. The reliability of the predictions depends on the availability and accuracy of experimental data associated with structural information. In this review, the following methods are proposed for in silico structure elucidation: sequence-dependent predictions of transmembrane regions, predictions of transmembrane helix-helix interactions, helix arrangements in membrane models, and testing their stability with molecular dynamics simulations. We also demonstrate the usage of the computational methods listed above by proposing a model for the molecular structure of the transmembrane protein bilitranslocase. Bilitranslocase is bilirubin membrane transporter, which shares similar tissue distribution and functional properties with some of the members of the Organic Anion Transporter family and is the only member classified in the Bilirubin Transporter Family. Regarding its unique properties, bilitranslocase is a potentially interesting drug target.

A systematic analysis of the PARP protein family identifies new functions critical for cell physiology

PubMed Central

Vyas, Sejal; Chesarone-Cataldo, Melissa; Todorova, Tanya; Huang, Yun-Han; Chang, Paul

2013-01-01

The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD+ as their substrate to modify acceptor proteins with adenosine diphosphate-ribose (ADPr) modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analyze the cell cycle localization of each PARP and of poly(ADP-ribose), a product of PARP activity, then identify the knock-down phenotype of each protein and perform secondary assays to elucidate function. We show that most PARPs are cytoplasmic, identify cell cycle differences in the ratio of nuclear to cytoplasmic poly(ADP-ribose), and identify four phenotypic classes of PARP function. These include the regulation of membrane structures, cell viability, cell division, and the actin cytoskeleton. Further analysis of PARP14 shows that it is a component of focal adhesion complexes required for proper cell motility and focal adhesion function. In total, we show that PARP proteins are critical regulators of eukaryotic physiology. PMID:23917125

Structural and Functional Characterizations of SsgB, a Conserved Activator of Developmental Cell Division in Morphologically Complex Actinomycetes*

PubMed Central

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

2009-01-01

SsgA-like proteins (SALPs) are a family of homologous cell division-related proteins that occur exclusively in morphologically complex actinomycetes. We show that SsgB, a subfamily of SALPs, is the archetypal SALP that is functionally conserved in all sporulating actinomycetes. Sporulation-specific cell division of Streptomyces coelicolor ssgB mutants is restored by introduction of distant ssgB orthologues from other actinomycetes. Interestingly, the number of septa (and spores) of the complemented null mutants is dictated by the specific ssgB orthologue that is expressed. The crystal structure of the SsgB from Thermobifida fusca was determined at 2.6 Å resolution and represents the first structure for this family. The structure revealed similarities to a class of eukaryotic “whirly” single-stranded DNA/RNA-binding proteins. However, the electro-negative surface of the SALPs suggests that neither SsgB nor any of the other SALPs are likely to interact with nucleotide substrates. Instead, we show that a conserved hydrophobic surface is likely to be important for SALP function and suggest that proteins are the likely binding partners. PMID:19567872

Family income, parental education and brain structure in children and adolescents.

PubMed

Noble, Kimberly G; Houston, Suzanne M; Brito, Natalie H; Bartsch, Hauke; Kan, Eric; Kuperman, Joshua M; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Libiger, Ondrej; Schork, Nicholas J; Murray, Sarah S; Casey, B J; Chang, Linda; Ernst, Thomas M; Frazier, Jean A; Gruen, Jeffrey R; Kennedy, David N; Van Zijl, Peter; Mostofsky, Stewart; Kaufmann, Walter E; Kenet, Tal; Dale, Anders M; Jernigan, Terry L; Sowell, Elizabeth R

2015-05-01

Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children.

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

PubMed

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

2016-03-24

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

Independent Evolution of Six Families of Halogenating Enzymes

PubMed Central

Xu, Gangming; Wang, Bin-Gui

2016-01-01

Halogenated natural products are widespread in the environment, and the halogen atoms are typically vital to their bioactivities. Thus far, six families of halogenating enzymes have been identified: cofactor-free haloperoxidases (HPO), vanadium-dependent haloperoxidases (V-HPO), heme iron-dependent haloperoxidases (HI-HPO), non-heme iron-dependent halogenases (NI-HG), flavin-dependent halogenases (F-HG), and S-adenosyl-L-methionine (SAM)-dependent halogenases (S-HG). However, these halogenating enzymes with similar biological functions but distinct structures might have evolved independently. Phylogenetic and structural analyses suggest that the HPO, V-HPO, HI-HPO, NI-HG, F-HG, and S-HG enzyme families may have evolutionary relationships to the α/β hydrolases, acid phosphatases, peroxidases, chemotaxis phosphatases, oxidoreductases, and SAM hydroxide adenosyltransferases, respectively. These halogenating enzymes have established sequence homology, structural conservation, and mechanistic features within each family. Understanding the distinct evolutionary history of these halogenating enzymes will provide further insights into the study of their catalytic mechanisms and halogenation specificity. PMID:27153321

The family B1 GPCR: structural aspects and interaction with accessory proteins.

PubMed

Couvineau, Alain; Laburthe, Marc

2012-01-01

G protein coupled receptors (GPCRs) play a crucial role in physiology and pathophysiology in humans. Beside the large family A (rhodopsin-like receptors) and family C GPCR (metabotropic glutamate receptors), the small family B1 GPCR (secretin-like receptors) includes important receptors such as vasoactive intestinal peptide receptors (VPAC), pituitary adenylyl cyclase activating peptide receptor (PAC1R), secretin receptor (SECR), growth hormone releasing factor receptor (GRFR), glucagon receptor (GCGR), glucagon like-peptide 1 and 2 receptors (GLPR), gastric inhibitory peptide receptor (GIPR), parathyroid hormone receptors (PTHR), calcitonin receptors (CTR) and corticotropin-releasing factor receptors (CRFR). They represent very promising targets for the development of drugs having therapeutical impact on many diseases such as chronic inflammation, neurodegeneration, diabetes, stress and osteoporosis. Over the past decade, structure-function relationship studies have demonstrated that the N-terminal ectodomain (N-ted) of family B1 receptors plays a pivotal role in natural ligand recognition. Structural analysis of some family B1 GPCR N-teds revealed the existence of a Sushi domain fold consisting of two antiparallel β sheets stabilized by three disulfide bonds and a salt bridge. The family B1 GPCRs promote cellular responses through a signaling pathway including predominantly the Gsadenylyl cyclase-cAMP pathway activation. Family B1 GPCRs also interact with a few accessory proteins which play a role in cell signaling, receptor expression and/or pharmacological profiles of receptors. These accessory proteins may represent new targets for the design of new drugs. Here, we review the current knowledge regarding: i) the structure of family B1 GPCR binding domain for natural ligands and ii) the interaction of family B1 GPCRs with accessory proteins.

[Relationships between venomous function and innate immune function].

PubMed

Goyffon, Max; Saul, Frederick; Faure, Grazyna

2015-01-01

Venomous function is investigated in relation to innate immune function in two cases selected from scorpion venom and serpent venom. In the first case, structural analysis of scorpion toxins and defensins reveals a close interrelation between both functions (toxic and innate immune system function). In the second case, structural and functional studies of natural inhibitors of toxic snake venom phospholipases A2 reveal homology with components of the innate immune system, leading to a similar conclusion. Although there is a clear functional distinction between neurotoxins, which act by targeting membrane ion channels, and the circulating defensins which protect the organism from pathogens, the scorpion short toxins and defensins share a common protein folding scaffold with a conserved cysteine-stabilized alpha-beta motif of three disulfide bridges linking a short alpha helix and an antiparallel beta sheet. Genomic analysis suggests that these proteins share a common ancestor (long venom toxins were separated from an early gene family which gave rise to separate short toxin and defensin families). Furthermore, a scorpion toxin has been experimentally synthetized from an insect defensin, and an antibacterial scorpion peptide, androctonin (whose structure is similar to that of a cone snail venom toxin), was shown to have a similar high affinity for the postsynaptic acetylcholine receptor of Torpedo sp. Natural inhibitors of phospholipase A2 found in the blood of snakes are associated with the resistance of venomous snakes to their own highly neurotoxic venom proteins. Three classes of phospholipases A2 inhibitors (PLI-α, PLI-β, PLI-γ) have been identified. These inhibitors display diverse structural motifs related to innate immune proteins including carbohydrate recognition domains (CRD), leucine rich repeat domains (found in Toll-like receptors) and three finger domains, which clearly differentiate them from components of the adaptive immune system. Thus, in structure, function and phylogeny, venomous function in both vertebrates and invertebrates are clearly interrelated with innate immune function. © Société de Biologie, 2016.

Defying stereotypes: the elusive search for a universal model of LysR-type regulation.

PubMed

Momany, Cory; Neidle, Ellen L

2012-02-01

LysR-type transcriptional regulators (LTTRs) compose the largest family of homologous regulators in bacteria. Considering their prevalence, it is not surprising that LTTRs control diverse metabolic functions. Arguably, the most unexpected aspect of LTTRs is the paucity of available structural information. Solubility issues are notoriously problematic, and structural studies have only recently begun to flourish. In this issue of Molecular Microbiology, Taylor et al. (2012) present the structure of AphB, a LysR-type regulator of virulence in Vibrio cholerae. This contribution adds significantly to the group of known full-length atomic LTTR structures, which remains small. Importantly, this report also describes an active-form variant. Small conformational changes in the effector-binding domain translate to global reorganization of the DNA-binding domain. Emerging from these results is a model of theme-and-variation among LTTRs rather than a unified regulatory scheme. Despite common structural folds, LTTRs exhibit differences in oligomerization, promoter recognition and communication with RNA polymerase. Such variation mirrors the diversity in sequence and function associated with members of this very large family. © 2012 Blackwell Publishing Ltd.

High efficiency family shuffling based on multi-step PCR and in vivo DNA recombination in yeast: statistical and functional analysis of a combinatorial library between human cytochrome P450 1A1 and 1A2.

PubMed

Abécassis, V; Pompon, D; Truan, G

2000-10-15

The design of a family shuffling strategy (CLERY: Combinatorial Libraries Enhanced by Recombination in Yeast) associating PCR-based and in vivo recombination and expression in yeast is described. This strategy was tested using human cytochrome P450 CYP1A1 and CYP1A2 as templates, which share 74% nucleotide sequence identity. Construction of highly shuffled libraries of mosaic structures and reduction of parental gene contamination were two major goals. Library characterization involved multiprobe hybridization on DNA macro-arrays. The statistical analysis of randomly selected clones revealed a high proportion of chimeric genes (86%) and a homogeneous representation of the parental contribution among the sequences (55.8 +/- 2.5% for parental sequence 1A2). A microtiter plate screening system was designed to achieve colorimetric detection of polycyclic hydrocarbon hydroxylation by transformed yeast cells. Full sequences of five randomly picked and five functionally selected clones were analyzed. Results confirmed the shuffling efficiency and allowed calculation of the average length of sequence exchange and mutation rates. The efficient and statistically representative generation of mosaic structures by this type of family shuffling in a yeast expression system constitutes a novel and promising tool for structure-function studies and tuning enzymatic activities of multicomponent eucaryote complexes involving non-soluble enzymes.

The varied functions of aluminium-activated malate transporters–much more than aluminium resistance

PubMed Central

Palmer, Antony J.; Baker, Alison; Muench, Stephen P.

2016-01-01

The ALMT (aluminium-activated malate transporter) family comprises a functionally diverse but structurally similar group of ion channels. They are found ubiquitously in plant species, expressed throughout different tissues, and located in either the plasma membrane or tonoplast. The first family member identified was TaALMT1, discovered in wheat root tips, which was found to be involved in aluminium resistance by means of malate exudation into the soil. However, since this discovery other family members have been shown to have many other functions such as roles in stomatal opening, general anionic homoeostasis, and in economically valuable traits such as fruit flavour. Recent evidence has also shown that ALMT proteins can act as key molecular actors in GABA (γ-aminobutyric acid) signalling, the first evidence that GABA can act as a signal transducer in plants. PMID:27284052

pocketZebra: a web-server for automated selection and classification of subfamily-specific binding sites by bioinformatic analysis of diverse protein families

PubMed Central

Suplatov, Dmitry; Kirilin, Eugeny; Arbatsky, Mikhail; Takhaveev, Vakil; Švedas, Vytas

2014-01-01

The new web-server pocketZebra implements the power of bioinformatics and geometry-based structural approaches to identify and rank subfamily-specific binding sites in proteins by functional significance, and select particular positions in the structure that determine selective accommodation of ligands. A new scoring function has been developed to annotate binding sites by the presence of the subfamily-specific positions in diverse protein families. pocketZebra web-server has multiple input modes to meet the needs of users with different experience in bioinformatics. The server provides on-site visualization of the results as well as off-line version of the output in annotated text format and as PyMol sessions ready for structural analysis. pocketZebra can be used to study structure–function relationship and regulation in large protein superfamilies, classify functionally important binding sites and annotate proteins with unknown function. The server can be used to engineer ligand-binding sites and allosteric regulation of enzymes, or implemented in a drug discovery process to search for potential molecular targets and novel selective inhibitors/effectors. The server, documentation and examples are freely available at http://biokinet.belozersky.msu.ru/pocketzebra and there are no login requirements. PMID:24852248

Structure and Function of the Unusual Tungsten Enzymes Acetylene Hydratase and Class II Benzoyl-Coenzyme A Reductase.

PubMed

Boll, Matthias; Einsle, Oliver; Ermler, Ulrich; Kroneck, Peter M H; Ullmann, G Matthias

2016-01-01

In biology, tungsten (W) is exclusively found in microbial enzymes bound to a bis-pyranopterin cofactor (bis-WPT). Previously known W enzymes catalyze redox oxo/hydroxyl transfer reactions by directly coordinating their substrates or products to the metal. They comprise the W-containing formate/formylmethanofuran dehydrogenases belonging to the dimethyl sulfoxide reductase (DMSOR) family and the aldehyde:ferredoxin oxidoreductase (AOR) families, which form a separate enzyme family within the Mo/W enzymes. In the last decade, initial insights into the structure and function of two unprecedented W enzymes were obtained: the acetaldehyde forming acetylene hydratase (ACH) belongs to the DMSOR and the class II benzoyl-coenzyme A (CoA) reductase (BCR) to the AOR family. The latter catalyzes the reductive dearomatization of benzoyl-CoA to a cyclic diene. Both are key enzymes in the degradation of acetylene (ACH) or aromatic compounds (BCR) in strictly anaerobic bacteria. They are unusual in either catalyzing a nonredox reaction (ACH) or a redox reaction without coordinating the substrate or product to the metal (BCR). In organic chemical synthesis, analogous reactions require totally nonphysiological conditions depending on Hg2+ (acetylene hydration) or alkali metals (benzene ring reduction). The structural insights obtained pave the way for biological or biomimetic approaches to basic reactions in organic chemistry. © 2016 S. Karger AG, Basel.

Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.

PubMed

Zeni, Cristian Patrick; Mwangi, Benson; Cao, Bo; Hasan, Khader M; Walss-Bass, Consuelo; Zunta-Soares, Giovana; Soares, Jair C

2016-01-01

Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls. We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls. We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences. small sample size, cross-sectional study. These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

Feminism and family therapy.

PubMed

Goldner, V

1985-03-01

Feminism has had a profound effect on contemporary culture and on thinking in most academic fields, including psychoanalysis. Interestingly, until very recently it had made virtually no impact on the theory and practice of family therapy. This paper proposes an explanation for this peculiar phenomenon and argues that family therapy has been considerably handicapped by its insularity from the feminist critique. Utilizing feminist scholarship in psychoanalysis, history, and sociology, the paper analyzes the structural contradictions in family life that family therapists have essentially ignored and then outlines their clinical implications. Key points in the discussion include the argument that systems theory is an inadequate explanatory matrix from which to build a theory of the family, that the archetypal "family case" of the overinvolved mother and peripheral father is best understood, not as a clinical problem, but as the product of a historical process two hundred years in the making, and that power relations between men and women in families function in terms of paradoxical, incongruous hierarchies that reflect the complex interpenetration between the structure of family relations and the world of work. This conceptual model then provides the basis for an analysis and critique of sexual politics as they emerge in the prototypical clinical situation.

A transthyretin-related protein is functionally expressed in Herbaspirillum seropedicae.

PubMed

Matiollo, Camila; Vernal, Javier; Ecco, Gabriela; Bertoldo, Jean Borges; Razzera, Guilherme; de Souza, Emanuel M; Pedrosa, Fábio O; Terenzi, Hernán

2009-10-02

Transthyretin-related proteins (TRPs) constitute a family of proteins structurally related to transthyretin (TTR) and are found in a large range of bacterial, fungal, plant, invertebrate, and vertebrate species. However, it was recently recognized that both prokaryotic and eukaryotic members of this family are not functionally related to transthyretins. TRPs are in fact involved in the purine catabolic pathway and function as hydroxyisourate hydrolases. An open reading frame encoding a protein similar to the Escherichia coli TRP was identified in Herbaspirillum seropedicae genome (Hs_TRP). It was cloned, overexpressed in E. coli, and purified to homogeneity. Mass spectrometry data confirmed the identity of this protein, and circular dichroism spectrum indicated a predominance of beta-sheet structure, as expected for a TRP. We have demonstrated that Hs_TRP is a 5-hydroxyisourate hydrolase and by site-directed mutagenesis the importance of three conserved catalytic residues for Hs_TRP activity was further confirmed. The production of large quantities of this recombinant protein opens up the possibility of obtaining its 3D-structure and will help further investigations into purine catabolism.

Effects of maternal traumatic distress on family functioning and child mental health: An examination of Southeast Asian refugee families in the U.S.

PubMed

Sangalang, Cindy C; Jager, Justin; Harachi, Tracy W

2017-07-01

The psychological effects of trauma are well-documented among refugee adults and children alone, yet less research has attended to the intergenerational transmission of trauma within refugee families. Additionally, there is considerable diversity between refugee populations as well as within-group variation in the experiences and effects of refugee trauma. The current study examines the longitudinal effects of maternal traumatic distress on family functioning and child mental health outcomes among Southeast Asian refugee women and their adolescent children. Given the potential for variation in these effects, we also explore group differences in these relationships by ethnicity and child nativity. Longitudinal data were collected from a random sample of 327 Southeast Asian refugee mothers and their children in the United States. We employed structural equation modeling to examine associations between latent variables representing maternal traumatic distress, family functioning, and child mental health outcomes (i.e., depressive symptoms, antisocial and delinquent behavior, and school problems). We then tested for group differences in these associations by ethnicity (Cambodian and Vietnamese subgroups) and child nativity (U.S.-born and foreign-born children). We found maternal traumatic distress was indirectly linked to child mental health outcomes, and that child nativity was associated with these paths while ethnicity was not. For foreign-born children, maternal traumatic distress was associated with diminished family functioning a year later, which was associated with increased school problems at the two-year mark. Maternal traumatic distress was indirectly associated with depressive symptoms and antisocial and delinquent behavior, respectively, after accounting for family functioning. For all children, weaker family functioning was significantly associated with poorer mental health. Findings suggest that refugee parents' trauma can adversely affect family relationships and the mental health of children. Interventions that address parental trauma and support intergenerational relationships may enhance mental health within refugee communities for future generations. Copyright © 2017. Published by Elsevier Ltd.

Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters

PubMed Central

Schmitt-Ulms, Gerold; Ehsani, Sepehr; Watts, Joel C.; Westaway, David; Wille, Holger

2009-01-01

In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of two metal ion transporters of the ZIP family, ZIP6 and ZIP10, to mammalian prion proteins in vivo. A subsequent bioinformatic analysis revealed the unexpected presence of a PrP-like amino acid sequence within the N-terminal, extracellular domain of a distinct sub-branch of the ZIP protein family that includes ZIP5, ZIP6 and ZIP10. Additional structural threading and orthologous sequence alignment analyses argued that the prion gene family is phylogenetically derived from a ZIP-like ancestral molecule. The level of sequence homology and the presence of prion protein genes in most chordate species place the split from the ZIP-like ancestor gene at the base of the chordate lineage. This relationship explains structural and functional features found within mammalian prion proteins as elements of an ancient involvement in the transmembrane transport of divalent cations. The phylogenetic and spatial connection to ZIP proteins is expected to open new avenues of research to elucidate the biology of the prion protein in health and disease. PMID:19784368

Parental attitude, depression, anxiety in mothers, family functioning and breath-holding spells: A case control study.

PubMed

Eliacik, Kayi; Bolat, Nurullah; Kanik, Ali; Sargin, Enis; Selkie, Ellen; Korkmaz, Nurhan; Baydan, Figen; Akar, Ebru; Sarioglu, Berrak

2016-05-01

This study aimed to identify differences in the antenatal stressful life events, parenting style, family functioning, depression and anxiety of mothers who have children with breath-holding spells (BHS) compared with controls. This case control study divided 66 children into a group of children with BHS and a control group, with the children's ages ranging between 6 months and 5 years of age. This study explored underlying anxiety and depression in mothers as well as functioning of their families. Socio-demographical data and stressful life events that the mother experienced during pregnancy were analysed. In order to evaluate the effects of family structure, depression and anxiety in mothers on BHS in children, the Family Assessment Device, and both the Parental Attitude Research Instrument and the Beck Depression Inventory as well as the State-Trait Anxiety Inventory were used to assess both groups. Exposure to stressful life events during pregnancy (P < 0.001), depressive traits (P < 0.001), state-trait anxiety (P < 0.001), overprotective maternal characteristics (P = 0.027) and most of the family functioning subscales were found to be significantly different between BHS and control groups. The association of anxiety, depression, prenatal stressful events and poor family functioning in mothers who have children with BHS is significantly higher than controls. An evaluation of these problems may be beneficial in the management of BHS. © 2016 The Authors. Journal of Paediatrics and Child Health © 2016 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

The importance of family functioning, mental health and social and emotional well-being on child oral health.

PubMed

Renzaho, A M N; de Silva-Sanigorski, A

2014-07-01

To examine the strength of associations between child oral health and aspects of the home environment (child behaviour, parental psychological distress and family functioning) in a large sample of 1- to 12-year-old Australian children. The current study used data from the 2006 Victorian Child Health and Wellbeing Study. Data were obtained on 4590 primary carers. Measures of the family environment included the level of family functioning, parental psychological distress, child's emotion and behavioural problems and the family structure. The odds of children having good oral health status were lower with increasing parental psychological distress and poor family functioning across all age groups, and lower with increasing child mental health or conduct problems among children aged 4 years or older. Socioeconomic factors were also related to child oral health status, but this was significant only among children aged 4-7 years, with the odds of children having good oral health status 68% higher in households with a yearly income ≥AUD$ 60 000 compared with households with income <$20 000 (P < 0.05). In order to address inequities in the experience of poor oral health, solutions that encompass social, economic and psychosocial dimensions will be required. Integrating intervention strategies that promote oral, healthy family functioning and the mental health of parents and children into existing systems reaching vulnerable community members may improve child oral health outcomes and reduce the unequal distribution of oral disease across the social gradient. © 2013 John Wiley & Sons Ltd.

Quality of life, social functioning, family structure, and treatment history associated with crack cocaine use in youth from the general population.

PubMed

Narvaez, Joana C M; Pechansky, Flávio; Jansen, Karen; Pinheiro, Ricardo T; Silva, Ricardo A; Kapczinski, Flávio; Magalhães, Pedro V

2015-01-01

To assess the relationship between crack cocaine use and dimensions of quality of life and social functioning in young adults. This was a cross-sectional, population-based study involving 1,560 participants in Pelotas, Brazil. Crack cocaine use and abuse were investigated using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) inventory. Outcomes of interest were quality of life, religiosity, and social functioning in terms of education, occupational status, family structure, and medical treatment history. Lifetime crack cocaine use was associated with poor quality of life, worse functioning, impaired academic performance, and lower religious involvement. A greater maternal presence and higher paternal absence were more also more pronounced in crack cocaine users, who were also more likely to seek psychological and psychiatric treatment than the general population. Quality of life was severely impacted by crack cocaine use, especially in terms of general and physical health. Social functioning also differed between the general population and crack users, who had lower educational attainment and religious involvement. Maternal presence, paternal absence, and mental health-seeking behaviors were also more frequent among crack cocaine users, although these individuals reported lower rates of treatment satisfaction. Crack cocaine users also had significant social impairment, so that interventions involving family management and a greater focus on general health, quality of life, and functioning may make crucial contributions to the recovery of this group.

Evaluation of variability in high-resolution protein structures by global distance scoring.

PubMed

Anzai, Risa; Asami, Yoshiki; Inoue, Waka; Ueno, Hina; Yamada, Koya; Okada, Tetsuji

2018-01-01

Systematic analysis of the statistical and dynamical properties of proteins is critical to understanding cellular events. Extraction of biologically relevant information from a set of high-resolution structures is important because it can provide mechanistic details behind the functional properties of protein families, enabling rational comparison between families. Most of the current structural comparisons are pairwise-based, which hampers the global analysis of increasing contents in the Protein Data Bank. Additionally, pairing of protein structures introduces uncertainty with respect to reproducibility because it frequently accompanies other settings for superimposition. This study introduces intramolecular distance scoring for the global analysis of proteins, for each of which at least several high-resolution structures are available. As a pilot study, we have tested 300 human proteins and showed that the method is comprehensively used to overview advances in each protein and protein family at the atomic level. This method, together with the interpretation of the model calculations, provide new criteria for understanding specific structural variation in a protein, enabling global comparison of the variability in proteins from different species.

Barriers and Facilitators to Implementing Functional Family Therapy in a Community Setting: Client and Practitioner Perspectives.

PubMed

McPherson, Kerri E; Kerr, Susan; Casey, Beth; Marshall, John

2017-10-01

While Functional Family Therapy (FFT) is known to be effective in addressing adolescent behavioral problems, there has been little exploration of issues relevant to its transport from the tightly controlled setting of clinical trials into routine service delivery. This study sought the views of key stakeholders, clients, and practitioners, on barriers and facilitators to the successful implementation of FFT. Undertaken in a community setting in Scotland, interviews were carried out with 12 adolescents, 14 parents/caregivers, and 6 practitioners. Results focus on: Referral process and pre-intervention contact; Engagement of families; Structure and delivery; Organizational factors. Although barriers to engagement were identified, FFT was viewed as an acceptable, appropriate and feasible intervention with the potential to improve adolescent wellbeing in 'real-world' settings. © 2017 American Association for Marriage and Family Therapy.

Genome-wide Identification and analysis of the stress-resistance function of the TPS (Trehalose-6-Phosphate Synthase) gene family in cotton.

PubMed

Mu, Min; Lu, Xu-Ke; Wang, Jun-Juan; Wang, De-Long; Yin, Zu-Jun; Wang, Shuai; Fan, Wei-Li; Ye, Wu-Wei

2016-03-18

Trehalose (a-D-glucopyranosyl a-D-glucopyranoside) is a nonreducing disaccharide and is widely distributed in bacteria, fungi, algae, plants and invertebrates. In the study, the identification of trehalose-6-phosphate synthase (TPS) genes stress-related in cotton, and the genetic structure analysis and molecular evolution analysis of TPSs were conducted with bioinformatics methods, which could lay a foundation for further research of TPS functions in cotton. The genome information of Gossypium raimondii (group D), G. arboreum L. (group A), and G. hirsutum L. (group AD) was used in the study. Fifty-three TPSs were identified comprising 15 genes in group D, 14 in group A, and 24 in group AD. Bioinformatics methods were used to analyze the genetic structure and molecular evolution of TPSs. Real-time PCR analysis was performed to investigate the expression patterns of gene family members. All TPS family members in cotton can be divided into two subfamilies: Class I and Class II. The similarity of the TPS sequence is high within the same species and close within their family relatives. The genetic structures of two TPS subfamily members are different, with more introns and a more complicated gene structure in Class I. There is a TPS domain(Glyco transf_20) at the N-terminal in all TPS family members and a TPP domain(Trehalose_PPase) at the C-terminal in all except GrTPS6, GhTPS4, and GhTPS9. All Class II members contain a UDP-forming domain. The responses to environmental stresses showed that stresses could induce the expression of TPSs but the expression patterns vary with different stresses. The distribution of TPSs varies with different species but is relatively uniform on chromosomes. Genetic structure varies with different gene members, and expression levels vary with different stresses and exhibit tissue specificity. The upregulated genes in upland cotton TM-1 is significantly more than that in G. raimondii and G. arboreum L. Shixiya 1.

Individual and Family Perfectionism and Its Relationship to Depression, Anxiety, and Self-Esteem among Latino College Students

ERIC Educational Resources Information Center

Ortega, Norma E.

2010-01-01

This study examined the relationship between individual and family perfectionism and mental health functioning among two hundred and seven Latino college students. One aim of this study was to test the factor structure of the Almost Perfect Scale-Revised (APS-R; Slaney, Rice, Mobley, Trippi, & Ashby, 2001) with Latino college students by…

Analyses of the NAC transcription factor gene family in Gossypium raimondii Ulbr.: chromosomal location, structure, phylogeny, and expression patterns.

PubMed

Shang, Haihong; Li, Wei; Zou, Changsong; Yuan, Youlu

2013-07-01

NAC domain proteins are plant-specific transcription factors known to play diverse roles in various plant developmental processes. In the present study, we performed the first comprehensive study of the NAC gene family in Gossypium raimondii Ulbr., incorporating phylogenetic, chromosomal location, gene structure, conserved motif, and expression profiling analyses. We identified 145 NAC transcription factor (NAC-TF) genes that were phylogenetically clustered into 18 distinct subfamilies. Of these, 127 NAC-TF genes were distributed across the 13 chromosomes, 80 (55%) were preferentially retained duplicates located in both duplicated regions and six were located in triplicated chromosomal regions. The majority of NAC-TF genes showed temporal-, spatial-, and tissue-specific expression patterns based on transcriptomic and qRT-PCR analyses. However, the expression patterns of several duplicate genes were partially redundant, suggesting the occurrence of sub-functionalization during their evolution. Based on their genomic organization, we concluded that genomic duplications contributed significantly to the expansion of the NAC-TF gene family in G. raimondii. Comprehensive analysis of their expression profiles could provide novel insights into the functional divergence among members of the NAC gene family in G. raimondii. © 2013 Institute of Botany, Chinese Academy of Sciences.

Functional diversity of Csk, Chk, and Src SH2 domains due to a single residue variation.

PubMed

Ayrapetov, Marina K; Nam, Nguyen Hai; Ye, Guofeng; Kumar, Anil; Parang, Keykavous; Sun, Gongqin

2005-07-08

The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk). Both phosphorylate and inactivate Src family kinases. Recent reports suggest that the Src homology (SH) 2 domains of Csk and Chk may bind to different phosphoproteins, which provides a basis for different cellular functions for Csk and Chk. To verify and characterize such a functional divergence, we compared the binding properties of the Csk, Chk, and Src SH2 domains and investigated the structural basis for the functional divergence. First, the study demonstrated striking functional differences between the Csk and Chk SH2 domains and revealed functional similarities between the Chk and Src SH2 domains. Second, structural analysis and mutagenic studies revealed that the functional differences among the three SH2 domains were largely controlled by one residue, Glu127 in Csk, Ile167 in Chk, and Lys200 in Src. Mutating these residues in the Csk or Chk SH2 domain to the Src counterpart resulted in dramatic gain of function similar to Src SH2 domain, whereas mutating Lys200 in Src SH2 domain to Glu (the Csk counterpart) resulted in loss of Src SH2 function. Third, a single point mutation of E127K rendered Csk responsive to activation by a Src SH2 domain ligand. Finally, the optimal phosphopeptide sequence for the Chk SH2 domain was determined. These results provide a compelling explanation for the functional differences between two homologous protein tyrosine kinases and reveal a new structure-function relationship for the SH2 domains.

Structural and Histone Binding Ability Characterizations of Human PWWP Domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Hong; Zeng, Hong; Lam, Robert

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,more » 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.« less

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development.

PubMed

Bedell, Victoria M; Person, Anthony D; Larson, Jon D; McLoon, Anna; Balciunas, Darius; Clark, Karl J; Neff, Kevin I; Nelson, Katie E; Bill, Brent R; Schimmenti, Lisa A; Beiraghi, Soraya; Ekker, Stephen C

2012-02-01

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.

Conserved and divergent features of the structure and function of La and La-related proteins (LARPs)

PubMed Central

Bayfield, Mark A.; Yang, Ruiqing; Maraia, Richard J.

2010-01-01

Genuine La proteins contain two RNA binding motifs, a La motif (LAM) followed by a RNA recognition motif (RRM), arranged in a unique way to bind RNA. These proteins interact with an extensive variety of cellular RNAs and exhibit activities in two broad categories: i) to promote the metabolism of nascent pol III transcripts, including precursor-tRNAs, by binding to their common, UUU-3’OH containing ends, and ii) to modulate the translation of certain mRNAs involving an unknown binding mechanism. Characterization of several La-RNA crystal structures as well as biochemical studies reveal insight into their unique two-motif domain architecture and how the LAM recognizes UUU-3’OH while the RRM binds other parts of a pre-tRNA. Recent studies of members of distinct families of conserved La-related proteins (LARPs) indicate that some of these harbor activity related to genuine La proteins, suggesting that their UUU-3’OH binding mode has been appropriated for the assembly and regulation of a specific snRNP (e.g., 7SK snRNA assembly by hLARP7/PIP7S). Analyses of other LARP family members (i.e., hLARP4, hLARP6) suggest more diverged RNA binding modes and specialization for cytoplasmic mRNA-related functions. Thus it appears that while genuine La proteins exhibit broad general involvement in both snRNA-related and mRNA-related functions, different LARP families may have evolved specialized activities in either snRNA or mRNA related functions. In this review, we summarize recent progress that has led to greater understanding of the structure and function of La proteins and their roles in tRNA processing and RNP assembly dynamics, as well as progress on the different LARPs. PMID:20138158

Conserved and divergent features of the structure and function of La and La-related proteins (LARPs).

PubMed

Bayfield, Mark A; Yang, Ruiqing; Maraia, Richard J

2010-01-01

Genuine La proteins contain two RNA binding motifs, a La motif (LAM) followed by a RNA recognition motif (RRM), arranged in a unique way to bind RNA. These proteins interact with an extensive variety of cellular RNAs and exhibit activities in two broad categories: i) to promote the metabolism of nascent pol III transcripts, including precursor-tRNAs, by binding to their common, UUU-3'OH containing ends, and ii) to modulate the translation of certain mRNAs involving an unknown binding mechanism. Characterization of several La-RNA crystal structures as well as biochemical studies reveal insight into their unique two-motif domain architecture and how the LAM recognizes UUU-3'OH while the RRM binds other parts of a pre-tRNA. Recent studies of members of distinct families of conserved La-related proteins (LARPs) indicate that some of these harbor activity related to genuine La proteins, suggesting that their UUU-3'OH binding mode has been appropriated for the assembly and regulation of a specific snRNP (e.g., 7SK snRNP assembly by hLARP7/PIP7S). Analyses of other LARP family members suggest more diverged RNA binding modes and specialization for cytoplasmic mRNA-related functions. Thus it appears that while genuine La proteins exhibit broad general involvement in both snRNA-related and mRNA-related functions, different LARP families may have evolved specialized activities in either snRNA or mRNA-related functions. In this review, we summarize recent progress that has led to greater understanding of the structure and function of La proteins and their roles in tRNA processing and RNP assembly dynamics, as well as progress on the different LARPs.

Cultural diversity: family path through terminal illness.

PubMed

Baider, L

2012-04-01

In trying to comprehend a culture and its ways of structuring the world, much can be learned from addressing the manner in which intimate family relationships are ordered and family crises channeled toward care. A family's experience with illness cannot be considered in isolation from the cultural milieu in which it occurs. Family adaptation to cancer diagnosis is a continuous motion between many critical strata--a fragile oscillation between hope and desperation. Processes for optimal functioning and the well-being of members are seen to vary over time, as challenges unfold and families evolve across the life cycle and illness trajectory. The manner in which the healthcare system and family manage illness and terminal care is a particularly helpful window into the cultural, religious and traditional values of every family in a particular society.

Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL): adapting the Partial Phylogenetic Profiling algorithm to scan sequences for signatures that predict protein function

PubMed Central

2010-01-01

Background Comparative genomics methods such as phylogenetic profiling can mine powerful inferences from inherently noisy biological data sets. We introduce Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL), a method that applies the Partial Phylogenetic Profiling (PPP) approach locally within a protein sequence to discover short sequence signatures associated with functional sites. The approach is based on the basic scoring mechanism employed by PPP, namely the use of binomial distribution statistics to optimize sequence similarity cutoffs during searches of partitioned training sets. Results Here we illustrate and validate the ability of the SIMBAL method to find functionally relevant short sequence signatures by application to two well-characterized protein families. In the first example, we partitioned a family of ABC permeases using a metabolic background property (urea utilization). Thus, the TRUE set for this family comprised members whose genome of origin encoded a urea utilization system. By moving a sliding window across the sequence of a permease, and searching each subsequence in turn against the full set of partitioned proteins, the method found which local sequence signatures best correlated with the urea utilization trait. Mapping of SIMBAL "hot spots" onto crystal structures of homologous permeases reveals that the significant sites are gating determinants on the cytosolic face rather than, say, docking sites for the substrate-binding protein on the extracellular face. In the second example, we partitioned a protein methyltransferase family using gene proximity as a criterion. In this case, the TRUE set comprised those methyltransferases encoded near the gene for the substrate RF-1. SIMBAL identifies sequence regions that map onto the substrate-binding interface while ignoring regions involved in the methyltransferase reaction mechanism in general. Neither method for training set construction requires any prior experimental characterization. Conclusions SIMBAL shows that, in functionally divergent protein families, selected short sequences often significantly outperform their full-length parent sequence for making functional predictions by sequence similarity, suggesting avenues for improved functional classifiers. When combined with structural data, SIMBAL affords the ability to localize and model functional sites. PMID:20102603

Family Histories of Anxiety in Overweight Men and Women with Binge Eating Disorder: A Preliminary Investigation

PubMed Central

Blomquist, Kerstin K.; Grilo, Carlos M.

2015-01-01

Objective A preliminary examination of the significance of family histories of anxiety in the expression of binge eating disorder (BED) and associated functioning. Methods Participants were 166 overweight patients with BED assessed using diagnostic interviews. Participants were administered a structured psychiatric history interview about their first-degree relatives (parents, siblings, children) (N=897) to determine lifetime diagnoses of DSM-IV anxiety disorders and completed a battery of questionnaires assessing current and historical eating and weight variables and associated psychological functioning (depression). Results BED patients with a family history of anxiety disorder were significantly more likely than BED patients without a family history of anxiety disorder to have lifetime diagnoses of anxiety disorders and mood disorders but not substance use disorders. A family history of anxiety was not significantly associated with timing or sequencing of age at onset of anxiety disorder, binge eating, dieting, or obesity, or with variability in current levels of binge eating, eating disorder psychopathology, or psychological functioning. Conclusions Although replication with direct interview method is needed, our preliminary findings suggest that a family history of anxiety confers greater risk for comorbid anxiety and mood disorders but is largely unrelated to the development of binge eating, dieting, or obesity and unrelated to variability in eating disorder psychopathology or psychological functioning in overweight patients with BED. PMID:26343481

Literacy House: Annual Report 1968.

ERIC Educational Resources Information Center

Literacy House, Lucknow (India).

The 1968 annual report of Literacy House focuses on functional literacy, food production, and family planning as well as on structural reorganization. A new organizational chart is included and the role of each individual in the organization is presented. The primary functions (training and research), and some details about the work of the…

Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis

PubMed Central

Bardet, Claire; Ribes, Sandy; Wu, Yong; Diallo, Mamadou Tidiane; Salmon, Benjamin; Breiderhoff, Tilman; Houillier, Pascal; Müller, Dominik; Chaussain, Catherine

2017-01-01

Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ) permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL). Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), were recently shown to be also involved in Amelogenesis Imperfecta (AI). In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO) mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis. PMID:28596736

Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis.

PubMed

Bardet, Claire; Ribes, Sandy; Wu, Yong; Diallo, Mamadou Tidiane; Salmon, Benjamin; Breiderhoff, Tilman; Houillier, Pascal; Müller, Dominik; Chaussain, Catherine

2017-01-01

Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ) permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL). Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), were recently shown to be also involved in Amelogenesis Imperfecta (AI). In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO) mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

Phylogenetic analysis of eIF4E-family members

PubMed Central

Joshi, Bhavesh; Lee, Kibwe; Maeder, Dennis L; Jagus, Rosemary

2005-01-01

Background Translation initiation in eukaryotes involves the recruitment of mRNA to the ribosome which is controlled by the translation factor eIF4E. eIF4E binds to the 5'-m7Gppp cap-structure of mRNA. Three dimensional structures of eIF4Es bound to cap-analogues resemble 'cupped-hands' in which the cap-structure is sandwiched between two conserved Trp residues (Trp-56 and Trp-102 of H. sapiens eIF4E). A third conserved Trp residue (Trp-166 of H. sapiens eIF4E) recognizes the 7-methyl moiety of the cap-structure. Assessment of GenBank NR and dbEST databases reveals that many organisms encode a number of proteins with homology to eIF4E. Little is understood about the relationships of these structurally related proteins to each other. Results By combining sequence data deposited in the Genbank databases, we have identified sequences encoding 411 eIF4E-family members from 230 species. These sequences have been deposited into an internet-accessible database designed for sequence comparisons of eIF4E-family members. Most members can be grouped into one of three classes. Class I members carry Trp residues equivalent to Trp-43 and Trp-56 of H. sapiens eIF4E and appear to be present in all eukaryotes. Class II members, possess Trp→Tyr/Phe/Leu and Trp→Tyr/Phe substitutions relative to Trp-43 and Trp-56 of H. sapiens eIF4E, and can be identified in Metazoa, Viridiplantae, and Fungi. Class III members possess a Trp residue equivalent to Trp-43 of H. sapiens eIF4E but carry a Trp→Cys/Tyr substitution relative to Trp-56 of H. sapiens eIF4E, and can be identified in Coelomata and Cnidaria. Some eIF4E-family members from Protista show extension or compaction relative to prototypical eIF4E-family members. Conclusion The expansion of sequenced cDNAs and genomic DNAs from all eukaryotic kingdoms has revealed a variety of proteins related in structure to eIF4E. Evolutionarily it seems that a single early eIF4E gene has undergone multiple gene duplications generating multiple structural classes, such that it is no longer possible to predict function from the primary amino acid sequence of an eIF4E-family member. The variety of eIF4E-family members provides a source of alternatives on the eIF4E structural theme that will benefit structure/function analyses and therapeutic drug design. PMID:16191198

Origins of coevolution between residues distant in protein 3D structures

PubMed Central

Ovchinnikov, Sergey; Kamisetty, Hetunandan; Baker, David

2017-01-01

Residue pairs that directly coevolve in protein families are generally close in protein 3D structures. Here we study the exceptions to this general trend—directly coevolving residue pairs that are distant in protein structures—to determine the origins of evolutionary pressure on spatially distant residues and to understand the sources of error in contact-based structure prediction. Over a set of 4,000 protein families, we find that 25% of directly coevolving residue pairs are separated by more than 5 Å in protein structures and 3% by more than 15 Å. The majority (91%) of directly coevolving residue pairs in the 5–15 Å range are found to be in contact in at least one homologous structure—these exceptions arise from structural variation in the family in the region containing the residues. Thirty-five percent of the exceptions greater than 15 Å are at homo-oligomeric interfaces, 19% arise from family structural variation, and 27% are in repeat proteins likely reflecting alignment errors. Of the remaining long-range exceptions (<1% of the total number of coupled pairs), many can be attributed to close interactions in an oligomeric state. Overall, the results suggest that directly coevolving residue pairs not in repeat proteins are spatially proximal in at least one biologically relevant protein conformation within the family; we find little evidence for direct coupling between residues at spatially separated allosteric and functional sites or for increased direct coupling between residue pairs on putative allosteric pathways connecting them. PMID:28784799

Exploring the structure and function of Thermotoga maritima CorA reveals the mechanism of gating and ion selectivity in Co2+/Mg2+ transport

PubMed Central

Nordin, Nurhuda; Guskov, Albert; Phua, Terri; Sahaf, Newsha; Xia, Yu; Lu, Siyan; Eshaghi, Hojjat; Eshaghi, Said

2013-01-01

The CorA family of divalent cation transporters utilizes Mg2+ and Co2+ as primary substrates. The molecular mechanism of its function, including ion selectivity and gating, has not been fully characterized. Recently we reported a new structure of a CorA homologue from Methanocaldococcus jannaschii, which provided novel structural details that offered the conception of a unique gating mechanism involving conversion of an open hydrophilic gate into a closed hydrophobic one. In the present study we report functional evidence for this novel gating mechanism in the Thermotoga maritima CorA together with an improved crystal structure of this CorA to 2.7 Å (1 Å=0.1 nm) resolution. The latter reveals the organization of the selectivity filter to be similar to that of M. jannaschii CorA and also the previously unknown organization of the second signature motif of the CorA family. The proposed gating is achieved by a helical rotation upon the binding of a metal ion substrate to the regulatory binding sites. Additionally, our data suggest that the preference of this CorA for Co2+ over Mg2+ is controlled by the presence of threonine side chains in the channel. Finally, the roles of the intracellular metal-binding sites have been assigned to increased thermostability and regulation of the gating. These mechanisms most likely apply to the entire CorA family as they are regulated by the highly conserved amino acids. PMID:23425532

Statistical discovery of site inter-dependencies in sub-molecular hierarchical protein structuring

PubMed Central

2012-01-01

Background Much progress has been made in understanding the 3D structure of proteins using methods such as NMR and X-ray crystallography. The resulting 3D structures are extremely informative, but do not always reveal which sites and residues within the structure are of special importance. Recently, there are indications that multiple-residue, sub-domain structural relationships within the larger 3D consensus structure of a protein can be inferred from the analysis of the multiple sequence alignment data of a protein family. These intra-dependent clusters of associated sites are used to indicate hierarchical inter-residue relationships within the 3D structure. To reveal the patterns of associations among individual amino acids or sub-domain components within the structure, we apply a k-modes attribute (aligned site) clustering algorithm to the ubiquitin and transthyretin families in order to discover associations among groups of sites within the multiple sequence alignment. We then observe what these associations imply within the 3D structure of these two protein families. Results The k-modes site clustering algorithm we developed maximizes the intra-group interdependencies based on a normalized mutual information measure. The clusters formed correspond to sub-structural components or binding and interface locations. Applying this data-directed method to the ubiquitin and transthyretin protein family multiple sequence alignments as a test bed, we located numerous interesting associations of interdependent sites. These clusters were then arranged into cluster tree diagrams which revealed four structural sub-domains within the single domain structure of ubiquitin and a single large sub-domain within transthyretin associated with the interface among transthyretin monomers. In addition, several clusters of mutually interdependent sites were discovered for each protein family, each of which appear to play an important role in the molecular structure and/or function. Conclusions Our results demonstrate that the method we present here using a k-modes site clustering algorithm based on interdependency evaluation among sites obtained from a sequence alignment of homologous proteins can provide significant insights into the complex, hierarchical inter-residue structural relationships within the 3D structure of a protein family. PMID:22793672

Statistical discovery of site inter-dependencies in sub-molecular hierarchical protein structuring.

PubMed

Durston, Kirk K; Chiu, David Ky; Wong, Andrew Kc; Li, Gary Cl

2012-07-13

Much progress has been made in understanding the 3D structure of proteins using methods such as NMR and X-ray crystallography. The resulting 3D structures are extremely informative, but do not always reveal which sites and residues within the structure are of special importance. Recently, there are indications that multiple-residue, sub-domain structural relationships within the larger 3D consensus structure of a protein can be inferred from the analysis of the multiple sequence alignment data of a protein family. These intra-dependent clusters of associated sites are used to indicate hierarchical inter-residue relationships within the 3D structure. To reveal the patterns of associations among individual amino acids or sub-domain components within the structure, we apply a k-modes attribute (aligned site) clustering algorithm to the ubiquitin and transthyretin families in order to discover associations among groups of sites within the multiple sequence alignment. We then observe what these associations imply within the 3D structure of these two protein families. The k-modes site clustering algorithm we developed maximizes the intra-group interdependencies based on a normalized mutual information measure. The clusters formed correspond to sub-structural components or binding and interface locations. Applying this data-directed method to the ubiquitin and transthyretin protein family multiple sequence alignments as a test bed, we located numerous interesting associations of interdependent sites. These clusters were then arranged into cluster tree diagrams which revealed four structural sub-domains within the single domain structure of ubiquitin and a single large sub-domain within transthyretin associated with the interface among transthyretin monomers. In addition, several clusters of mutually interdependent sites were discovered for each protein family, each of which appear to play an important role in the molecular structure and/or function. Our results demonstrate that the method we present here using a k-modes site clustering algorithm based on interdependency evaluation among sites obtained from a sequence alignment of homologous proteins can provide significant insights into the complex, hierarchical inter-residue structural relationships within the 3D structure of a protein family.

Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins

PubMed Central

Cremonez, Caroline M.; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A. A.; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M. C.; Arantes, Eliane C.; Tytgat, Jan

2016-01-01

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx. PMID:27706049

Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins.

PubMed

Cremonez, Caroline M; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A A; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M C; Arantes, Eliane C; Tytgat, Jan

2016-09-30

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx.

INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions.

PubMed

Cánepa, Eduardo T; Scassa, María E; Ceruti, Julieta M; Marazita, Mariela C; Carcagno, Abel L; Sirkin, Pablo F; Ogara, María F

2007-07-01

The cyclin D-Cdk4-6/INK4/Rb/E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli. The members of INK4 family, comprising p16(INK4a), p15(INK4b), p18(INK4c), and p19(INK4d), block the progression of the cell cycle by binding to either Cdk4 or Cdk6 and inhibiting the action of cyclin D. These INK4 proteins share a similar structure dominated by several ankyrin repeats. Although they appear to be structurally redundant and equally potent as inhibitors, the INK4 family members are differentially expressed during mouse development. The striking diversity in the pattern of expression of INK4 genes suggested that this family of cell cycle inhibitors might have cell lineage-specific or tissue-specific functions. The INK4 proteins are commonly lost or inactivated by mutations in diverse types of cancer, and they represent established or candidate tumor suppressors. Apart from their capacity to arrest cells in the G1-phase of the cell cycle they have been shown to participate in an increasing number of cellular processes. Given their emerging roles in fundamental physiological as well as pathological processes, it is interesting to explore the diverse roles for the individual INK4 family members in different functions other than cell cycle regulation. Extensive studies, over the past few years, uncover the involvement of INK4 proteins in senescence, apoptosis, DNA repair, and multistep oncogenesis. We will focus the discussion here on these unexpected issues.

Structure-Function Analysis of a Broad Specificity Populus trichocarpa Endo-β-glucanase Reveals an Evolutionary Link between Bacterial Licheninases and Plant XTH Gene Products*

PubMed Central

Eklöf, Jens M.; Shojania, Shaheen; Okon, Mark; McIntosh, Lawrence P.; Brumer, Harry

2013-01-01

The large xyloglucan endotransglycosylase/hydrolase (XTH) gene family continues to be the focus of much attention in studies of plant cell wall morphogenesis due to the unique catalytic functions of the enzymes it encodes. The XTH gene products compose a subfamily of glycoside hydrolase family 16 (GH16), which also comprises a broad range of microbial endoglucanases and endogalactanases, as well as yeast cell wall chitin/β-glucan transglycosylases. Previous whole-family phylogenetic analyses have suggested that the closest relatives to the XTH gene products are the bacterial licheninases (EC 3.2.1.73), which specifically hydrolyze linear mixed linkage β(1→3)/β(1→4)-glucans. In addition to their specificity for the highly branched xyloglucan polysaccharide, XTH gene products are distinguished from the licheninases and other GH16 enzyme subfamilies by significant active site loop alterations and a large C-terminal extension. Given these differences, the molecular evolution of the XTH gene products in GH16 has remained enigmatic. Here, we present the biochemical and structural analysis of a unique, mixed function endoglucanase from black cottonwood (Populus trichocarpa), which reveals a small, newly recognized subfamily of GH16 members intermediate between the bacterial licheninases and plant XTH gene products. We postulate that this clade comprises an important link in the evolution of the large plant XTH gene families from a putative microbial ancestor. As such, this analysis provides new insights into the diversification of GH16 and further unites the apparently disparate members of this important family of proteins. PMID:23572521

Genome-Wide Screening and Characterization of the Dof Gene Family in Physic Nut (Jatropha curcas L.).

PubMed

Wang, Peipei; Li, Jing; Gao, Xiaoyang; Zhang, Di; Li, Anlin; Liu, Changning

2018-05-29

Physic nut ( Jatropha curcas L.) is a species of flowering plant with great potential for biofuel production and as an emerging model organism for functional genomic analysis, particularly in the Euphorbiaceae family. DNA binding with one finger (Dof) transcription factors play critical roles in numerous biological processes in plants. Nevertheless, the knowledge about members, and the evolutionary and functional characteristics of the Dof gene family in physic nut is insufficient. Therefore, we performed a genome-wide screening and characterization of the Dof gene family within the physic nut draft genome. In total, 24 JcDof genes (encoding 33 JcDof proteins) were identified. All the JcDof genes were divided into three major groups based on phylogenetic inference, which was further validated by the subsequent gene structure and motif analysis. Genome comparison revealed that segmental duplication may have played crucial roles in the expansion of the JcDof gene family, and gene expansion was mainly subjected to positive selection. The expression profile demonstrated the broad involvement of JcDof genes in response to various abiotic stresses, hormonal treatments and functional divergence. This study provides valuable information for better understanding the evolution of JcDof genes, and lays a foundation for future functional exploration of JcDof genes.

Left-behind children in rural China experience higher levels of anxiety and poorer living conditions.

PubMed

Zhao, Xue; Chen, Jian; Chen, Ming-Chun; Lv, Xiao-Ling; Jiang, Yu-Hong; Sun, Ye-Huan

2014-06-01

The number of rural Chinese parents who leave their children with family members to work in the cities has increased dramatically over the last decade. This study compared the social anxiety of left-behind children (LBC) and children not left behind (non-LBC). We investigated 1694 LBC and 1223 non-LBC, aged seven to 17 years, in a Chinese province using a structured questionnaire that included questions about socio-demographic characteristics, social anxiety, family function, quality of life, neglect and physical abuse. LBC displayed higher social anxiety scores, more neglect, lower parental educational level, lower quality of life, lower family function and lower prevalence of physical abuse than non-LBC. Multiple linear regression models showed that higher Social Anxiety Scales for Children (SASC) scores in LBC were clearly associated with lower quality of life, poorer family function, physical abuse, being female, having more siblings and minorities. In non-LBC, they were associated with lower quality of life, poorer family function, neglect, being female and physical abuse. LBC have a relatively higher level of social anxiety and poorer living conditions than non-LBC, and there are differences in social anxiety, and its relevant factors, between the two groups. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Pattern similarity study of functional sites in protein sequences: lysozymes and cystatins

PubMed Central

Nakai, Shuryo; Li-Chan, Eunice CY; Dou, Jinglie

2005-01-01

Background Although it is generally agreed that topography is more conserved than sequences, proteins sharing the same fold can have different functions, while there are protein families with low sequence similarity. An alternative method for profile analysis of characteristic conserved positions of the motifs within the 3D structures may be needed for functional annotation of protein sequences. Using the approach of quantitative structure-activity relationships (QSAR), we have proposed a new algorithm for postulating functional mechanisms on the basis of pattern similarity and average of property values of side-chains in segments within sequences. This approach was used to search for functional sites of proteins belonging to the lysozyme and cystatin families. Results Hydrophobicity and β-turn propensity of reference segments with 3–7 residues were used for the homology similarity search (HSS) for active sites. Hydrogen bonding was used as the side-chain property for searching the binding sites of lysozymes. The profiles of similarity constants and average values of these parameters as functions of their positions in the sequences could identify both active and substrate binding sites of the lysozyme of Streptomyces coelicolor, which has been reported as a new fold enzyme (Cellosyl). The same approach was successfully applied to cystatins, especially for postulating the mechanisms of amyloidosis of human cystatin C as well as human lysozyme. Conclusion Pattern similarity and average index values of structure-related properties of side chains in short segments of three residues or longer were, for the first time, successfully applied for predicting functional sites in sequences. This new approach may be applicable to studying functional sites in un-annotated proteins, for which complete 3D structures are not yet available. PMID:15904486

A cost-effective protocol for the over-expression and purification of fully-functional and more stable Erwinia chrisanthemi ligand-gated ion channel

PubMed Central

Elberson, Benjamin W.; Whisenant, Ty E.; Cortes, D. Marien; Cuello, Luis G.

2017-01-01

The Erwinia chrisanthemi ligand-gated ion channel, ELIC, is considered an excellent structural and functional surrogate for the whole pentameric ligand-gated ion channel family. Despite its simplicity, ELIC is structurally capable of undergoing ligand-dependent activation and a concomitant desensitization process. To determine at the molecular level the structural changes underlying ELIC’s function, it is desirable to produce large quantities of protein. This protein should be properly folded, fully-functional and amenable to structural determinations. In the current paper, we report a completely new protocol for the expression and purification of milligram quantities of fully-functional, more stable and crystallizable ELIC. The use of an autoinduction media and inexpensive detergents during ELIC extraction, in addition to the high-quality and large quantity of the purified channel, are the highlights of this improved biochemical protocol. PMID:28279818

Is family functioning and communication associated with health-related quality of life for Chinese- and Korean-American breast cancer survivors?

PubMed Central

Lim, Jung-won; Ashing-Giwa, Kimlin T.

2012-01-01

Purpose This study aims to investigate direct and indirect pathways of family flexibility, social support, and family communication on health-related quality of life (HRQOL) for Chinese- and Korean-American breast cancer survivors (BCS). Methods A total of 157 Chinese (n = 86)- and Korean-American (n = 71) BCS were recruited from the California Cancer Surveillance Program and area hospitals in Los Angeles County. The present study was guided by the Resiliency Model of Family Stress, Adjustment, and Adaptation. Results Structural equation modeling demonstrated that (1) family communication was directly associated with HRQOL for both groups; (2) family flexibility was indirectly associated with HRQOL through family communication for Korean-Americans only; (3) social support mediated the relationship between family flexibility and family communication for Chinese-Americans only; and (4) acculturation was directly related to social support for both groups. Multigroup analysis demonstrated that the structural paths were equivalent between Chinese- and Korean-American BCS, although statistical differences in baseline parameters were noted. Conclusions Our findings suggest that family communication impacts HRQOL among Asian-American BCS. Our results show that while there are commonalities in family characteristics among Asian-Americans, specific ethnic variations also exist. Therefore, specific cultural and familial contexts should be assessed to better inform interventions to enhance family communication strategies and improve HRQOL. PMID:22875219

Local phylogenetic divergence and global evolutionary convergence of skull function in reef fishes of the family Labridae.

PubMed

Westneat, Mark W; Alfaro, Michael E; Wainwright, Peter C; Bellwood, David R; Grubich, Justin R; Fessler, Jennifer L; Clements, Kendall D; Smith, Lydia L

2005-05-22

The Labridae is one of the most structurally and functionally diversified fish families on coral and rocky reefs around the world, providing a compelling system for examination of evolutionary patterns of functional change. Labrid fishes have evolved a diverse array of skull forms for feeding on prey ranging from molluscs, crustaceans, plankton, detritus, algae, coral and other fishes. The species richness and diversity of feeding ecology in the Labridae make this group a marine analogue to the cichlid fishes. Despite the importance of labrids to coastal reef ecology, we lack evolutionary analysis of feeding biomechanics among labrids. Here, we combine a molecular phylogeny of the Labridae with the biomechanics of skull function to reveal a broad pattern of repeated convergence in labrid feeding systems. Mechanically fast jaw systems have evolved independently at least 14 times from ancestors with forceful jaws. A repeated phylogenetic pattern of functional divergence in local regions of the labrid tree produces an emergent family-wide pattern of global convergence in jaw function. Divergence of close relatives, convergence among higher clades and several unusual 'breakthroughs' in skull function characterize the evolution of functional complexity in one of the most diverse groups of reef fishes.

Structural and Functional Analyses of a Glycoside Hydrolase Family 5 Enzyme with an Unexpected [beta]-Fucosidase Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshida, Shosuke; Park, David S.; Bae, Brian

2012-02-15

We present characterization of PbFucA, a family 5 glycoside hydrolase (GH5) from Prevotella bryantii B{sub 1}4. While GH5 members typically are xylanases, PbFucA shows no activity toward xylan polysaccharides. A screen against a panel of p-nitrophenol coupled sugars identifies PbFucA as a {beta}-D-fucosidase. We also present the 2.2 {angstrom} resolution structure of PbFucA and use structure-based mutational analysis to confirm the role of catalytically essential residues. A comparison of the active sites of PbFucA with those of family 5 and 51 glycosidases reveals that while the essential catalytic framework is identical between these enzymes, the steric contours of the respectivemore » active site clefts are distinct and likely account for substrate discrimination. Our results show that members of this cluster of orthologous group (COG) 5520 have {beta}-D-fucosidase activities, despite showing an overall sequence and structural similarity to GH-5 xylanases.« less

Variations in Nuclear Localization Strategies Among Pol X Family Enzymes.

PubMed

Kirby, Thomas W; Pedersen, Lars C; Gabel, Scott A; Gassman, Natalie R; London, Robert E

2018-06-22

Despite the essential roles of pol X family enzymes in DNA repair, information about the structural basis of their nuclear import is limited. Recent studies revealed the unexpected presence of a functional NLS in DNA polymerase β, indicating the importance of active nuclear targeting, even for enzymes likely to leak into and out of the nucleus. The current studies further explore the active nuclear transport of these enzymes by identifying and structurally characterizing the functional NLS sequences in the three remaining human pol X enzymes: terminal deoxynucleotidyl transferase (TdT), DNA polymerase μ (pol μ), and DNA polymerase λ (pol λ). NLS identifications are based on Importin α (Impα) binding affinity determined by fluorescence polarization of fluorescein-labeled NLS peptides, X-ray crystallographic analysis of the Impα∆IBB•NLS complexes, and fluorescence-based subcellular localization studies. All three polymerases use NLS sequences located near their N-terminus; TdT and pol μ utilize monopartite NLS sequences, while pol λ utilizes a bipartite sequence, unique among the pol X family members. The pol μ NLS has relatively weak measured affinity for Impα, due in part to its proximity to the N-terminus that limits non-specific interactions of flanking residues preceding the NLS. However, this effect is partially mitigated by an N-terminal sequence unsupportive of Met1 removal by methionine aminopeptidase, leading to a 3-fold increase in affinity when the N-terminal methionine is present. Nuclear targeting is unique to each pol X family enzyme with variations dependent on the structure and unique functional role of each polymerase. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Crystal structure of Bacillus subtilis YabJ, a purine regulatory protein and member of the highly conserved YjgF family

PubMed Central

Sinha, Sangita; Rappu, Pekka; Lange, S. C.; Mäntsälä, Pekka; Zalkin, Howard; Smith, Janet L.

1999-01-01

The yabJ gene in Bacillus subtilis is required for adenine-mediated repression of purine biosynthetic genes in vivo and codes for an acid-soluble, 14-kDa protein. The molecular mechanism of YabJ is unknown. YabJ is a member of a large, widely distributed family of proteins of unknown biochemical function. The 1.7-Å crystal structure of YabJ reveals a trimeric organization with extensive buried hydrophobic surface and an internal water-filled cavity. The most important finding in the structure is a deep, narrow cleft between subunits lined with nine side chains that are invariant among the 25 most similar homologs. This conserved site is proposed to be a binding or catalytic site for a ligand or substrate that is common to YabJ and other members of the YER057c/YjgF/UK114 family of proteins. PMID:10557275

Family Income, Parental Education and Brain Structure in Children and Adolescents

PubMed Central

Noble, Kimberly G.; Houston, Suzanne M.; Brito, Natalie H.; Bartsch, Hauke; Kan, Eric; Kuperman, Joshua M.; Akshoomoff, Natacha; Amaral, David G.; Bloss, Cinnamon S.; Libiger, Ondrej; Schork, Nicholas J.; Murray, Sarah S.; Casey, B. J.; Chang, Linda; Ernst, Thomas M.; Frazier, Jean A.; Gruen, Jeffrey R.; Kennedy, David N.; Zijl, Peter Van; Mostofsky, Stewart; Kaufmann, Walter E.; Kenet, Tal; Dale, Anders M.; Jernigan, Terry L.; Sowell, Elizabeth R.

2015-01-01

Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. Here, we investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1099 typically developing individuals between 3 and 20 years. Income was logarithmically associated with brain surface area. Specifically, among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data indicate that income relates most strongly to brain structure among the most disadvantaged children. Potential implications are discussed. PMID:25821911

Structural basis for the fast maturation of Arthropoda green fluorescent protein

PubMed Central

Evdokimov, Artem G; Pokross, Matthew E; Egorov, Nikolay S; Zaraisky, Andrey G; Yampolsky, Ilya V; Merzlyak, Ekaterina M; Shkoporov, Andrey N; Sander, Ian; Lukyanov, Konstantin A; Chudakov, Dmitriy M

2006-01-01

Since the cloning of Aequorea victoria green fluorescent protein (GFP) in 1992, a family of known GFP-like proteins has been growing rapidly. Today, it includes more than a hundred proteins with different spectral characteristics cloned from Cnidaria species. For some of these proteins, crystal structures have been solved, showing diversity in chromophore modifications and conformational states. However, we are still far from a complete understanding of the origin, functions and evolution of the GFP family. Novel proteins of the family were recently cloned from evolutionarily distant marine Copepoda species, phylum Arthropoda, demonstrating an extremely rapid generation of fluorescent signal. Here, we have generated a non-aggregating mutant of Copepoda fluorescent protein and solved its high-resolution crystal structure. It was found that the protein β-barrel contains a pore, leading to the chromophore. Using site-directed mutagenesis, we showed that this feature is critical for the fast maturation of the chromophore. PMID:16936637

T-RMSD: a fine-grained, structure-based classification method and its application to the functional characterization of TNF receptors.

PubMed

Magis, Cedrik; Stricher, François; van der Sloot, Almer M; Serrano, Luis; Notredame, Cedric

2010-07-16

This study addresses the relation between structural and functional similarity in proteins. We introduce a novel method named tree based on root mean square deviation (T-RMSD), which uses distance RMSD (dRMSD) variations to build fine-grained structure-based classifications of proteins. The main improvement of the T-RMSD over similar methods, such as Dali, is its capacity to produce the equivalent of a bootstrap value for each cluster node. We validated our approach on two domain families studied extensively for their role in many biological and pathological pathways: the small GTPase RAS superfamily and the cysteine-rich domains (CRDs) associated with the tumor necrosis factor receptors (TNFRs) family. Our analysis showed that T-RMSD is able to automatically recover and refine existing classifications. In the case of the small GTPase ARF subfamily, T-RMSD can distinguish GTP- from GDP-bound states, while in the case of CRDs it can identify two new subgroups associated with well defined functional features (ligand binding and formation of ligand pre-assembly complex). We show how hidden Markov models (HMMs) can be built on these new groups and propose a methodology to use these models simultaneously in order to do fine-grained functional genomic annotation without known 3D structures. T-RMSD, an open source freeware incorporated in the T-Coffee package, is available online. 2010 Elsevier Ltd. All rights reserved.

Glossary

MedlinePlus

... Research Grants Funded Projects Patient Evaluation for Professionals Energy Metabolism Review Mitochondrial Structure, Function and Diseases Review ... General Fund! Donor Privacy Policy Donate to… … an Energy for Life Walkathon … an Event … a Family Research ...

The varied functions of aluminium-activated malate transporters-much more than aluminium resistance.

PubMed

Palmer, Antony J; Baker, Alison; Muench, Stephen P

2016-06-15

The ALMT (aluminium-activated malate transporter) family comprises a functionally diverse but structurally similar group of ion channels. They are found ubiquitously in plant species, expressed throughout different tissues, and located in either the plasma membrane or tonoplast. The first family member identified was TaALMT1, discovered in wheat root tips, which was found to be involved in aluminium resistance by means of malate exudation into the soil. However, since this discovery other family members have been shown to have many other functions such as roles in stomatal opening, general anionic homoeostasis, and in economically valuable traits such as fruit flavour. Recent evidence has also shown that ALMT proteins can act as key molecular actors in GABA (γ-aminobutyric acid) signalling, the first evidence that GABA can act as a signal transducer in plants. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Biological (Molecular and Cellular) Markers of Toxicity.

DTIC Science & Technology

1991-12-15

capability to maintain the integrity of it’s DNA (repair and chromosomal structure -function), will provide the basis for determining bioavailability...examined in this research. In Phase I metabolism, catalyzed by the mixed function oxidase (MFO) enzyme system, a reactive functional group (such as -OH...the incorporation of many organic chemicals in tissues, organisms will induce a family of enzymes better known as the Mixed-Function Oxidase (MFO

Active Fragments from Pro- and Antiapoptotic BCL-2 Proteins Have Distinct Membrane Behavior Reflecting Their Functional Divergence

PubMed Central

Guillemin, Yannis; Lopez, Jonathan; Gimenez, Diana; Fuertes, Gustavo; Valero, Juan Garcia; Blum, Loïc; Gonzalo, Philippe; Salgado, Jesùs; Girard-Egrot, Agnès; Aouacheria, Abdel

2010-01-01

Background The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction. Methodology/Principal Findings Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death. Conclusion/Significance BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains. PMID:20140092

A Structural Equation Model on Korean Adolescents' Excessive Use of Smartphones.

PubMed

Lee, Hana; Kim, JooHyun

2018-03-31

We develop a unified structural model that defines multi-relationships between systematic factors causing excessive use of smartphones and the corresponding results. We conducted a survey with adolescents who live in Seoul, Pusan, Gangneung, Donghae, and Samcheok from Feb. to Mar. 2016. We utilized SPSS Ver. 22 and Amos Ver. 22 to analyze the survey result at a 0.05 significance level. To investigate demographic characteristics of the participants and their variations, we employed descriptive analysis. We adopted the maximum likelihood estimate method to verify the fitness of the hypothetical model and the hypotheses therein. We used χ 2 statistics, GFI, AGFI, CFI, NFI, IFI, RMR, and RMSEA to verify the fitness of our structural model. (1) Our proposed structural model demonstrated a fine fitness level. (2) Our proposed structural model could describe the excessive use of a smartphone with 88.6% accuracy. (3) The absence of the family function and relationship between friends, impulsiveness, and low self-esteem were confirmed as key factors that cause excessive use of smartphones. (4) Further, impulsiveness and low self-esteem are closely related to the absence of family functions and relations between friends by 68.3% and 54.4%, respectively. We suggest that nursing intervention programs from various angles are required to reduce adolescents' excessive use of smartphones. For example, family communication programs would be helpful for both parents and children. Consultant programs about friend relationship also meaningful for the program. Copyright © 2018. Published by Elsevier B.V.

Uronic polysaccharide degrading enzymes.

PubMed

Garron, Marie-Line; Cygler, Miroslaw

2014-10-01

In the past several years progress has been made in the field of structure and function of polysaccharide lyases (PLs). The number of classified polysaccharide lyase families has increased to 23 and more detailed analysis has allowed the identification of more closely related subfamilies, leading to stronger correlation between each subfamily and a unique substrate. The number of as yet unclassified polysaccharide lyases has also increased and we expect that sequencing projects will allow many of these unclassified sequences to emerge as new families. The progress in structural analysis of PLs has led to having at least one representative structure for each of the families and for two unclassified enzymes. The newly determined structures have folds observed previously in other PL families and their catalytic mechanisms follow either metal-assisted or Tyr/His mechanisms characteristic for other PL enzymes. Comparison of PLs with glycoside hydrolases (GHs) shows several folds common to both classes but only for the β-helix fold is there strong indication of divergent evolution from a common ancestor. Analysis of bacterial genomes identified gene clusters containing multiple polysaccharide cleaving enzymes, the Polysaccharides Utilization Loci (PULs), and their gene complement suggests that they are organized to process completely a specific polysaccharide. Copyright © 2014 Elsevier Ltd. All rights reserved.

Aging and Family Life: A Decade Review

PubMed Central

Silverstein, Merril; Giarrusso, Roseann

2010-01-01

In this review, we summarize and critically evaluate the major empirical, conceptual, and theoretical directions that studies of aging families have taken during the first decade of the 21st century. The field has benefited from an expanded perspective based on four overarching themes: (a) complexity in emotional relations, (b) diversity in family structures and households, (c) interdependence of family roles and functions, and (d) patterns and outcomes of caregiving. Although research on aging families has advanced theory and applied innovative statistical techniques, the literature has fallen short in fully representing diverse populations and in applying the broadest set of methodological tools available. We discuss these and other frontier areas of scholarship in light of the aging of baby boomers and their families. PMID:22930600

The Custodial Parent-Child Relationship as a Mediating Factor in the Effects of Divorce on Children.

ERIC Educational Resources Information Center

Rasmussen, Janis Carol

Hess and Camara (1979) have shown that it is post-divorce family functioning, rather than family structure, that is most important in influencing the effects of divorce on children. A child's adjustment to divorce should be viewed as a developmental process rather than as a single event. Consequently, it is important to focus on the ways in which…

The structure of mouse cytomegalovirus m04 protein obtained from sparse NMR data reveals a conserved fold of the m02-m06 viral immune modulator family.

PubMed

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

2014-09-02

Immunoevasins are key proteins used by viruses to subvert host immune responses. Determining their high-resolution structures is key to understanding virus-host interactions toward the design of vaccines and other antiviral therapies. Mouse cytomegalovirus encodes a unique set of immunoevasins, the m02-m06 family, that modulates major histocompatibility complex class I (MHC-I) antigen presentation to CD8+ T cells and natural killer cells. Notwithstanding the large number of genetic and functional studies, the structural biology of immunoevasins remains incompletely understood, largely because of crystallization bottlenecks. Here we implement a technology using sparse nuclear magnetic resonance data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain. The structure reveals a β fold that is representative of the m02-m06 family of viral proteins, several of which are known to bind MHC-I molecules and interfere with antigen presentation, suggesting its role as a diversified immune regulation module. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prediction of a common beta-propeller catalytic domain for fructosyltransferases of different origin and substrate specificity.

PubMed

Pons, T; Hernández, L; Batista, F R; Chinea, G

2000-11-01

The three-dimensional (3D) structure of fructan biosynthetic enzymes is still unknown. Here, we have explored folding similarities between reported microbial and plant enzymes that catalyze transfructosylation reactions. A sequence-structure compatibility search using TOPITS, SDP, 3D-PSSM, and SAM-T98 programs identified a beta-propeller fold with scores above the confidence threshold that indicate a structurally conserved catalytic domain in fructosyltransferases (FTFs) of diverse origin and substrate specificity. The predicted fold appeared related to that of neuraminidase and sialidase, of glycoside hydrolase families 33 and 34, respectively. The most reliable structural model was obtained using the crystal structure of neuraminidase (Protein Data Bank file: 5nn9) as template, and it is consistent with the location of previously identified functional residues of bacterial levansucrases (Batista et al., 1999; Song & Jacques, 1999). The sequence-sequence analysis presented here reinforces the recent inclusion of fungal and plant FTFs into glycoside hydrolase family 32, and suggests a modified sequence pattern H-x (2)-[PTV]-x (4)-[LIVMA]-[NSCAYG]-[DE]-P-[NDSC][GA]3 for this family.

Prediction of a common beta-propeller catalytic domain for fructosyltransferases of different origin and substrate specificity.

PubMed Central

Pons, T.; Hernández, L.; Batista, F. R.; Chinea, G.

2000-01-01

The three-dimensional (3D) structure of fructan biosynthetic enzymes is still unknown. Here, we have explored folding similarities between reported microbial and plant enzymes that catalyze transfructosylation reactions. A sequence-structure compatibility search using TOPITS, SDP, 3D-PSSM, and SAM-T98 programs identified a beta-propeller fold with scores above the confidence threshold that indicate a structurally conserved catalytic domain in fructosyltransferases (FTFs) of diverse origin and substrate specificity. The predicted fold appeared related to that of neuraminidase and sialidase, of glycoside hydrolase families 33 and 34, respectively. The most reliable structural model was obtained using the crystal structure of neuraminidase (Protein Data Bank file: 5nn9) as template, and it is consistent with the location of previously identified functional residues of bacterial levansucrases (Batista et al., 1999; Song & Jacques, 1999). The sequence-sequence analysis presented here reinforces the recent inclusion of fungal and plant FTFs into glycoside hydrolase family 32, and suggests a modified sequence pattern H-x (2)-[PTV]-x (4)-[LIVMA]-[NSCAYG]-[DE]-P-[NDSC][GA]3 for this family. PMID:11305239

First cytoplasmic loop of glucagon-like peptide-1 receptor can function at the third cytoplasmic loop position of rhodopsin.

PubMed

Yamashita, Takahiro; Tose, Koji; Shichida, Yoshinori

2008-01-01

G protein-coupled receptors (GPCRs) are classified into several families based on their amino acid sequences. In family 1, GPCRs such as rhodopsin and adrenergic receptor, the structure-function relationship has been extensively investigated to demonstrate that exposure of the third cytoplasmic loop is essential for selective G protein activation. In contrast, much less is known about other families. Here we prepared chimeric mutants between Gt-coupled rhodopsin and Gi/Go- and Gs-coupled glucagon-like peptide-1 (GLP-1) receptor of family 2 and tried to identify the loop region that functions at the third cytoplasmic loop position of rhodopsin. We succeeded in expressing a mutant having the first cytoplasmic loop of GLP-1 receptor and found that this mutant activated Gi and Go efficiently but did not activate Gt. Moreover, the rhodopsin mutant having the first loop of Gs-coupled secretin receptor of family 2 decreased the Gi and Go activation efficiencies. Therefore, the first loop of GLP-1 receptor would share a similar role to the third loop of rhodopsin in G protein activation. This result strongly suggested that different families of GPCRs have maintained molecular architectures of their ancestral types to generate a common mechanism, namely exposure of the cytoplasmic loop, to activate peripheral G protein.

Evaluating the satisfaction of immigrant women from a rural community regarding family functioning and health-related quality of life.

PubMed

Tsai, Su-Ying; Sun, Wen-Jung

2013-01-01

Transnational marriages in Taiwan are largely mediated by marriage brokers. The present study was conducted to evaluate the satisfaction of immigrant women with their family function and health-related quality of life in a rural township in southern Taiwan. Data were collected from January 1, 2006 to November 31, 2006, and 157 immigrants agreed to participate in the study, with a 79.3% response rate. A structured questionnaire was used for data collection. The interviewers also collected information on the immigrants' and husbands' demographics, self-reported mental conditions, family function using a Family APGAR questionnaire (Adaptability, Partnership, Growth, Affection, and Resolve), and health-related quality of life. Marriage arranged through a marriage broker and having emotional distress were factors that were strongly associated with lower Family APGAR scores. Based on multiple regression models, higher Family APGAR scores were more positively related to vitality and mental health scales. Self-reported mental conditions, including feeling economic distress, emotional distress, loneliness, and having sleep problems, were negatively associated with most scales of the health-related quality of life. Female migrants' mental health was significantly related to their health-related quality of life. These findings suggest that migrant women must be educated regarding the importance of mental health by physicians and hygiene authorities in Taiwan.

Functional Annotation, Genome Organization and Phylogeny of the Grapevine (Vitis vinifera) Terpene Synthase Gene Family Based on Genome Assembly, FLcDNA Cloning, and Enzyme Assays

PubMed Central

2010-01-01

Background Terpenoids are among the most important constituents of grape flavour and wine bouquet, and serve as useful metabolite markers in viticulture and enology. Based on the initial 8-fold sequencing of a nearly homozygous Pinot noir inbred line, 89 putative terpenoid synthase genes (VvTPS) were predicted by in silico analysis of the grapevine (Vitis vinifera) genome assembly [1]. The finding of this very large VvTPS family, combined with the importance of terpenoid metabolism for the organoleptic properties of grapevine berries and finished wines, prompted a detailed examination of this gene family at the genomic level as well as an investigation into VvTPS biochemical functions. Results We present findings from the analysis of the up-dated 12-fold sequencing and assembly of the grapevine genome that place the number of predicted VvTPS genes at 69 putatively functional VvTPS, 20 partial VvTPS, and 63 VvTPS probable pseudogenes. Gene discovery and annotation included information about gene architecture and chromosomal location. A dense cluster of 45 VvTPS is localized on chromosome 18. Extensive FLcDNA cloning, gene synthesis, and protein expression enabled functional characterization of 39 VvTPS; this is the largest number of functionally characterized TPS for any species reported to date. Of these enzymes, 23 have unique functions and/or phylogenetic locations within the plant TPS gene family. Phylogenetic analyses of the TPS gene family showed that while most VvTPS form species-specific gene clusters, there are several examples of gene orthology with TPS of other plant species, representing perhaps more ancient VvTPS, which have maintained functions independent of speciation. Conclusions The highly expanded VvTPS gene family underpins the prominence of terpenoid metabolism in grapevine. We provide a detailed experimental functional annotation of 39 members of this important gene family in grapevine and comprehensive information about gene structure and phylogeny for the entire currently known VvTPS gene family. PMID:20964856

Genome-wide analysis of the R2R3-MYB transcription factor gene family in sweet orange (Citrus sinensis).

PubMed

Liu, Chaoyang; Wang, Xia; Xu, Yuantao; Deng, Xiuxin; Xu, Qiang

2014-10-01

MYB transcription factor represents one of the largest gene families in plant genomes. Sweet orange (Citrus sinensis) is one of the most important fruit crops worldwide, and recently the genome has been sequenced. This provides an opportunity to investigate the organization and evolutionary characteristics of sweet orange MYB genes from whole genome view. In the present study, we identified 100 R2R3-MYB genes in the sweet orange genome. A comprehensive analysis of this gene family was performed, including the phylogeny, gene structure, chromosomal localization and expression pattern analyses. The 100 genes were divided into 29 subfamilies based on the sequence similarity and phylogeny, and the classification was also well supported by the highly conserved exon/intron structures and motif composition. The phylogenomic comparison of MYB gene family among sweet orange and related plant species, Arabidopsis, cacao and papaya suggested the existence of functional divergence during evolution. Expression profiling indicated that sweet orange R2R3-MYB genes exhibited distinct temporal and spatial expression patterns. Our analysis suggested that the sweet orange MYB genes may play important roles in different plant biological processes, some of which may be potentially involved in citrus fruit quality. These results will be useful for future functional analysis of the MYB gene family in sweet orange.

Exploring the functional impact of adaptive seating on the lives of individual children and their families: a collective case study.

PubMed

Stier, Carly D; Chieu, Ivan B; Howell, Lori; Ryan, Stephen E

2017-07-01

This study examined parent-reported change in the functional performance of four school-aged children with wheeled mobility needs who had used a new adaptive seating system for 6 weeks. The collective case study involved four mothers whose children, ages 6-9 years, received a new adaptive seating system for a manual wheelchair or stroller. Mothers completed the Family Impact of Assistive Technology Scale for Adaptive Seating (FIATS-AS) at the time their child received a new seating system, and then after 6 weeks of daily use. Other questionnaires, health records, and semi-structured interviews provided additional data about the seating interventions and their functional effects on individual children and their families. The FIATS-AS detected overall functional gain in one family, and both gains and losses in 2-7 dimensions for all families. Functional status and change scores showed consistency with measures of seating intervention satisfaction, global functional change, and home participation. Interview themes also suggested consistency with change scores, but provided a deeper understanding of important factors that influenced adaptive seating outcomes. This study supports the need to explore further the complexity, temporality and meaningfulness of adaptive seating outcomes in individual children and their families. Implications for Rehabilitation Assistive technology practitioners need to adopt practical measurement strategies that consider the complexity, temporality, and meaningfulness of outcomes to make evidence-informed decisions about how to improve adaptive seating services and interventions. Health measurement scales that measure adaptive seating outcomes for service applications must have adequate levels of reliability and validity, as well as demonstrate responsive to important change over time for individual children and their families. Needs-specific measurement scales provide a promising avenue for understanding functional outcomes for individual children and youth who use adaptive seating systems.

Activation and desensitization of ionotropic glutamate receptors by selectively triggering pre-existing motions.

PubMed

Krieger, James; Lee, Ji Young; Greger, Ingo H; Bahar, Ivet

2018-02-23

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are key players in synaptic transmission and plasticity. They are composed of four subunits, each containing four functional domains, the quaternary packing and collective structural dynamics of which are important determinants of their molecular mechanism of function. With the explosion of structural studies on different members of the family, including the structures of activated open channels, the mechanisms of action of these central signaling machines are now being elucidated. We review the current state of computational studies on two major members of the family, AMPA and NMDA receptors, with focus on molecular simulations and elastic network model analyses that have provided insights into the coupled movements of extracellular and transmembrane domains. We describe the newly emerging mechanisms of activation, allosteric signaling and desensitization, as mainly a selective triggering of pre-existing soft motions, as deduced from computational models and analyses that leverage structural data on intact AMPA and NMDA receptors in different states. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3

DOE PAGES

Golczak, Marcin; Sears, Avery E.; Kiser, Philip D.; ...

2014-11-10

Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. In this paper, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-Å crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompaniedmore » by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. Finally, these findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family.« less

[Am]Mn(H2POO)3: A New Family of Hybrid Perovskites Based on the Hypophosphite Ligand.

PubMed

Wu, Yue; Shaker, Sammy; Brivio, Federico; Murugavel, Ramaswamy; Bristowe, Paul D; Cheetham, Anthony K

2017-11-29

A family of five hybrid ABX 3 perovskites has been synthesized using hypophosphite (H 2 POO) - as the X-site ion. These compounds adopt the general formula [Am]Mn(H 2 POO) 3 , where Am = guanidinium (GUA), formamidinium (FA), imidazolium, triazolium, and dabconium. We explore the diverse structural and phase transition behavior of these materials through single-crystal diffraction measurements and demonstrate contrasting magnetism in two of the phases, Am = GUA and FA, that arises from structural distortions. The results show that hypophosphite perovskites offer a promising platform for generating new functional materials.

Novel arrangement and comparative analysis of hsp90 family genes in three thermotolerant species of Stratiomyidae (Diptera).

PubMed

Astakhova, L N; Zatsepina, O G; Przhiboro, A A; Evgen'ev, M B; Garbuz, D G

2013-06-01

The heat shock proteins belonging to the Hsp90 family (Hsp83 in Diptera) play a crucial role in the protection of cells due to their chaperoning functions. We sequenced hsp90 genes from three species of the family Stratiomyidae (Diptera) living in thermally different habitats and characterized by extraordinarily high thermotolerance. The sequence variation and structure of the hsp90 family genes were compared with previously described features of hsp70 copies isolated from the same species. Two functional hsp83 genes were found in the species studied, that are arranged in tandem orientation at least in one of them. This organization was not previously described. Stratiomyidae hsp83 genes share a high level of identity with hsp83 of Drosophila, and the deduced protein possesses five conserved amino acid sequence motifs characteristic of the Hsp90 family as well as the C-terminus MEEVD sequence characteristic of the cytosolic isoform. A comparison of the hsp83 promoters of two Stratiomyidae species from thermally contrasting habitats demonstrated that while both species contain canonical heat shock elements in the same position, only one of the species contains functional GAF-binding elements. Our data indicate that in the same species, hsp83 family genes show a higher evolution rate than the hsp70 family. © 2013 Royal Entomological Society.

Patterns of Morphosyntactic and Functional Diversification in the Usage of Cognate Verbs in Indo-Iranian

ERIC Educational Resources Information Center

Shirtz, Shahar Baruch

2017-01-01

This is a study of processes of structural and functional diversification of the uses of three cognate verbs across the Indo-Iranian language family: "do/make", "be/become", and "give". First, this study identifies over sixty distinct construction types in which these verbs are used, including complex predicate…

Positive semidefinite tensor factorizations of the two-electron integral matrix for low-scaling ab initio electronic structure.

PubMed

Hoy, Erik P; Mazziotti, David A

2015-08-14

Tensor factorization of the 2-electron integral matrix is a well-known technique for reducing the computational scaling of ab initio electronic structure methods toward that of Hartree-Fock and density functional theories. The simplest factorization that maintains the positive semidefinite character of the 2-electron integral matrix is the Cholesky factorization. In this paper, we introduce a family of positive semidefinite factorizations that generalize the Cholesky factorization. Using an implementation of the factorization within the parametric 2-RDM method [D. A. Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)], we study several inorganic molecules, alkane chains, and potential energy curves and find that this generalized factorization retains the accuracy and size extensivity of the Cholesky factorization, even in the presence of multi-reference correlation. The generalized family of positive semidefinite factorizations has potential applications to low-scaling ab initio electronic structure methods that treat electron correlation with a computational cost approaching that of the Hartree-Fock method or density functional theory.

The LSD1 Family of Histone Demethylases and the Pumilio Posttranscriptional Repressor Function in a Complex Regulatory Feedback Loop

PubMed Central

Miles, Wayne O.; Lepesant, Julie M. J.; Bourdeaux, Jessie; Texier, Manuela; Kerenyi, Marc A.; Nakakido, Makoto; Hamamoto, Ryuji; Orkin, Stuart H.; Dyson, Nicholas J.

2015-01-01

The lysine (K)-specific demethylase (LSD1) family of histone demethylases regulates chromatin structure and the transcriptional potential of genes. LSD1 is frequently deregulated in tumors, and depletion of LSD1 family members causes developmental defects. Here, we report that reductions in the expression of the Pumilio (PUM) translational repressor complex enhanced phenotypes due to dLsd1 depletion in Drosophila. We show that the PUM complex is a target of LSD1 regulation in fly and mammalian cells and that its expression is inversely correlated with LSD1 levels in human bladder carcinoma. Unexpectedly, we find that PUM posttranscriptionally regulates LSD1 family protein levels in flies and human cells, indicating the existence of feedback loops between the LSD1 family and the PUM complex. Our results highlight a new posttranscriptional mechanism regulating LSD1 activity and suggest that the feedback loop between the LSD1 family and the PUM complex may be functionally important during development and in human malignancies. PMID:26438601

The actin family protein ARP6 contributes to the structure and the function of the nucleolus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitamura, Hiroshi; Matsumori, Haruka; Kalendova, Alzbeta

2015-08-21

The actin family members, consisting of actin and actin-related proteins (ARPs), are essential components of chromatin remodeling complexes. ARP6, one of the nuclear ARPs, is part of the Snf-2-related CREB-binding protein activator protein (SRCAP) chromatin remodeling complex, which promotes the deposition of the histone variant H2A.Z into the chromatin. In this study, we showed that ARP6 influences the structure and the function of the nucleolus. ARP6 is localized in the central region of the nucleolus, and its knockdown induced a morphological change in the nucleolus. We also found that in the presence of high concentrations of glucose ARP6 contributed tomore » the maintenance of active ribosomal DNA (rDNA) transcription by placing H2A.Z into the chromatin. In contrast, under starvation, ARP6 was required for cell survival through the repression of rDNA transcription independently of H2A.Z. These findings reveal novel pleiotropic roles for the actin family in nuclear organization and metabolic homeostasis. - Highlights: • ARP6, an actin related protein, is important for nucleolar function and structure. • A population of ARP6 is localized in the center of nucleolus. • Depletion of ARP6 resulted in aberrant shape of the nucleolus. • ARP6 maintains the active rDNA transcription under high glucose. • ARP6 is required for the repression of rDNA transcription under starvation.« less

Rapid functional diversification in the structurally conserved ELAV family of neuronal RNA binding proteins

PubMed Central

Samson, Marie-Laure

2008-01-01

Background The Drosophila gene embryonic lethal abnormal visual system (elav) is the prototype of a gene family present in all metazoans. Its members encode structurally conserved neuronal proteins with three RNA Recognition Motifs (RRM) but they paradoxically act at diverse levels of post-transcriptional regulation. In an attempt to understand the history of this family, we searched for orthologs in eleven completely sequenced genomes, including those of humans, D. melanogaster and C. elegans, for which cDNAs are available. Results We analyzed 23 orthologs/paralogs of elav, and found evidence of gain/loss of gene copy number. For one set of genes, including elav itself, the coding sequences are free of introns and their products most resemble ELAV. The remaining genes show remarkable conservation of their exon organization, and their products most resemble FNE and RBP9, proteins encoded by the two elav paralogs of Drosophila. Remarkably, three of the conserved exon junctions are both close to structural elements, involved respectively in protein-RNA interactions and in the regulation of sub-cellular localization, and in the vicinity of diverse sequence variations. Conclusion The data indicate that the essential elav gene of Drosophila is newly emerged, restricted to dipterans and of retrotransposed origin. We propose that the conserved exon junctions constitute potential sites for sequence/function modifications, and that RRM binding proteins, whose function relies upon plastic RNA-protein interactions, may have played an important role in brain evolution. PMID:18715504

New genes and new biological roles for expansins

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

2000-01-01

Expansins are extracellular proteins that loosen plant cell walls in novel ways. They are thought to function in cell enlargement, pollen tube invasion of the stigma (in grasses), wall disassembly during fruit ripening, abscission and other cell separation events. Expansins are encoded by two multigene families and each gene is often expressed in highly specific locations and cell types. Structural analysis indicates that one expansin region resembles the catalytic domain of family-45 endoglucanases but glucanase activity has not been detected. The genome projects have revealed numerous expansin-related sequences but their putative wall-loosening functions remain to be assessed.

The FASTK family of proteins: emerging regulators of mitochondrial RNA biology

PubMed Central

Jourdain, Alexis A.; Popow, Johannes; de la Fuente, Miguel A.; Martinou, Jean-Claude

2017-01-01

Abstract The FASTK family proteins have recently emerged as key post-transcriptional regulators of mitochondrial gene expression. FASTK, the founding member and its homologs FASTKD1–5 are architecturally related RNA-binding proteins, each having a different function in the regulation of mitochondrial RNA biology, from mRNA processing and maturation to ribosome assembly and translation. In this review, we outline the structure, evolution and function of these FASTK proteins and discuss the individual role that each has in mitochondrial RNA biology. In addition, we highlight the aspects of FASTK research that still require more attention. PMID:29036396

The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives.

PubMed

Maraia, Richard J; Mattijssen, Sandy; Cruz-Gallardo, Isabel; Conte, Maria R

2017-11-01

La was first identified as a polypeptide component of ribonucleic protein complexes targeted by antibodies in autoimmune patients and is now known to be a eukaryote cell-ubiquitous protein. Structure and function studies have shown that La binds to a common terminal motif, UUU-3'-OH, of nascent RNA polymerase III (RNAP III) transcripts and protects them from exonucleolytic decay. For precursor-tRNAs, the most diverse and abundant of these transcripts, La also functions as an RNA chaperone that helps to prevent their misfolding. Related to this, we review evidence that suggests that La and its link to RNAP III were significant in the great expansions of the tRNAomes that occurred in eukaryotes. Four families of La-related proteins (LARPs) emerged during eukaryotic evolution with specialized functions. We provide an overview of the high-resolution structural biology of La and LARPs. LARP7 family members most closely resemble La but function with a single RNAP III nuclear transcript, 7SK, or telomerase RNA. A cytoplasmic isoform of La protein as well as LARPs 6, 4, and 1 function in mRNA metabolism and translation in distinct but similar ways, sometimes with the poly(A)-binding protein, and in some cases by direct binding to poly(A)-RNA. New structures of LARP domains, some complexed with RNA, provide novel insights into the functional versatility of these proteins. We also consider LARPs in relation to ancestral La protein and potential retention of links to specific RNA-related pathways. One such link may be tRNA surveillance and codon usage by LARP-associated mRNAs. WIREs RNA 2017, 8:e1430. doi: 10.1002/wrna.1430 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Structural Diversity in the Dandelion (Taraxacum officinale) Polyphenol Oxidase Family Results in Different Responses to Model Substrates

PubMed Central

Dirks-Hofmeister, Mareike E.; Singh, Ratna; Leufken, Christine M.; Inlow, Jennifer K.; Moerschbacher, Bruno M.

2014-01-01

Polyphenol oxidases (PPOs) are ubiquitous type-3 copper enzymes that catalyze the oxygen-dependent conversion of o-diphenols to the corresponding quinones. In most plants, PPOs are present as multiple isoenzymes that probably serve distinct functions, although the precise relationship between sequence, structure and function has not been addressed in detail. We therefore compared the characteristics and activities of recombinant dandelion PPOs to gain insight into the structure–function relationships within the plant PPO family. Phylogenetic analysis resolved the 11 isoenzymes of dandelion into two evolutionary groups. More detailed in silico and in vitro analyses of four representative PPOs covering both phylogenetic groups were performed. Molecular modeling and docking predicted differences in enzyme-substrate interactions, providing a structure-based explanation for grouping. One amino acid side chain positioned at the entrance to the active site (position HB2+1) potentially acts as a “selector” for substrate binding. In vitro activity measurements with the recombinant, purified enzymes also revealed group-specific differences in kinetic parameters when the selected PPOs were presented with five model substrates. The combination of our enzyme kinetic measurements and the in silico docking studies therefore indicate that the physiological functions of individual PPOs might be defined by their specific interactions with different natural substrates. PMID:24918587

Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase

NASA Astrophysics Data System (ADS)

Glukhova, Alisa; Hinkovska-Galcheva, Vania; Kelly, Robert; Abe, Akira; Shayman, James A.; Tesmer, John J. G.

2015-03-01

Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

Modulation of Tight Junction Structure and Function by Kinases and Phosphatases Targeting Occludin

PubMed Central

Dörfel, Max Johannes; Huber, Otmar

2012-01-01

Tight junctions (TJs) typically represent the most apical contacts in epithelial and endothelial cell layers where they play an essential role in the separation of extracellular or luminal spaces from underlying tissues in the body. Depending on the protein composition, TJs define the barrier characteristics and in addition maintain cell polarity. Two major families of integral membrane proteins form the typical TJ strand network, the tight junction-associated MARVEL protein (TAMP) family members occludin, tricellulin, and MarvelD3 as well as a specific set of claudins. Occludin was the first identified member of these tetraspanins and is now widely accepted as a regulator of TJ assembly and function. Therefore, occludin itself has to be tightly regulated. Phosphorylation of occludin appears to be of central importance in this context. Here we want to summarize current knowledge on the kinases and phosphatases directly modifying occludin, and their role in the regulation of TJ structure, function, and dynamics. PMID:22315516

OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids.

PubMed

Hornung, Veit; Hartmann, Rune; Ablasser, Andrea; Hopfner, Karl-Peter

2014-08-01

Recent discoveries in the field of innate immunity have highlighted the existence of a family of nucleic acid-sensing proteins that have similar structural and functional properties. These include the well-known oligoadenylate synthase (OAS) family proteins and the recently identified OAS homologue cyclic GMP-AMP (cGAMP) synthase (cGAS). The OAS proteins and cGAS are template-independent nucleotidyltransferases that, once activated by double-stranded nucleic acids in the cytosol, produce unique classes of 2'-5'-linked second messenger molecules, which - through distinct mechanisms - have crucial antiviral functions. 2'-5'-linked oligoadenylates limit viral propagation through the activation of the enzyme RNase L, which degrades host and viral RNA, and 2'-5'-linked cGAMP activates downstream signalling pathways to induce de novo antiviral gene expression. In this Progress article, we describe the striking functional and structural similarities between OAS proteins and cGAS, and highlight their roles in antiviral immunity.

Automatic classification of protein structures using physicochemical parameters.

PubMed

Mohan, Abhilash; Rao, M Divya; Sunderrajan, Shruthi; Pennathur, Gautam

2014-09-01

Protein classification is the first step to functional annotation; SCOP and Pfam databases are currently the most relevant protein classification schemes. However, the disproportion in the number of three dimensional (3D) protein structures generated versus their classification into relevant superfamilies/families emphasizes the need for automated classification schemes. Predicting function of novel proteins based on sequence information alone has proven to be a major challenge. The present study focuses on the use of physicochemical parameters in conjunction with machine learning algorithms (Naive Bayes, Decision Trees, Random Forest and Support Vector Machines) to classify proteins into their respective SCOP superfamily/Pfam family, using sequence derived information. Spectrophores™, a 1D descriptor of the 3D molecular field surrounding a structure was used as a benchmark to compare the performance of the physicochemical parameters. The machine learning algorithms were modified to select features based on information gain for each SCOP superfamily/Pfam family. The effect of combining physicochemical parameters and spectrophores on classification accuracy (CA) was studied. Machine learning algorithms trained with the physicochemical parameters consistently classified SCOP superfamilies and Pfam families with a classification accuracy above 90%, while spectrophores performed with a CA of around 85%. Feature selection improved classification accuracy for both physicochemical parameters and spectrophores based machine learning algorithms. Combining both attributes resulted in a marginal loss of performance. Physicochemical parameters were able to classify proteins from both schemes with classification accuracy ranging from 90-96%. These results suggest the usefulness of this method in classifying proteins from amino acid sequences.

Structural Insight into and Mutational Analysis of Family 11 Xylanases: Implications for Mechanisms of Higher pH Catalytic Adaptation.

PubMed

Bai, Wenqin; Zhou, Cheng; Zhao, Yueju; Wang, Qinhong; Ma, Yanhe

2015-01-01

To understand the molecular basis of higher pH catalytic adaptation of family 11 xylanases, we compared the structures of alkaline, neutral, and acidic active xylanases and analyzed mutants of xylanase Xyn11A-LC from alkalophilic Bacillus sp. SN5. It was revealed that alkaline active xylanases have increased charged residue content, an increased ratio of negatively to positively charged residues, and decreased Ser, Thr, and Tyr residue content relative to non-alkaline active counterparts. Between strands β6 and β7, alkaline xylanases substitute an α-helix for a coil or turn found in their non-alkaline counterparts. Compared with non-alkaline xylanases, alkaline active enzymes have an inserted stretch of seven amino acids rich in charged residues, which may be beneficial for xylanase function in alkaline conditions. Positively charged residues on the molecular surface and ionic bonds may play important roles in higher pH catalytic adaptation of family 11 xylanases. By structure comparison, sequence alignment and mutational analysis, six amino acids (Glu16, Trp18, Asn44, Leu46, Arg48, and Ser187, numbering based on Xyn11A-LC) adjacent to the acid/base catalyst were found to be responsible for xylanase function in higher pH conditions. Our results will contribute to understanding the molecular mechanisms of higher pH catalytic adaptation in family 11 xylanases and engineering xylanases to suit industrial applications.

Structural Insight into and Mutational Analysis of Family 11 Xylanases: Implications for Mechanisms of Higher pH Catalytic Adaptation

PubMed Central

Bai, Wenqin; Zhou, Cheng; Zhao, Yueju; Wang, Qinhong; Ma, Yanhe

2015-01-01

To understand the molecular basis of higher pH catalytic adaptation of family 11 xylanases, we compared the structures of alkaline, neutral, and acidic active xylanases and analyzed mutants of xylanase Xyn11A-LC from alkalophilic Bacillus sp. SN5. It was revealed that alkaline active xylanases have increased charged residue content, an increased ratio of negatively to positively charged residues, and decreased Ser, Thr, and Tyr residue content relative to non-alkaline active counterparts. Between strands β6 and β7, alkaline xylanases substitute an α-helix for a coil or turn found in their non-alkaline counterparts. Compared with non-alkaline xylanases, alkaline active enzymes have an inserted stretch of seven amino acids rich in charged residues, which may be beneficial for xylanase function in alkaline conditions. Positively charged residues on the molecular surface and ionic bonds may play important roles in higher pH catalytic adaptation of family 11 xylanases. By structure comparison, sequence alignment and mutational analysis, six amino acids (Glu16, Trp18, Asn44, Leu46, Arg48, and Ser187, numbering based on Xyn11A-LC) adjacent to the acid/base catalyst were found to be responsible for xylanase function in higher pH conditions. Our results will contribute to understanding the molecular mechanisms of higher pH catalytic adaptation in family 11 xylanases and engineering xylanases to suit industrial applications. PMID:26161643

Distantly related lipocalins share two conserved clusters of hydrophobic residues: use in homology modeling

PubMed Central

Adam, Benoit; Charloteaux, Benoit; Beaufays, Jerome; Vanhamme, Luc; Godfroid, Edmond; Brasseur, Robert; Lins, Laurence

2008-01-01

Background Lipocalins are widely distributed in nature and are found in bacteria, plants, arthropoda and vertebra. In hematophagous arthropods, they are implicated in the successful accomplishment of the blood meal, interfering with platelet aggregation, blood coagulation and inflammation and in the transmission of disease parasites such as Trypanosoma cruzi and Borrelia burgdorferi. The pairwise sequence identity is low among this family, often below 30%, despite a well conserved tertiary structure. Under the 30% identity threshold, alignment methods do not correctly assign and align proteins. The only safe way to assign a sequence to that family is by experimental determination. However, these procedures are long and costly and cannot always be applied. A way to circumvent the experimental approach is sequence and structure analyze. To further help in that task, the residues implicated in the stabilisation of the lipocalin fold were determined. This was done by analyzing the conserved interactions for ten lipocalins having a maximum pairwise identity of 28% and various functions. Results It was determined that two hydrophobic clusters of residues are conserved by analysing the ten lipocalin structures and sequences. One cluster is internal to the barrel, involving all strands and the 310 helix. The other is external, involving four strands and the helix lying parallel to the barrel surface. These clusters are also present in RaHBP2, a unusual "outlier" lipocalin from tick Rhipicephalus appendiculatus. This information was used to assess assignment of LIR2 a protein from Ixodes ricinus and to build a 3D model that helps to predict function. FTIR data support the lipocalin fold for this protein. Conclusion By sequence and structural analyzes, two conserved clusters of hydrophobic residues in interactions have been identified in lipocalins. Since the residues implicated are not conserved for function, they should provide the minimal subset necessary to confer the lipocalin fold. This information has been used to assign LIR2 to lipocalins and to investigate its structure/function relationship. This study could be applied to other protein families with low pairwise similarity, such as the structurally related fatty acid binding proteins or avidins. PMID:18190694

Are controls in schizophrenia research "normal"?

PubMed

Olson, S C; Bornstein, R A; Schwarzkopf, S B; Nasrallah, H A

1993-03-01

The psychiatric assessment by structured interview and family history of mental disorder in normal volunteers recruited by advertisement for a study of brain structure and function in psychosis is described. Nine of 51 volunteers (17.6%) who passed a phone screen were excluded after a structured interview for major psychopathology. Of 35 completers, 10 (28.6%) had subthreshold mood or substance use but were included in the study. Only 16 subjects (45%) had a negative family history by FH-RDC. Diagnoses in family members included substance abuse (31%), mood disorder (11%), psychosis (9%), and other/undiagnosed (14%). Ventricular enlargement was evaluated by magnetic resonance imaging in two planes. Ventricular size was bimodally distributed in the males, and the group with larger ventricles was more educated and had higher scores on the 8 (Schizophrenia) scale of the MMPI (F = 5.44, p = .0099). Our results suggest that 'normal' volunteers for psychiatric research have personal or family psychopathology which motivates them to participate. As the sensitivity of biological instrumentation increases, the characteristics of the control group must be anticipated in the design and recruitment.

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

DOE PAGES

Ye, Qiaozhen; Rosenberg, Scott C.; Moeller, Arne; ...

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from amore » signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.« less

Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi

PubMed Central

McCormick, Susan P.; Lee, Theresa; Vaughan, Martha M.; Alexander, Nancy J.; Busman, Mark

2018-01-01

Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus Fusarium are among the mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some Fusarium species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.e., molecules that share the same core structure but differ in patterns of substituents attached to the core structure. Here, we carried out genomic, phylogenetic, gene-function, and analytical chemistry studies of strains from nine fungal genera to identify genetic variation responsible for trichothecene structural diversity and to gain insight into evolutionary processes that have contributed to the variation. The results indicate that structural diversity has resulted from gain, loss, and functional changes of trichothecene biosynthetic (TRI) genes. The results also indicate that the presence of some substituents has arisen independently in different fungi by gain of different genes with the same function. Variation in TRI gene duplication and number of TRI loci was also observed among the fungi examined, but there was no evidence that such genetic differences have contributed to trichothecene structural variation. We also inferred ancestral states of the TRI cluster and trichothecene biosynthetic pathway, and proposed scenarios for changes in trichothecene structures during divergence of TRI cluster homologs. Together, our findings provide insight into evolutionary processes responsible for structural diversification of toxins produced by pathogenic fungi. PMID:29649280

Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi.

PubMed

Proctor, Robert H; McCormick, Susan P; Kim, Hye-Seon; Cardoza, Rosa E; Stanley, April M; Lindo, Laura; Kelly, Amy; Brown, Daren W; Lee, Theresa; Vaughan, Martha M; Alexander, Nancy J; Busman, Mark; Gutiérrez, Santiago

2018-04-01

Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus Fusarium are among the mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some Fusarium species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.e., molecules that share the same core structure but differ in patterns of substituents attached to the core structure. Here, we carried out genomic, phylogenetic, gene-function, and analytical chemistry studies of strains from nine fungal genera to identify genetic variation responsible for trichothecene structural diversity and to gain insight into evolutionary processes that have contributed to the variation. The results indicate that structural diversity has resulted from gain, loss, and functional changes of trichothecene biosynthetic (TRI) genes. The results also indicate that the presence of some substituents has arisen independently in different fungi by gain of different genes with the same function. Variation in TRI gene duplication and number of TRI loci was also observed among the fungi examined, but there was no evidence that such genetic differences have contributed to trichothecene structural variation. We also inferred ancestral states of the TRI cluster and trichothecene biosynthetic pathway, and proposed scenarios for changes in trichothecene structures during divergence of TRI cluster homologs. Together, our findings provide insight into evolutionary processes responsible for structural diversification of toxins produced by pathogenic fungi.

Lamin-like analogues in plants: the characterization of NMCP1 in Allium cepa

PubMed Central

Moreno Díaz de la Espina, Susana

2013-01-01

The nucleoskeleton of plants contains a peripheral lamina (also called plamina) and, even though lamins are absent in plants, their roles are still fulfilled in plant nuclei. One of the most intriguing topics in plant biology concerns the identity of lamin protein analogues in plants. Good candidates to play lamin functions in plants are the members of the NMCP (nuclear matrix constituent protein) family, which exhibit the typical tripartite structure of lamins. This paper describes a bioinformatics analysis and classification of the NMCP family based on phylogenetic relationships, sequence similarity and the distribution of conserved regions in 76 homologues. In addition, NMCP1 in the monocot Allium cepa characterized by its sequence and structure, biochemical properties, and subnuclear distribution and alterations in its expression throughout the root were identified. The results demonstrate that these proteins exhibit many similarities to lamins (structural organization, conserved regions, subnuclear distribution, and solubility) and that they may fulfil the functions of lamins in plants. These findings significantly advance understanding of the structural proteins of the plant lamina and nucleoskeleton and provide a basis for further investigation of the protein networks forming these structures. PMID:23378381

TIM Barrel Protein Structure Classification Using Alignment Approach and Best Hit Strategy

NASA Astrophysics Data System (ADS)

Chu, Jia-Han; Lin, Chun Yuan; Chang, Cheng-Wen; Lee, Chihan; Yang, Yuh-Shyong; Tang, Chuan Yi

2007-11-01

The classification of protein structures is essential for their function determination in bioinformatics. It has been estimated that around 10% of all known enzymes have TIM barrel domains from the Structural Classification of Proteins (SCOP) database. With its high sequence variation and diverse functionalities, TIM barrel protein becomes to be an attractive target for protein engineering and for the evolution study. Hence, in this paper, an alignment approach with the best hit strategy is proposed to classify the TIM barrel protein structure in terms of superfamily and family levels in the SCOP. This work is also used to do the classification for class level in the Enzyme nomenclature (ENZYME) database. Two testing data sets, TIM40D and TIM95D, both are used to evaluate this approach. The resulting classification has an overall prediction accuracy rate of 90.3% for the superfamily level in the SCOP, 89.5% for the family level in the SCOP and 70.1% for the class level in the ENZYME. These results demonstrate that the alignment approach with the best hit strategy is a simple and viable method for the TIM barrel protein structure classification, even only has the amino acid sequences information.

Lamin-like analogues in plants: the characterization of NMCP1 in Allium cepa.

PubMed

Ciska, Malgorzata; Masuda, Kiyoshi; Moreno Díaz de la Espina, Susana

2013-04-01

The nucleoskeleton of plants contains a peripheral lamina (also called plamina) and, even though lamins are absent in plants, their roles are still fulfilled in plant nuclei. One of the most intriguing topics in plant biology concerns the identity of lamin protein analogues in plants. Good candidates to play lamin functions in plants are the members of the NMCP (nuclear matrix constituent protein) family, which exhibit the typical tripartite structure of lamins. This paper describes a bioinformatics analysis and classification of the NMCP family based on phylogenetic relationships, sequence similarity and the distribution of conserved regions in 76 homologues. In addition, NMCP1 in the monocot Allium cepa characterized by its sequence and structure, biochemical properties, and subnuclear distribution and alterations in its expression throughout the root were identified. The results demonstrate that these proteins exhibit many similarities to lamins (structural organization, conserved regions, subnuclear distribution, and solubility) and that they may fulfil the functions of lamins in plants. These findings significantly advance understanding of the structural proteins of the plant lamina and nucleoskeleton and provide a basis for further investigation of the protein networks forming these structures.

Dissimilar sweet proteins from plants: oddities or normal components?

PubMed

Picone, Delia; Temussi, Piero Andrea

2012-10-01

The fruits of a few tropical plants contain intensely sweet proteins. Their common property points to a protein family. Generally, proteins belonging to the same family share similar folds, similar sequences and, at least in part, similar function but sweet proteins constitute an exception to this rule. Apart from sharing the rather unusual taste function, they show no obvious similarities either in their sequences or in three-dimensional structures. In this review we describe the nature, structure and mechanism of action of the best known sweet tasting proteins, including two taste modifying proteins. Sweet proteins stand out among sweet molecules because their volume is not compatible with an interaction with orthosteric active sites of the sweet taste receptor. The best explanation of their mechanism of action is the interaction with the external surface of the sweet taste receptor, according to a model that has been named "wedge model". It is hypothesized that this mode of action may be related to the ability of other members of their protein families to inhibit different enzymes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The actin family protein ARP6 contributes to the structure and the function of the nucleolus.

PubMed

Kitamura, Hiroshi; Matsumori, Haruka; Kalendova, Alzbeta; Hozak, Pavel; Goldberg, Ilya G; Nakao, Mitsuyoshi; Saitoh, Noriko; Harata, Masahiko

2015-08-21

The actin family members, consisting of actin and actin-related proteins (ARPs), are essential components of chromatin remodeling complexes. ARP6, one of the nuclear ARPs, is part of the Snf-2-related CREB-binding protein activator protein (SRCAP) chromatin remodeling complex, which promotes the deposition of the histone variant H2A.Z into the chromatin. In this study, we showed that ARP6 influences the structure and the function of the nucleolus. ARP6 is localized in the central region of the nucleolus, and its knockdown induced a morphological change in the nucleolus. We also found that in the presence of high concentrations of glucose ARP6 contributed to the maintenance of active ribosomal DNA (rDNA) transcription by placing H2A.Z into the chromatin. In contrast, under starvation, ARP6 was required for cell survival through the repression of rDNA transcription independently of H2A.Z. These findings reveal novel pleiotropic roles for the actin family in nuclear organization and metabolic homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

The actin family protein ARP6 contributes to the structure and the function of the nucleolus

PubMed Central

Kitamura, Hiroshi; Matsumori, Haruka; Kalendova, Alzbeta; Hozak, Pavel; Goldberg, Ilya G.; Nakao, Mitsuyoshi; Saitoh, Noriko; Harata, Masahiko

2018-01-01

The actin family members, consisting of actin and actin-related proteins (ARPs), are essential components of chromatin remodeling complexes. ARP6, one of the nuclear ARPs, is part of the Snf-2-related CREB-binding protein activator protein (SRCAP) chromatin remodeling complex, which promotes the deposition of the histone variant H2A.Z into the chromatin. In this study, we showed that ARP6 influences the structure and the function of the nucleolus. ARP6 is localized in the central region of the nucleolus, and its knockdown induced a morphological change in the nucleolus. We also found that in the presence of high concentrations of glucose ARP6 contributed to the maintenance of active ribosomal DNA (rDNA) transcription by placing H2A.Z into the chromatin. In contrast, under starvation, ARP6 was required for cell survival through the repression of rDNA transcription independently of H2A.Z. These findings reveal novel pleiotropic roles for the actin family in nuclear organization and metabolic homeostasis. PMID:26164235

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development

PubMed Central

Bedell, Victoria M.; Person, Anthony D.; Larson, Jon D.; McLoon, Anna; Balciunas, Darius; Clark, Karl J.; Neff, Kevin I.; Nelson, Katie E.; Bill, Brent R.; Schimmenti, Lisa A.; Beiraghi, Soraya; Ekker, Stephen C.

2012-01-01

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity. PMID:22274699

Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.

PubMed

Howard, Rebecca J; Trudell, James R; Harris, R Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy.

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

PubMed Central

Trudell, James R.; Harris, R. Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

The Collagen Family

PubMed Central

Ricard-Blum, Sylvie

2011-01-01

Collagens are the most abundant proteins in mammals. The collagen family comprises 28 members that contain at least one triple-helical domain. Collagens are deposited in the extracellular matrix where most of them form supramolecular assemblies. Four collagens are type II membrane proteins that also exist in a soluble form released from the cell surface by shedding. Collagens play structural roles and contribute to mechanical properties, organization, and shape of tissues. They interact with cells via several receptor families and regulate their proliferation, migration, and differentiation. Some collagens have a restricted tissue distribution and hence specific biological functions. PMID:21421911

The Assessment of Family Functions, Dyadic Adjustment, and Parental Attitude in Adolescents with Substance Use Disorder

PubMed Central

ÖNGEL ATAR, Ayça; YALÇIN, Özhan; UYGUN, Ersin; ÇİFTÇİ DEMİRCİ, Arzu; ERDOĞAN, Ayten

2016-01-01

Introduction Family structure and family attitudes have been reported to be important factors in the development of substance use disorders. In this study, we aimed to assess the relationship between substance use and family functions, parental attitude, and parental dyadic adjustment of adolescents with substance use disorder. Methods The study was conducted on 50 patients, comprising 9 female and 41 male adolescents between the ages of 14 and 18 years, treated at Bakırköy Mental Health Hospital, Substance Abuse Research, Treatment and Education Center for Children Adolescents (ÇEMATEM), Turkey, with the diagnosis of substance use disorder according to DSM-5 and their parents and a control group comprising 50 healthy adolescents without any psychopathology or substance use disorder and their parents. The study was designed as a matched case–control study for age and gender. Sociodemographic Data Form (SDF), Parental Attitude Scale (PAS), Dyadic Adjustment Scale (DAS), and Family Assessment Device (FAD) were applied to both groups. Results When the study and control groups were compared with regard to the PAS, the study group scores determined for “involvement-acceptance,” “psychological autonomy,” and “control-supervision” dimensions were significantly lower than the control group scores. Compared with the control group, dyadic adjustment was lower in terms of “dyadic cohesion,” “dyadic consensus,” and “affectional expression.” Living with biological parents and the togetherness of parents were lower in the study group. “Problem solving,” “communication,” “roles,” “affective responsiveness,” “affective involvement,” “behavior control,” and “general functioning” dimension scores according to FAD were also significantly higher in the study group. Conclusion Compared with togetherness of the controls, the dyadic adjustment of their parents was lower and family functions as perceived by the parents and adolescents were unhealthier in the adolescents using substances. These findings indicate that the family functions, dyadic adjustment, and parental attitude styles need to be assessed in the risk groups to determine familial risk factors and to structure protective measures. These assessments may guide clinicians and policy-makers toward good clinical practice and help build protective measures. PMID:28360764

Genome-wide identification and expression analysis of the ClTCP transcription factors in Citrullus lanatus.

PubMed

Shi, Pibiao; Guy, Kateta Malangisha; Wu, Weifang; Fang, Bingsheng; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

2016-04-12

The plant-specific TCP transcription factor family, which is involved in the regulation of cell growth and proliferation, performs diverse functions in multiple aspects of plant growth and development. However, no comprehensive analysis of the TCP family in watermelon (Citrullus lanatus) has been undertaken previously. A total of 27 watermelon TCP encoding genes distributed on nine chromosomes were identified. Phylogenetic analysis clustered the genes into 11 distinct subgroups. Furthermore, phylogenetic and structural analyses distinguished two homology classes within the ClTCP family, designated Class I and Class II. The Class II genes were differentiated into two subclasses, the CIN subclass and the CYC/TB1 subclass. The expression patterns of all members were determined by semi-quantitative PCR. The functions of two ClTCP genes, ClTCP14a and ClTCP15, in regulating plant height were confirmed by ectopic expression in Arabidopsis wild-type and ortholog mutants. This study represents the first genome-wide analysis of the watermelon TCP gene family, which provides valuable information for understanding the classification and functions of the TCP genes in watermelon.

Intrinsic disorder in spondins and some of their interacting partners

PubMed Central

Alowolodu, Oluwole; Johnson, Gbemisola; Addou, Iqbal; Zhdanova, Irina V.; Uversky, Vladimir N.

2016-01-01

ABSTRACT Spondins, which are proteins that inhibit and promote adherence of embryonic cells so as to aid axonal growth are part of the thrombospondin-1 family. Spondins function in several important biological processes, such as apoptosis, angiogenesis, etc. Spondins constitute a thrombospondin subfamily that includes F-spondin, a protein that interacts with Aβ precursor protein and inhibits its proteolytic processing; R-spondin, a 4-membered group of proteins that regulates Wnt pathway and have other functions, such as regulation of kidney proliferation, induction of epithelial proliferation, the tumor suppressant action; M-spondin that mediates mechanical linkage between the muscles and apodemes; and the SCO-spondin, a protein important for neuronal development. In this study, we investigated intrinsic disorder status of human spondins and their interacting partners, such as members of the LRP family, LGR family, Frizzled family, and several other binding partners in order to establish the existence and importance of disordered regions in spondins and their interacting partners by conducting a detailed analysis of their sequences, finding disordered regions, and establishing a correlation between their structure and biological functions. PMID:28232900

Representation of analysis results involving aleatory and epistemic uncertainty.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Jay Dean; Helton, Jon Craig; Oberkampf, William Louis

2008-08-01

Procedures are described for the representation of results in analyses that involve both aleatory uncertainty and epistemic uncertainty, with aleatory uncertainty deriving from an inherent randomness in the behavior of the system under study and epistemic uncertainty deriving from a lack of knowledge about the appropriate values to use for quantities that are assumed to have fixed but poorly known values in the context of a specific study. Aleatory uncertainty is usually represented with probability and leads to cumulative distribution functions (CDFs) or complementary cumulative distribution functions (CCDFs) for analysis results of interest. Several mathematical structures are available for themore » representation of epistemic uncertainty, including interval analysis, possibility theory, evidence theory and probability theory. In the presence of epistemic uncertainty, there is not a single CDF or CCDF for a given analysis result. Rather, there is a family of CDFs and a corresponding family of CCDFs that derive from epistemic uncertainty and have an uncertainty structure that derives from the particular uncertainty structure (i.e., interval analysis, possibility theory, evidence theory, probability theory) used to represent epistemic uncertainty. Graphical formats for the representation of epistemic uncertainty in families of CDFs and CCDFs are investigated and presented for the indicated characterizations of epistemic uncertainty.« less

Mutations Affecting G-Protein Subunit α11 in Hypercalcemia and Hypocalcemia

PubMed Central

Babinsky, Valerie N.; Head, Rosie A.; Cranston, Treena; Rust, Nigel; Hobbs, Maurine R.; Heath, Hunter; Thakker, Rajesh V.

2013-01-01

BACKGROUND Familial hypocalciuric hypercalcemia is a genetically heterogeneous disorder with three variants: types 1, 2, and 3. Type 1 is due to loss-of-function mutations of the calcium-sensing receptor, a guanine nucleotide–binding protein (G-protein)–coupled receptor that signals through the G-protein subunit α11 (Gα11). Type 3 is associated with adaptor-related protein complex 2, sigma 1 subunit (AP2S1) mutations, which result in altered calcium-sensing receptor endocytosis. We hypothesized that type 2 is due to mutations effecting Gα11 loss of function, since Gα11 is involved in calcium-sensing receptor signaling, and its gene (GNA11) and the type 2 locus are colocalized on chromosome 19p13.3. We also postulated that mutations effecting Gα11 gain of function, like the mutations effecting calcium-sensing receptor gain of function that cause autosomal dominant hypocalcemia type 1, may lead to hypocalcemia. METHODS We performed GNA11 mutational analysis in a kindred with familial hypocalciuric hypercalcemia type 2 and in nine unrelated patients with familial hypocalciuric hypercalcemia who did not have mutations in the gene encoding the calcium-sensing receptor (CASR) or AP2S1. We also performed this analysis in eight unrelated patients with hypocalcemia who did not have CASR mutations. In addition, we studied the effects of GNA11 mutations on Gα11 protein structure and calcium-sensing receptor signaling in human embryonic kidney 293 (HEK293) cells. RESULTS The kindred with familial hypocalciuric hypercalcemia type 2 had an in-frame deletion of a conserved Gα11 isoleucine (Ile200del), and one of the nine unrelated patients with familial hypocalciuric hypercalcemia had a missense GNA11 mutation (Leu135Gln). Missense GNA11 mutations (Arg181Gln and Phe341Leu) were detected in two unrelated patients with hypocalcemia; they were therefore identified as having autosomal dominant hypocalcemia type 2. All four GNA11 mutations predicted disrupted protein structures, and assessment on the basis of in vitro expression showed that familial hypocalciuric hypercalcemia type 2–associated mutations decreased the sensitivity of cells expressing calcium-sensing receptors to changes in extracellular calcium concentrations, whereas autosomal dominant hypocalcemia type 2–associated mutations increased cell sensitivity. CONCLUSIONS Gα11 mutants with loss of function cause familial hypocalciuric hypercalcemia type 2, and Gα11 mutants with gain of function cause a clinical disorder designated as autosomal dominant hypocalcemia type 2. (Funded by the United Kingdom Medical Research Council and others.) PMID:23802516

A phylogenetic analysis of normal modes evolution in enzymes and its relationship to enzyme function.

PubMed

Lai, Jason; Jin, Jing; Kubelka, Jan; Liberles, David A

2012-09-21

Since the dynamic nature of protein structures is essential for enzymatic function, it is expected that functional evolution can be inferred from the changes in protein dynamics. However, dynamics can also diverge neutrally with sequence substitution between enzymes without changes of function. In this study, a phylogenetic approach is implemented to explore the relationship between enzyme dynamics and function through evolutionary history. Protein dynamics are described by normal mode analysis based on a simplified harmonic potential force field applied to the reduced C(α) representation of the protein structure while enzymatic function is described by Enzyme Commission numbers. Similarity of the binding pocket dynamics at each branch of the protein family's phylogeny was analyzed in two ways: (1) explicitly by quantifying the normal mode overlap calculated for the reconstructed ancestral proteins at each end and (2) implicitly using a diffusion model to obtain the reconstructed lineage-specific changes in the normal modes. Both explicit and implicit ancestral reconstruction identified generally faster rates of change in dynamics compared with the expected change from neutral evolution at the branches of potential functional divergences for the α-amylase, D-isomer-specific 2-hydroxyacid dehydrogenase, and copper-containing amine oxidase protein families. Normal mode analysis added additional information over just comparing the RMSD of static structures. However, the branch-specific changes were not statistically significant compared to background function-independent neutral rates of change of dynamic properties and blind application of the analysis would not enable prediction of changes in enzyme specificity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Functional role of oligomerization for bacterial and plant SWEET sugar transporter family.

PubMed

Xuan, Yuan Hu; Hu, Yi Bing; Chen, Li-Qing; Sosso, Davide; Ducat, Daniel C; Hou, Bi-Huei; Frommer, Wolf B

2013-09-24

Eukaryotic sugar transporters of the MFS and SWEET superfamilies consist of 12 and 7 α-helical transmembrane domains (TMs), respectively. Structural analyses indicate that MFS transporters evolved from a series of tandem duplications of an ancestral 3-TM unit. SWEETs are heptahelical proteins carrying a tandem repeat of 3-TM separated by a single TM. Here, we show that prokaryotes have ancestral SWEET homologs with only 3-TM and that the Bradyrhizobium japonicum SemiSWEET1, like Arabidopsis SWEET11, mediates sucrose transport. Eukaryotic SWEETs most likely evolved by internal duplication of the 3-TM, suggesting that SemiSWEETs form oligomers to create a functional pore. However, it remains elusive whether the 7-TM SWEETs are the functional unit or require oligomerization to form a pore sufficiently large to allow for sucrose passage. Split ubiquitin yeast two-hybrid and split GFP assays indicate that Arabidopsis SWEETs homo- and heterooligomerize. We examined mutant SWEET variants for negative dominance to test if oligomerization is necessary for function. Mutation of the conserved Y57 or G58 in SWEET1 led to loss of activity. Coexpression of the defective mutants with functional A. thaliana SWEET1 inhibited glucose transport, indicating that homooligomerization is necessary for function. Collectively, these data imply that the basic unit of SWEETs, similar to MFS sugar transporters, is a 3-TM unit and that a functional transporter contains at least four such domains. We hypothesize that the functional unit of the SWEET family of transporters possesses a structure resembling the 12-TM MFS structure, however, with a parallel orientation of the 3-TM unit.

Functional role of oligomerization for bacterial and plant SWEET sugar transporter family

PubMed Central

Xuan, Yuan Hu; Hu, Yi Bing; Chen, Li-Qing; Sosso, Davide; Ducat, Daniel C.; Hou, Bi-Huei; Frommer, Wolf B.

2013-01-01

Eukaryotic sugar transporters of the MFS and SWEET superfamilies consist of 12 and 7 α-helical transmembrane domains (TMs), respectively. Structural analyses indicate that MFS transporters evolved from a series of tandem duplications of an ancestral 3-TM unit. SWEETs are heptahelical proteins carrying a tandem repeat of 3-TM separated by a single TM. Here, we show that prokaryotes have ancestral SWEET homologs with only 3-TM and that the Bradyrhizobium japonicum SemiSWEET1, like Arabidopsis SWEET11, mediates sucrose transport. Eukaryotic SWEETs most likely evolved by internal duplication of the 3-TM, suggesting that SemiSWEETs form oligomers to create a functional pore. However, it remains elusive whether the 7-TM SWEETs are the functional unit or require oligomerization to form a pore sufficiently large to allow for sucrose passage. Split ubiquitin yeast two-hybrid and split GFP assays indicate that Arabidopsis SWEETs homo- and heterooligomerize. We examined mutant SWEET variants for negative dominance to test if oligomerization is necessary for function. Mutation of the conserved Y57 or G58 in SWEET1 led to loss of activity. Coexpression of the defective mutants with functional A. thaliana SWEET1 inhibited glucose transport, indicating that homooligomerization is necessary for function. Collectively, these data imply that the basic unit of SWEETs, similar to MFS sugar transporters, is a 3-TM unit and that a functional transporter contains at least four such domains. We hypothesize that the functional unit of the SWEET family of transporters possesses a structure resembling the 12-TM MFS structure, however, with a parallel orientation of the 3-TM unit. PMID:24027245

The hypothetical protein Atu4866 from Agrobacterium tumefaciens adopts a streptavidin-like fold

PubMed Central

Ai, Xuanjun; Semesi, Anthony; Yee, Adelinda; Arrowsmith, Cheryl H.; Choy, Wing-Yiu; Li, Shawn S.C.

2008-01-01

Atu4866 is a 79-residue conserved hypothetical protein of unknown function from Agrobacterium tumefaciens. Protein sequence alignments show that it shares ≥60% sequence identity with 20 other hypothetical proteins of bacterial origin. However, the structures and functions of these proteins remain unknown so far. To gain insight into the function of this family of proteins, we have determined the structure of Atu4866 as a target of a structural genomics project using solution NMR spectroscopy. Our results reveal that Atu4866 adopts a streptavidin-like fold featuring a β-barrel/sandwich formed by eight antiparallel β-strands. Further structural analysis identified a continuous patch of conserved residues on the surface of Atu4866 that may constitute a potential ligand-binding site. PMID:18042676

Protein–DNA Interactions: The Story so Far and a New Method for Prediction

DOE PAGES

Jones, Susan; Thornton, Janet M.

2003-01-01

This review describes methods for the prediction of DNA binding function, and specifically summarizes a new method using 3D structural templates. The new method features the HTH motif that is found in approximately one-third of DNAbinding protein families. A library of 3D structural templates of HTH motifs was derived from proteins in the PDB. Templates were scanned against complete protein structures and the optimal superposition of a template on a structure calculated. Significance thresholds in terms of a minimum root mean squared deviation (rmsd) of an optimal superposition, and a minimum motif accessible surface area (ASA), have been calculated. Inmore » this way, it is possible to scan the template library against proteins of unknown function to make predictions about DNA-binding functionality.« less

Comparative genomic analysis of the Lipase3 gene family in five plant species reveals distinct evolutionary origins.

PubMed

Wang, Dan; Zhang, Lin; Hu, JunFeng; Gao, Dianshuai; Liu, Xin; Sha, Yan

2018-04-01

Lipases are physiologically important and ubiquitous enzymes that share a conserved domain and are classified into eight different families based on their amino acid sequences and fundamental biological properties. The Lipase3 family of lipases was reported to possess a canonical fold typical of α/β hydrolases and a typical catalytic triad, suggesting a distinct evolutionary origin for this family. Genes in the Lipase3 family do not have the same functions, but maintain the conserved Lipase3 domain. There have been extensive studies of Lipase3 structures and functions, but little is known about their evolutionary histories. In this study, all lipases within five plant species were identified, and their phylogenetic relationships and genetic properties were analyzed and used to group them into distinct evolutionary families. Each identified lipase family contained at least one dicot and monocot Lipase3 protein, indicating that the gene family was established before the split of dicots and monocots. Similar intron/exon numbers and predicted protein sequence lengths were found within individual groups. Twenty-four tandem Lipase3 gene duplications were identified, implying that the distinctive function of Lipase3 genes appears to be a consequence of translocation and neofunctionalization after gene duplication. The functional genes EDS1, PAD4, and SAG101 that are reportedly involved in pathogen response were all located in the same group. The nucleotide diversity (Dxy) and the ratio of nonsynonymous to synonymous nucleotide substitutions rates (Ka/Ks) of the three genes were significantly greater than the average across the genomes. We further observed evidence for selection maintaining diversity on three genes in the Toll-Interleukin-1 receptor type of nucleotide binding/leucine-rich repeat immune receptor (TIR-NBS LRR) immunity-response signaling pathway, indicating that they could be vulnerable to pathogen effectors.

Ferritin family proteins and their use in bionanotechnology

PubMed Central

He, Didi; Marles-Wright, Jon

2015-01-01

Ferritin family proteins are found in all kingdoms of life and act to store iron within a protein cage and to protect the cell from oxidative damage caused by the Fenton reaction. The structural and biochemical features of the ferritins have been widely exploited in bionanotechnology applications: from the production of metal nanoparticles; as templates for semi-conductor production; and as scaffolds for vaccine design and drug delivery. In this review we first discuss the structural properties of the main ferritin family proteins, and describe how their organisation specifies their functions. Second, we describe materials science applications of ferritins that rely on their ability to sequester metal within their cavities. Finally, we explore the use of ferritin as a container for drug delivery and as a scaffold for the production of vaccines. PMID:25573765

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

DOE PAGES

Xu, Qingping; Mengin-Lecreulx, Dominique; Patin, Delphine; ...

2014-11-20

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Qingping; Mengin-Lecreulx, Dominique; Patin, Delphine

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

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

PubMed

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

2014-12-02

GlcNAc-1,6-anhydro-MurNAc-tetrapeptide is a major peptidoglycan degradation intermediate and a cytotoxin. It is generated by lytic transglycosylases and further degraded and recycled by various enzymes. We have identified and characterized a highly specific N-acetylmuramoyl-L-alanine amidase (AmiA) from Bacteroides uniformis, a member of the DUF1460 protein family, that hydrolyzes GlcNAc-1,6-anhydro-MurNAc-peptide into disaccharide and stem peptide. The high-resolution apo structure at 1.15 Å resolution shows that AmiA is related to NlpC/P60 γ-D-Glu-meso-diaminopimelic acid amidases and shares a common catalytic core and cysteine peptidase-like active site. AmiA has evolved structural adaptations that reconfigure the substrate recognition site. The preferred substrates for AmiA were predicted in silico based on structural and bioinformatics data, and subsequently were characterized experimentally. Further crystal structures of AmiA in complexes with GlcNAc-1,6-anhydro-MurNAc and GlcNAc have enabled us to elucidate substrate recognition and specificity. DUF1460 is highly conserved in structure and defines another amidase family. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure of Rhodococcus equi virulence-associated protein B (VapB) reveals an eight-stranded antiparallel β-barrel consisting of two Greek-key motifs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geerds, Christina; Wohlmann, Jens; Haas, Albert

The structure of VapB, a member of the Vap protein family that is involved in virulence of the bacterial pathogen R. equi, was determined by SAD phasing and reveals an eight-stranded antiparallel β-barrel similar to avidin, suggestive of a binding function. Made up of two Greek-key motifs, the topology of VapB is unusual or even unique. Members of the virulence-associated protein (Vap) family from the pathogen Rhodococcus equi regulate virulence in an unknown manner. They do not share recognizable sequence homology with any protein of known structure. VapB and VapA are normally associated with isolates from pigs and horses, respectively.more » To contribute to a molecular understanding of Vap function, the crystal structure of a protease-resistant VapB fragment was determined at 1.4 Å resolution. The structure was solved by SAD phasing employing the anomalous signal of one endogenous S atom and two bound Co ions with low occupancy. VapB is an eight-stranded antiparallel β-barrel with a single helix. Structural similarity to avidins suggests a potential binding function. Unlike other eight- or ten-stranded β-barrels found in avidins, bacterial outer membrane proteins, fatty-acid-binding proteins and lysozyme inhibitors, Vaps do not have a next-neighbour arrangement but consist of two Greek-key motifs with strand order 41238567, suggesting an unusual or even unique topology.« less

Expression, purification and crystallization of a plant polyketide cyclase from Cannabis sativa.

PubMed

Yang, Xinmei; Matsui, Takashi; Mori, Takahiro; Taura, Futoshi; Noguchi, Hiroshi; Abe, Ikuro; Morita, Hiroyuki

2015-12-01

Plant polyketides are a structurally diverse family of natural products. In the biosynthesis of plant polyketides, the construction of the carbocyclic scaffold is a key step in diversifying the polyketide structure. Olivetolic acid cyclase (OAC) from Cannabis sativa L. is the only known plant polyketide cyclase that catalyzes the C2-C7 intramolecular aldol cyclization of linear pentyl tetra-β-ketide-CoA to generate olivetolic acid in the biosynthesis of cannabinoids. The enzyme is also thought to belong to the dimeric α+β barrel (DABB) protein family. However, because of a lack of functional analysis of other plant DABB proteins and low sequence identity with the functionally distinct bacterial DABB proteins, the catalytic mechanism of OAC has remained unclear. To clarify the intimate catalytic mechanism of OAC, the enzyme was overexpressed in Escherichia coli and crystallized using the vapour-diffusion method. The crystals diffracted X-rays to 1.40 Å resolution and belonged to space group P3121 or P3221, with unit-cell parameters a = b = 47.3, c = 176.0 Å. Further crystallographic analysis will provide valuable insights into the structure-function relationship and catalytic mechanism of OAC.

Family functioning and mental health in runaway youth: association with posttraumatic stress symptoms.

PubMed

Thompson, Sanna J; Cochran, Gerald; Barczyk, Amanda N

2012-10-01

This study examined the direct effects of physical and sexual abuse, neglect, poor family communication and worries concerning family relationships, depression, anxiety, and dissociation on posttraumatic stress symptoms. Runaway youth were recruited from emergency youth shelters in New York and Texas. Interviews were completed with 350 youth who averaged 15 years of age. Structural equation modeling was used to examine family functioning, maltreatment, depression, dissociation, and anxiety in relation to posttraumatic stress symptoms. Results indicated that direct effects of family relationship worry to dissociation, β = .77, p < .001; depression, β = .85, p < .001; and anxiety, β = .90, p < .001 were significant, as were relationships between family communication and youth dissociation, β = .42, p < .001; depression, β = .46, p < .001; and anxiety, β = .32, p < .001. No significant effects of physical/sexual abuse or neglect were found. Higher levels of dissociation, β = .21, p < .001 and anxiety symptoms, β = .34, p = .01 were positively and significantly associated with posttraumatic stress symptoms, but depression was not. Findings underscore the critical role of family relationships in mental health symptoms experienced by runaway adolescents. Copyright © 2012 International Society for Traumatic Stress Studies.

Moderators, mediators, and bidirectional relationships in the International Classification of Functioning, Disability and Health (ICF) framework: An empirical investigation using a longitudinal design and Structural Equation Modeling (SEM).

PubMed

Rouquette, Alexandra; Badley, Elizabeth M; Falissard, Bruno; Dub, Timothée; Leplege, Alain; Coste, Joël

2015-06-01

The International Classification of Functioning, Disability and Health (ICF) published in 2001 describes the consequences of health conditions with three components of impairments in body structures or functions, activity limitations and participation restrictions. Two of the new features of the conceptual model were the possibility of feedback effects between each ICF component and the introduction of contextual factors conceptualized as moderators of the relationship between the components. The aim of this longitudinal study is to provide empirical evidence of these two kinds of effect. Structural equation modeling was used to analyze data from a French population-based cohort of 548 patients with knee osteoarthritis recruited between April 2007 and March 2009 and followed for three years. Indicators of the body structure and function, activity and participation components of the ICF were derived from self-administered standardized instruments. The measurement model revealed four separate factors for body structures impairments, body functions impairments, activity limitations and participation restrictions. The classic sequence from body impairments to participation restrictions through activity limitations was found at each assessment time. Longitudinal study of the ICF component relationships showed a feedback pathway indicating that the level of participation restrictions at baseline was predictive of activity limitations three years later. Finally, the moderating role of personal (age, sex, mental health, etc.) and environmental factors (family relationships, mobility device use, etc.) was investigated. Three contextual factors (sex, family relationships and walking stick use) were found to be moderators for the relationship between the body impairments and the activity limitations components. Mental health was found to be a mediating factor of the effect of activity limitations on participation restrictions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Crystal structures of MW1337R and lin2004: Representatives of a novel protein family that adopt a four-helical bundle fold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozbial, Piotr; Xu, Qingping; Chiu, Hsiu-Ju

2009-08-28

To extend the structural coverage of proteins with unknown functions, we targeted a novel protein family (Pfam accession number PF08807, DUF1798) for which we proposed and determined the structures of two representative members. The MW1337R gene of Staphylococcus aureus subsp. aureus Rosenbach (Wood 46) encodes a protein with a molecular weight of 13.8 kDa (residues 1-116) and a calculated isoelectric point of 5.15. The lin2004 gene of the nonspore-forming bacterium Listeria innocua Clip11262 encodes a protein with a molecular weight of 14.6 kDa (residues 1-121) and a calculated isoelectric point of 5.45. MW1337R and lin2004, as well as their homologs,more » which, so far, have been found only in Bacillus, Staphylococcus, Listeria, and related genera (Geobacillus, Exiguobacterium, and Oceanobacillus), have unknown functions and are annotated as hypothetical proteins. The genomic contexts of MW1337R and lin2004 are similar and conserved in related species. In prokaryotic genomes, most often, functionally interacting proteins are coded by genes, which are colocated in conserved operons. Proteins from the same operon as MW1337R and lin2004 either have unknown functions (i.e., belong to DUF1273, Pfam accession number PF06908) or are similar to ypsB from Bacillus subtilis. The function of ypsB is unclear, although it has a strong similarity to the N-terminal region of DivIVA, which was characterized as a bifunctional protein with distinct roles during vegetative growth and sporulation. In addition, members of the DUF1273 family display distant sequence similarity with the DprA/Smf protein, which acts downstream of the DNA uptake machinery, possibly in conjunction with RecA. The RecA activities in Bacillus subtilis are modulated by RecU Holliday-junction resolvase. In all analyzed cases, the gene coding for RecU is in the vicinity of MW1337R, lin2004, or their orthologs, but on a different operon located in the complementary DNA strand. Here, we report the crystal structures of MW1337R and lin2004, which were determined using the semiautomated, high-throughput pipeline of the Joint Center for Structural Genomics (JCSG), part of the National Institute of General Medical Sciences Protein Structure Initiative.« less

A Novel WT1 Gene Mutation in a Three-Generation Family with Progressive Isolated Focal Segmental Glomerulosclerosis

PubMed Central

Caridi, Gianluca; Malaventura, Cristina; Dagnino, Monica; Leonardi, Emanuela; Artifoni, Lina; Ghiggeri, Gian Marco; Tosatto, Silvio C.E.; Murer, Luisa

2010-01-01

Background and objectives: Wilms tumor-suppressor gene-1 (WT1) plays a key role in kidney development and function. WT1 mutations usually occur in exons 8 and 9 and are associated with Denys-Drash, or in intron 9 and are associated with Frasier syndrome. However, overlapping clinical and molecular features have been reported. Few familial cases have been described, with intrafamilial variability. Sporadic cases of WT1 mutations in isolated diffuse mesangial sclerosis or focal segmental glomerulosclerosis have also been reported. Design, setting, participants, & measurements: Molecular analysis of WT1 exons 8 and 9 was carried out in five members on three generations of a family with late-onset isolated proteinuria. The effect of the detected amino acid substitution on WT1 protein's structure was studied by bioinformatics tools. Results: Three family members reached end-stage renal disease in full adulthood. None had genital abnormalities or Wilms tumor. Histologic analysis in two subjects revealed focal segmental glomerulosclerosis. The novel sequence variant c.1208G>A in WT1 exon 9 was identified in all of the affected members of the family. Conclusions: The lack of Wilms tumor or other related phenotypes suggests the expansion of WT1 gene analysis in patients with focal segmental glomerulosclerosis, regardless of age or presence of typical Denys-Drash or Frasier syndrome clinical features. Structural analysis of the mutated protein revealed that the mutation hampers zinc finger-DNA interactions, impairing target gene transcription. This finding opens up new issues about WT1 function in the maintenance of the complex gene network that regulates normal podocyte function. PMID:20150449

Methylation guide RNA evolution in archaea: structure, function and genomic organization of 110 C/D box sRNA families across six Pyrobaculum species.

PubMed

Lui, Lauren M; Uzilov, Andrew V; Bernick, David L; Corredor, Andrea; Lowe, Todd M; Dennis, Patrick P

2018-05-16

Archaeal homologs of eukaryotic C/D box small nucleolar RNAs (C/D box sRNAs) guide precise 2'-O-methyl modification of ribosomal and transfer RNAs. Although C/D box sRNA genes constitute one of the largest RNA gene families in archaeal thermophiles, most genomes have incomplete sRNA gene annotation because reliable, fully automated detection methods are not available. We expanded and curated a comprehensive gene set across six species of the crenarchaeal genus Pyrobaculum, particularly rich in C/D box sRNA genes. Using high-throughput small RNA sequencing, specialized computational searches and comparative genomics, we analyzed 526 Pyrobaculum C/D box sRNAs, organizing them into 110 families based on synteny and conservation of guide sequences which determine methylation targets. We examined gene duplications and rearrangements, including one family that has expanded in a pattern similar to retrotransposed repetitive elements in eukaryotes. New training data and inclusion of kink-turn secondary structural features enabled creation of an improved search model. Our analyses provide the most comprehensive, dynamic view of C/D box sRNA evolutionary history within a genus, in terms of modification function, feature plasticity, and gene mobility.

Structural and functional studies of a family of Dictyostelium discoideum developmentally regulated, prestalk genes coding for small proteins.

PubMed

Vicente, Juan J; Galardi-Castilla, María; Escalante, Ricardo; Sastre, Leandro

2008-01-03

The social amoeba Dictyostelium discoideum executes a multicellular development program upon starvation. This morphogenetic process requires the differential regulation of a large number of genes and is coordinated by extracellular signals. The MADS-box transcription factor SrfA is required for several stages of development, including slug migration and spore terminal differentiation. Subtractive hybridization allowed the isolation of a gene, sigN (SrfA-induced gene N), that was dependent on the transcription factor SrfA for expression at the slug stage of development. Homology searches detected the existence of a large family of sigN-related genes in the Dictyostelium discoideum genome. The 13 most similar genes are grouped in two regions of chromosome 2 and have been named Group1 and Group2 sigN genes. The putative encoded proteins are 87-89 amino acids long. All these genes have a similar structure, composed of a first exon containing a 13 nucleotides long open reading frame and a second exon comprising the remaining of the putative coding region. The expression of these genes is induced at10 hours of development. Analyses of their promoter regions indicate that these genes are expressed in the prestalk region of developing structures. The addition of antibodies raised against SigN Group 2 proteins induced disintegration of multi-cellular structures at the mound stage of development. A large family of genes coding for small proteins has been identified in D. discoideum. Two groups of very similar genes from this family have been shown to be specifically expressed in prestalk cells during development. Functional studies using antibodies raised against Group 2 SigN proteins indicate that these genes could play a role during multicellular development.

Functional analysis of the Brassica napus L. phytoene synthase (PSY) gene family.

PubMed

López-Emparán, Ada; Quezada-Martinez, Daniela; Zúñiga-Bustos, Matías; Cifuentes, Víctor; Iñiguez-Luy, Federico; Federico, María Laura

2014-01-01

Phytoene synthase (PSY) has been shown to catalyze the first committed and rate-limiting step of carotenogenesis in several crop species, including Brassica napus L. Due to its pivotal role, PSY has been a prime target for breeding and metabolic engineering the carotenoid content of seeds, tubers, fruits and flowers. In Arabidopsis thaliana, PSY is encoded by a single copy gene but small PSY gene families have been described in monocot and dicotyledonous species. We have recently shown that PSY genes have been retained in a triplicated state in the A- and C-Brassica genomes, with each paralogue mapping to syntenic locations in each of the three "Arabidopsis-like" subgenomes. Most importantly, we have shown that in B. napus all six members are expressed, exhibiting overlapping redundancy and signs of subfunctionalization among photosynthetic and non photosynthetic tissues. The question of whether this large PSY family actually encodes six functional enzymes remained to be answered. Therefore, the objectives of this study were to: (i) isolate, characterize and compare the complete protein coding sequences (CDS) of the six B. napus PSY genes; (ii) model their predicted tridimensional enzyme structures; (iii) test their phytoene synthase activity in a heterologous complementation system and (iv) evaluate their individual expression patterns during seed development. This study further confirmed that the six B. napus PSY genes encode proteins with high sequence identity, which have evolved under functional constraint. Structural modeling demonstrated that they share similar tridimensional protein structures with a putative PSY active site. Significantly, all six B. napus PSY enzymes were found to be functional. Taking into account the specific patterns of expression exhibited by these PSY genes during seed development and recent knowledge of PSY suborganellar localization, the selection of transgene candidates for metabolic engineering the carotenoid content of oilseeds is discussed.

The planetary biology of cytochrome P450 aromatases.

PubMed

Gaucher, Eric A; Graddy, Logan G; Li, Tang; Simmen, Rosalia C M; Simmen, Frank A; Schreiber, David R; Liberles, David A; Janis, Christine M; Benner, Steven A

2004-08-17

Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system. Here, we report an example of such an expansion, where tools from planetary biology were used to analyze three genes from the pig Sus scrofa that encode cytochrome P450 aromatases-enzymes that convert androgens into estrogens. The evolutionary history of the vertebrate aromatase gene family was reconstructed. Transition redundant exchange silent substitution metrics were used to interpolate dates for the divergence of family members, the paleontological record was consulted to identify changes in physiology that correlated in time with the change in molecular behavior, and new aromatase sequences from peccary were obtained. Metrics that detect changing function in proteins were then applied, including KA/KS values and those that exploit structural biology. These identified specific amino acid replacements that were associated with changing substrate and product specificity during the time of presumed adaptive change. The combined analysis suggests that aromatase paralogs arose in pigs as a result of selection for Suoidea with larger litters than their ancestors, and permitted the Suoidea to survive the global climatic trauma that began in the Eocene. This combination of bioinformatics analysis, molecular evolution, paleontology, cladistics, global climatology, structural biology, and organic chemistry serves as a paradigm in planetary biology. As the geological, paleontological, and genomic records improve, this approach should become widely useful to make systems biology statements about high-level function for biomolecular systems.

The planetary biology of cytochrome P450 aromatases

PubMed Central

Gaucher, Eric A; Graddy, Logan G; Li, Tang; Simmen, Rosalia CM; Simmen, Frank A; Schreiber, David R; Liberles, David A; Janis, Christine M; Benner, Steven A

2004-01-01

Background Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system. Results Here, we report an example of such an expansion, where tools from planetary biology were used to analyze three genes from the pig Sus scrofa that encode cytochrome P450 aromatases–enzymes that convert androgens into estrogens. The evolutionary history of the vertebrate aromatase gene family was reconstructed. Transition redundant exchange silent substitution metrics were used to interpolate dates for the divergence of family members, the paleontological record was consulted to identify changes in physiology that correlated in time with the change in molecular behavior, and new aromatase sequences from peccary were obtained. Metrics that detect changing function in proteins were then applied, including KA/KS values and those that exploit structural biology. These identified specific amino acid replacements that were associated with changing substrate and product specificity during the time of presumed adaptive change. The combined analysis suggests that aromatase paralogs arose in pigs as a result of selection for Suoidea with larger litters than their ancestors, and permitted the Suoidea to survive the global climatic trauma that began in the Eocene. Conclusions This combination of bioinformatics analysis, molecular evolution, paleontology, cladistics, global climatology, structural biology, and organic chemistry serves as a paradigm in planetary biology. As the geological, paleontological, and genomic records improve, this approach should become widely useful to make systems biology statements about high-level function for biomolecular systems. PMID:15315709

Solution structure and backbone dynamics of an endopeptidase HycI from Escherichia coli: implications for mechanism of the [NiFe] hydrogenase maturation.

PubMed

Yang, Fan; Hu, Wei; Xu, Huimin; Li, Congmin; Xia, Bin; Jin, Changwen

2007-02-09

[NiFe] hydrogenases are metalloenzymes involved in many biological processes concerning the metabolism of hydrogen. The maturation of the large subunit of these hydrogenases requires the cleavage of a peptide at the C terminus by an endopeptidase before the final formation of the [NiFe] metallocenter. HycI is an endopeptidase of the M52 family and responsible for the C-terminal cleavage of the large subunit of hydrogenase 3 in Escherichia coli. Although extensive studies were performed, the molecular mechanism of recognition and cleavage of hydrogenase 3 remains elusive. Herein, we report the solution structure of E. coli HycI determined by high resolution nuclear magnetic resonance spectroscopy. This is the first solution structure of the apo form of endopeptidase of the M52 family reported thus far. The overall structure is similar to the crystal structure of holo-HybD in the same family. However, significant diversity was observed between the two structures. Especially, HycI shows an open conformation at the putative nickel-binding site, whereas HybD adopts a closed conformation. In addition, we performed backbone dynamic studies to probe the motional properties of the apo form of HycI. Furthermore, the metal ion titration experiments provide insightful information on the substrate recognition and cleavage processes. Taken together, our current structural, biochemical, and dynamic studies extend the knowledge of the M52 family proteins and provide novel insights into the biological function of HycI.

Associations between soil bacterial community structure and nutrient cycling functions in long-term organic farm soils following cover crop and organic fertilizer amendment.

PubMed

Fernandez, Adria L; Sheaffer, Craig C; Wyse, Donald L; Staley, Christopher; Gould, Trevor J; Sadowsky, Michael J

2016-10-01

Agricultural management practices can produce changes in soil microbial populations whose functions are crucial to crop production and may be detectable using high-throughput sequencing of bacterial 16S rRNA. To apply sequencing-derived bacterial community structure data to on-farm decision-making will require a better understanding of the complex associations between soil microbial community structure and soil function. Here 16S rRNA sequencing was used to profile soil bacterial communities following application of cover crops and organic fertilizer treatments in certified organic field cropping systems. Amendment treatments were hairy vetch (Vicia villosa), winter rye (Secale cereale), oilseed radish (Raphanus sativus), buckwheat (Fagopyrum esculentum), beef manure, pelleted poultry manure, Sustane(®) 8-2-4, and a no-amendment control. Enzyme activities, net N mineralization, soil respiration, and soil physicochemical properties including nutrient levels, organic matter (OM) and pH were measured. Relationships between these functional and physicochemical parameters and soil bacterial community structure were assessed using multivariate methods including redundancy analysis, discriminant analysis, and Bayesian inference. Several cover crops and fertilizers affected soil functions including N-acetyl-β-d-glucosaminidase and β-glucosidase activity. Effects, however, were not consistent across locations and sampling timepoints. Correlations were observed among functional parameters and relative abundances of individual bacterial families and phyla. Bayesian analysis inferred no directional relationships between functional activities, bacterial families, and physicochemical parameters. Soil functional profiles were more strongly predicted by location than by treatment, and differences were largely explained by soil physicochemical parameters. Composition of soil bacterial communities was predictive of soil functional profiles. Differences in soil function were better explained using both soil physicochemical test values and bacterial community structure data than using soil tests alone. Pursuing a better understanding of bacterial community composition and how it is affected by farming practices is a promising avenue for increasing our ability to predict the impact of management practices on important soil functions. Copyright © 2016. Published by Elsevier B.V.

Structure and function of polyketide biosynthetic enzymes: various strategies for production of structurally diverse polyketides.

PubMed

Miyanaga, Akimasa

2017-12-01

Polyketides constitute a large family of natural products that display various biological activities. Polyketides exhibit a high degree of structural diversity, although they are synthesized from simple acyl building blocks. Recent biochemical and structural studies provide a better understanding of the biosynthetic logic of polyketide diversity. This review highlights the biosynthetic mechanisms of structurally unique polyketides, β-amino acid-containing macrolactams, enterocin, and phenolic lipids. Functional and structural studies of macrolactam biosynthetic enzymes have revealed the unique biosynthetic machinery used for selective incorporation of a rare β-amino acid starter unit into the polyketide skeleton. Biochemical and structural studies of cyclization enzymes involved in the biosynthesis of enterocin and phenolic lipids provide mechanistic insights into how these enzymes diversify the carbon skeletons of their products.

Genome-wide analysis of the Dof transcription factor gene family reveals soybean-specific duplicable and functional characteristics.

PubMed

Guo, Yong; Qiu, Li-Juan

2013-01-01

The Dof domain protein family is a classic plant-specific zinc-finger transcription factor family involved in a variety of biological processes. There is great diversity in the number of Dof genes in different plants. However, there are only very limited reports on the characterization of Dof transcription factors in soybean (Glycine max). In the present study, 78 putative Dof genes were identified from the whole-genome sequence of soybean. The predicted GmDof genes were non-randomly distributed within and across 19 out of 20 chromosomes and 97.4% (38 pairs) were preferentially retained duplicate paralogous genes located in duplicated regions of the genome. Soybean-specific segmental duplications contributed significantly to the expansion of the soybean Dof gene family. These Dof proteins were phylogenetically clustered into nine distinct subgroups among which the gene structure and motif compositions were considerably conserved. Comparative phylogenetic analysis of these Dof proteins revealed four major groups, similar to those reported for Arabidopsis and rice. Most of the GmDofs showed specific expression patterns based on RNA-seq data analyses. The expression patterns of some duplicate genes were partially redundant while others showed functional diversity, suggesting the occurrence of sub-functionalization during subsequent evolution. Comprehensive expression profile analysis also provided insights into the soybean-specific functional divergence among members of the Dof gene family. Cis-regulatory element analysis of these GmDof genes suggested diverse functions associated with different processes. Taken together, our results provide useful information for the functional characterization of soybean Dof genes by combining phylogenetic analysis with global gene-expression profiling.

Relationship between Mental Health and Burden among Primary Caregivers of Outpatients with Schizophrenia.

PubMed

Yu, Wenjun; Chen, Jia; Hu, Jize; Hu, JingChu

2018-01-24

There is growing recognition that caring for a patient with schizophrenia often results in high levels of perceived burden and poorer overall mental health for caregivers. A quantitative cross-sectional design and standardized instruments were used to collect data from 355 primary caregivers of adults in outpatient care with schizophrenia in China. Structural equation modeling was used to examine the association between caregiver burden and mental health among primary caregivers and whether this association is influenced by personality, coping style, and family functioning, based on a diathesis-stress perspective. Goodness-of-fit indices (χ 2 /df = 1.406, GFI = 0.919, CFI = 0.957, etc.) confirmed that the modified model fit the data well. In line with the diathesis-stress model, and with this study's hypotheses, we found that caregiver burden was significantly related to mental health outcomes directly. The final model showed that personality traits, coping style, and family function influenced the relationship between caregiver burden and mental health. The neuroticism personality traits have a direct effect on caregiver burden and family functioning in this sample. Coping style had a direct effect on the caregiver burden, and family functioning had a direct effect on the caregiver burden. Our final model about primary caregivers can be applied clinically to predict mental health outcomes from caregiver burden. © 2018 Family Process Institute.

Structure of caa(3) cytochrome c oxidase--a nature-made enzyme-substrate complex.

PubMed

Noor, Mohamed Radzi; Soulimane, Tewfik

2013-05-01

Aerobic respiration, the energetically most favorable metabolic reaction, depends on the action of terminal oxidases that include cytochrome c oxidases. The latter forms a part of the heme-copper oxidase superfamily and consists of three different families (A, B, and C types). The crystal structures of all families have now been determined, allowing a detailed structural comparison from evolutionary and functional perspectives. The A2-type oxidase, exemplified by the Thermus thermophilus caa(3) oxidase, contains the substrate cytochrome c covalently bound to the enzyme complex. In this article, we highlight the various features of caa(3) enzyme and provide a discussion of their importance, including the variations in the proton and electron transfer pathways.