WorldWideScience

Sample records for reproductive protein family

  1. IGSF9 Family Proteins

    DEFF Research Database (Denmark)

    Hansen, Maria; Walmod, Peter Schledermann

    2013-01-01

    The Drosophila protein Turtle and the vertebrate proteins immunoglobulin superfamily (IgSF), member 9 (IGSF9/Dasm1) and IGSF9B are members of an evolutionarily ancient protein family. A bioinformatics analysis of the protein family revealed that invertebrates contain only a single IGSF9 family gene......, the longest isoforms of the proteins have the same general organization as the neural cell adhesion molecule family of cell adhesion molecule proteins, and like this family of proteins, IGSF9 family members are expressed in the nervous system. A review of the literature revealed that Drosophila Turtle...... facilitates homophilic cell adhesion. Moreover, IGSF9 family proteins have been implicated in the outgrowth and branching of neurites, axon guidance, synapse maturation, self-avoidance, and tiling. However, despite the few published studies on IGSF9 family proteins, reports on the functions of both Turtle...

  2. Comparative genomics in Chlamydomonas and Plasmodium identifies an ancient nuclear envelope protein family essential for sexual reproduction in protists, fungi, plants, and vertebrates.

    Science.gov (United States)

    Ning, Jue; Otto, Thomas D; Pfander, Claudia; Schwach, Frank; Brochet, Mathieu; Bushell, Ellen; Goulding, David; Sanders, Mandy; Lefebvre, Paul A; Pei, Jimin; Grishin, Nick V; Vanderlaan, Gary; Billker, Oliver; Snell, William J

    2013-05-15

    Fertilization is a crucial yet poorly characterized event in eukaryotes. Our previous discovery that the broadly conserved protein HAP2 (GCS1) functioned in gamete membrane fusion in the unicellular green alga Chlamydomonas and the malaria pathogen Plasmodium led us to exploit the rare biological phenomenon of isogamy in Chlamydomonas in a comparative transcriptomics strategy to uncover additional conserved sexual reproduction genes. All previously identified Chlamydomonas fertilization-essential genes fell into related clusters based on their expression patterns. Out of several conserved genes in a minus gamete cluster, we focused on Cre06.g280600, an ortholog of the fertilization-related Arabidopsis GEX1. Gene disruption, cell biological, and immunolocalization studies show that CrGEX1 functions in nuclear fusion in Chlamydomonas. Moreover, CrGEX1 and its Plasmodium ortholog, PBANKA_113980, are essential for production of viable meiotic progeny in both organisms and thus for mosquito transmission of malaria. Remarkably, we discovered that the genes are members of a large, previously unrecognized family whose first-characterized member, KAR5, is essential for nuclear fusion during yeast sexual reproduction. Our comparative transcriptomics approach provides a new resource for studying sexual development and demonstrates that exploiting the data can lead to the discovery of novel biology that is conserved across distant taxa.

  3. The tubby family proteins

    OpenAIRE

    Mukhopadhyay, Saikat; Jackson, Peter K

    2011-01-01

    The tubby mouse shows a tripartite syndrome characterized by maturity-onset obesity, blindness and deafness. The causative gene Tub is the founding member of a family of related proteins present throughout the animal and plant kingdoms, each characterized by a signature carboxy-terminal tubby domain. This domain consists of a β barrel enclosing a central α helix and binds selectively to specific membrane phosphoinositides. The vertebrate family of tubby-like proteins (TULPs) includes the foun...

  4. The semenogelins: proteins with functions beyond reproduction?

    Science.gov (United States)

    Jonsson, M; Lundwall, A; Malm, J

    2006-12-01

    The coagulum proteins of human semen, semenogelins I and II, are secreted in abundance by the seminal vesicles. Their function in reproduction is poorly understood as they are rapidly degraded in ejaculated semen. However, more recent results indicate that it is time to put the semenogelins in a broader physiological perspective that goes beyond reproduction and fertility.

  5. The semenogelins: proteins with functions beyond reproduction?

    OpenAIRE

    Jonsson, Magnus; Lundwall, Åke; Malm, Johan

    2006-01-01

    The coagulum proteins of human semen, semenogelins I and II, are secreted in abundance by the seminal vesicles. Their function in reproduction is poorly understood as they are rapidly degraded in ejaculated semen. However, more recent results indicate that it is time to put the semenogelins in a broader physiological perspective that goes beyond reproduction and fertility.

  6. The netrin protein family.

    Science.gov (United States)

    Rajasekharan, Sathyanath; Kennedy, Timothy E

    2009-01-01

    The name netrin is derived from the Sanskrit Netr, meaning 'guide'. Netrins are a family of extracellular proteins that direct cell and axon migration during embryogenesis. Three secreted netrins (netrins 1, 3 and 4), and two glycosylphosphatidylinositol (GPI)-anchored membrane proteins, netrins G1 and G2, have been identified in mammals. The secreted netrins are bifunctional, acting as attractants for some cell types and repellents for others. Receptors for the secreted netrins include the Deleted in Colorectal Cancer (DCC) family, the Down's syndrome cell adhesion molecule (DSCAM), and the UNC-5 homolog family: Unc5A, B, C and D in mammals. Netrin Gs do not appear to interact with these receptors, but regulate synaptic interactions between neurons by binding to the transmembrane netrin G ligands NGL1 and 2. The chemotropic function of secreted netrins has been best characterized with regard to axon guidance during the development of the nervous system. Extending axons are tipped by a flattened, membranous structure called the growth cone. Multiple extracellular guidance cues direct axonal growth cones to their ultimate targets where synapses form. Such cues can be locally derived (short-range), or can be secreted diffusible cues that allow target cells to signal axons from a distance (long-range). The secreted netrins function as short-range and long-range guidance cues in different circumstances. In addition to directing cell migration, functional roles for netrins have been identified in the regulation of cell adhesion, the maturation of cell morphology, cell survival and tumorigenesis.

  7. Migration and reproductive behavior in Turkish migrant families

    OpenAIRE

    Nauck, Bernhard

    1987-01-01

    Migration and reproductive behavior in Turkish migrant families : a situational explanation. - In: Growth and progress in cross-cultural psychology / ed. by Cigdem Kagitcibasi. - Lisse u.a. : Swets & Zeitlinger, 1987. - S. 336- 345

  8. The Family in Us: Family History, Family Identity and Self-Reproductive Adaptive Behavior.

    Science.gov (United States)

    Ferring, Dieter

    2017-06-01

    This contribution is an essay about the notion of family identity reflecting shared significant experiences within a family system originating a set of signs used in social communication within and between families. Significant experiences are considered as experiences of events that have an immediate impact on the adaptation of the family in a given socio-ecological and cultural context at a given historical time. It is assumed that family history is stored in a shared "family memory" holding both implicit and explicit knowledge and exerting an influence on the behavior of each family member. This is described as transgenerational family memory being constituted of a system of meaningful signs. The crucial dimension underlying the logic of this essay are the ideas of adaptation as well as self-reproduction of systems.

  9. Differential roles of TGIF family genes in mammalian reproduction

    Directory of Open Access Journals (Sweden)

    Renfree Marilyn B

    2011-09-01

    Full Text Available Abstract Background TG-interacting factors (TGIFs belong to a family of TALE-homeodomain proteins including TGIF1, TGIF2 and TGIFLX/Y in human. Both TGIF1 and TGIF2 act as transcription factors repressing TGF-β signalling. Human TGIFLX and its orthologue, Tex1 in the mouse, are X-linked genes that are only expressed in the adult testis. TGIF2 arose from TGIF1 by duplication, whereas TGIFLX arose by retrotransposition to the X-chromosome. These genes have not been characterised in any non-eutherian mammals. We therefore studied the TGIF family in the tammar wallaby (a marsupial mammal to investigate their roles in reproduction and how and when these genes may have evolved their functions and chromosomal locations. Results Both TGIF1 and TGIF2 were present in the tammar genome on autosomes but TGIFLX was absent. Tammar TGIF1 shared a similar expression pattern during embryogenesis, sexual differentiation and in adult tissues to that of TGIF1 in eutherian mammals, suggesting it has been functionally conserved. Tammar TGIF2 was ubiquitously expressed throughout early development as in the human and mouse, but in the adult, it was expressed only in the gonads and spleen, more like the expression pattern of human TGIFLX and mouse Tex1. Tammar TGIF2 mRNA was specifically detected in round and elongated spermatids. There was no mRNA detected in mature spermatozoa. TGIF2 protein was specifically located in the cytoplasm of spermatids, and in the residual body and the mid-piece of the mature sperm tail. These data suggest that tammar TGIF2 may participate in spermiogenesis, like TGIFLX does in eutherians. TGIF2 was detected for the first time in the ovary with mRNA produced in the granulosa and theca cells, suggesting it may also play a role in folliculogenesis. Conclusions The restricted and very similar expression of tammar TGIF2 to X-linked paralogues in eutherians suggests that the evolution of TGIF1, TGIF2 and TGIFLX in eutherians was accompanied by

  10. Islamic logics, reproductive rationalities: family planning in northern Pakistan.

    Science.gov (United States)

    Varley, Emma

    2012-01-01

    This paper explores the use of Islamic doctrine and jurisprudence by family planning organizations in the Gilgit-Baltistan region of northern Pakistan. It examines how particular interpretations of Islam are promoted in order to encourage fertility reductions, and the ways Muslim clerics, women and their families react to this process. The paper first discusses how Pakistan's demographic crisis, as the world's sixth most populous nation, has been widely blamed on under-funding for reproductive health services and wavering political commitment to family planning. Critics have called for innovative policy and programming to counter 'excessive reproduction' by also addressing socio-cultural and religious barriers to contraceptive uptake. Drawing on two years of ethnographic research, the paper examines how family planning organizations in Gilgit-Baltistan respond to this shift by employing moderate interpretations of Islam that qualify contraceptive use as a 'rational' reproductive strategy and larger families as 'irrational'. However, the use of Islamic rhetoric to enhance women's health-seeking agency and enable fertility reductions is challenged by conservative Sunni ulema (clergy), who seek to reassert collective control over women's bodies and fertility by deploying Islamic doctrine that honors frequent childbearing. Sunnis' minority status and the losses incurred by regional Shia-Sunni conflicts have further strengthened clerics' pronatalist campaigns. The paper then analyses how Sunni women navigate the multiple reproductive rationalities espoused by 'Islamized' family planning and conservative ulema. Although Islamized family planning legitimizes contraceptive use and facilitates many women's stated desire for smaller families, it frequently positions women against the interests of family, community and conservative Islam.

  11. Grandparental investment: The influence of reproductive timing and family size.

    Science.gov (United States)

    Coall, David A; Meier, Marc; Hertwig, Ralph; Wänke, Michaela; Höpflinger, François

    2009-01-01

    The influence that grandparents have on the life history traits of their descendants has been studied extensively. However, no attention has been paid to the potential influence a grandparent's own reproductive history has on the investment they make in their grandchildren. We use data from 658 Swiss grandchildren and 591 of their grandparents to investigate whether grandparents' reproductive scheduling and family size influence the amount of investment grandparents make in a focal grandchild (shared contacts, occasions to meet, activities, discussions, interests, and important roles the grandparent plays). Grandparents who were younger when they had their first child had more children and grandchildren; this relationship strengthened after controlling for grandparental age, sex, lineage, and education (all P children or grandchildren was associated with reduced levels of grandparental investment. After adjustment for a wide range of factors known to influence investment, having more children or grandchildren and having a first child or grandchild at a younger age were associated with reduced investment in 14 of 24 analyses (all P family size. Interestingly, these relationships were only present in data reported from the grandchild's point of view, not the grandparent's. This analysis provides preliminary evidence that grandparents' reproductive strategies have consequences for the amount of investment they make in their grandchildren. These results are examined in terms of the trade-offs between current and future reproduction and offspring quality and quantity. 2009 Wiley-Liss, Inc.

  12. Reproductive hacking. A male seminal protein acts through intact reproductive pathways in female Drosophila.

    Science.gov (United States)

    Rubinstein, C Dustin; Wolfner, Mariana F

    2014-01-01

    Seminal proteins are critical for reproductive success in all animals that have been studied. Although seminal proteins have been identified in many taxa, and female reproductive responses to receipt of these proteins have been documented in several, little is understood about the mechanisms by which seminal proteins affect female reproductive physiology. To explore this topic, we investigated how a Drosophila seminal protein, ovulin, increases ovulation rate in mated females. Ovulation is a relatively simple physiological process, with known female regulators: previous studies have shown that ovulation rate is promoted by the neuromodulator octopamine (OA) in D. melanogaster and other insects. We found that ovulin stimulates ovulation by increasing OA signaling in the female. This finding supports a model in which a male seminal protein acts through "hacking" a well-conserved, regulatory system females use to adjust reproductive output, rather than acting downstream of female mechanisms of control or in parallel pathways altogether. We also discuss similarities between 2 forms of intersexual control of behavior through chemical communication: seminal proteins and pheromones.

  13. Exploiting genomic data to identify proteins involved in abalone reproduction.

    Science.gov (United States)

    Mendoza-Porras, Omar; Botwright, Natasha A; McWilliam, Sean M; Cook, Mathew T; Harris, James O; Wijffels, Gene; Colgrave, Michelle L

    2014-08-28

    Aside from their critical role in reproduction, abalone gonads serve as an indicator of sexual maturity and energy balance, two key considerations for effective abalone culture. Temperate abalone farmers face issues with tank restocking with highly marketable abalone owing to inefficient spawning induction methods. The identification of key proteins in sexually mature abalone will serve as the foundation for a greater understanding of reproductive biology. Addressing this knowledge gap is the first step towards improving abalone aquaculture methods. Proteomic profiling of female and male gonads of greenlip abalone, Haliotis laevigata, was undertaken using liquid chromatography-mass spectrometry. Owing to the incomplete nature of abalone protein databases, in addition to searching against two publicly available databases, a custom database comprising genomic data was used. Overall, 162 and 110 proteins were identified in females and males respectively with 40 proteins common to both sexes. For proteins involved in sexual maturation, sperm and egg structure, motility, acrosomal reaction and fertilization, 23 were identified only in females, 18 only in males and 6 were common. Gene ontology analysis revealed clear differences between the female and male protein profiles reflecting a higher rate of protein synthesis in the ovary and higher metabolic activity in the testis. A comprehensive mass spectrometry-based analysis was performed to profile the abalone gonad proteome providing the foundation for future studies of reproduction in abalone. Key proteins involved in both reproduction and energy balance were identified. Genomic resources were utilised to build a database of molluscan proteins yielding >60% more protein identifications than in a standard workflow employing public protein databases. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. The economic consequences of reproductive health and family planning.

    Science.gov (United States)

    Canning, David; Schultz, T Paul

    2012-07-14

    We consider the evidence for the effect of access to reproductive health services on the achievement of Millennium Development Goals 1, 2, and 3, which aim to eradicate extreme poverty and hunger, achieve universal primary education, and promote gender equality and empower women. At the household level, controlled trials in Matlab, Bangladesh, and Navrongo, Ghana, have shown that increasing access to family planning services reduces fertility and improves birth spacing. In the Matlab study, findings from long-term follow-up showed that women's earnings, assets, and body-mass indexes, and children's schooling and body-mass indexes, substantially improved in areas with improved access to family planning services compared with outcomes in control areas. At the macroeconomic level, reductions in fertility enhance economic growth as a result of reduced youth dependency and an increased number of women participating in paid labour. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Relaxin family peptides in the male reproductive system--a critical appraisal.

    Science.gov (United States)

    Ivell, Richard; Kotula-Balak, Malgorzata; Glynn, Danielle; Heng, Kee; Anand-Ivell, Ravinder

    2011-02-01

    The human genome project has identified, besides ovarian relaxin (RLN), six other relaxin-like molecules (RLN3, H1-RLN, INSL3-6), most of which appear to be expressed in the testis and/or male reproductive system, together with four different G-protein-coupled receptors responsive to one or other of these peptides. Earlier work on relaxin in the male assumed the simplistic hypothesis of only a single relaxin-like entity. This review systematically examines the expression and physiology of relaxin-like molecules in the male reproductive system in order to reappraise the importance of this hormone system for male reproductive function. Although there are important species differences, only INSL3 and INSL6 appear to be generally expressed at a moderately high level within the testis, whereas ovarian RLN is consistently a major secretory product of the prostate epithelium. However, all members of this relaxin-like family appear to be expressed also at a low level in different organs of the male reproductive system, suggesting possible autocrine/paracrine effects. The four receptors (RXFP1-4) for these peptides are also expressed to differing levels in both somatic and seminiferous compartments of the testis and in the prostate, supporting relevant functions for most members of this interesting peptide family. Recent studies of relaxin family peptides in prostate pathology highlight their functional importance in the clinical context as potential causative, diagnostic and therapeutic agents and warrant more specific and detailed studies of their roles also in regard to male fertility and other aspects of male reproductive function.

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

    DEFF Research Database (Denmark)

    Hartmann-Petersen, Rasmus; Gordon, Colin

    2004-01-01

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

  17. Role of sperm surface proteins in reproduction

    Czech Academy of Sciences Publication Activity Database

    Jonáková, Věra; Maňásková, Pavla; Davidová, Nina; Tichá, M.; Pěknicová, Jana

    2009-01-01

    Roč. 30, Supplement (2009), s. 63-64 ISSN 0196-3635. [9th International Congress of Andrology. 07.03.2009-10.03.2009, Barcelona] R&D Projects: GA MŠk(CZ) 1M06011; GA ČR(CZ) GA523/08/H064; GA ČR(CZ) GA303/06/0895 Institutional research plan: CEZ:AV0Z50520701 Keywords : boar seminal plasma proteins * spermadhesins * proteinase inhibitor * DQH * boar spermatozoa Subject RIV: CE - Biochemistry

  18. The human protein disulfide isomerase gene family

    Directory of Open Access Journals (Sweden)

    Galligan James J

    2012-07-01

    Full Text Available Abstract Enzyme-mediated disulfide bond formation is a highly conserved process affecting over one-third of all eukaryotic proteins. The enzymes primarily responsible for facilitating thiol-disulfide exchange are members of an expanding family of proteins known as protein disulfide isomerases (PDIs. These proteins are part of a larger superfamily of proteins known as the thioredoxin protein family (TRX. As members of the PDI family of proteins, all proteins contain a TRX-like structural domain and are predominantly expressed in the endoplasmic reticulum. Subcellular localization and the presence of a TRX domain, however, comprise the short list of distinguishing features required for gene family classification. To date, the PDI gene family contains 21 members, varying in domain composition, molecular weight, tissue expression, and cellular processing. Given their vital role in protein-folding, loss of PDI activity has been associated with the pathogenesis of numerous disease states, most commonly related to the unfolded protein response (UPR. Over the past decade, UPR has become a very attractive therapeutic target for multiple pathologies including Alzheimer disease, Parkinson disease, alcoholic and non-alcoholic liver disease, and type-2 diabetes. Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR.

  19. Resources, attractiveness, family commitment; reproductive decisions in human mate choice.

    Science.gov (United States)

    Bereczkei, T; Voros, S; Gal, A; Bernath, L

    1997-08-01

    This study of reproductive decisions in human mate selection used data from "lonely hearts" advertisements to examine a series of predictions based on the mate preferences of male and females relating to age; physical appearance; financial condition and socioeconomic status; family commitment and personal traits; short- and long-term mating; and marital status and preexisting children. The sample consisted of 1000 personal advertisements (500 male) placed in two daily, national papers between February and October 1994 in Hungary. The research procedure included a pilot study of 150 advertisers (75 male) to refine the categories examined. Analysis was performed using 1) a matrix with one axis referring to offers and the other to demands of males and females separately; 2) a matrix of offers only to derive correlated traits of claims by males and females; and 3) a matrix with columns describing sex, offers, demands, advertiser's age, and required age and a row for each of the 1000 samples. It was found that men preferred younger mates, while women preferred older ones. Men were more likely to seek physical attractiveness, while women were more likely to seek financial resources (ranked 7th) and high status (ranked 6th). Women strongly preferred male domestic virtue and family commitment, and twice as many women as men demanded long-term relationships. Women more frequently declared preexisting children, and men exhibited a reluctance to accept these children. Both males and females employed "trade-off" strategies, making greater demands if they felt they had attractive offers.

  20. Effect of feeding different dietary protein levels on reproductive ...

    African Journals Online (AJOL)

    A feeding trial was conducted to evaluate effects of feeding different dietary protein levels on reproductive biology of African mud catfish under hapa system. Catfish fingerlings (mean body weight (4.50± 0.01g) and total length (8.0±0.2cm) were randomly stocked at 20 fish per hapa (1m3). Five experimental diets with crude ...

  1. Families Created by Assisted Reproduction: Parent-Child Relationships in Late Adolescence

    Science.gov (United States)

    Owen, Lucy; Golombok, Susan

    2009-01-01

    This paper presents the findings of the third phase of a longitudinal study of families created by assisted reproduction. The quality of parent-child relationships was examined close to the adolescent's 18th birthday in 26 "in vitro" fertilization (IVF) families and 26 donor insemination (DI) families in comparison with 38 adoptive families and 63…

  2. Characterization of paralogous protein families in rice

    Directory of Open Access Journals (Sweden)

    Zhu Wei

    2008-02-01

    Full Text Available Abstract Background High gene numbers in plant genomes reflect polyploidy and major gene duplication events. Oryza sativa, cultivated rice, is a diploid monocotyledonous species with a ~390 Mb genome that has undergone segmental duplication of a substantial portion of its genome. This, coupled with other genetic events such as tandem duplications, has resulted in a substantial number of its genes, and resulting proteins, occurring in paralogous families. Results Using a computational pipeline that utilizes Pfam and novel protein domains, we characterized paralogous families in rice and compared these with paralogous families in the model dicotyledonous diploid species, Arabidopsis thaliana. Arabidopsis, which has undergone genome duplication as well, has a substantially smaller genome (~120 Mb and gene complement compared to rice. Overall, 53% and 68% of the non-transposable element-related rice and Arabidopsis proteins could be classified into paralogous protein families, respectively. Singleton and paralogous family genes differed substantially in their likelihood of encoding a protein of known or putative function; 26% and 66% of singleton genes compared to 73% and 96% of the paralogous family genes encode a known or putative protein in rice and Arabidopsis, respectively. Furthermore, a major skew in the distribution of specific gene function was observed; a total of 17 Gene Ontology categories in both rice and Arabidopsis were statistically significant in their differential distribution between paralogous family and singleton proteins. In contrast to mammalian organisms, we found that duplicated genes in rice and Arabidopsis tend to have more alternative splice forms. Using data from Massively Parallel Signature Sequencing, we show that a significant portion of the duplicated genes in rice show divergent expression although a correlation between sequence divergence and correlation of expression could be seen in very young genes. Conclusion

  3. Classification of EA1-box proteins and new insights into their role during reproduction in grasses.

    Science.gov (United States)

    Uebler, Susanne; Márton, Mihaela L; Dresselhaus, Thomas

    2015-12-01

    EA1-box protein classification. Success in reproduction and vegetative development in flowering plants strongly depends on precise cell-to-cell signaling events mediated by secreted peptides.A small peptide family named as EA1-like (EAL) has been first described 10 years ago and includes EA1 involved in pollen tubes attraction by the female gametophyte and EAL1-regulating germ cell identity in maize. EALs consist of an N-terminal endoplasmic reticulum-targeting motif, the highly conserved EA1-box and a short C-terminal alanine-rich domain. Whereas EAL peptides are exclusively found in the Gramineae, the EA1-box is widely distributed throughout the plant kingdom. Based on in silico analysis and subcellular localization studies, we report here a new classification of EA1-box proteins in flowering plants. They can be distinguished into three protein classes: the already defined EAL proteins, the EAG (EA1-box glycine-rich) proteins and the EAC (EA1-box containing)proteins. While fusion proteins of EAL and EAC classes locate to the secretory pathway, EAGs are cytoplasmic and locate also to the nucleus. Moreover, we further show that the third EAL protein of Zea mays, EAL2, appears to be also involved in processes related to late embryogenic development as its peptide level increases after formation of leaf primordia. Immunohistochemical studies indicate its presence in the scutellar parenchyma and around the vasculature, where it is secreted to the extracellular space. In conclusion, the members of the maize EAL family possess very diverse functions during reproduction and it will now be exciting to elucidate the functions of EAGs and EACs in plants.

  4. Reproductive protein evolution in two cryptic species of marine chordate

    Science.gov (United States)

    2011-01-01

    Background Reproductive character displacement (RCD) is a common and taxonomically widespread pattern. In marine broadcast spawning organisms, behavioral and mechanical isolation are absent and prezygotic barriers between species often operate only during the fertilization process. Such barriers are usually a consequence of differences in the way in which sperm and egg proteins interact, so RCD can be manifest as faster evolution of these proteins between species in sympatry than allopatry. Rapid evolution of these proteins often appears to be a consequence of positive (directional) selection. Here, we identify a set of candidate gamete recognition proteins (GRPs) in the ascidian Ciona intestinalis and showed that these GRPs evolve more rapidly than control proteins (those not involved in gamete recognition). Choosing a subset of these gamete recognition proteins that show evidence of positive selection (CIPRO37.40.1, CIPRO60.5.1, CIPRO100.7.1), we then directly test the RCD hypothesis by comparing divergence (omega) and polymorphism (McDonald-Kreitman, Tajima's D, Fu and Li's D and F, Fay and Wu's H) statistics in sympatric and allopatric populations of two distinct forms of C. intestinalis (Types A and B) between which there are strong post-zygotic barriers. Results Candidate gamete recognition proteins from two lineages of C. intestinalis (Type A and B) are evolving more rapidly than control proteins, consistent with patterns seen in insects and mammals. However, ω (dN/dS) is not significantly different between the sympatric and allopatric populations, and none of the polymorphism statistics show significant differences between sympatric and allopatric populations. Conclusions Enhanced prezygotic isolation in sympatry has become a well-known feature of gamete recognition proteins in marine broadcast spawners. But in most cases the evolutionary process or processes responsible for this pattern have not been identified. Although gamete recognition proteins in C

  5. Reproductive protein evolution in two cryptic species of marine chordate

    Directory of Open Access Journals (Sweden)

    Harrison Richard G

    2011-01-01

    Full Text Available Abstract Background Reproductive character displacement (RCD is a common and taxonomically widespread pattern. In marine broadcast spawning organisms, behavioral and mechanical isolation are absent and prezygotic barriers between species often operate only during the fertilization process. Such barriers are usually a consequence of differences in the way in which sperm and egg proteins interact, so RCD can be manifest as faster evolution of these proteins between species in sympatry than allopatry. Rapid evolution of these proteins often appears to be a consequence of positive (directional selection. Here, we identify a set of candidate gamete recognition proteins (GRPs in the ascidian Ciona intestinalis and showed that these GRPs evolve more rapidly than control proteins (those not involved in gamete recognition. Choosing a subset of these gamete recognition proteins that show evidence of positive selection (CIPRO37.40.1, CIPRO60.5.1, CIPRO100.7.1, we then directly test the RCD hypothesis by comparing divergence (omega and polymorphism (McDonald-Kreitman, Tajima's D, Fu and Li's D and F, Fay and Wu's H statistics in sympatric and allopatric populations of two distinct forms of C. intestinalis (Types A and B between which there are strong post-zygotic barriers. Results Candidate gamete recognition proteins from two lineages of C. intestinalis (Type A and B are evolving more rapidly than control proteins, consistent with patterns seen in insects and mammals. However, ω (dN/dS is not significantly different between the sympatric and allopatric populations, and none of the polymorphism statistics show significant differences between sympatric and allopatric populations. Conclusions Enhanced prezygotic isolation in sympatry has become a well-known feature of gamete recognition proteins in marine broadcast spawners. But in most cases the evolutionary process or processes responsible for this pattern have not been identified. Although gamete

  6. Reproductive health/family planning and the health of infants, girls and women.

    Science.gov (United States)

    Sadik, N

    1997-01-01

    The 1994 International Conference on Population and Development developed international consensus amongst health providers, policy makers, and group representing the whole of civil society regarding the concept of reproductive health and its definition. In line with this definition, reproductive health care is defined as the constellation of methods, techniques and services that contribute to reproductive health and well-being by preventing and solving reproductive health problems. Reproductive health care saves lives and prevents significant levels of morbidity through family planning programmes, antenatal, delivery and post-natal services, prevention and management programmes for reproductive tract infections (including sexually transmitted diseases and HIV/AIDS), prevention of abortion and management of its complications, cancers of the reproductive system, and harmful practices that impact on reproductive function. Reproductive health care needs are evident at all stages of the life cycle and account for a greater proportion of disability adjusted life years (DALYS) in girls and women than in boys and men. Reproductive health protects infant health by enabling birth spacing and birth limitation to be practiced through family planning. The prevention and early detection of reproductive tract infections, including sexually transmitted diseases and HIV, through the integration of preventive measures in family planning service delivery not only improves the quality of care provided but is also directly responsible for improvement in survival and health of infants. Addressing harmful practices such as son preference, sex selection, sexual violence and female genital mutilation complements the positive impact of planned and spaced children through family planning services on infant mortality and the reproductive health of young girls and women. They are also in addition to prenatal, delivery and postnatal services, positive determinants of low maternal mortality and

  7. Receptor-interacting protein (RIP) kinase family

    OpenAIRE

    Zhang, Duanwu; Lin, Juan; Han, Jiahuai

    2010-01-01

    Receptor-interacting protein (RIP) kinases are a group of threonine/serine protein kinases with a relatively conserved kinase domain but distinct non-kinase regions. A number of different domain structures, such as death and caspase activation and recruitment domain (CARD) domains, were found in different RIP family members, and these domains should be keys in determining the specific function of each RIP kinase. It is known that RIP kinases participate in different biological processes, incl...

  8. Family planning in contermporary reproductive health and rights ...

    African Journals Online (AJOL)

    Key strategies to promote family planning include domestication of provisions of international conventions on family planning into state laws, and ensuring their implementation; development of community friendly family planning services; establishment of effective family planning commodities logistics management system; ...

  9. A Longitudinal Study of Families Formed Through Reproductive Donation: Parent-Adolescent Relationships and Adolescent Adjustment at Age 14

    OpenAIRE

    Golombok, Susan; Ilioi, Elena; Blake, Lucy; Roman, Gabriela; Jadva, Vasanti

    2017-01-01

    The aim of the 6th phase of this longitudinal study was to establish whether children born through assisted reproduction involving reproductive donation were at risk for psychological problems following the transition to adolescence at age 14 and, if so, to examine the nature of these problems and the mechanisms involved. Eighty-seven families formed through reproductive donation, including 32 donor insemination families, 27 egg donation families, and 28 surrogacy families, were compared with...

  10. Family Resources and Reproductive Health of Girls: a Focus on ...

    African Journals Online (AJOL)

    The major objective of this paper is to throw some light on how proper use of family resources could help resolve the problem. All families have certain resources such as money, time, energy, skills of members, and some community resources like schools and traditional society's puberty rites. However, most families do not ...

  11. Reproductive health control of the families with mutagenic exposures after Chernobyl disaster

    International Nuclear Information System (INIS)

    Genyk-Berezovska, S.O.; Havrylyuk, Yu.Y.

    2003-01-01

    The aim of this work is to estimate the additional genetic risk (hazard) of mutagenic radiation for evacuated families in relatively ecologically favorable region. The reproductive characteristics, birth defects prevalence and antropometric data compare was held among newborns for 130 families before and after mutagenic exposure, when they were evacuated from radiation polluted region. The study results indicated no evidence of low-dose radiation exposure impact on realization of additional mutagenic burden in the liquidators and evacuees families through the extent of reproductive losses and CM

  12. Association between protein feeding and reproductive efficiency in the dairy cow: specific emphasis on protein feeding in Finland

    OpenAIRE

    K.J. SHINGFIELD; M. JOKELA; K. KAUSTELL

    2008-01-01

    Associations between protein feeding and reproductive efficiency in the dairy cow are reviewed. Examination of published data indicated that reproductive responses assessed as days open, services per conception or conception rate following changes in protein feeding tend to be inconsistent. Discrepancies can arise due to between-study variations in experimental design, statistical analysis, sample population size, uterine health, cow age, parity, reproductive management or nutrient intake. De...

  13. Factors influencing family planning practice among reproductive age married women in Hlaing Township, Myanmar.

    Science.gov (United States)

    Lwin, Myo Min; Munsawaengsub, Chokchai; Nanthamongkokchai, Sutham

    2013-12-01

    To study the factors that influence the family planning practice among married, reproductive age women in Hlaing Township, Myanmar. Cross-sectional survey research was conducted among 284 married, reproductive age women using stratified random sampling. The data were collected through questionnaire interviews during February and March 2012 and analyzed by frequency, percentage, Chi-square test, and multiple logistic regression. The proportion of families practicing family planning was 74.7%, contraceptive injection being the most commonly used method. The factors influencing family planning practice were attitude towards family planning, 24-hour availability of family planning services, health worker support, and partner and friends support. The women with a positive attitude toward family planning practiced family planning 3.7 times more than women who had a negative attitude. If family planning services were available for 24 hours, then women would practice 3.4 times more than if they were not available for 24 hours. When women got fair to good support from health workers, they practiced 15.0 times more on family planning and 4.3 times more who got fair to good support from partners and friends than women who got low support. The factors influencing family planning practice of married, reproductive age women were attitude toward family planning, 24-hour availability of family planning services, health worker support, and partner and friends support. The findings suggest that empowerment of health workers, training of volunteers, pharmacists and contraceptive drug providers, encouraging inter-spousal communication, and peer support, as well as an integrated approach to primary health care in order to target different populations to change women's attitudes on family planning, could increase family planning practice among Myanmar women.

  14. Receptor-interacting protein (RIP) kinase family

    Science.gov (United States)

    Zhang, Duanwu; Lin, Juan; Han, Jiahuai

    2010-01-01

    Receptor-interacting protein (RIP) kinases are a group of threonine/serine protein kinases with a relatively conserved kinase domain but distinct non-kinase regions. A number of different domain structures, such as death and caspase activation and recruitment domain (CARD) domains, were found in different RIP family members, and these domains should be keys in determining the specific function of each RIP kinase. It is known that RIP kinases participate in different biological processes, including those in innate immunity, but their downstream substrates are largely unknown. This review will give an overview of the structures and functions of RIP family members, and an update of recent progress in RIP kinase research. PMID:20383176

  15. Protein domain evolution is associated with reproductive diversification and adaptive radiation in the genus Eucalyptus.

    Science.gov (United States)

    Kersting, Anna R; Mizrachi, Eshchar; Bornberg-Bauer, Erich; Myburg, Alexander A

    2015-06-01

    Eucalyptus is a pivotal genus within the rosid order Myrtales with distinct geographic history and adaptations. Comparative analysis of protein domain evolution in the newly sequenced Eucalyptus grandis genome and other rosid lineages sheds light on the adaptive mechanisms integral to the success of this genus of woody perennials. We reconstructed the ancestral domain content to elucidate the gain, loss and expansion of protein domains and domain arrangements in Eucalyptus in the context of rosid phylogeny. We used functional gene ontology (GO) annotation of genes to investigate the possible biological and evolutionary consequences of protein domain expansion. We found that protein modulation within the angiosperms occurred primarily on the level of expansion of certain domains and arrangements. Using RNA-Seq data from E. grandis, we showed that domain expansions have contributed to tissue-specific expression of tandemly duplicated genes. Our results indicate that tandem duplication of genes, a key feature of the Eucalyptus genome, has played an important role in the expansion of domains, particularly in proteins related to the specialization of reproduction and biotic and abiotic interactions affecting root and floral biology, and that tissue-specific expression of proteins with expanded domains has facilitated subfunctionalization in domain families. © 2014 University of Pretoria New Phytologist © 2014 New Phytologist Trust.

  16. Reproductive Health, Family Planning and HIV/AIDS

    DEFF Research Database (Denmark)

    Richey, Lisa Ann

    2010-01-01

    of the Cairo consensus and process? How has the health of people around the world been affected by neo-liberal economic policies? What have these meant for women's rights, including reproductive rights? The book presents detailed case studies from various countries ranging from India and China, to Egypt......, Tanzania, Uganda and across Africa to Argentina, Peru and throughout Latin America, as well as overarching themed essays. From the politics of abortion and immigration to rising levels of fundamentalist violence and sex selective abortions, the volume explores a range of issues from several vantage points...

  17. Targeting functional motifs of a protein family

    Science.gov (United States)

    Bhadola, Pradeep; Deo, Nivedita

    2016-10-01

    The structural organization of a protein family is investigated by devising a method based on the random matrix theory (RMT), which uses the physiochemical properties of the amino acid with multiple sequence alignment. A graphical method to represent protein sequences using physiochemical properties is devised that gives a fast, easy, and informative way of comparing the evolutionary distances between protein sequences. A correlation matrix associated with each property is calculated, where the noise reduction and information filtering is done using RMT involving an ensemble of Wishart matrices. The analysis of the eigenvalue statistics of the correlation matrix for the β -lactamase family shows the universal features as observed in the Gaussian orthogonal ensemble (GOE). The property-based approach captures the short- as well as the long-range correlation (approximately following GOE) between the eigenvalues, whereas the previous approach (treating amino acids as characters) gives the usual short-range correlations, while the long-range correlations are the same as that of an uncorrelated series. The distribution of the eigenvector components for the eigenvalues outside the bulk (RMT bound) deviates significantly from RMT observations and contains important information about the system. The information content of each eigenvector of the correlation matrix is quantified by introducing an entropic estimate, which shows that for the β -lactamase family the smallest eigenvectors (low eigenmodes) are highly localized as well as informative. These small eigenvectors when processed gives clusters involving positions that have well-defined biological and structural importance matching with experiments. The approach is crucial for the recognition of structural motifs as shown in β -lactamase (and other families) and selectively identifies the important positions for targets to deactivate (activate) the enzymatic actions.

  18. Clustering evolving proteins into homologous families.

    Science.gov (United States)

    Chan, Cheong Xin; Mahbob, Maisarah; Ragan, Mark A

    2013-04-08

    Clustering sequences into groups of putative homologs (families) is a critical first step in many areas of comparative biology and bioinformatics. The performance of clustering approaches in delineating biologically meaningful families depends strongly on characteristics of the data, including content bias and degree of divergence. New, highly scalable methods have recently been introduced to cluster the very large datasets being generated by next-generation sequencing technologies. However, there has been little systematic investigation of how characteristics of the data impact the performance of these approaches. Using clusters from a manually curated dataset as reference, we examined the performance of a widely used graph-based Markov clustering algorithm (MCL) and a greedy heuristic approach (UCLUST) in delineating protein families coded by three sets of bacterial genomes of different G+C content. Both MCL and UCLUST generated clusters that are comparable to the reference sets at specific parameter settings, although UCLUST tends to under-cluster compositionally biased sequences (G+C content 33% and 66%). Using simulated data, we sought to assess the individual effects of sequence divergence, rate heterogeneity, and underlying G+C content. Performance decreased with increasing sequence divergence, decreasing among-site rate variation, and increasing G+C bias. Two MCL-based methods recovered the simulated families more accurately than did UCLUST. MCL using local alignment distances is more robust across the investigated range of sequence features than are greedy heuristics using distances based on global alignment. Our results demonstrate that sequence divergence, rate heterogeneity and content bias can individually and in combination affect the accuracy with which MCL and UCLUST can recover homologous protein families. For application to data that are more divergent, and exhibit higher among-site rate variation and/or content bias, MCL may often be the better

  19. Reproductive health care strategy -- a gender-sensitive approach to family welfare.

    Science.gov (United States)

    Anita

    1996-01-01

    The author advocates a reproductive health care strategy to revitalize India's family welfare program. A major shift in focus is needed in population policy and programs to incorporate a gender-sensitive approach. That shift should help to clear the path toward improved health status for women and female children. Consensus reached at the UN's 1994 International Conference on Population and Development supported a change in population and development policies, affording women's empowerment, gender equality, and equity greater priority for a meaningful policy of human-centered sustainable development. Reproductive health care, reproductive health in practice, the quality of care in reproductive health, gender equality as a human right, and empowering women are discussed.

  20. Socializing Messages in Blue-Collar Families: Communicative Pathways to Social Mobility and Reproduction

    Science.gov (United States)

    Lucas, Kristen

    2011-01-01

    This study explicitly links processes of anticipatory socialization to social mobility and reproduction. An examination of the socializing messages exchanged between blue-collar parents (n = 41) and their children (n = 25) demonstrate that family-based messages about work and career seldom occur in straightforward, unambiguous ways. Instead,…

  1. Reproductive health and family planning needs among HIV-infected women in Sub-Saharan Africa.

    Science.gov (United States)

    Sarnquist, Clea C; Rahangdale, Lisa; Maldonado, Yvonne

    2013-03-01

    Review key topics and recent literature regarding reproductive health and family planning needs for HIV-infected women in Sub-Saharan Africa. Electronic searches performed in PubMed, JSTOR, and Web of Science; identified articles reviewed for inclusion. Most HIV-infected women in Sub-Saharan Africa bear children, and access to antiretroviral therapy may increase childbearing desires and/or fertility, resulting in greater need for contraception. Most contraceptive options can be safely and effectively used by HIV-infected women. Unmet need for contraception is high in this population, with 66- 92% of women reporting not wanting another child (now or ever), but only 20-43% using contraception. During pregnancy and delivery, HIV-infected women need access to prevention of mother-to-child transmission (PMTCT) services, a skilled birth attendant, and quality post-partum care to prevent HIV infection in the infant and maximize maternal health. Providers may lack resources as well as appropriate training and support to provide such services to women with HIV. Innovations in biomedical and behavioral interventions may improve reproductive healthcare for HIV-infected women, but in Sub-Saharan Africa, models of integrating HIV and PMTCT services with family planning and reproductive health services will be important to improve reproductive outcomes. HIV-infected women in Sub-Saharan Africa have myriad needs related to reproductive health, including access to high-quality family planning information and options, high-quality pregnancy care, and trained providers. Integrated services that help prevent unintended pregnancy and optimize maternal and infant health before, during and after pregnancy will both maximize limited resources as well as provide improved reproductive outcomes.

  2. Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature.

    Science.gov (United States)

    Arn, P H; Younie, L; Russo, S; Zackowski, J L; Mankinen, C; Estabrooks, L

    1995-07-03

    We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocentric chromosomes. We recommend that prenatal counseling of individuals with satellited nonacrocentric chromosomes should be cautious.

  3. Vitellogenin RNAi halts ovarian growth and diverts reproductive proteins and lipids in young grasshoppers.

    Science.gov (United States)

    Tokar, Derek R; Veleta, Katherine A; Canzano, Joseph; Hahn, Daniel A; Hatle, John D

    2014-11-01

    Reduced reproduction extends lifespan of females in many animals. To test the effects of reproduction on storage of macronutrients, we block reproductive output in the lubber grasshopper by injecting RNAi against the precursor to egg-yolk protein, vitellogenin, in early adulthood. Controls were injected with either buffer or RNAi against the major storage protein in the hemolymph, hexamerin-90. Vitellogenin RNAi greatly reduced both levels of mRNA for vitellogenin and ovarian growth, in comparison to both controls. Fat body mass was increased upon vitellogenin RNAi, but concentrations of the three hexameric storage proteins from the hemolymph were not. Surprisingly, hemolymph vitellogenin levels were increased upon vitellogenin RNAi. Total reproductive protein (hemolymph vitellogenin plus ovarian vitellin) was unchanged by vitellogenin RNAi, as reproductive protein was diverted to the hemolymph. Similarly, the increased lipid storage upon vitellogenin RNAi was largely attributable to the reduction in lipid in the ovary, due to decreased ovarian growth. A BLAST search revealed that the 515 bp sequence of vitellogenin used for RNAi had three 11 bp regions identical to the vitellogenin receptor of the cockroach Leucophaea maderae. This suggests that our treatment, in addition to reducing levels of vitellogenin transcript, may have also blocked transport of vitellogenin from the hemolymph to the ovary. This would be consistent with halted ovarian growth simultaneous with high levels of vitellogenin in the hemolymph. Nonetheless, the accumulation of vitellogenin, instead of hexameric storage proteins, is inconsistent with a simple model of the trade-off between reproduction and storage. This was observed in young females; future studies will address whether investment of proteins may shift to the soma as individuals age. Overall, our results suggest that blockage of reproduction in young grasshoppers redirects lipids to storage and reproductive proteins to the hemolymph

  4. The debate on family planning and reproductive rights in Bolivia.

    Science.gov (United States)

    De La Fuente, M

    1991-01-01

    Using Bolivia as the example, the author critiques international organization and health professional emphasis upon providing family planning services as inadequate to meet the needs and interests of poor women. The feminist and women's movements should be expected to fight to regain the right of self-determination, and to demand integral health care for women. Contraception will constitute but a component of this holistic approach. Poverty, natalism, development, and population policies are all interrelated issues in Bolivia as the country proceeds through a period of democratization. Where total fertility averages 5 children/women as it does in Bolivia, women should certainly have the right to choose contraception in the control of fertility. Simple provision of such services and supplies will not, however, suffice to solve more deeply rooted social and economic problems faced by those women. The author further fears that some parts of the feminist movement have forgotten that population and related policies developed and imposed by other cultures have little interest in respecting the self-determination of women as individuals. Support for these policies by movement members only reinforces and helps to reproduce existing conditions of poverty and unequal rights.

  5. Association between protein feeding and reproductive efficiency in the dairy cow: specific emphasis on protein feeding in Finland

    Directory of Open Access Journals (Sweden)

    K.J. SHINGFIELD

    2008-12-01

    Full Text Available Associations between protein feeding and reproductive efficiency in the dairy cow are reviewed. Examination of published data indicated that reproductive responses assessed as days open, services per conception or conception rate following changes in protein feeding tend to be inconsistent. Discrepancies can arise due to between-study variations in experimental design, statistical analysis, sample population size, uterine health, cow age, parity, reproductive management or nutrient intake. Detri-mental effects on reproductive efficiency following periods of excessive protein feeding are often attributed to increases in tissue urea and ammonia oncentrations leading to impaired reproductive hysiology, modified endocrine function or exacerbated postpartum negative energy balance. Examination of data collected from Finnish dairy herds (n = 16 051 participating in the national milk recording scheme during 1993 indicated that milk production was maximised in herds fed diets containing 180 g crude protein/kg dry matter. In contrast, no consistent relationships were identified between increases in on-farm protein feeding necessary to secure higher milk production and herd reproductive efficiency assessed as calving interval, first service interval and number of inseminations per calving. Further examination of data derived from 5 437 herds within the National recording scheme indicated that on-farm reproductive efficiency was independent of large variations in the mean annual urea concentration of bulk tank milk. It is concluded that increases in the crude protein content of Finnish dairy cow rations from 150 to between 170 and 180 g/kg dry matter would allow improvements in milk production to be realised without leading to significant reductions in reproductive efficiency.;

  6. A family planning clinic partner violence intervention to reduce risk associated with reproductive coercion

    Science.gov (United States)

    Miller, Elizabeth; Decker, Michele R.; McCauley, Heather L.; Tancredi, Daniel J.; Levenson, Rebecca R.; Waldman, Jeffrey; Schoenwald, Phyllis; Silverman, Jay G.

    2010-01-01

    Background This study examined the efficacy of a family planning clinic-based intervention to address intimate partner violence (IPV) and reproductive coercion. Study Design Four free-standing urban family planning clinics in Northern California were randomized to intervention (trained family planning counselors) or standard-of-care. English-and Spanish-speaking females ages 16-29 years (N=906) completed audio computer-assisted surveys prior to a clinic visit and 12 to 24 weeks later (75% retention rate). Analyses included assessment of intervention effects on recent IPV, awareness of IPV services, and reproductive coercion. Results Among women reporting past 3-month IPV at baseline, there was a 71% reduction in the odds of pregnancy coercion among participants in intervention clinics compared to participants from the control clinics that provided standard of care. Women in the intervention arm were more likely to report ending a relationship because the relationship was unhealthy or unsafe regardless of IPV status (AOR 1.63, 95% CI 1.01 – 2.63). Conclusions Results of this pilot study suggest that this intervention may reduce risk for reproductive coercion from abusive male partners among family planning clients and support such women to leave unsafe relationships. PMID:21310291

  7. Milk protein concentration, estimated breeding value for fertility, and reproductive performance in lactating dairy cows.

    Science.gov (United States)

    Morton, John M; Auldist, Martin J; Douglas, Meaghan L; Macmillan, Keith L

    2017-07-01

    Milk protein concentration in dairy cows has been positively associated with a range of measures of reproductive performance, and genetic factors affecting both milk protein concentration and reproductive performance may contribute to the observed phenotypic associations. It was of interest to assess whether these beneficial phenotypic associations are accounted for or interact with the effects of estimated breeding values for fertility. The effects of a multitrait estimated breeding value for fertility [the Australian breeding value for daughter fertility (ABV fertility)] on reproductive performance were also of interest. Interactions of milk protein concentration and ABV fertility with the interval from calving date to the start of the herd's seasonally concentrated breeding period were also assessed. A retrospective single cohort study was conducted using data collected from 74 Australian seasonally and split calving dairy herds. Associations between milk protein concentration, ABV fertility, and reproductive performance in Holstein cows were assessed using random effects logistic regression. Between 52,438 and 61,939 lactations were used for analyses of 4 reproductive performance measures. Milk protein concentration was strongly and positively associated with reproductive performance in dairy cows, and this effect was not accounted for by the effects of ABV fertility. Increases in ABV fertility had important additional beneficial effects on the probability of pregnancy by wk 6 and 21 of the herd's breeding period. For cows calved before the start of the breeding period, the effects of increases in both milk protein concentration and ABV fertility were beneficial regardless of their interval from calving to the start of the breeding period. These findings demonstrate the potential for increasing reproductive performance through identifying the causes of the association between milk protein concentration and reproductive performance and then devising management

  8. The PANTHER database of protein families, subfamilies, functions and pathways

    OpenAIRE

    Mi, Huaiyu; Lazareva-Ulitsky, Betty; Loo, Rozina; Kejariwal, Anish; Vandergriff, Jody; Rabkin, Steven; Guo, Nan; Muruganujan, Anushya; Doremieux, Olivier; Campbell, Michael J.; Kitano, Hiroaki; Thomas, Paul D.

    2004-01-01

    PANTHER is a large collection of protein families that have been subdivided into functionally related subfamilies, using human expertise. These subfamilies model the divergence of specific functions within protein families, allowing more accurate association with function (ontology terms and pathways), as well as inference of amino acids important for functional specificity. Hidden Markov models (HMMs) are built for each family and subfamily for classifying additional protein sequences. The l...

  9. Reproductive Goals and Family Planning Attitudes in Pakistan: A Couple-level Analysis

    OpenAIRE

    Naushin Mahmood

    1998-01-01

    Based on the responses of 1260 matched couples in the 1990-91 Pakistan Demographic and Health Survey, this study examines how congruent wives’ and husbands’ attitudes towards fertility and family planning are, and to what extent the similarity or difference in attitudes affects their reproductive control behaviour. The results show that about 60 percent of the couples have given similar responses (agreeing either positively or negatively) to several fertility-related questions, whereas the re...

  10. Familial differences in the effects of mercury on reproduction in zebra finches

    International Nuclear Information System (INIS)

    Varian-Ramos, Claire W.; Swaddle, John P.; Cristol, Daniel A.

    2013-01-01

    Ecotoxicologists often implicitly assume that populations are homogenous entities in which all individuals have similar responses to a contaminant. However, genetically variable responses occur within populations. This variation can be visualized using dose–response curves of genetically related groups, similar to the way that evolutionary biologists construct reaction norms. We assessed the variation in reproductive success of full-sibling families of captive zebra finches (Taeniopygia guttata) experimentally exposed to methylmercury. We found significant variation among families in the effects of methylmercury on several reproductive parameters. This variation suggests that there may be strong responses to selection for resistant genotypes in contaminated areas. This has important implications for the evolution of tolerance as well as risk assessment and wildlife conservation efforts on sites with legacy contamination. -- Highlights: •Dose-response curves can visualize genetic differences in response to pollutants. •Families of zebra finch respond differently to mercury contamination. •Differences in reproductive success can lead to selection for resistant genotypes. •Resistance to contamination has implications for risk assessment and conservation. -- Genetic variation in response to contaminants can lead to adaptation on long-term contaminated sites, with implications for risk assessment and conservation of impacted populations

  11. Twins conceived using assisted reproduction: parent mental health, family relationships and child adjustment at middle childhood.

    Science.gov (United States)

    Anderson, Kayla N; Koh, Bibiana D; Connor, Jennifer J; Koerner, Ascan F; Damario, Mark; Rueter, Martha A

    2014-10-10

    Compared with singletons, what is the parent mental health, parent-child and couple relationship satisfaction, and child adjustment of 6- to 12-year-old assisted reproduction technology (ART) twins and their families? There are no differences between 6- and 12-year-old ART twin and singleton families in parent mental health or family relationships; however, twins had significantly fewer behavior and attention problems than singletons in middle childhood. When ART twins are younger than 5 years old, parents have more mental health difficulties and poorer parent-child relationship quality, and no differences have been found in ART twin and singletons' psychosocial adjustment. However, studies have only examined the implications of ART twin status in families with infant and toddler aged children. A cross-sectional study of 300 6-12-year-old ART children (n = 124 twins and n = 176 singletons) from 206 families at a reproductive endocrinology clinic in the USA. Patients from one clinic with a child born between 1998 and 2004 were invited to participate in an online survey (82% recruitment rate). Participants provided information on each 6- to 12-year-old ART child in the family, and responded to questions on parent mental health, family relationships and child adjustment. There were no differences in parent mental health or family relationships in families with 6- to 12-year-old ART twins versus singletons. However, twins (M = 2.40, SE = 0.35) had significantly fewer behavior problems than singletons (M = 3.47, SE = 0.36; F(1, 201) = 4.54, b = 1.08, P difficulties and lower parent-child relationship quality than singleton families. This study indicates the negative effects of twin status may have ameliorated by middle childhood, and twins may even have more optimum psychosocial adjustment than singletons in this developmental period. This research is based on a collaborative research effort supported by University of Minnesota Agriculture Experiment Station Project

  12. Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway.

    Science.gov (United States)

    Andrade, Luiza Freire de; Mourão, Marina de Moraes; Geraldo, Juliana Assis; Coelho, Fernanda Sales; Silva, Larissa Lopes; Neves, Renata Heisler; Volpini, Angela; Machado-Silva, José Roberto; Araujo, Neusa; Nacif-Pimenta, Rafael; Caffrey, Conor R; Oliveira, Guilherme

    2014-06-01

    Protein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear. We employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade. We conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development.

  13. HMM Logos for visualization of protein families

    Directory of Open Access Journals (Sweden)

    Schultz Jörg

    2004-01-01

    Full Text Available Abstract Background Profile Hidden Markov Models (pHMMs are a widely used tool for protein family research. Up to now, however, there exists no method to visualize all of their central aspects graphically in an intuitively understandable way. Results We present a visualization method that incorporates both emission and transition probabilities of the pHMM, thus extending sequence logos introduced by Schneider and Stephens. For each emitting state of the pHMM, we display a stack of letters. The stack height is determined by the deviation of the position's letter emission frequencies from the background frequencies. The stack width visualizes both the probability of reaching the state (the hitting probability and the expected number of letters the state emits during a pass through the model (the state's expected contribution. A web interface offering online creation of HMM Logos and the corresponding source code can be found at the Logos web server of the Max Planck Institute for Molecular Genetics http://logos.molgen.mpg.de. Conclusions We demonstrate that HMM Logos can be a useful tool for the biologist: We use them to highlight differences between two homologous subfamilies of GTPases, Rab and Ras, and we show that they are able to indicate structural elements of Ras.

  14. Evolution of the Yellow/Major Royal Jelly Protein family and the emergence of social behavior in honey bees.

    Science.gov (United States)

    Drapeau, Mark David; Albert, Stefan; Kucharski, Robert; Prusko, Carsten; Maleszka, Ryszard

    2006-11-01

    The genomic architecture underlying the evolution of insect social behavior is largely a mystery. Eusociality, defined by overlapping generations, parental brood care, and reproductive division of labor, has most commonly evolved in the Hymenopteran insects, including the honey bee Apis mellifera. In this species, the Major Royal Jelly Protein (MRJP) family is required for all major aspects of eusocial behavior. Here, using data obtained from the A. mellifera genome sequencing project, we demonstrate that the MRJP family is encoded by nine genes arranged in an approximately 60-kb tandem array. Furthermore, the MRJP protein family appears to have evolved from a single progenitor gene that encodes a member of the ancient Yellow protein family. Five genes encoding Yellow-family proteins flank the genomic region containing the genes encoding MRJPs. We describe the molecular evolution of these protein families. We then characterize developmental-stage-specific, sex-specific, and caste-specific expression patterns of the mrjp and yellow genes in the honey bee. We review empirical evidence concerning the functions of Yellow proteins in fruit flies and social ants, in order to shed light on the roles of both Yellow and MRJP proteins in A. mellifera. In total, the available evidence suggests that Yellows and MRJPs are multifunctional proteins with diverse, context-dependent physiological and developmental roles. However, many members of the Yellow/MRJP family act as facilitators of reproductive maturation. Finally, it appears that MRJP protein subfamily evolution from the Yellow protein family may have coincided with the evolution of honey bee eusociality.

  15. Prenatal famine, birthweight, reproductive performance and age at menopause: the Dutch hunger winter families study.

    Science.gov (United States)

    Yarde, F; Broekmans, F J M; van der Pal-de Bruin, K M; Schönbeck, Y; te Velde, E R; Stein, A D; Lumey, L H

    2013-12-01

    Is there an association between acute prenatal famine exposure or birthweight and subsequent reproductive performance and age at menopause? No association was found between intrauterine famine exposure and reproductive performance, but survival analysis showed that women exposed in utero were 24% more likely to experience menopause at any age. Associations between prenatal famine and subsequent reproductive performance have been examined previously with inconsistent results. Evidence for the effects of famine exposure on age at natural menopause is limited to one study of post-natal exposure. This cohort study included men and women born around the time of the Dutch famine of 1944-1945. The study participants (n = 1070) underwent standardized interviews on reproductive parameters at a mean age of 59 years. The participants were grouped as men and women with prenatal famine exposure (n = 407), their same-sex siblings (family controls, n = 319) or other men and women born before or after the famine period (time controls, n = 344). Associations of famine exposure with reproductive performance and menopause were analysed using logistic regression and survival analysis with competing risk, after controlling for family clustering. Gestational famine exposure was not associated with nulliparity, age at birth of first child, difficulties conceiving or pregnancy outcome (all P> 0.05) in men or women. At any given age, women were more likely to experience menopause after gestational exposure to famine (hazard ratio 1.24; 95% CI 1.03, 1.51). The association was not attenuated with an additional control for a woman's birthweight. In this study, there was no association between birthweight and age at menopause after adjustment for gestational famine exposure. Age at menopause was self-reported and assessed retrospectively. The study power to examine associations with specific gestational periods of famine exposure and reproductive function was limited. Our findings support

  16. Low-protein diet does not alter reproductive, biochemical, and hematological parameters in pregnant Wistar rats

    Directory of Open Access Journals (Sweden)

    M.A.V. Barros

    2018-05-01

    Full Text Available The aim of this study was to investigate the reproductive, biochemical, and hematological outcomes of pregnant rats exposed to protein restriction. Wistar rat dams were fed a control normal-protein (NP, 17% protein, n=8 or a low-protein (LP, 8% protein, n=14 diet from the 1st to the 20th day of pregnancy. On the 20th day, the clinical signs of toxicity were evaluated. The pregnant rats were then anesthetized and blood samples were collected for biochemical-hematological analyses, and laparotomy was performed to evaluate reproductive parameters. No sign of toxicity, or differences (P>0.05 in body weight gain and biochemical parameters (urea, creatinine, albumin, globulin, and total protein between NP and LP pregnant dams were observed. Similarly, hematological data, including red blood cell count, white blood cell count, hemoglobin, hematocrit, red blood cell distribution width (coefficient of variation, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, % lymphocytes, absolute lymphocyte count, platelet count, and mean platelet volume were similar (P>0.05 at the end of pregnancy. Reproductive parameters (the dam-offspring relationship, ovary mass, placenta mass, number of corpora lutea, implantation index, resorption index, and the pre- and post-implantation loss rates were also not different (P>0.05 between NP and LP pregnant dams. The present data showed that a protein-restricted diet during pregnancy did not alter reproductive, biochemical, and hematological parameters and seems not to have any toxic effect on pregnant Wistar rats.

  17. Protein catabolism in pregnant snakes (Epicrates cenchria maurus Boidae) compromises musculature and performance after reproduction.

    Science.gov (United States)

    Lourdais, O; Brischoux, F; DeNardo, D; Shine, R

    2004-07-01

    In many species the high energetic demands of reproduction induce a negative energy balance, and thus females must rely on tissue catabolism to complete the reproductive process. Previous works have shown that both fat and protein are energy resources during prolonged fasting in vertebrates. While many ecological studies on energy costs of reproduction have focused on variations in fat stores, the impact of protein investment on the female has not been thoroughly investigated. Notably, as there is no specialized storage form for proteins, intense catabolism is likely to entail structural (musculature) loss that may compromise maternal physical performance after reproduction. Measurements on captive rainbow boas ( Epicrates cenchria maurus) confirm that reproducing females undergo significant protein catabolism (as indicated by elevated plasma uric acid levels) and show considerable musculature loss during gestation (as detected by reduced width of the epaxial muscles). Protein mobilization entailed a significant functional loss that was illustrated by decrements in tests of strength and constriction after parturition. In wild situations, such effects are likely to decrease the snakes' ability to forage and apprehend prey. Hence, the time period needed to recover from reproduction can be extended not only because the female must compensate losses of both fat stores and functional muscle, but also because the ability to do so may be compromised. Performance alteration is likely to be of equal or greater importance than reduced energy stores in the physiological mediation of elevated post-reproduction mortality rates and infrequent reproductive bouts (e.g. biannual or triannual), two common ecological traits of female snakes.

  18. Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis.

    Science.gov (United States)

    Douma, Kirsten F L; Aaronson, Neil K; Vasen, Hans F A; Verhoef, Senno; Gundy, Chad M; Bleiker, Eveline M A

    2010-02-01

    Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study, questionnaires were sent to individuals from families at high risk for FAP assessing attitudes toward and experiences with childhood testing, PND and PGD, as well as several sociodemographic, clinical and psychosocial variables. Of the individuals from FAP families invited to participate in the study, 525 members participated (response rate=64%). Most parents who had children who were minors (n=93) (82%) were satisfied with the DNA testing procedure. One-third of all individuals wanted DNA testing for their children before age 12. Forty percent of FAP patients indicated that the disease influenced their desire to have children. Only 15% considered termination of pregnancy for FAP acceptable. Approximately 30% of individuals with a FAP diagnosis and their partners considered PND and PGD as acceptable for themselves. A positive attitude was associated with higher levels of guilt and a positive attitude toward termination of pregnancy. Importantly, of those with FAP at childbearing age, 84% had had no previous information at all about either PND or PGD. Future efforts should be aimed at educating FAP family members about reproductive options, allowing them to make an informed choice about family planning. Routine discussion of all reproductive options with a medical specialist should be encouraged.

  19. Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Arn, P.H.; Younie, L.; Russo, S. [Nemours Children`s Clinic, Jacksonville, FL (United States)] [and others

    1995-07-03

    We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocentric chromosomes. We recommend that prenatal counseling of individuals with satellited nonacrocentric chromosomes should be cautious. 23 refs., 2 figs., 1 tab.

  20. Reproductive justice & preventable deaths: State funding, family planning, abortion, and infant mortality, US 1980–2010

    Directory of Open Access Journals (Sweden)

    Nancy Krieger

    2016-12-01

    Full Text Available Introduction: Little current research examines associations between infant mortality and US states’ funding for family planning services and for abortion, despite growing efforts to restrict reproductive rights and services and documented associations between unintended pregnancy and infant mortality. Material and methods: We obtained publicly available data on state-only public funding for family planning and abortion services (years available: 1980, 1987, 1994, 2001, 2006, and 2010 and corresponding annual data on US county infant death rates. We modeled the funding as both fraction of state expenditures and per capita spending (per woman, age 15–44. State-level covariates comprised: Title X and Medicaid per capita funding, fertility rate, and percent of counties with no abortion services; county-level covariates were: median family income, and percent: black infants, adults without a high school education, urban, and female labor force participation. We used Possion log-linear models for: (1 repeat cross-sectional analyses, with random state and county effects; and (2 panel analysis, with fixed state effects. Results: Four findings were robust to analytic approach. First, since 2000, the rate ratio for infant death comparing states in the top funding quartile vs. no funding for abortion services ranged (in models including all covariates between 0.94 and 0.98 (95% confidence intervals excluding 1, except for the 2001 cross-sectional analysis, whose upper bound equaled 1, yielding an average 15% reduction in risk (range: 8–22%. Second, a similar risk reduction for state per capita funding for family planning services occurred in 1994. Third, the excess risk associated with lower county income increased over time, and fourth, remained persistently high for counties with a high percent of black infants. Conclusions: Insofar as reducing infant mortality is a government priority, our data underscore the need, despite heightened contention

  1. Knowledge and Attitude Regarding Reproductive Health Issues and Family Formation Among Adolescent Girls of Puducherry

    Directory of Open Access Journals (Sweden)

    Aarthi G

    2014-12-01

    Full Text Available Introduction: Adolescents are an important resource of any country. Adolescent girls need adequate information about the physical, psychological changes that take place during puberty, menstruation, pregnancy and child birth. This study aims to assess knowledge and attitude of adolescent girls of the age group 17-19 years on family formation and reproductive health issues in an urban area of Pondicherry. Methods: A cross-sectional study was carried out among adolescent girls (aged 17 to 19 years residing in an urban ward of Puducherry. Data collection was through house to house survey using a structured questionnaire. Results: 120 girls were approached and response rate was 100%. One fifth (21% and one third (31% of the study subjects knew the legal age for marriage for boys and girls respectively. 90% of girls were aware of small family norm, and perceived ideal family size as two. Awareness on contraception was poor (9%. Around 78% subjects considered fruits and vegetables as essential in the diet of pregnant women. Nearly 73% subjects were aware of Janani Suraksha Yojana and 89% were aware that immunization is essential for infants. Though 98% of the girls were aware that breast milk was the ideal food for babies, only 34.2% of the girls were aware of exclusive breast feeding. Conclusion: In this study, adolescent girls were aware regarding legal age at marriage, small family norm and dietary care during pregnancy. However, knowledge levels on contraceptive measures, exclusive breast feeding and supplementary feeding is less than satisfactory. These gaps in knowledge on reproductive health and family formation need to be addressed through innovative ways of health education in a non-threatening environment at the school and community levels.

  2. Reproductive goals and family planning attitudes in Pakistan: a couple-level analysis.

    Science.gov (United States)

    Mahmood, N

    1998-01-01

    This paper examined reproductive goals and family planning attitudes at the couple level in Pakistan. Data were based on the responses of the 1260 matched couples in the 1990-91 Pakistan Demographic and Health Survey. The questions integrated in the interview were on desired fertility, family size ideas, son preference, and family planning attitude. Findings of the analysis showed that about 60% of the couples have given similar responses (agreeing either positively or negatively) to several fertility-related questions, whereas the remaining 40% differ in their attitudes. This divergence may partly be of the environmental factors such as spouse rural background, lack of education, and minimal communication between spouses. This implies that a couple's joint approval, discussion of family planning, and husband's desire for no more children have the strongest effect on promoting contraceptive use. Thus, it is concluded that the role of couple agreement is important in promoting the use of family planning, and men should be made equal targets of such programs in Pakistan.

  3. Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins.

    LENUS (Irish Health Repository)

    Morgan, Claire C

    2010-01-01

    ABSTRACT: BACKGROUND: Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, the mammalia are a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety of mammalia. RESULTS: We show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality. CONCLUSION: Our in silico analyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across the mammalia and specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.

  4. HIPPI: highly accurate protein family classification with ensembles of HMMs

    Directory of Open Access Journals (Sweden)

    Nam-phuong Nguyen

    2016-11-01

    Full Text Available Abstract Background Given a new biological sequence, detecting membership in a known family is a basic step in many bioinformatics analyses, with applications to protein structure and function prediction and metagenomic taxon identification and abundance profiling, among others. Yet family identification of sequences that are distantly related to sequences in public databases or that are fragmentary remains one of the more difficult analytical problems in bioinformatics. Results We present a new technique for family identification called HIPPI (Hierarchical Profile Hidden Markov Models for Protein family Identification. HIPPI uses a novel technique to represent a multiple sequence alignment for a given protein family or superfamily by an ensemble of profile hidden Markov models computed using HMMER. An evaluation of HIPPI on the Pfam database shows that HIPPI has better overall precision and recall than blastp, HMMER, and pipelines based on HHsearch, and maintains good accuracy even for fragmentary query sequences and for protein families with low average pairwise sequence identity, both conditions where other methods degrade in accuracy. Conclusion HIPPI provides accurate protein family identification and is robust to difficult model conditions. Our results, combined with observations from previous studies, show that ensembles of profile Hidden Markov models can better represent multiple sequence alignments than a single profile Hidden Markov model, and thus can improve downstream analyses for various bioinformatic tasks. Further research is needed to determine the best practices for building the ensemble of profile Hidden Markov models. HIPPI is available on GitHub at https://github.com/smirarab/sepp .

  5. Metagenome and Metatranscriptome Analyses Using Protein Family Profiles.

    Directory of Open Access Journals (Sweden)

    Cuncong Zhong

    2016-07-01

    Full Text Available Analyses of metagenome data (MG and metatranscriptome data (MT are often challenged by a paucity of complete reference genome sequences and the uneven/low sequencing depth of the constituent organisms in the microbial community, which respectively limit the power of reference-based alignment and de novo sequence assembly. These limitations make accurate protein family classification and abundance estimation challenging, which in turn hamper downstream analyses such as abundance profiling of metabolic pathways, identification of differentially encoded/expressed genes, and de novo reconstruction of complete gene and protein sequences from the protein family of interest. The profile hidden Markov model (HMM framework enables the construction of very useful probabilistic models for protein families that allow for accurate modeling of position specific matches, insertions, and deletions. We present a novel homology detection algorithm that integrates banded Viterbi algorithm for profile HMM parsing with an iterative simultaneous alignment and assembly computational framework. The algorithm searches a given profile HMM of a protein family against a database of fragmentary MG/MT sequencing data and simultaneously assembles complete or near-complete gene and protein sequences of the protein family. The resulting program, HMM-GRASPx, demonstrates superior performance in aligning and assembling homologs when benchmarked on both simulated marine MG and real human saliva MG datasets. On real supragingival plaque and stool MG datasets that were generated from healthy individuals, HMM-GRASPx accurately estimates the abundances of the antimicrobial resistance (AMR gene families and enables accurate characterization of the resistome profiles of these microbial communities. For real human oral microbiome MT datasets, using the HMM-GRASPx estimated transcript abundances significantly improves detection of differentially expressed (DE genes. Finally, HMM

  6. Unmet need for family planning among married women of reproductive age group in urban Tamil Nadu

    Directory of Open Access Journals (Sweden)

    Malini M Bhattathiry

    2014-01-01

    Full Text Available Context: Unmet need for family planning (FP, which refers to the condition in which there is the desire to avoid or post-pone child bearing, without the use of any means of contraception, has been a core concept in the field of international population for more than three decades. Objectives: The very objective of this study is to determine the prevalence of "unmet need for FP" and its socio-demographic determinants among married reproductive age group women in Chidambaram. Materials and Methods: The study was a community-based cross-sectional study of married women of the reproductive age group, between 15 and 49 years. The sample size required was 700. The cluster sampling method was adopted. Unmarried, separated, divorced and widows were excluded. Results: The prevalence of unmet need for FP was 39%, with spacing as 12% and limiting as 27%. The major reason for unmet need for FP among the married group was 18%, for low perceived risk of pregnancy, 9%, feared the side effects of contraception 5% lacked information on contraceptives, 4% had husbands who opposed it and 3% gave medical reasons. Higher education, late marriage, more than the desired family size, poor knowledge of FP, poor informed choice in FP and poor male participation were found to be associated with high unmet need for FP. Conclusion: Unmet need for younger women was spacing of births, whereas for older women, it was a limitation of births. Efforts should be made to identify the issues in a case by case approach. Male participation in reproductive issues should be addressed.

  7. Orm family proteins mediate sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Breslow, David K; Collins, Sean R; Bodenmiller, Bernd

    2010-01-01

    a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression...... or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

  8. The SGS3 protein involved in PTGS finds a family

    Directory of Open Access Journals (Sweden)

    Bateman Alex

    2002-08-01

    Full Text Available Abstract Background Post transcriptional gene silencing (PTGS is a recently discovered phenomenon that is an area of intense research interest. Components of the PTGS machinery are being discovered by genetic and bioinformatics approaches, but the picture is not yet complete. Results The gene for the PTGS impaired Arabidopsis mutant sgs3 was recently cloned and was not found to have similarity to any other known protein. By a detailed analysis of the sequence of SGS3 we have defined three new protein domains: the XH domain, the XS domain and the zf-XS domain, that are shared with a large family of uncharacterised plant proteins. This work implicates these plant proteins in PTGS. Conclusion The enigmatic SGS3 protein has been found to contain two predicted domains in common with a family of plant proteins. The other members of this family have been predicted to be transcription factors, however this function seems unlikely based on this analysis. A bioinformatics approach has implicated a new family of plant proteins related to SGS3 as potential candidates for PTGS related functions.

  9. The contribution of reproductive factors and family history towards premenopausal breast cancer risk in Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Razif, S Mohd; Sulaiman, S; Hanie, S Soraya; Aina, E Nor; Rohaizak, M; Fuad, I; Nurismah, M I; Sharifah, N A

    2011-08-01

    Breast cancer is the most common cancer among Malaysian women. This study aimed to determine the reproductive for premenopausal breast cancer risk in Kuala Lumpur, Malaysia. A case-control study was conducted in 216 histopathologically confirmed cases of premenopausal breast cancer and 216 community-based controls that were matched by age within a 5-year period and ethnicity. The results of this study showed that premenopausal breast cancer risks were strongly related to parity, number of live births and family history of breast cancer. Premenopausal women with these known reproductive and family history risk factors should take extra measures to undergo appropriate screening method for early detection of breast cancer.

  10. Family Planning Practice Among Rural Reproductive-Age Married Women in Myanmar.

    Science.gov (United States)

    Jirapongsuwan, Ann; Latt, Kyaw Thu; Siri, Sukhontha; Munsawaengsub, Chokchai

    2016-05-01

    A cross-sectional study was undertaken to investigate family planning (FP) practices and associated factors among reproductive-age married women. Data were collected by interviewing the 300 married women living in a rural area of Myanmar. The questionnaire had reliability coefficients ranging from .8 to .9. Results indicated that 73.3% of women performed FP, and contraceptive injection was the most common method. Significant associations were found with age 21 to 35 years (adjusted odds ratio [adj OR] = 3.748, 95% CI = 2.179-6.445), adequacy of income (adj OR = 2.520, 95% CI = 1.477-4.290), good attitude toward FP (adj OR = 0.386, 95% CI = 0.228-0.656), good support from health care providers (adj OR = 0.129, 95% CI = 0.054-0.313), good support from family (adj OR = 0.304, 95% CI = 0.163-0.565), good support from friends (adj OR = 0.344, 95% CI = 0.193-0.613), and FP practice. It is recommended that designing FP programs with peers and family involvement could increase the practice of FP among rural Myanmar women. © 2016 APJPH.

  11. Secretory proteins in the reproductive tract of the snapping turtle, Chelhydra serpentina.

    Science.gov (United States)

    Mahmoud, I Y; Paulson, J R; Dudley, M; Patzlaff, J S; Al-Kindi, A Y A

    2004-12-01

    SDS-polyacrylamide gel electrophoresis was used to separate the secretory proteins produced by the epithelial and endometrial glands of the uterine tube and uterus in the snapping turtle Chelydra serpentina. The proteins were analyzed throughout the phases of the reproductive cycle from May to August, including preovulatory, ovulatory, postovulatory or luteal, and vitellogenic phases. The pattern of secretory proteins is quite uniform along the length of the uterine tube, and the same is true of the uterus, but the patterns for uterine tube and uterus are clearly different. We identify 13 major proteins in C. serpentina egg albumen. Bands co-migrating with 11 of these are found in the uterine tube, but at most 4 are found in the uterus, suggesting that the majority of the albumen proteins are most likely secreted in the uterine tube, not in the uterus. Although some of the egg albumen proteins are present in the uterine tube only at the time of ovulation, most of the bands corresponding to albumen proteins are present throughout the breeding season even though the snapping turtle is a monoclutch species. These results suggest that the glandular secretory phase in the uterine tube is active and quite homogeneous in function regardless of location or phase of the reproductive cycle.

  12. Applicable value of real time interventional ultrasound guidance in family planning reproduction operation

    International Nuclear Information System (INIS)

    Wu Guoping; Zou Dongfang; Sun Jian; Dong Weihua

    2007-01-01

    Objective: To determine the clinical value of real time interventional ultrasound guidance in family planning reproduction operation. Methods: Under the guidance of ultrasound monitoring, 522 cases with high risk and difficult uterine operation were undertaken in our department. Results: The abdominal endoscopic contraceptive uterine operation under real time ultrasound monitoring was carried out for 522 cases in 4 years, with successful rates for high risk pregnancy as 287/289 cases, high risk troublesome withdrawal of contraceptive ring as 129/130 cases and puzzling uterine operation as 103/103 cases. The total successful rate reached 99.42%, without uterine rupture and other complications. Conclusion: The former complex, blind and difficult uterine operations turn to be simple, safe and reliable under the guidance of real time ultrasound. (authors)

  13. The Relationship between Domestic Violence and Reproductive Health and Family Planning Services in Bolivia, 2003

    Directory of Open Access Journals (Sweden)

    Pinto Aguirre, Guido

    2010-01-01

    Full Text Available The main purpose of this paper is to understand the relationship existing between Gender-Based Violence (GVB and the Use of Reproductive Health and Family Planning services. To carry out this task, we use multivariate logit regression models to explore the direction and strength of the relationship, using a population-based sample for Bolivian women during 2003-2004. Results show a strong, negative and significant relationship between GVB and use of RH/FP services at the population-level, after adjusting for respondent’s and partner’s individual and household characteristics. That is, GBV is strongly and significantly associated with the use of RH/FP services, in a way that women experiencing domestic violence are less likely to use those services.

  14. Identification and characterization of cytosolic Hansenula polymorpha proteins belonging to the Hsp70 protein family

    NARCIS (Netherlands)

    Titorenko, Vladimir I.; Evers, Melchior E.; Diesel, Andre; Samyn, Bart; Beeumen, Josef van; Roggenkamp, Rainer; Kiel, Jan A.K.W.; Klei, Ida J. van der; Veenhuis, Marten

    We have isolated two members of the Hsp70 protein family from the yeast Hansenula polymorpha using affinity chromatography. Both proteins were located in the cytoplasm. One of these, designated Hsp72, was inducible in nature (e.g. by heat shock). The second protein (designated Hsc74) was

  15. Disorder and function: a review of the dehydrin protein family

    Directory of Open Access Journals (Sweden)

    Steffen P Graether

    2014-10-01

    Full Text Available Dehydration proteins (dehydrins are group 2 members of the late embryogenesis abundant (LEA protein family. The protein architecture of dehydrins can be described by the presence of three types of conserved sequence motifs that have been named the K-, Y- and S-segments. By definition, a dehydrin must contain at least one copy of the lysine-rich K-segment. Abiotic stresses such as drought, cold, and salinity cause the upregulation of dehydrin mRNA and protein levels. Despite the large body of genetic and protein evidence of the importance of these proteins in stress response, the in vivo protective mechanism is not fully known. In vitro experimental evidence from biochemical assays and localization experiments suggest multiple roles for dehydrins, including membrane protection, cryoprotection of enzymes, and protection from reactive oxygen species. Membrane binding by dehydrins is likely to be as a peripheral membrane protein, since the protein sequences are highly hydrophilic and contain many charged amino acids. Because of this, dehydrins in solution are intrinsically disordered proteins, that is, they have no well-defined secondary or tertiary structure. Despite their disorder, dehydrins have been shown to gain structure when bound to ligands such as membranes, and to possibly change their oligomeric state when bound to ions. We review what is currently known about dehydrin sequences and their structures, and examine the various ligands that have been shown to bind to this family of proteins.

  16. The mate recognition protein gene mediates reproductive isolation and speciation in the Brachionus plicatilis cryptic species complex.

    Science.gov (United States)

    Gribble, Kristin E; Mark Welch, David B

    2012-08-01

    Chemically mediated prezygotic barriers to reproduction likely play an important role in speciation. In facultatively sexual monogonont rotifers from the Brachionus plicatilis cryptic species complex, mate recognition of females by males is mediated by the Mate Recognition Protein (MRP), a globular glycoprotein on the surface of females, encoded by the mmr-b gene family. In this study, we sequenced mmr-b copies from 27 isolates representing 11 phylotypes of the B. plicatilis species complex, examined the mode of evolution and selection of mmr-b, and determined the relationship between mmr-b genetic distance and mate recognition among isolates. Isolates of the B. plicatilis species complex have 1-4 copies of mmr-b, each composed of 2-9 nearly identical tandem repeats. The repeats within a gene copy are generally more similar than are gene copies among phylotypes, suggesting concerted evolution. Compared to housekeeping genes from the same isolates, mmr-b has accumulated only half as many synonymous differences but twice as many non-synonymous differences. Most of the amino acid differences between repeats appear to occur on the outer face of the protein, and these often result in changes in predicted patterns of phosphorylation. However, we found no evidence of positive selection driving these differences. Isolates with the most divergent copies were unable to mate with other isolates and rarely self-crossed. Overall the degree of mate recognition was significantly correlated with the genetic distance of mmr-b. Discrimination of compatible mates in the B. plicatilis species complex is determined by proteins encoded by closely related copies of a single gene, mmr-b. While concerted evolution of the tandem repeats in mmr-b may function to maintain identity, it can also lead to the rapid spread of a mutation through all copies in the genome and thus to reproductive isolation. The mmr-b gene is evolving rapidly, and novel alleles may be maintained and increase in

  17. The mate recognition protein gene mediates reproductive isolation and speciation in the Brachionus plicatilis cryptic species complex

    Directory of Open Access Journals (Sweden)

    Gribble Kristin E

    2012-08-01

    Full Text Available Abstract Background Chemically mediated prezygotic barriers to reproduction likely play an important role in speciation. In facultatively sexual monogonont rotifers from the Brachionus plicatilis cryptic species complex, mate recognition of females by males is mediated by the Mate Recognition Protein (MRP, a globular glycoprotein on the surface of females, encoded by the mmr-b gene family. In this study, we sequenced mmr-b copies from 27 isolates representing 11 phylotypes of the B. plicatilis species complex, examined the mode of evolution and selection of mmr-b, and determined the relationship between mmr-b genetic distance and mate recognition among isolates. Results Isolates of the B. plicatilis species complex have 1–4 copies of mmr-b, each composed of 2–9 nearly identical tandem repeats. The repeats within a gene copy are generally more similar than are gene copies among phylotypes, suggesting concerted evolution. Compared to housekeeping genes from the same isolates, mmr-b has accumulated only half as many synonymous differences but twice as many non-synonymous differences. Most of the amino acid differences between repeats appear to occur on the outer face of the protein, and these often result in changes in predicted patterns of phosphorylation. However, we found no evidence of positive selection driving these differences. Isolates with the most divergent copies were unable to mate with other isolates and rarely self-crossed. Overall the degree of mate recognition was significantly correlated with the genetic distance of mmr-b. Conclusions Discrimination of compatible mates in the B. plicatilis species complex is determined by proteins encoded by closely related copies of a single gene, mmr-b. While concerted evolution of the tandem repeats in mmr-b may function to maintain identity, it can also lead to the rapid spread of a mutation through all copies in the genome and thus to reproductive isolation. The mmr-b gene is evolving

  18. Practical analysis of specificity-determining residues in protein families.

    Science.gov (United States)

    Chagoyen, Mónica; García-Martín, Juan A; Pazos, Florencio

    2016-03-01

    Determining the residues that are important for the molecular activity of a protein is a topic of broad interest in biomedicine and biotechnology. This knowledge can help understanding the protein's molecular mechanism as well as to fine-tune its natural function eventually with biotechnological or therapeutic implications. Some of the protein residues are essential for the function common to all members of a family of proteins, while others explain the particular specificities of certain subfamilies (like binding on different substrates or cofactors and distinct binding affinities). Owing to the difficulty in experimentally determining them, a number of computational methods were developed to detect these functional residues, generally known as 'specificity-determining positions' (or SDPs), from a collection of homologous protein sequences. These methods are mature enough for being routinely used by molecular biologists in directing experiments aimed at getting insight into the functional specificity of a family of proteins and eventually modifying it. In this review, we summarize some of the recent discoveries achieved through SDP computational identification in a number of relevant protein families, as well as the main approaches and software tools available to perform this type of analysis. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  19. Localization of porcine seminal plasma (PSP) proteins in the boar reproductive tract and spermatozoa

    Czech Academy of Sciences Publication Activity Database

    Maňásková, Pavla; Jonáková, Věra

    2008-01-01

    Roč. 78, č. 1 (2008), s. 40-48 ISSN 0165-0378 R&D Projects: GA ČR GA303/06/0895; GA MŠk 1M06011 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : porcine seminal plasma proteins * boar reproductive tract * spermatozoa Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.778, year: 2008

  20. Factors affecting unmet need for family planning in married women of reproductive age group in urban slums of Lucknow

    Directory of Open Access Journals (Sweden)

    Anjali Pal

    2014-03-01

    Full Text Available Background: Unmet need for family planning signifies the gap between the reproductive intentions of couples and their actual contraceptive behaviour. The National Family Health Surveys carried out in India in 1992-93, 1998-99 and 2004-2005 have revealed that for a sizable proportion of the population in the reproductive age group, the need for contraceptive services are not met with despite the existence of a National Policy on family planning since 1983. This study was carried out to assess the extent of unmet need for family planning among married women of reproductive age group in urban slums of Lucknow and identify the various factors affecting it. Study design: Cross sectional Setting: four urban slums of Lucknow Participants: 414 married women in the age group of 15- 44 years Study variables: age, education, occupation, religion, parity Statistical analysis: chi- square test, logistic regression analysis, fisher’s exact test Results: the extent of unmet need among married women of reproductive age group was 53.1%. The unmet need was found to be significantly associated with age, number of living sons, discussion of family planning with husband, perception of husband’s view on family planning and husbands’ behaviour towards use of family planning method. Logistic regression analysis of unmet need showed that the lower age of the woman, lesser number of living sons and husband’s discouragement towards the use of FP method were correlated with the unmet need for Family Planning.

  1. DAZ Family Proteins, Key Players for Germ Cell Development

    Science.gov (United States)

    Fu, Xia-Fei; Cheng, Shun-Feng; Wang, Lin-Qing; Yin, Shen; De Felici, Massimo; Shen, Wei

    2015-01-01

    DAZ family proteins are found almost exclusively in germ cells in distant animal species. Deletion or mutations of their encoding genes usually severely impair either oogenesis or spermatogenesis or both. The family includes Boule (or Boll), Dazl (or Dazla) and DAZ genes. Boule and Dazl are situated on autosomes while DAZ, exclusive of higher primates, is located on the Y chromosome. Deletion of DAZ gene is the most common causes of infertility in humans. These genes, encoding for RNA binding proteins, contain a highly conserved RNA recognition motif and at least one DAZ repeat encoding for a 24 amino acids sequence able to bind other mRNA binding proteins. Basically, Daz family proteins function as adaptors for target mRNA transport and activators of their translation. In some invertebrate species, BOULE protein play a pivotal role in germline specification and a conserved regulatory role in meiosis. Depending on the species, DAZL is expressed in primordial germ cells (PGCs) and/or pre-meiotic and meiotic germ cells of both sexes. Daz is found in fetal gonocytes, spermatogonia and spermatocytes of adult testes. Here we discuss DAZ family genes in a phylogenic perspective, focusing on the common and distinct features of these genes, and their pivotal roles during gametogenesis evolved during evolution. PMID:26327816

  2. [Roles of G protein-coupled estrogen receptor in the male reproductive system].

    Science.gov (United States)

    Chen, Kai-hong; Zhang, Xian; Jiang, Xue-wu

    2016-02-01

    The G protein-coupled estrogen receptor (GPER), also known as G protein-coupled receptor 30 (GPR30), was identified in the recent years as a functional membrane receptor different from the classical nuclear estrogen receptors. This receptor is widely expressed in the cortex, cerebellum, hippocampus, heart, lung, liver, skeletal muscle, and the urogenital system. It is responsible for the mediation of nongenomic effects associated with estrogen and its derivatives, participating in the physiological activities of the body. The present study reviews the molecular structure, subcellular localization, signaling pathways, distribution, and function of GPER in the male reproductive system.

  3. Reproductive biology, family conflict, and size of offspring in marine invertebrates.

    Science.gov (United States)

    Kamel, Stephanie J; Oyarzun, Fernanda X; Grosberg, Richard K

    2010-10-01

    All organisms face two fundamental trade-offs in the allocation of energetic resources: one between many small versus a few large offspring, and the second between present and future reproduction. Nowhere are these trade-offs more apparent than in the vast range of variation in the sizes of eggs and offspring exhibited among species of marine invertebrates. It has become increasingly clear that, in many taxa of marine organisms, there is also substantial intraspecific variation in the size of eggs and hatchings. This variation has largely been attributed to adaptive maternal effects. In theory, however, the inevitable conflicts of interest that arise in families of sexually reproducing organisms over the optimal distribution of parental resources among siblings could also account for much of this variation in egg and offspring size. Here, we explore the potential impacts of family conflict on offspring traits by comparing the life histories of two exemplar species of marine organisms, the polychaete Boccardia proboscidea and the gastropod Solenosteira macrospira, emphasizing how differences in modes of fertilization and parental care might influence the phenotype and, consequently, the fitness of offspring. © The Author 2010. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.

  4. Paralogous SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes differentially regulate leaf initiation and reproductive phase change in petunia.

    Science.gov (United States)

    Preston, Jill C; Jorgensen, Stacy A; Orozco, Rebecca; Hileman, Lena C

    2016-02-01

    Duplicated petunia clade-VI SPL genes differentially promote the timing of inflorescence and flower development, and leaf initiation rate. The timing of plant reproduction relative to favorable environmental conditions is a critical component of plant fitness, and is often associated with variation in plant architecture and habit. Recent studies have shown that overexpression of the microRNA miR156 in distantly related annual species results in plants with perennial characteristics, including late flowering, weak apical dominance, and abundant leaf production. These phenotypes are largely mediated through the negative regulation of a subset of genes belonging to the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family of transcription factors. In order to determine how and to what extent paralogous SPL genes have partitioned their roles in plant growth and development, we functionally characterized petunia clade-VI SPL genes under different environmental conditions. Our results demonstrate that PhSBP1and PhSBP2 differentially promote discrete stages of the reproductive transition, and that PhSBP1, and possibly PhCNR, accelerates leaf initiation rate. In contrast to the closest homologs in annual Arabidopsis thaliana and Mimulus guttatus, PhSBP1 and PhSBP2 transcription is not mediated by the gibberellic acid pathway, but is positively correlated with photoperiod and developmental age. The developmental functions of clade-VI SPL genes have, thus, evolved following both gene duplication and speciation within the core eudicots, likely through differential regulation and incomplete sub-functionalization.

  5. Effects of dietary protein level on nutrients digestibility and reproductive performance of female mink (Neovison vison during gestation

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    Qingkui Jiang

    2015-06-01

    Full Text Available The objective of this study was to determine whether nutrient digestibility and reproductive performance of pregnant mink (Neovison vison were affected by different dietary protein levels. One hundred and twenty female mink were randomly assigned to four groups, receiving diets of fresh material with different protein levels. The dietary protein levels, expressed as percentage of dry matter (DM, were 32, 36, 40 and 44% respectively. These values corresponded to average 320, 360, 400 and 440 g protein/kg DM, respectively. Results were as follows. All of crude protein digestibility, nitrogen (N intake, N retention increased along with dietary protein level increasing. Low protein level (32% significantly reduced the above indicators (P < 0.05. DM digestibility and ether extract digestibility were not affected by dietary protein level. Results of mated females, barren females, kids per litter, live born kids per mated female, birth survival rate, and birth weight showed that mink achieved optimal reproductive performance when dietary protein level was 36%. In conclusion, dietary protein was anticipated to significantly influence some nutrients' utilization. Adopting the appropriate dietary protein level allow better reproduction performance. The most preferable reproductive performance was achieved when diet contained 275.5 g digestible protein per kg DM for female mink in gestation.

  6. The DExH/D protein family database.

    Science.gov (United States)

    Jankowsky, E; Jankowsky, A

    2000-01-01

    DExH/D proteins are essential for all aspects of cellular RNA metabolism and processing, in the replication of many viruses and in DNA replication. DExH/D proteins are subject to current biological, biochemical and biophysical research which provides a continuous wealth of data. The DExH/D protein family database compiles this information and makes it available over the WWW (http://www.columbia.edu/ ej67/dbhome.htm ). The database can be fully searched by text based queries, facilitating fast access to specific information about this important class of enzymes.

  7. Redundancy and divergence in the amyloid precursor protein family.

    Science.gov (United States)

    Shariati, S Ali M; De Strooper, Bart

    2013-06-27

    Gene duplication provides genetic material required for functional diversification. An interesting example is the amyloid precursor protein (APP) protein family. The APP gene family has experienced both expansion and contraction during evolution. The three mammalian members have been studied quite extensively in combined knock out models. The underlying assumption is that APP, amyloid precursor like protein 1 and 2 (APLP1, APLP2) are functionally redundant. This assumption is primarily supported by the similarities in biochemical processing of APP and APLPs and on the fact that the different APP genes appear to genetically interact at the level of the phenotype in combined knockout mice. However, unique features in each member of the APP family possibly contribute to specification of their function. In the current review, we discuss the evolution and the biology of the APP protein family with special attention to the distinct properties of each homologue. We propose that the functions of APP, APLP1 and APLP2 have diverged after duplication to contribute distinctly to different neuronal events. Our analysis reveals that APLP2 is significantly diverged from APP and APLP1. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Mitochondrial Band-7 family proteins: scaffolds for respiratory chain assembly?

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    Bernadette eGehl

    2014-04-01

    Full Text Available The band-7 protein family comprises a diverse set of membrane-bound proteins characterised by the presence of a conserved domain. The exact function of this band-7 domain remains elusive, but examples from animal and bacterial stomatin-type proteins demonstrate binding to lipids and the ability to assemble into membrane-bound oligomers that form putative scaffolds. Some members, such as prohibitins and human stomatin-like protein 2 (HsSLP2, localise to the mitochondrial inner membrane where they function in cristae formation and hyperfusion. In Arabidopsis, the band-7 protein family has diversified and includes plant-specific members. Mitochondrial-localised members include prohibitins (AtPHBs and two stomatin-like proteins (AtSLP1 and -2. Studies into PHB function in plants have demonstrated an involvement in root meristem proliferation and putative scaffold formation for mAAA proteases, but it remains unknown how these roles are achieved at the molecular level. In this minireview we summarise the current status of band-7 protein functions in Arabidopsis, and speculate how the mitochondrial members might recruit specific lipids to form microdomains that could shape the organisation and functioning of the respiratory chain.

  9. A novel family of small proteins that affect plant development

    Energy Technology Data Exchange (ETDEWEB)

    John Charles Walker

    2011-04-29

    The DVL genes represent a new group of plant proteins that influence plant growth and development. Overexpression of DVL1, and other members of the DVL family, causes striking phenotypic changes. The DVL proteins share sequence homology in their C-terminal half. Point mutations in the C-terminal domain show it is necessary and deletion studies demonstrate the C-terminal domain is sufficient to confer the overexpression phenotypes. The phenotypes observed, and the conservation of the protein sequence in the plant kingdom, does suggest the DVL proteins have a role in modulating plant growth and development. Our working hypothesis is the DVL proteins function as regulators of cellular signaling pathways that control growth and development.

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

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    Aronson Nathan N

    2007-06-01

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

  11. The small envelope protein of porcine reproductive and respiratory syndrome virus possesses ion channel protein-like properties

    International Nuclear Information System (INIS)

    Lee, Changhee; Yoo, Dongwan

    2006-01-01

    The small envelope (E) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is a hydrophobic 73 amino acid protein encoded in the internal open reading frame (ORF) of the bicistronic mRNA2. As a first step towards understanding the biological role of E protein during PRRSV replication, E gene expression was blocked in a full-length infectious clone by mutating the ATG translational initiation to GTG, such that the full-length mutant genomic clone was unable to synthesize the E protein. DNA transfection of PRRSV-susceptible cells with the E gene knocked-out genomic clone showed the absence of virus infectivity. P129-ΔE-transfected cells however produced virion particles in the culture supernatant, and these particles contained viral genomic RNA, demonstrating that the E protein is essential for PRRSV infection but dispensable for virion assembly. Electron microscopy suggests that the P129-ΔE virions assembled in the absence of E had a similar appearance to the wild-type particles. Strand-specific RT-PCR demonstrated that the E protein-negative, non-infectious P129-ΔE virus particles were able to enter cells but further steps of replication were interrupted. The entry of PRRSV has been suggested to be via receptor-mediated endocytosis, and lysomotropic basic compounds and known ion-channel blocking agents both inhibited PRRSV replication effectively during the uncoating process. The expression of E protein in Escherichia coli-mediated cell growth arrests and increased the membrane permeability. Cross-linking experiments in cells infected with PRRSV or transfected with E gene showed that the E protein was able to form homo-oligomers. Taken together, our data suggest that the PRRSV E protein is likely an ion-channel protein embedded in the viral envelope and facilitates uncoating of virus and release of the genome in the cytoplasm

  12. In silico modeling of the yeast protein and protein family interaction network

    Science.gov (United States)

    Goh, K.-I.; Kahng, B.; Kim, D.

    2004-03-01

    Understanding of how protein interaction networks of living organisms have evolved or are organized can be the first stepping stone in unveiling how life works on a fundamental ground. Here we introduce an in silico ``coevolutionary'' model for the protein interaction network and the protein family network. The essential ingredient of the model includes the protein family identity and its robustness under evolution, as well as the three previously proposed: gene duplication, divergence, and mutation. This model produces a prototypical feature of complex networks in a wide range of parameter space, following the generalized Pareto distribution in connectivity. Moreover, we investigate other structural properties of our model in detail with some specific values of parameters relevant to the yeast Saccharomyces cerevisiae, showing excellent agreement with the empirical data. Our model indicates that the physical constraints encoded via the domain structure of proteins play a crucial role in protein interactions.

  13. A novel family of plant nuclear envelope-associated proteins.

    Science.gov (United States)

    Pawar, Vidya; Poulet, Axel; Détourné, Gwénaëlle; Tatout, Christophe; Vanrobays, Emmanuel; Evans, David E; Graumann, Katja

    2016-10-01

    This paper describes the characterisation of a new family of higher plant nuclear envelope-associated proteins (NEAPs) that interact with other proteins of the nuclear envelope. In the model plant Arabidopsis thaliana, the family consists of three genes expressed ubiquitously (AtNEAP1-3) and a pseudogene (AtNEAP4). NEAPs consist of extensive coiled-coil domains, followed by a nuclear localisation signal and a C-terminal predicted transmembrane domain. Domain deletion mutants confirm the presence of a functional nuclear localisation signal and transmembrane domain. AtNEAP proteins localise to the nuclear periphery as part of stable protein complexes, are able to form homo- and heteromers, and interact with the SUN domain proteins AtSUN1 and AtSUN2, involved in the linker of nucleoskeleton and cytoskeleton (LINC) complex. An A. thaliana cDNA library screen identified a putative transcription factor called AtbZIP18 as a novel interactor of AtNEAP1, which suggest a connection between NEAP and chromatin. An Atneap1 Atneap3 double-knockout mutant showed reduced root growth, and altered nuclear morphology and chromatin structure. Thus AtNEAPs are suggested as inner nuclear membrane-anchored coiled-coil proteins with roles in maintaining nuclear morphology and chromatin structure. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Evolutionary hierarchy of vertebrate-like heterotrimeric G protein families.

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    Krishnan, Arunkumar; Mustafa, Arshi; Almén, Markus Sällman; Fredriksson, Robert; Williams, Michael J; Schiöth, Helgi B

    2015-10-01

    Heterotrimeric G proteins perform a crucial role as molecular switches controlling various cellular responses mediated by G protein-coupled receptor (GPCR) signaling pathway. Recent data have shown that the vertebrate-like G protein families are found across metazoans and their closest unicellular relatives. However, an overall evolutionary hierarchy of vertebrate-like G proteins, including gene family annotations and in particular mapping individual gene gain/loss events across diverse holozoan lineages is still incomplete. Here, with more expanded invertebrate taxon sampling, we have reconstructed phylogenetic trees for each of the G protein classes/families and provide a robust classification and hierarchy of vertebrate-like heterotrimeric G proteins. Our results further extend the evidence that the common ancestor (CA) of holozoans had at least five ancestral Gα genes corresponding to all major vertebrate Gα classes and contain a total of eight genes including two Gβ and one Gγ. Our results also indicate that the GNAI/O-like gene likely duplicated in the last CA of metazoans to give rise to GNAI- and GNAO-like genes, which are conserved across invertebrates. Moreover, homologs of GNB1-4 paralogon- and GNB5 family-like genes are found in most metazoans and that the unicellular holozoans encode two ancestral Gβ genes. Similarly, most bilaterian invertebrates encode two Gγ genes which include a representative of the GNG gene cluster and a putative homolog of GNG13. Interestingly, our results also revealed key evolutionary events such as the Drosophila melanogaster eye specific Gβ subunit that is found conserved in most arthropods and several previously unidentified species specific expansions within Gαi/o, Gαs, Gαq, Gα12/13 classes and the GNB1-4 paralogon. Also, we provide an overall proposed evolutionary scenario on the expansions of all G protein families in vertebrate tetraploidizations. Our robust classification/hierarchy is essential to further

  15. Developmental expression of Drosophila Wiskott-Aldrich Syndrome family proteins

    Science.gov (United States)

    Rodriguez-Mesa, Evelyn; Abreu-Blanco, Maria Teresa; Rosales-Nieves, Alicia E.; Parkhurst, Susan M.

    2012-01-01

    Background Wiskott-Aldrich Syndrome (WASP) family proteins participate in many cellular processes involving rearrangements of the actin cytoskeleton. To the date, four WASP subfamily members have been described in Drosophila: Wash, WASp, SCAR, and Whamy. Wash, WASp, and SCAR are essential during early Drosophila development where they function in orchestrating cytoplasmic events including membrane-cytoskeleton interactions. A mutant for Whamy has not yet been reported. Results We generated monoclonal antibodies that are specific to Drosophila Wash, WASp, SCAR, and Whamy, and use these to describe their spatial and temporal localization patterns. Consistent with the importance of WASP family proteins in flies, we find that Wash, WASp, SCAR, and Whamy are dynamically expressed throughout oogenesis and embryogenesis. For example, we find that Wash accumulates at the oocyte cortex. WASp is highly expressed in the PNS, while SCAR is the most abundantly expressed in the CNS. Whamy exhibits an asymmetric subcellular localization that overlaps with mitochondria and is highly expressed in muscle. Conclusion All four WASP family members show specific expression patterns, some of which reflect their previously known roles and others revealing new potential functions. The monoclonal antibodies developed offer valuable new tools to investigate how WASP family proteins regulate actin cytoskeleton dynamics. PMID:22275148

  16. European accomplishments in regulation of the family status of the child conceived by artificial reproduction technologies

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    Kovaček-Stanić Gordana

    2015-01-01

    Full Text Available In this paper, the author analyzes family status of the child conceived by artificial reproduction technologies using the following treatments: homologues artificial insemination, heterologus artificial insemination (artificial insemination by donor, ovum donation, embryo donation and surrogate motherhood. One specific situation of homologues artificial insemination is posthumous insemination, insemination after the death of the husband/partner. This procedure is allowed in, for instance, United Kingdom, but not allowed in France, Switzerland, and Italy. Considering genetics elements in this situation there is no doubt on fatherhood - father is a man whose sperm is used for insemination, regardless of the fact if frozen sperm or frozen embryo is used in the procedure. Nevertheless, until 2008 in United Kingdom, the husband/partner was not considered as legal father, because of the fact that the child was born after his death. Heterologous artificial insemination could be used in three different situations. First, when subjects are spouses or unmarried partners of different sexes. Second, when subjects are spouses or unmarried partners of the same sex and the third if a single woman is an only subject. Most recent procedure is the one in which subjects are spouses or unmarried partners of the same sex, specifically two women. This procedure is allowed in the United Kingdom and Sweden. In these legislatures, there is a rule that the woman who delivers the child is legal mother, and her spouse/partner is a second parent of the child. The most recent procedure of egg donation is a donation of only a part of an egg, mitochondrial DNA. In this case, there are in fact three genetic parents of the child: two genetic mothers and a father. Legally, the child has one mother (the woman who delivers a child and a father. One of potential outcomes of the recent research is the ability to create human embryo without any male genetic contribution - by

  17. Evolution of the MAGUK protein gene family in premetazoan lineages

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    Ruiz-Trillo Iñaki

    2010-04-01

    Full Text Available Abstract Background Cell-to-cell communication is a key process in multicellular organisms. In multicellular animals, scaffolding proteins belonging to the family of membrane-associated guanylate kinases (MAGUK are involved in the regulation and formation of cell junctions. These MAGUK proteins were believed to be exclusive to Metazoa. However, a MAGUK gene was recently identified in an EST survey of Capsaspora owczarzaki, an unicellular organism that branches off near the metazoan clade. To further investigate the evolutionary history of MAGUK, we have undertook a broader search for this gene family using available genomic sequences of different opisthokont taxa. Results Our survey and phylogenetic analyses show that MAGUK proteins are present not only in Metazoa, but also in the choanoflagellate Monosiga brevicollis and in the protist Capsaspora owczarzaki. However, MAGUKs are absent from fungi, amoebozoans or any other eukaryote. The repertoire of MAGUKs in Placozoa and eumetazoan taxa (Cnidaria + Bilateria is quite similar, except for one class that is missing in Trichoplax, while Porifera have a simpler MAGUK repertoire. However, Vertebrata have undergone several independent duplications and exhibit two exclusive MAGUK classes. Three different MAGUK types are found in both M. brevicollis and C. owczarzaki: DLG, MPP and MAGI. Furthermore, M. brevicollis has suffered a lineage-specific diversification. Conclusions The diversification of the MAGUK protein gene family occurred, most probably, prior to the divergence between Metazoa+choanoflagellates and the Capsaspora+Ministeria clade. A MAGI-like, a DLG-like, and a MPP-like ancestral genes were already present in the unicellular ancestor of Metazoa, and new gene members have been incorporated through metazoan evolution within two major periods, one before the sponge-eumetazoan split and another within the vertebrate lineage. Moreover, choanoflagellates have suffered an independent MAGUK

  18. Target Molecular Simulations of RecA Family Protein Filaments

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    Yeng-Tseng Wang

    2012-06-01

    Full Text Available Modeling of the RadA family mechanism is crucial to understanding the DNA SOS repair process. In a 2007 report, the archaeal RadA proteins function as rotary motors (linker region: I71-K88 such as shown in Figure 1. Molecular simulations approaches help to shed further light onto this phenomenon. We find 11 rotary residues (R72, T75-K81, M84, V86 and K87 and five zero rotary residues (I71, K74, E82, R83 and K88 in the simulations. Inclusion of our simulations may help to understand the RadA family mechanism.

  19. Influence of rumen protein degradability on productive and reproductive performance in buffalo cows.

    Science.gov (United States)

    Campanile, Giuseppe; Di Palo, Rossella; Infascelli, Federico; Gasparrini, Bianca; Neglia, Gianluca; Zicarelli, Fabio; D'Occhio, Michael J

    2003-01-01

    The present study aimed to ascertain the influence of crude protein (CP) digestibility in the rumen on the quantity and quality of milk production and reproductive performance, blood (BU) and milk (MU) urea, haematological profile and vaginal mucus urea, ammonia and potassium of buffalo cows. Lactating buffaloes (n = 84), 60 days in milk, were randomly subdivided into Group C (control, n = 42) and Group T (fed a diet supplemented with Aspergillus oryzae, n = 42). In three fistulated buffalo, the diet supplemented with Aspergillus oryzae showed a decrease (P milk, were used to study the haematological profile and to determine milk urea and ammonia in the vaginal mucus. The animals in Group T1 had higher ammonia values in the blood (P mucus than Group C1. A relationship was found between MU and BU. MU was influenced by CP intake and dry matter intake. No differences between the treatments were observed in reproductive performance and the conception rate and calving interval were 37.9% and 41.4% (90 trial-day) and 449 and 419 days respectively in Groups T and C. Reproductive performance was not influenced by high levels of BU nor by blood ammonia levels, although the latter were higher in the group fed the diet supplemented with Aspergillus oryzae.

  20. [Family of ribosomal proteins S1 contains unique conservative domain].

    Science.gov (United States)

    Deriusheva, E I; Machulin, A V; Selivanova, O M; Serdiuk, I N

    2010-01-01

    Different representatives of bacteria have different number of amino acid residues in the ribosomal proteins S1. This number varies from 111 (Spiroplasma kunkelii) to 863 a.a. (Treponema pallidum). Traditionally and for lack of this protein three-dimensional structure, its architecture is represented as repeating S1 domains. Number of these domains depends on the protein's length. Domain's quantity and its boundaries data are contained in the specialized databases, such as SMART, Pfam and PROSITE. However, for the same object these data may be very different. For search of domain's quantity and its boundaries, new approach, based on the analysis of dicted secondary structure (PsiPred), was used. This approach allowed us to reveal structural domains in amino acid sequences of S1 proteins and at that number varied from one to six. Alignment of S1 proteins, containing different domain's number, with the S1 RNAbinding domain of Escherichia coli PNPase elicited a fact that in family of ribosomal proteins SI one domain has maximal homology with S1 domain from PNPase. This conservative domain migrates along polypeptide chain and locates in proteins, containing different domain's number, according to specified pattern. In this domain as well in the S1 domain from PNPase, residues Phe-19, Phe-22, His-34, Asp-64 and Arg-68 are clustered on the surface and formed RNA binding site.

  1. A mosquito hemolymph odorant-binding protein family member specifically binds juvenile hormone

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Il Hwan; Pham, Van; Jablonka, Willy; Goodman, Walter G.; Ribeiro, José M. C.; Andersen, John F.

    2017-07-27

    Juvenile hormone (JH) is a key regulator of insect development and reproduction. In adult mosquitoes, it is essential for maturation of the ovary and normal male reproductive behavior, but how JH distribution and activity is regulated after secretion is unclear. Here, we report a new type of specific JH-binding protein, given the name mosquito juvenile hormone-binding protein (mJHBP), which circulates in the hemolymph of pupal and adult Aedes aegypti males and females. mJHBP is a member of the odorant-binding protein (OBP) family, and orthologs are present in the genomes of Aedes, Culex, and Anopheles mosquito species. Using isothermal titration calorimetry, we show that mJHBP specifically binds JH II and JH III but not eicosanoids or JH derivatives. mJHBP was crystallized in the presence of JH III and found to have a double OBP domain structure reminiscent of salivary “long” D7 proteins of mosquitoes. We observed that a single JH III molecule is contained in the N-terminal domain binding pocket that is closed in an apparent conformational change by a C-terminal domain-derived α-helix. The electron density for the ligand indicated a high occupancy of the natural 10R enantiomer of JH III. Of note, mJHBP is structurally unrelated to hemolymph JHBP from lepidopteran insects. A low level of expression of mJHBP in Ae. aegypti larvae suggests that it is primarily active during the adult stage where it could potentially influence the effects of JH on egg development, mating behavior, feeding, or other processes.

  2. A mosquito hemolymph odorant-binding protein family member specifically binds juvenile hormone.

    Science.gov (United States)

    Kim, Il Hwan; Pham, Van; Jablonka, Willy; Goodman, Walter G; Ribeiro, José M C; Andersen, John F

    2017-09-15

    Juvenile hormone (JH) is a key regulator of insect development and reproduction. In adult mosquitoes, it is essential for maturation of the ovary and normal male reproductive behavior, but how JH distribution and activity is regulated after secretion is unclear. Here, we report a new type of specific JH-binding protein, given the name mosquito juvenile hormone-binding protein (mJHBP), which circulates in the hemolymph of pupal and adult Aedes aegypti males and females. mJHBP is a member of the odorant-binding protein (OBP) family, and orthologs are present in the genomes of Aedes , Culex , and Anopheles mosquito species. Using isothermal titration calorimetry, we show that mJHBP specifically binds JH II and JH III but not eicosanoids or JH derivatives. mJHBP was crystallized in the presence of JH III and found to have a double OBP domain structure reminiscent of salivary "long" D7 proteins of mosquitoes. We observed that a single JH III molecule is contained in the N-terminal domain binding pocket that is closed in an apparent conformational change by a C-terminal domain-derived α-helix. The electron density for the ligand indicated a high occupancy of the natural 10 R enantiomer of JH III. Of note, mJHBP is structurally unrelated to hemolymph JHBP from lepidopteran insects. A low level of expression of mJHBP in Ae. aegypti larvae suggests that it is primarily active during the adult stage where it could potentially influence the effects of JH on egg development, mating behavior, feeding, or other processes.

  3. Analysis of substructural variation in families of enzymatic proteins with applications to protein function prediction

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    Fofanov Viacheslav Y

    2010-05-01

    Full Text Available Abstract Background Structural variations caused by a wide range of physico-chemical and biological sources directly influence the function of a protein. For enzymatic proteins, the structure and chemistry of the catalytic binding site residues can be loosely defined as a substructure of the protein. Comparative analysis of drug-receptor substructures across and within species has been used for lead evaluation. Substructure-level similarity between the binding sites of functionally similar proteins has also been used to identify instances of convergent evolution among proteins. In functionally homologous protein families, shared chemistry and geometry at catalytic sites provide a common, local point of comparison among proteins that may differ significantly at the sequence, fold, or domain topology levels. Results This paper describes two key results that can be used separately or in combination for protein function analysis. The Family-wise Analysis of SubStructural Templates (FASST method uses all-against-all substructure comparison to determine Substructural Clusters (SCs. SCs characterize the binding site substructural variation within a protein family. In this paper we focus on examples of automatically determined SCs that can be linked to phylogenetic distance between family members, segregation by conformation, and organization by homology among convergent protein lineages. The Motif Ensemble Statistical Hypothesis (MESH framework constructs a representative motif for each protein cluster among the SCs determined by FASST to build motif ensembles that are shown through a series of function prediction experiments to improve the function prediction power of existing motifs. Conclusions FASST contributes a critical feedback and assessment step to existing binding site substructure identification methods and can be used for the thorough investigation of structure-function relationships. The application of MESH allows for an automated

  4. [Sexual and reproductive health in Roma women: the family planning programme of Polígono Sur in Seville (Spain)].

    Science.gov (United States)

    Escobar-Ballesta, Marta; García-Ramírez, Manuel; Albar-Marín, M ª Jesús; Paloma, Virginia

    2018-04-05

    To describe the challenges, resources and strategies of the staff of the family planning programme of the Polígono Sur Healthcare Centre in Seville (Spain) in their care of Roma women. This is a descriptive study in which in-depth interviews and discussion groups were held with all programme professionals, including a documentary review of the programme. The information was analyzed based on the Roma Health Integration Policy Index, a tool that evaluates the entitlement, accessibility, sensitivity and capacity for change of health programmes for the Roma population. The professionals encountered multiple challenges to implement the family planning programme with Roma women due to the characteristics of the users and the low sensitivity of the programme towards them. The absence of specific actions for Roma women within the family planning programme, agreed to by the healthcare district, obliges professionals to develop adaptations and strategies to ensure quality sexual and reproductive health services for their users. It is necessary to adapt sexual and reproductive health programmes targeted at Roma women by (a) detecting, evaluating, systematizing and disseminating good practices, (b) developing actions that address the multiple vulnerabilities of Roma women, (c) acknowledging professionals who advocate for the health of these women within their organizations, and (d) promoting reproductive justice as the goal of these programmes. Copyright © 2018 SESPAS. All rights reserved.

  5. Nuclear imprisonment of host cellular mRNA by nsp1β protein of porcine reproductive and respiratory syndrome virus

    International Nuclear Information System (INIS)

    Han, Mingyuan; Ke, Hanzhong; Zhang, Qingzhan; Yoo, Dongwan

    2017-01-01

    Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1β was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1β with the consensus sequence of 126 -LQxxLxxxGL- 135 . In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1β-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-α production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export. - Highlights: •PRRS virus blocks host mRNA nuclear export to the cytoplasm. •PRRSV nsp1β is the viral protein responsible for host mRNA nuclear retention. •SAP domain in nsp1β is essential for host mRNA nuclear retention and type I interferon suppression. •Mutation in the SAP domain of nsp1β causes the loss of function. •Host mRNA nuclear retention by nsp1β is common in the family Arteriviridae, except equine arteritis virus.

  6. Nuclear imprisonment of host cellular mRNA by nsp1β protein of porcine reproductive and respiratory syndrome virus

    Energy Technology Data Exchange (ETDEWEB)

    Han, Mingyuan, E-mail: hanming@umich.edu; Ke, Hanzhong; Zhang, Qingzhan; Yoo, Dongwan, E-mail: dyoo@illinois.edu

    2017-05-15

    Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1β was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1β with the consensus sequence of {sub 126}-LQxxLxxxGL-{sub 135}. In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1β-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-α production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export. - Highlights: •PRRS virus blocks host mRNA nuclear export to the cytoplasm. •PRRSV nsp1β is the viral protein responsible for host mRNA nuclear retention. •SAP domain in nsp1β is essential for host mRNA nuclear retention and type I interferon suppression. •Mutation in the SAP domain of nsp1β causes the loss of function. •Host mRNA nuclear retention by nsp1β is common in the family Arteriviridae, except equine

  7. The Reproduction of Privilege: Young Women, the Family and Private Education

    Science.gov (United States)

    Maxwell, Claire; Aggleton, Peter

    2014-01-01

    The paper examines processes of cultural production and reproduction among members of the elite and upper-middle classes. Drawing on findings from a study of private education in England, it explores the utility of a conceptual framework to examine how practices in and across different sites may be reproductive of various forms of…

  8. Observed Mother- and Father-Child Interaction Differences in Families with Medically Assisted Reproduction-Conceived Twins and Singletons.

    Science.gov (United States)

    Anderson, Kayla N; Rueter, Martha A; Connor, Jennifer J; Koh, Bibiana D

    2017-12-01

    Increased medically assisted reproduction (MAR) use to treat infertility has resulted in a growing twin birth rate. Little is known about parent-child relationships for twin relative to singleton children in middle childhood. This study fills this gap by examining parent-child relationships in 57 families with eighty 6- to 12-year-old MAR twin and singleton children using observational data (warm and supportive communication, control, and hostility). Nested ANCOVAs indicate that while mothers exhibit similar interactional behaviors toward twins and singletons, fathers have less optimum behaviors toward twins relative to singletons. Twins displayed less engaged behavior with mothers and fathers relative to singletons. Given the vitality of parent-child relationships for family and child adjustment, future studies should examine determinants and outcomes of twin-singleton relationship differences to bolster twins' and their families' functioning. © 2016 Family Process Institute.

  9. Characterization of polyclonal antibodies against nonstructural protein 9 from the porcine reproductive and respiratory syndrome virus

    Directory of Open Access Journals (Sweden)

    Mengmeng ZHAO,Juanjuan QIAN,Jiexiong XIE,Tiantian CUI,Songling FENG,Guoqiang WANG,Ruining WANG,Guihong ZHANG

    2016-06-01

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is considered to be one of the most important infectious diseases impacting the swine industry and is characterized by reproductive failure in late term gestation in sows and respiratory disease in pigs of all ages. The nonstructural protein 9 gene, Nsp9, encoding the RNA-dependent RNA polymerase, is generally regarded as fairly conserved when compared to other viral proteins. Antibodies against Nsp9 will be of great importance for the diagnosis and treatment of the causal agent, PRRS virus. A study was undertaken to generate polyclonal antibodies against the immunodominant Nsp9. For this purpose, the Nsp9 was expressed in Escherichia coli and subsequently used as an antigen to immunize New Zealand rabbits. Antiserum was identified via an indirect ELISA, and then verified based on the ability to react with both naturally and artificially expressed Nsp9. Results of virus neutralization test showed that this antiserum could not neutralize the PRRSV. Nevertheless, this antiserum as a diagnostic core reagent should prove invaluable for further investigations into the mechanism of PRRS pathogenesis.

  10. Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive organ development in Arabidopsis.

    Science.gov (United States)

    Kim, Soo Youn; Xu, Zheng-Yi; Song, Kyungyoung; Kim, Dae Heon; Kang, Hyangju; Reichardt, Ilka; Sohn, Eun Ju; Friml, Jirí; Juergens, Gerd; Hwang, Inhwan

    2013-08-01

    Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.

  11. Evolutionary plasticity of plasma membrane interaction in DREPP family proteins.

    Science.gov (United States)

    Vosolsobě, Stanislav; Petrášek, Jan; Schwarzerová, Kateřina

    2017-05-01

    The plant-specific DREPP protein family comprises proteins that were shown to regulate the actin and microtubular cytoskeleton in a calcium-dependent manner. Our phylogenetic analysis showed that DREPPs first appeared in ferns and that DREPPs have a rapid and plastic evolutionary history in plants. Arabidopsis DREPP paralogues called AtMDP25/PCaP1 and AtMAP18/PCaP2 are N-myristoylated, which has been reported as a key factor in plasma membrane localization. Here we show that N-myristoylation is neither conserved nor ancestral for the DREPP family. Instead, by using confocal microscopy and a new method for quantitative evaluation of protein membrane localization, we show that DREPPs rely on two mechanisms ensuring their plasma membrane localization. These include N-myristoylation and electrostatic interaction of a polybasic amino acid cluster. We propose that various plasma membrane association mechanisms resulting from the evolutionary plasticity of DREPPs are important for refining plasma membrane interaction of these signalling proteins under various conditions and in various cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The ubiquitin family meets the Fanconi anemia proteins.

    Science.gov (United States)

    Renaudin, Xavier; Koch Lerner, Leticia; Menck, Carlos Frederico Martins; Rosselli, Filippo

    2016-01-01

    Fanconi anaemia (FA) is a hereditary disorder characterized by bone marrow failure, developmental defects, predisposition to cancer and chromosomal abnormalities. FA is caused by biallelic mutations that inactivate genes encoding proteins involved in replication stress-associated DNA damage responses. The 20 FANC proteins identified to date constitute the FANC pathway. A key event in this pathway involves the monoubiquitination of the FANCD2-FANCI heterodimer by the collective action of at least 10 different proteins assembled in the FANC core complex. The FANC core complex-mediated monoubiquitination of FANCD2-FANCI is essential to assemble the heterodimer in subnuclear, chromatin-associated, foci and to regulate the process of DNA repair as well as the rescue of stalled replication forks. Several recent works have demonstrated that the activity of the FANC pathway is linked to several other protein post-translational modifications from the ubiquitin-like family, including SUMO and NEDD8. These modifications are related to DNA damage responses but may also affect other cellular functions potentially related to the clinical phenotypes of the syndrome. This review summarizes the interplay between the ubiquitin and ubiquitin-like proteins and the FANC proteins that constitute a major pathway for the surveillance of the genomic integrity and addresses the implications of their interactions in maintaining genome stability. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. NMR studies of a new family of DNA binding proteins: the THAP proteins

    International Nuclear Information System (INIS)

    Gervais, Virginie; Campagne, Sébastien; Durand, Jade; Muller, Isabelle; Milon, Alain

    2013-01-01

    The THAP (THanatos-Associated Protein) domain is an evolutionary conserved C2CH zinc-coordinating domain shared with a large family of cellular factors (THAP proteins). Many members of the THAP family act as transcription factors that control cell proliferation, cell cycle progression, angiogenesis, apoptosis and epigenetic gene silencing. They recognize specific DNA sequences in the promoters of target genes and subsequently recruit effector proteins. Recent structural and functional studies have allowed getting better insight into the nuclear and cellular functions of some THAP members and the molecular mechanisms by which they recognize DNA. The present article reviews recent advances in the knowledge of the THAP domains structures and their interaction with DNA, with a particular focus on NMR. It provides the solution structure of the THAP domain of THAP11, a recently characterized human THAP protein with important functions in transcription and cell growth in colon cancer.

  14. NMR studies of a new family of DNA binding proteins: the THAP proteins

    Energy Technology Data Exchange (ETDEWEB)

    Gervais, Virginie, E-mail: virginie.gervais@ipbs.fr [IPBS (Institut de Pharmacologie et de Biologie Structurale), CNRS (France); Campagne, Sebastien [ETH Zurich (Switzerland); Durand, Jade; Muller, Isabelle; Milon, Alain, E-mail: alain.milon@ipbs.fr [IPBS (Institut de Pharmacologie et de Biologie Structurale), CNRS (France)

    2013-05-15

    The THAP (THanatos-Associated Protein) domain is an evolutionary conserved C2CH zinc-coordinating domain shared with a large family of cellular factors (THAP proteins). Many members of the THAP family act as transcription factors that control cell proliferation, cell cycle progression, angiogenesis, apoptosis and epigenetic gene silencing. They recognize specific DNA sequences in the promoters of target genes and subsequently recruit effector proteins. Recent structural and functional studies have allowed getting better insight into the nuclear and cellular functions of some THAP members and the molecular mechanisms by which they recognize DNA. The present article reviews recent advances in the knowledge of the THAP domains structures and their interaction with DNA, with a particular focus on NMR. It provides the solution structure of the THAP domain of THAP11, a recently characterized human THAP protein with important functions in transcription and cell growth in colon cancer.

  15. The Desmosomal Plaque Proteins of the Plakophilin Family

    Directory of Open Access Journals (Sweden)

    Steffen Neuber

    2010-01-01

    Full Text Available Three related proteins of the plakophilin family (PKP1_3 have been identified as junctional proteins that are essential for the formation and stabilization of desmosomal cell contacts. Failure of PKP expression can have fatal effects on desmosomal adhesion, leading to abnormal tissue and organ development. Thus, loss of functional PKP 1 in humans leads to ectodermal dysplasia/skin fragility (EDSF syndrome, a genodermatosis with severe blistering of the epidermis as well as abnormal keratinocytes differentiation. Mutations in the human PKP 2 gene have been linked to severe heart abnormalities that lead to arrhythmogenic right ventricular cardiomyopathy (ARVC. In the past few years it has been shown that junctional adhesion is not the only function of PKPs. These proteins have been implicated in cell signaling, organization of the cytoskeleton, and control of protein biosynthesis under specific cellular circumstances. Clearly, PKPs are more than just cell adhesion proteins. In this paper we will give an overview of our current knowledge on the very distinct roles of plakophilins in the cell.

  16. The importance of ADAM family proteins in malignant tumors

    Directory of Open Access Journals (Sweden)

    Katarzyna Walkiewicz

    2016-02-01

    Full Text Available Increasing numbers of reports about the role of adamalysins (ADAM in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin-like growth factors (IGF1, IGF2, vascular growth factor (VEGF, tumor necrosis factor α (TNFα and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients.

  17. [The importance of ADAM family proteins in malignant tumors].

    Science.gov (United States)

    Walkiewicz, Katarzyna; Gętek, Monika; Muc-Wierzgoń, Małgorzata; Kokot, Teresa; Nowakowska-Zajdel, Ewa

    2016-02-11

    Increasing numbers of reports about the role of adamalysins (ADAM) in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin-like growth factors (IGF1, IGF2), vascular growth factor (VEGF), tumor necrosis factor α (TNFα) and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients.

  18. Knowledge Networking for Family Planning: The Potential for Virtual Communities of Practice to Move Forward the Global Reproductive Health Agenda

    Directory of Open Access Journals (Sweden)

    Megan O’Brien

    2010-06-01

    Full Text Available This paper highlights experience from five years of using virtual communication tools developed by the World Health Organization Department of Reproductive Health and Research (WHO/RHR and its partners in the Implementing Best Practices (IBP in Reproductive Health Initiative to help bridge the knowledge-to-practice gap among family planning and reproductive health professionals. It explores how communities of practice and virtual networks offer a unique low-cost way to convene public health practitioners around the world to share experiences. It offers examples of how communities of practice can contribute to the development and dissemination of evidence-based health information products, and explores the potential for online networking and collaboration to enhance and inform program design and management. The paper is intended to inform the reproductive health community, as well as others working in health and development, of the potential for using virtual communities of practice to work towards achieving common goals and provide some examples of their successful use.

  19. Distribution of protein kinase Mzeta and the complete protein kinase C isoform family in rat brain

    DEFF Research Database (Denmark)

    Naik, M U; Benedikz, Eirikur; Hernandez, I

    2000-01-01

    Protein kinase C (PKC) is a multigene family of at least ten isoforms, nine of which are expressed in brain (alpha, betaI, betaII, gamma, delta, straightepsilon, eta, zeta, iota/lambda). Our previous studies have shown that many of these PKCs participate in synaptic plasticity in the CA1 region...

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

    OpenAIRE

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

    2011-01-01

    Membrane-associated guanylate kinases (MAGUK) family proteins contain an inactive guanylate kinase (GK) domain, whose function has been elusive. Here, this domain is revealed as a new type of phospho-peptide-binding module, in which the GMP-binding site has evolved to accommodate phospho-serines or -threonines.

  1. A protein relational database and protein family knowledge bases to facilitate structure-based design analyses.

    Science.gov (United States)

    Mobilio, Dominick; Walker, Gary; Brooijmans, Natasja; Nilakantan, Ramaswamy; Denny, R Aldrin; Dejoannis, Jason; Feyfant, Eric; Kowticwar, Rupesh K; Mankala, Jyoti; Palli, Satish; Punyamantula, Sairam; Tatipally, Maneesh; John, Reji K; Humblet, Christine

    2010-08-01

    The Protein Data Bank is the most comprehensive source of experimental macromolecular structures. It can, however, be difficult at times to locate relevant structures with the Protein Data Bank search interface. This is particularly true when searching for complexes containing specific interactions between protein and ligand atoms. Moreover, searching within a family of proteins can be tedious. For example, one cannot search for some conserved residue as residue numbers vary across structures. We describe herein three databases, Protein Relational Database, Kinase Knowledge Base, and Matrix Metalloproteinase Knowledge Base, containing protein structures from the Protein Data Bank. In Protein Relational Database, atom-atom distances between protein and ligand have been precalculated allowing for millisecond retrieval based on atom identity and distance constraints. Ring centroids, centroid-centroid and centroid-atom distances and angles have also been included permitting queries for pi-stacking interactions and other structural motifs involving rings. Other geometric features can be searched through the inclusion of residue pair and triplet distances. In Kinase Knowledge Base and Matrix Metalloproteinase Knowledge Base, the catalytic domains have been aligned into common residue numbering schemes. Thus, by searching across Protein Relational Database and Kinase Knowledge Base, one can easily retrieve structures wherein, for example, a ligand of interest is making contact with the gatekeeper residue.

  2. Impact of the Urban Reproductive Health Initiative on family planning uptake at facilities in Kenya, Nigeria, and Senegal.

    Science.gov (United States)

    Winston, Jennifer; Calhoun, Lisa M; Corroon, Meghan; Guilkey, David; Speizer, Ilene

    2018-01-05

    The 2012 London Summit on Family Planning set ambitious goals to enable 120 million more women and adolescent girls to use modern contraceptives by 2020. The Urban Reproductive Health Initiative (URHI) was a Bill & Melinda Gates Foundation funded program designed to help contribute to these goals in urban areas in India, Kenya, Nigeria, and Senegal. URHI implemented a range of country-specific demand and supply side interventions, with supply interventions generally focused on improved service quality, provider training, outreach to patients, and commodity stock management. This study uses data collected by the Measurement, Learning & Evaluation (MLE) Project to examine the effectiveness of these supply-side interventions by considering URHI's influence on the number of family planning clients at health facilities over a four-year period in Kenya, Nigeria, and Senegal. The analysis used facility audits and provider surveys. Principal-components analysis was used to create country-specific program exposure variables for health facilities. Fixed-effects regression was used to determine whether family planning uptake increased at facilities with higher exposure. Outcomes of interest were the number of new family planning acceptors and the total number of family planning clients per reproductive health care provider in the last year. Higher program component scores were associated with an increase in new family planning acceptors per provider in Kenya (β = 18, 95% CI = 7-29), Nigeria (β = 14, 95% CI = 8-20), and Senegal (β = 7, 95% CI = 3-12). Higher scores were also associated with more family planning clients per provider in Kenya (β = 31, 95% CI = 7-56) and Nigeria (β = 26, 95% CI = 15-38), but not in Senegal. Supply-side interventions have increased the number of new family planning acceptors at facilities in urban Nigeria, Kenya, and Senegal and the overall number of clients in urban Nigeria and Kenya. While tailoring

  3. Adducin family proteins possess different nuclear export potentials.

    Science.gov (United States)

    Liu, Chia-Mei; Hsu, Wen-Hsin; Lin, Wan-Yi; Chen, Hong-Chen

    2017-05-10

    The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are actin-binding proteins that play important roles in the stabilization of membrane cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly conserved bipartite nuclear localization signal (NLS) at the carboxyl termini, but only ADD1 can localize to the nucleus. The reason for this discrepancy is not clear. To avoid the potential effect of cell-cell junctions on the distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were transiently expressed in NIH3T3 fibroblasts and their distribution in the cytoplasm and nucleus was examined by immunofluorescence staining. Several nuclear proteins were identified to interact with ADD1 by mass spectrometry, which were further verified by co-immunoprecipitation. In this study, we found that ADD1 was detectable both in the cytoplasm and nucleus, whereas ADD2 and ADD3 were detected only in the cytoplasm. However, ADD2 and ADD3 were partially (~40%) sequestered in the nucleus by leptomycin B, a CRM1/exportin1 inhibitor. Upon the removal of leptomycin B, ADD2 and ADD3 re-distributed to the cytoplasm. These results indicate that ADD2 and ADD3 possess functional NLS and are quickly transported to the cytoplasm upon entering the nucleus. Indeed, we found that ADD2 and ADD3 possess much higher potential to counteract the activity of the NLS derived from Simian virus 40 large T-antigen than ADD1. All the ADD proteins appear to contain multiple nuclear export signals mainly in their head and neck domains. However, except for the leucine-rich motif ( 377 FEALMRMLDWLGYRT 391 ) in the neck domain of ADD1, no other classic nuclear export signal was identified in the ADD proteins. In addition, the nuclear retention of ADD1 facilitates its interaction with RNA polymerase II and zinc-finger protein 331. Our results suggest that ADD2 and ADD3 possess functional NLS and shuttle between the cytoplasm and nucleus. The discrepancy in the

  4. [Interconnection between architecture of protein globule and disposition of conformational conservative oligopeptides in proteins from one protein family].

    Science.gov (United States)

    Batianovskiĭ, A V; Filatov, I V; Namiot, V A; Esipova, N G; Volotovskiĭ, I D

    2012-01-01

    It was shown that selective interactions between helical segments of macromolecules can realize in globular proteins in the segments characterized by the same periodicities of charge distribution i.e. between conformationally conservative oligopeptides. It was found that in the macromolecules of alpha-helical proteins conformationally conservative oligopeptides are disposed at a distance being characteristic of direct interactions. For representatives of many structural families of alpha-type proteins specific disposition of conformationally conservative segments is observed. This disposition is inherent to a particular structural family. Disposition of conformationally conservative segments is not related to homology of the amino acid sequence but reflects peculiarities of native 3D-architectures of protein globules.

  5. Palmitoylation of POTE family proteins for plasma membrane targeting

    International Nuclear Information System (INIS)

    Das, Sudipto; Ise, Tomoko; Nagata, Satoshi; Maeda, Hiroshi; Bera, Tapan K.; Pastan, Ira

    2007-01-01

    The POTE gene family is composed of 13 paralogs and likely evolved by duplications and remodeling of the human genome. One common property of POTE proteins is their localization on the inner aspect of the plasma membrane. To determine the structural elements required for membrane localization, we expressed mutants of different POTEs in 293T cells as EGFP fusion proteins. We also tested their palmitoylation by a biotin-switch assay. Our data indicate that the membrane localizations of different POTEs are mediated by similar 3-4 short cysteine rich repeats (CRRs) near the amino-terminuses and that palmitoylation on paired cysteine residues in each CRR motif is responsible for the localization. Multiple palmitoylation in the small CRRs can result in the strong association of whole POTEs with plasma membrane

  6. Women's career priority is associated with attitudes towards family planning and ethical acceptance of reproductive technologies.

    Science.gov (United States)

    Simoni, Michael K; Mu, Lin; Collins, Stephen C

    2017-10-01

    Do women who place high importance on career success have different perceptions of pregnancy planning, delayed reproduction, and the ethical acceptability of ART than women with less emphasis on their career? Career-focused women place more importance on pregnancy planning, have greater confidence in delayed childbearing, and are more ethically accepting of donor gamete ART than women who do not place as much importance on career success. Women in high-professional careers are more likely to delay childbearing while simultaneously possessing a stronger desire for motherhood. The underlying values which enable these competing desires have not been elucidated. This cross-sectional study utilized data from the National Survey of Fertility Barriers (NSFB), a nationally representative telephone survey of US women aged 25-45. Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the NSFB surveyed 4712 women from 2004 to 2007. In addition to demographic data, the NSFB obtained information about the reproductive history and personal values of participants. Weighted multivariate regression analysis was used to assess reproductive values in career-focused women. In total, 48.8% of women considered success in work very important, while 17.3% considered it somewhat or not important. Women who placed less value on career success were less likely to consider pregnancy planning important and were less optimistic about the success of delayed childbearing than their work-centric counterparts. Women less focused on their careers were also more likely to have serious ethical concerns about donor gametes, but less likely to have ethical concerns about IUI or IVF, when compared to career-focused women. Intention to bear children could not be evaluated in the setting of career intentions due to a lack of data on when the participant intended on pursuing motherhood. Political preferences on reproductive health were also not evaluated. The validity

  7. A retrospective study of New Zealand case law involving assisted reproduction technology and the social recognition of 'new' family.

    Science.gov (United States)

    Legge, M; Fitzgerald, R; Frank, N

    2007-01-01

    The New Zealand Human Assisted Reproductive Technology (HART) Act became law in 2004. In this article, we provide a retrospective analysis of New Zealand case law from September 1990 to March 2004, leading up to the creation of the HART Act. We examine the new understandings of parenting (developed through the routine use of ART in New Zealand) which the case law attempted to test. We examine these concepts against the previous understandings of family enshrined in the pre-existing legislation, which formed the basis for judicial rulings in the various cases to which we refer. In conclusion, we provide a brief summary of the 2004 HART legislation and draw comparisons between the old and new legislative and bureaucratic frameworks that define and support New Zealand family structure. We suggest that a change in cultural backdrop is occurring from the traditional western ideology of the nuclear family towards the traditional Maori concept of family formation, which includes a well-accepted traditional practice of guardianship and a more open and extended family structure. This 'new' structure reflects the contemporary lived experience of family kinship in western societies as individualized and open to choice.

  8. Implementation of a Family Planning Clinic-Based Partner Violence and Reproductive Coercion Intervention: Provider and Patient Perspectives.

    Science.gov (United States)

    Miller, Elizabeth; McCauley, Heather L; Decker, Michele R; Levenson, Rebecca; Zelazny, Sarah; Jones, Kelley A; Anderson, Heather; Silverman, Jay G

    2017-06-01

    Despite multiple calls for clinic-based services to identify and support women victimized by partner violence, screening remains uncommon in family planning clinics. Furthermore, traditional screening, based on disclosure of violence, may miss women who fear reporting their experiences. Strategies that are sensitive to the signs, symptoms and impact of trauma require exploration. In 2011, as part of a cluster randomized controlled trial, staff at 11 Pennsylvania family planning clinics were trained to offer a trauma-informed intervention addressing intimate partner violence and reproductive coercion to all women seeking care, regardless of exposure to violence. The intervention sought to educate women about available resources and harm reduction strategies. In 2013, at the conclusion of the trial, 18 providers, five administrators and 49 patients completed semistructured interviews exploring acceptability of the intervention and barriers to implementation. Consensus and open coding strategies were used to analyze the data. Providers reported that the intervention increased their confidence in discussing intimate partner violence and reproductive coercion. They noted that asking patients to share the educational information with other women facilitated the conversation. Barriers to implementation included lack of time and not having routine reminders to offer the intervention. Patients described how receiving the intervention gave them important information, made them feel supported and less isolated, and empowered them to help others. A universal intervention may be acceptable to providers and patients. However, successful implementation in family planning settings may require attention to system-level factors that providers view as barriers. Copyright © 2017 by the Guttmacher Institute.

  9. A Deg-protease family protein in marine Synechococcus is involved in outer membrane protein organization

    Directory of Open Access Journals (Sweden)

    Rhona Kayra Stuart

    2014-06-01

    Full Text Available Deg-family proteases are a periplasm-associated group of proteins that are known to be involved in envelope stress responses and are found in most microorganisms. Orthologous genes SYNW2176 (in strain WH8102 and sync_2523 (strain CC9311 are predicted members of the Deg-protease family and are among the few genes induced by copper stress in both open ocean and coastal marine Synechococcus strains. In contrast to the lack of a phenotype in a similar knockout in Synechocystis PCC6803, a SYNW2176 knockout mutant in strain WH8102 was much more resistant to copper than the wild-type. The mutant also exhibited a significantly altered outer membrane protein composition which may contribute to copper resistance, longer lag phase after transfer, low-level consistent alkaline phosphatase activity, and an inability to induce high alkaline phosphatase activity in response to phosphate stress. This phenotype suggests a protein-quality-control role for SYNW2176, the absence of which leads to a constitutively activated stress response. Deg-protease family proteins in this ecologically important cyanobacterial group thus help to determine outer membrane responses to both nutrients and toxins.

  10. Unifying mechanical and thermodynamic descriptions across the thioredoxin protein family.

    Science.gov (United States)

    Mottonen, James M; Xu, Minli; Jacobs, Donald J; Livesay, Dennis R

    2009-05-15

    We compare various predicted mechanical and thermodynamic properties of nine oxidized thioredoxins (TRX) using a Distance Constraint Model (DCM). The DCM is based on a nonadditive free energy decomposition scheme, where entropic contributions are determined from rigidity and flexibility of structure based on distance constraints. We perform averages over an ensemble of constraint topologies to calculate several thermodynamic and mechanical response functions that together yield quantitative stability/flexibility relationships (QSFR). Applied to the TRX protein family, QSFR metrics display a rich variety of similarities and differences. In particular, backbone flexibility is well conserved across the family, whereas cooperativity correlation describing mechanical and thermodynamic couplings between the residue pairs exhibit distinctive features that readily standout. The diversity in predicted QSFR metrics that describe cooperativity correlation between pairs of residues is largely explained by a global flexibility order parameter describing the amount of intrinsic flexibility within the protein. A free energy landscape is calculated as a function of the flexibility order parameter, and key values are determined where the native-state, transition-state, and unfolded-state are located. Another key value identifies a mechanical transition where the global nature of the protein changes from flexible to rigid. The key values of the flexibility order parameter help characterize how mechanical and thermodynamic response is linked. Variation in QSFR metrics and key characteristics of global flexibility are related to the native state X-ray crystal structure primarily through the hydrogen bond network. Furthermore, comparison of three TRX redox pairs reveals differences in thermodynamic response (i.e., relative melting point) and mechanical properties (i.e., backbone flexibility and cooperativity correlation) that are consistent with experimental data on thermal stabilities

  11. Reproductive aspects and knowledge of family planning among women with Acquired Immunodeficiency Syndrome.

    Science.gov (United States)

    Lima, Ivana Cristina Vieira de; Cunha, Maria da Conceição Dos Santos Oliveira; Cunha, Gilmara Holanda da; Galvão, Marli Teresinha Gimeniz

    2017-05-25

    To analyze the reproductive aspects and knowledge of family planning among women with Acquired Immunodeficiency Syndrome (AIDS). Cross-sectional and descriptive study carried out from January to December, 2015, in the outpatient care of infectious disease unit in a hospital located in Fortaleza, Ceará. Data were collected through a form applied by interview in a private setting. 102 women participated in the study. Most were aware that they were serologically positive with human immunodeficiency virus (HIV) during prenatal care (96.1%) and did not intend to have more children (63.7%). Women who were less than 39 years of age, had a higher educational level, and a shorter time of antiretroviral therapy had better chances of having children (p≤0.05). Having a steady partner increased the chance of desiring to have children, while tubal ligation was higher among women that did not receive counseling on family planning. Knowledge of family planning was limited because of lack of assistance provided by health professionals. Analisar aspectos reprodutivos e conhecimento sobre planejamento familiar de mulheres com síndrome da imunodeficiência adquirida (Aids). Estudo transversal, descritivo, realizado de janeiro a dezembro de 2015, no ambulatório de infectologia de um hospital em Fortaleza, Ceará. Os dados foram coletados por meio de formulário, aplicado por entrevista em ambiente privativo. Participaram do estudo 102 mulheres. A maioria delas teve conhecimento da sorologia positiva para vírus da imunodeficiência humana (HIV) durante o pré-natal (96,1%), e estas não pretendiam mais ter filhos (63,7%). Mulheres com idade menor que 39 anos, maior escolaridade e menor tempo de terapia antirretroviral tiveram maiores chances de ter filhos (p≤0,05). Mulheres com idade menor que 39 anos e maior escolaridade tiveram maiores chances de ter informações corretas sobre ter filhos na vigência do HIV (p≤0,05). Ter parceiro fixo aumentou a chance de desejar ter

  12. Identification of differentially expressed reproductive and metabolic proteins in the female abalone (Haliotis laevigata) gonad following artificial induction of spawning.

    Science.gov (United States)

    Mendoza-Porras, Omar; Botwright, Natasha A; Reverter, Antonio; Cook, Mathew T; Harris, James O; Wijffels, Gene; Colgrave, Michelle L

    2017-12-01

    Inefficient control of temperate abalone spawning prevents pair-wise breeding and production of abalone with highly marketable traits. Traditionally, abalone farmers have used a combination of UV irradiation and application of temperature gradients to the tank water to artificially induce spawning. Proteins are known to regulate crucial processes such as respiration, muscle contraction, feeding, growth and reproduction. Spawning as a pre-requisite of abalone reproduction is likely to be regulated, in part, by endogenous proteins. A first step in elucidating the mechanisms that regulate spawning is to identify which proteins are directly involved during spawning. The present study examined protein expression following traditional spawning induction in the Haliotis laevigata female. Gonads were collected from abalone in the following physiological states: (1) spawning; (2) post-spawning; and (3) failed-to-spawn. Differential protein abundance was initially assessed using two-dimensional difference in-gel electrophoresis coupled with mass spectrometry for protein identification. A number of reproductive proteins such as vitellogenin, vitelline envelope zona pellucida domain 29 and prohibitin, and metabolic proteins such as thioredoxin peroxidase, superoxide dismutase and heat shock proteins were identified. Differences in protein abundance levels between physiological states were further assessed using scheduled multiple reaction monitoring mass spectrometry. Positive associations were observed between the abundance of specific proteins, such as heat shock cognate 70 and peroxiredoxin 6, and the propensity or failure to spawn in abalone. These findings have contributed to better understand both the effects of oxidative and heat stress over abalone physiology and their influence on abalone spawning. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  13. Identification and analysis of YELLOW protein family genes in the silkworm, Bombyx mori

    Directory of Open Access Journals (Sweden)

    Yi Yong-Zhu

    2006-08-01

    Full Text Available Abstract Background The major royal jelly proteins/yellow (MRJP/YELLOW family possesses several physiological and chemical functions in the development of Apis mellifera and Drosophila melanogaster. Each protein of the family has a conserved domain named MRJP. However, there is no report of MRJP/YELLOW family proteins in the Lepidoptera. Results Using the YELLOW protein sequence in Drosophila melanogaster to BLAST silkworm EST database, we found a gene family composed of seven members with a conserved MRJP domain each and named it YELLOW protein family of Bombyx mori. We completed the cDNA sequences with RACE method. The protein of each member possesses a MRJP domain and a putative cleavable signal peptide consisting of a hydrophobic sequence. In view of genetic evolution, the whole Bm YELLOW protein family composes a monophyletic group, which is distinctly separate from Drosophila melanogaster and Apis mellifera. We then showed the tissue expression profiles of Bm YELLOW protein family genes by RT-PCR. Conclusion A Bombyx mori YELLOW protein family is found to be composed of at least seven members. The low homogeneity and unique pattern of gene expression by each member among the family ensure us to prophesy that the members of Bm YELLOW protein family would play some important physiological functions in silkworm development.

  14. Building Irish families through surrogacy: medical and judicial issues for the advanced reproductive technologies.

    LENUS (Irish Health Repository)

    Sills, Eric Scott

    2008-01-01

    Surrogacy involves one woman (surrogate mother) carrying a child for another person\\/s (commissioning person\\/couple), based on a mutual agreement requiring the child to be handed over to the commissioning person\\/couple following birth. Reasons for seeking surrogacy include situations where a woman has non-functional or absent reproductive organs, or as a remedy for recurrent pregnancy loss. Additionally, surrogacy may find application in any medical context where pregnancy is contraindicated, or where a couple consisting of two males seek to become parents through oocyte donation. Gestational surrogacy is one of the main issues at the forefront of bioethics and the advanced reproductive technologies, representing an important challenge to medical law. This analysis reviews the history of surrogacy and clinical and legal issues pertaining to this branch of reproductive medicine. Interestingly, the Medical Council of Ireland does not acknowledge surrogacy in its current practice guidelines, nor is there specific legislation addressing surrogacy in Ireland at present. We therefore have developed a contract-based model for surrogacy in which, courts in Ireland may consider when confronted with a surrogacy dispute, and formulated a system to resolve any potential dispute arising from a surrogacy arrangement. While the 2005 report by the Commission on Assisted Human Reproduction (CAHR) is an expert opinion guiding the Oireachtas\\' development of specific legislation governing assisted human reproduction and surrogacy, our report represents independent scholarship on the contractual elements of surrogacy with particular focus on how Irish courts might decide on surrogacy matters in a modern day Ireland. This joint medico-legal collaborative also reviews the contract for services arrangement between the commissioning person\\/s and the surrogate, and the extent to which the contract may be enforced.

  15. Building Irish families through surrogacy: medical and judicial issues for the advanced reproductive technologies

    Science.gov (United States)

    Sills, Eric Scott; Healy, Clifford M

    2008-01-01

    Surrogacy involves one woman (surrogate mother) carrying a child for another person/s (commissioning person/couple), based on a mutual agreement requiring the child to be handed over to the commissioning person/couple following birth. Reasons for seeking surrogacy include situations where a woman has non-functional or absent reproductive organs, or as a remedy for recurrent pregnancy loss. Additionally, surrogacy may find application in any medical context where pregnancy is contraindicated, or where a couple consisting of two males seek to become parents through oocyte donation. Gestational surrogacy is one of the main issues at the forefront of bioethics and the advanced reproductive technologies, representing an important challenge to medical law. This analysis reviews the history of surrogacy and clinical and legal issues pertaining to this branch of reproductive medicine. Interestingly, the Medical Council of Ireland does not acknowledge surrogacy in its current practice guidelines, nor is there specific legislation addressing surrogacy in Ireland at present. We therefore have developed a contract-based model for surrogacy in which, courts in Ireland may consider when confronted with a surrogacy dispute, and formulated a system to resolve any potential dispute arising from a surrogacy arrangement. While the 2005 report by the Commission on Assisted Human Reproduction (CAHR) is an expert opinion guiding the Oireachtas' development of specific legislation governing assisted human reproduction and surrogacy, our report represents independent scholarship on the contractual elements of surrogacy with particular focus on how Irish courts might decide on surrogacy matters in a modern day Ireland. This joint medico-legal collaborative also reviews the contract for services arrangement between the commissioning person/s and the surrogate, and the extent to which the contract may be enforced. PMID:18983640

  16. Building Irish families through surrogacy: medical and judicial issues for the advanced reproductive technologies

    Directory of Open Access Journals (Sweden)

    Healy Clifford M

    2008-11-01

    Full Text Available Abstract Surrogacy involves one woman (surrogate mother carrying a child for another person/s (commissioning person/couple, based on a mutual agreement requiring the child to be handed over to the commissioning person/couple following birth. Reasons for seeking surrogacy include situations where a woman has non-functional or absent reproductive organs, or as a remedy for recurrent pregnancy loss. Additionally, surrogacy may find application in any medical context where pregnancy is contraindicated, or where a couple consisting of two males seek to become parents through oocyte donation. Gestational surrogacy is one of the main issues at the forefront of bioethics and the advanced reproductive technologies, representing an important challenge to medical law. This analysis reviews the history of surrogacy and clinical and legal issues pertaining to this branch of reproductive medicine. Interestingly, the Medical Council of Ireland does not acknowledge surrogacy in its current practice guidelines, nor is there specific legislation addressing surrogacy in Ireland at present. We therefore have developed a contract-based model for surrogacy in which, courts in Ireland may consider when confronted with a surrogacy dispute, and formulated a system to resolve any potential dispute arising from a surrogacy arrangement. While the 2005 report by the Commission on Assisted Human Reproduction (CAHR is an expert opinion guiding the Oireachtas' development of specific legislation governing assisted human reproduction and surrogacy, our report represents independent scholarship on the contractual elements of surrogacy with particular focus on how Irish courts might decide on surrogacy matters in a modern day Ireland. This joint medico-legal collaborative also reviews the contract for services arrangement between the commissioning person/s and the surrogate, and the extent to which the contract may be enforced.

  17. Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility.

    NARCIS (Netherlands)

    Dijk, M.R. van; Schaijk, B.C.L. van; Khan, S.M.; Dooren, M.W. van; Ramesar, J.; Kaczanowski, S.; Gemert, G.J.A. van; Kroeze, H.; Stunnenberg, H.G.; Eling, W.M.C.; Sauerwein, R.W.; Waters, A.P.; Janse, C.J.

    2010-01-01

    The process of fertilization is critically dependent on the mutual recognition of gametes and in Plasmodium, the male gamete surface protein P48/45 is vital to this process. This protein belongs to a family of 10 structurally related proteins, the so called 6-cys family. To identify the role of

  18. The structural influence of family and parenting on young people's sexual and reproductive health in rural northern Tanzania.

    Science.gov (United States)

    Wamoyi, Joyce; Wight, Daniel; Remes, Pieter

    2015-01-01

    This paper explores the structural role of the family and parenting in young people's sexual and reproductive health. The study involved eight weeks of participant observation, 26 in-depth interviews, and 11 group discussions with young people aged 14-24 years, and 20 in-depth interviews and 6 group discussions with parents/carers of children in this age group. At an individual level, parenting and family structure were found to affect young people's sexual behaviour by influencing children's self-confidence and interactional competence, limiting discussion of sexual health and shaping economic provision for children, which in turn affected parental authority and daughters' engagement in risky sexual behaviour. Sexual norms are reproduced both through parents' explicit prohibitions and their own behaviours. Girls are socialised to accept men's superiority, which shapes their negotiation of sexual relationships. Interventions to improve young people's sexual and reproductive health should recognise the structural effects of parenting, both in terms of direct influences on children and the dynamics by which structural barriers such as gendered power relations and cultural norms around sexuality are transmitted across generations.

  19. Mars is close to venus--female reproductive proteins are expressed in the fat body and reproductive tract of honey bee (Apis mellifera L.) drones.

    Science.gov (United States)

    Colonello-Frattini, Nínive Aguiar; Guidugli-Lazzarini, Karina Rosa; Simões, Zilá Luz Paulino; Hartfelder, Klaus

    2010-11-01

    Vitellogenin (Vg) and lipophorin (Lp) are lipoproteins which play important roles in female reproductive physiology of insects. Both are actively taken up by growing oocytes and especially Vg and its receptor are considered as female-specifically expressed. The finding that the fat body of in honey bee (Apis mellifera) drones synthesizes Vg and is present in hemolymph has long been viewed as a curiosity. The recent paradigm change concerning the role played by Vg in honey bee life history, especially social division of labor, has now led us to investigate whether a physiological constellation similar to that seen in female reproduction may also be represented in the male sex. By means of Western blot analysis we could show that both Vg and Lp are present in the reproductive tract of adult drones, including the accessory (mucus) glands, but apparently are not secreted. Furthermore, we analyzed the transcript levels of the genes encoding these proteins (vg and lp), as well as their putative receptors (Amvgr and Amlpr) in fat body and accessory glands. Whereas lp, vg and Amlpr transcript levels decreased with age in both tissues, Amvgr mRNA levels increased with age in fat body. To our knowledge this is the first report that vitellogenin and its receptor are co-expressed in the reproductive system of a male insect. We interpret these findings as a cross-sexual transfer of a social physiological trait, associated with the rewiring of the juvenile hormone/vitellogenin circuitry that occurred in the female sex of honey bees. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. PATtyFams: Protein families for the microbial genomes in the PATRIC database

    Directory of Open Access Journals (Sweden)

    James J Davis

    2016-02-01

    Full Text Available The ability to build accurate protein families is a fundamental operation in bioinformatics that influences comparative analyses, genome annotation and metabolic modeling. For several years we have been maintaining protein families for all microbial genomes in the PATRIC database (Pathosystems Resource Integration Center, patricbrc.org in order to drive many of the comparative analysis tools that are available through the PATRIC website. However, due to the burgeoning number of genomes, traditional approaches for generating protein families are becoming prohibitive. In this report, we describe a new approach for generating protein families, which we call PATtyFams. This method uses the k-mer-based function assignments available through RAST (Rapid Annotation using Subsystem Technology to rapidly guide family formation, and then differentiates the function-based groups into families using a Markov Cluster algorithm (MCL. This new approach for generating protein families is rapid, scalable and has properties that are consistent with alignment-based methods.

  1. Balanced intake of protein and carbohydrate maximizes lifetime reproductive success in the mealworm beetle, Tenebrio molitor (Coleoptera: Tenebrionidae).

    Science.gov (United States)

    Rho, Myung Suk; Lee, Kwang Pum

    2016-01-01

    Recent developments in insect gerontological and nutritional research have suggested that the dietary protein:carbohydrate (P:C) balance is a critical determinant of lifespan and reproduction in many insects. However, most studies investigating this important role of dietary P:C balance have been conducted using dipteran and orthopteran species. In this study, we used the mealworm beetles, Tenebrio molitor L. (Coleoptera: Tenebrionidae), to test the effects of dietary P:C balance on lifespan and reproduction. Regardless of their reproductive status, both male and female beetles had the shortest lifespan at the protein-biased ratio of P:C 5:1. Mean lifespan was the longest at P:C 1:1 for males and at both P:C 1:1 and 1:5 for females. Mating significantly curtailed the lifespan of both males and females, indicating the survival cost of mating. Age-specific egg laying was significantly higher at P:C 1:1 than at the two imbalanced P:C ratios (1:5 or 5:1) at any given age throughout their lives, resulting in the highest lifetime reproductive success at P:C 1:1. When given a choice, beetles actively regulated their intake of protein and carbohydrate to a slightly carbohydrate-biased ratio (P:C 1:1.54-1:1.64 for males and P:C 1:1.3-1:1.36 for females). The self-selected P:C ratio was significantly higher for females than males, reflecting a higher protein requirement for egg production. Collectively, our results add to a growing body of evidence suggesting the key role played by dietary macronutrient balance in shaping lifespan and reproduction in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A New MAP Kinase Protein Involved in Estradiol-Stimulated Reproduction of the Helminth Parasite Taenia crassiceps

    Science.gov (United States)

    Escobedo, Galileo; Soldevila, Gloria; Ortega-Pierres, Guadalupe; Chávez-Ríos, Jesús Ramsés; Nava, Karen; Fonseca-Liñán, Rocío; López-Griego, Lorena; Hallal-Calleros, Claudia; Ostoa-Saloma, Pedro; Morales-Montor, Jorge

    2010-01-01

    MAP kinases (MAPK) are involved in the regulation of cellular processes such as reproduction and growth. In parasites, the role of MAPK has been scarcely studied. Here, we describe the participation of an ERK-like protein in estrogen-dependent reproduction of the helminth parasite Taenia crassiceps. Our results show that 17β-estradiol induces a concentration-dependent increase in the bud number of in vitro cultured cysticerci. If parasites are also incubated in presence of an ERK-inhibitor, the stimulatory effect of estrogen is blocked. The expression of ERK-like mRNA and its corresponding protein was detected in the parasite. The ERK-like protein was over-expressed by all treatments. Nevertheless, a strong induction of phosphorylation of this protein was observed only in response to 17β-estradiol. Cross-contamination by host cells was discarded by flow cytometry analysis. Parasite cells expressing the ERK-like protein were exclusively located at the subtegument tissue by confocal microscopy. Finally, the ERK-like protein was separated by bidimensional electrophoresis and then sequenced, showing the conserved TEY activation motif, typical of all known ERK 1/2 proteins. Our results show that an ERK-like protein is involved in the molecular signalling during the interaction between the host and T. crassiceps, and may be considered as target for anti-helminth drugs design. PMID:20145710

  3. Proteogenomic Analysis Greatly Expands the Identification of Proteins Related to Reproduction in the Apogamous Fern Dryopteris affinis ssp. affinis.

    Science.gov (United States)

    Grossmann, Jonas; Fernández, Helena; Chaubey, Pururawa M; Valdés, Ana E; Gagliardini, Valeria; Cañal, María J; Russo, Giancarlo; Grossniklaus, Ueli

    2017-01-01

    Performing proteomic studies on non-model organisms with little or no genomic information is still difficult. However, many specific processes and biochemical pathways occur only in species that are poorly characterized at the genomic level. For example, many plants can reproduce both sexually and asexually, the first one allowing the generation of new genotypes and the latter their fixation. Thus, both modes of reproduction are of great agronomic value. However, the molecular basis of asexual reproduction is not well understood in any plant. In ferns, it combines the production of unreduced spores (diplospory) and the formation of sporophytes from somatic cells (apogamy). To set the basis to study these processes, we performed transcriptomics by next-generation sequencing (NGS) and shotgun proteomics by tandem mass spectrometry in the apogamous fern D. affinis ssp. affinis . For protein identification we used the public viridiplantae database (VPDB) to identify orthologous proteins from other plant species and new transcriptomics data to generate a "species-specific transcriptome database" (SSTDB). In total 1,397 protein clusters with 5,865 unique peptide sequences were identified (13 decoy proteins out of 1,410, protFDR 0.93% on protein cluster level). We show that using the SSTDB for protein identification increases the number of identified peptides almost four times compared to using only the publically available VPDB. We identified homologs of proteins involved in reproduction of higher plants, including proteins with a potential role in apogamy. With the increasing availability of genomic data from non-model species, similar proteogenomics approaches will improve the sensitivity in protein identification for species only distantly related to models.

  4. Decline of traditional family system and reproductive behaviour in rural Bangladesh.

    Science.gov (United States)

    Sarker, P C

    1993-01-01

    This paper is based on data taken from the study entitled Social Structure and Fertility Behavior in a Rural Community of Bangladesh. The field-work was carried out during 1985-86 in Kamnagar, a village in the north-eastern corner of Rajshahi metropolitan city, with a total population of 884. 54.4% of the villagers had no education. Basic information was collected from every household by questionnaires interviewing the head of the household. In the 2nd phase questionnaires were administered to 140 eligible husbands and 140 wives separately to collect information on fertility behavior. 56.8% of the families were nuclear. 12.1% of the families were supplementary nuclear, with parents and their unmarried children including 1 or more additional members. 24.9% of the families were joint, in which related males belonging to 2 or 3 generations lived together with their dependents. 6.2% of the families were extended. As far as the authority structure was concerned, 68.1% of the families were patriarchal, 9.9% of the families were matriarchal, and 22% of the families were egalitarian. The egalitarian authority system is increasing with the spread of female literacy, economic activities outside the home, and women's mobility. Couples in nuclear families are more free to decide on the number of children, birth spacing, and adoption of contraception than those in joint, extended, and supplementary nuclear families with patriarchal and matriarchal authority structures. In nuclear families with an egalitarian authority structure, husband-wife communication can help decide about the number of children wanted, the acceptance of contraceptives, and child spacing. Nuclear families favor lower fertility than supplementary nuclear, joint, and extended families with a patriarchal or matriarchal authority structure. The number of traditional joint and extended families is on the decline with the trend to nuclear families as a result of the increasing landlessness in rural Bangladesh

  5. Mens Perspectives on Family Planning and Their Knowledge on Reproductive Health

    Directory of Open Access Journals (Sweden)

    Ayse Cakir Gungor

    2013-10-01

    Full Text Available Aim: Many training programs for females about contraception have been developed. In this study, we aimed to investigate the perspectives of males on contraception and their knowledge on reproductive health. Material and Method: Husbands of pregnant women who presented in our obstetric clinic were invited to complete a questionnaire. Results: A total of 178 men answered our questionnaire. Among their wives, 11.1% (17/153 terminated their at least one unintended pregnancy. 142 of them (79.8% knew about modern contraceptive methods, and 104 (58.4% of them used at least one of these methods. Condoms were perceived as the best contraceptive method for 46.1% (35/76 because of their easiness to use and cheapness, and 41.7% (25/60 of the participants stated that they would like to use condom from then on. 55.6% (40/72 stated that they would never use oral contraceptives because of their possible side effects on their wives. 20 of the questions addressed to the participants were about reproductive health. The participants answered approximately 70% of all questions correctly. The correct answering rate for every question ranged between 39.6% and 96.1%. Discussion: In our study, we investigated attitudes and knowledge about contraception and reproductive health among men who were married and fertile. The findings from this study can provide a foundation for further education programs for men in these areas.

  6. Family planning and reproductive health supply stockouts: problems and remedies for faith-based health facilities in Africa

    Directory of Open Access Journals (Sweden)

    Amy M. Metzger

    2017-01-01

    Full Text Available Background and aims: Faith-based organizations (FBOs provide a substantial portion of the health care services in many African countries. FBO facilities do consider family planning and reproductive health services as essential to reducing maternal and child mortality, and to the growth of healthy families. Many health facilities, however, struggle to maintain adequate stocks of reproductive health (RH supplies because of the various RH supply chains and funding sources, which often operate separately from other medicines and supplies. The purpose of this study is to identify the types of supply chain systems used by African faith-based health facilities to acquire reproductive health products (clotrimazole, combined oral contraceptive pills, contraceptive implants, CycleBeads®, emergency contraception, Erythromycin, female condoms, injectable contraceptives, intra-uterine contraceptive devices, magnesium sulfate, male condoms, Methyldopa, Misoprostol, Nifedpine, Oxytocin, and Progestin-only pills, to describe their problems and challenges, and to identify possible corrective actions. Methods: Through email surveys, phone interviews, and on-site visits, we studied the supply chains of 46 faith-based health facilities in 13 African countries. Sixteen RH commodities, including contraceptives, were selected as indicators. Results: Of the 46 facilities surveyed, 55 percent faced stockouts of one or more products in the three months prior to the survey. Stockouts were less common for contraceptives than for other RH products. Significant strengths of the FBO supply chain included creativity in finding other sources of commodities in the face of stockouts, staff designated to monitor quality of the commodities, high capacity for storage, low incidence of expired products, few instances of poor quality, and strong financial sustainability mechanisms, often including patient fees. Weaknesses included unreliable commodity sources and power supplies, long

  7. The Impact of Reproductive Health Legislation on Family Planning Clinic Services in Texas

    Science.gov (United States)

    Hopkins, Kristine; Aiken, Abigail R. A.; Stevenson, Amanda; Hubert, Celia; Grossman, Daniel; Potter, Joseph E.

    2015-01-01

    We examined the impact of legislation in Texas that dramatically cut and restricted participation in the state’s family planning program in 2011 using surveys and interviews with leaders at organizations that received family planning funding. Overall, 25% of family planning clinics in Texas closed. In 2011, 71% of organizations widely offered long-acting reversible contraception; in 2012–2013, only 46% did so. Organizations served 54% fewer clients than they had in the previous period. Specialized family planning providers, which were the targets of the legislation, experienced the largest reductions in services, but other agencies were also adversely affected. The Texas experience provides valuable insight into the potential effects that legislation proposed in other states may have on low-income women’s access to family planning services. PMID:25790404

  8. Using behavior change communication to lead a comprehensive family planning program: the Nigerian Urban Reproductive Health Initiative

    Science.gov (United States)

    Krenn, Susan; Cobb, Lisa; Babalola, Stella; Odeku, Mojisola; Kusemiju, Bola

    2014-01-01

    ABSTRACT Background: The Nigerian Urban Reproductive Health Initiative (NURHI), a 6-year comprehensive family planning program (2009–2015) in 4 cities, intentionally applies communication theories to all program elements, not just the demand generation ones, relying mainly on a theory called ideation—the concept that contraceptive use is influenced by people's beliefs, ideas, and feelings and that changing these ideational factors can change people's behavior. Program Description: The project used multiple communication channels to foster dialogue about family planning, increase social approval for it, and improve accurate knowledge about contraceptives. Mobile service delivery was started in the third year to improve access to clinical methods in slums. Methods: Data from representative baseline (2010–11) and midterm (2012) surveys of women of reproductive age in the project cities were analyzed. We also used propensity score matching to create a statistically equivalent control group of women not exposed to project activities, and we examined service delivery data from NURHI-supported clinics (January 2011–May 2013) to determine the contribution of mobile services to total family planning services. Results: Three years into the initiative, analysis of longitudinal data shows that use of modern contraceptives has increased in each city, varying from 2.3 to 15.5 percentage points, and that the observed increases were predicted by exposure to NURHI activities. Of note is that modern method use increased substantially among the poorest wealth quintiles in project cities, on average, by 8.4 percentage points. The more project activities women were exposed to, the greater their contraceptive use. For example, among women not using a modern method at baseline, contraceptive prevalence among those with no exposure by midterm was 19.1% vs. 43.4% among those with high exposure. Project exposure had a positive dose-response relationship with ideation, as did

  9. Prioritization of candidate genes for cattle reproductive traits, based on protein-protein interactions, gene expression, and text-mining

    DEFF Research Database (Denmark)

    Hulsegge, Ina; Woelders, Henri; Smits, Mari

    2013-01-01

    Reproduction is of significant economic importance in dairy cattle. Improved understanding of mechanisms that control estrous behavior and other reproduction traits could help in developing strategies to improve and/or monitor these traits. The objective of this study was to predict and rank gene...

  10. High Temperature During Rice Grain Filling Enhances Aspartate Metabolism in Grains and Results in Accumulation of Aspartate-Family Amino Acids and Protein Components

    Directory of Open Access Journals (Sweden)

    Cheng-gang LIANG

    2013-09-01

    Full Text Available Global warming causes the exacerbation of rice growing environment, which seriously affects rice growth and reproduction, and finally results in the decrease of rice yield and quality. We investigated the activities of aspartate metabolism enzymes in grains, and the contents of Aspartate-family amino acids and protein components to further understand the effects of high temperature (HT on rice nutritional quality during rice grain filling. Under HT, the average activities of aspartate aminotransferase (AAT and aspartokinase (AK in grains significantly increased, the amino acid contents of aspartate (Asp, lysine (Lys, threonine (Thr, methionine (Met and isoleucine (Ile and the protein contents of albumin, globulin, prolamin and glutelin also significantly increased. The results indicated that HT enhanced Asp metabolism during rice grain filling and the enhancement of Asp metabolism might play an important role in the increase of Asp-family amino acids and protein components in grains. In case of the partial appraisal of the change of Asp-family amino acids and protein components under HT, we introduced eight indicators (amino acid or protein content, ratio of amino acid or protein, amino acid or protein content per grain and amino acid or protein content per panicle to estimate the effects of HT. It is suggested that HT during rice grain filling was benefit for the accumulation of Asp-family amino acids and protein components. Combined with the improvement of Asp-family amino acid ratio in grains under HT, it is suggested that HT during grain filling may improve the rice nutritional quality. However, the yields of parts of Asp-family amino acids and protein components were decreased under HT during rice grain filling.

  11. Effect of Water Deficit-Induced at Vegetative and Reproductive Stages on Protein and Oil Content in Soybean Grains

    Directory of Open Access Journals (Sweden)

    Liliane M. Mertz-Henning

    2017-12-01

    Full Text Available Soybean is one of the most common grain crops worldwide, representing an important protein and oil source. Although genetic variability in the chemical composition of grains is seen in soybean, the mean levels of proteins have remained stagnant or, in some cases, have decreased over time, arousing concern in the agricultural industry. Furthermore, environmental conditions influence the chemical composition of grains. Thus, the present study evaluated the effect of water deficit (WD induced at the vegetative period (vegetative stress (VS and reproductive period (reproductive stress (RS on the protein and oil contents of grains in different soybean genotypes. Yield and its components were evaluated to evaluate the interrelation of these traits. The experiment was completed over three crop seasons under field conditions in Londrina, Paraná (PR, Brazil. WD was induced using rainout shelters and then stress treatments with irrigated and non-irrigated conditions were compared. WD negatively affected yield and its components. All evaluated genotypes showed similar responses for oil and protein contents under different water conditions. Higher protein content and lower oil content were observed in grains under RS. Such a relationship was not equally established under VS. Additionally, negative relationships between protein and oil content and between protein content and yield were confirmed.

  12. What is a family? Kinship, reproductive practices and single mothers by choice

    DEFF Research Database (Denmark)

    Ravn, Tine

    of single mothers by choice, the paper explores how the women conceive and enact the notions of family and kinship in terms of creating significant relations and networks. Furthermore, the paper shows and discusses how a complex interplay of biogenetic and social ties impacts on these family conceptions...... to one emerging ‘new’ family form represented by single mothers by choice (SMC’s) who by means of donor insemination and/or IVF treatment, intentionally choose to conceive a child and act as the sole parent. Based on very initial findings from a larger Danish biographical narrative interview study...

  13. The PSI family of nuclear proteins is required for growth in arabidopsis.

    Science.gov (United States)

    Stührwohldt, Nils; Hartmann, Jens; Dahlke, Renate I; Oecking, Claudia; Sauter, Margret

    2014-10-01

    PSI1 was identified as a gene that is co-expressed with the phytosulfokine (PSK) receptor genes PSKR1 and PSKR2 in Arabidopsis thaliana. It represents a plant-specific protein family of unknown function with six members in two clades. Clade 1 members PSI1, PSI2 and PSI3 were characterized in this study. All three are nuclear localized. A predicted N-terminal myristoylation site was functionally analyzed. psi1-1 seedlings have shorter roots and hypocotyls. This growth-retarded phenotype was restored by expression of either wildtype PSI1 or PSI1 G2A with a mutated myristate attachment site in the psi1-1 background suggesting that myristate attachment was not essential for PSI1 function. psi2-1 and psi3-1 seedlings have a wildtype phenotype but overexpression of PSI1 or PSI2 promoted seedling growth. PSI2 activity appears to be linked to PSK signaling as psi2-1 and psi2-1 psi3-1 roots are unresponsive to PSK. PSI3 functions in vegetative plant growth synergistic with PSI2. psi3-1 and particularly psi2-1 psi3-1 rosettes are small. Overexpression of PSI3 promoted plant growth indicating that PSI3 is limiting at the vegetative stage. Severe dwarfism of psi2-1 psi3-1 plants results from reduced cell growth and proliferation and premature leaf growth arrest. Plants further display reduced fertility and premature senescence revealing a crucial function of PSI proteins in vegetative growth and reproduction. Psi single and double knock-out plants have less and PSI3ox plants have more starch compared to wt and growth retardation is partially rescued by sucrose. Our studies reveal a crucial function of the nuclear-localized PSI proteins in growth possibly through metabolic control.

  14. The nuclear IκB family of proteins controls gene regulation and immune homeostasis.

    Science.gov (United States)

    MaruYama, Takashi

    2015-10-01

    The inhibitory IκB family of proteins is subdivided into two groups based on protein localization in the cytoplasm or in the nucleus. These proteins interact with NF-κB, a major transcription factor regulating the expression of many inflammatory cytokines, by modulating its transcriptional activity. However, nuclear IκB family proteins not only interact with NF-κB to change its transcriptional activity, but they also bind to chromatin and control gene expression. This review provides an overview of nuclear IκB family proteins and their role in immune homeostasis. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. ErpC, a member of the complement regulator-acquiring family of surface proteins from Borrelia burgdorferi, possesses an architecture previously unseen in this protein family

    International Nuclear Information System (INIS)

    Caesar, Joseph J. E.; Johnson, Steven; Kraiczy, Peter; Lea, Susan M.

    2013-01-01

    The structure of ErpC, a member of the complement regulator-acquiring surface protein family from B. burgdorferi, has been solved, providing insights into the strategies of complement evasion by this zoonotic bacterium and suggesting a common architecture for other members of this protein family. Borrelia burgdorferi is a spirochete responsible for Lyme disease, the most commonly occurring vector-borne disease in Europe and North America. The bacterium utilizes a set of proteins, termed complement regulator-acquiring surface proteins (CRASPs), to aid evasion of the human complement system by recruiting and presenting complement regulator factor H on its surface in a manner that mimics host cells. Presented here is the atomic resolution structure of a member of this protein family, ErpC. The structure provides new insights into the mechanism of recruitment of factor H and other factor H-related proteins by acting as a molecular mimic of host glycosaminoglycans. It also describes the architecture of other CRASP proteins belonging to the OspE/F-related paralogous protein family and suggests that they have evolved to bind specific complement proteins, aiding survival of the bacterium in different hosts

  16. An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers.

    Science.gov (United States)

    Linhoff, Michael W; Laurén, Juha; Cassidy, Robert M; Dobie, Frederick A; Takahashi, Hideto; Nygaard, Haakon B; Airaksinen, Matti S; Strittmatter, Stephen M; Craig, Ann Marie

    2009-03-12

    Delineating the molecular basis of synapse development is crucial for understanding brain function. Cocultures of neurons with transfected fibroblasts have demonstrated the synapse-promoting activity of candidate molecules. Here, we performed an unbiased expression screen for synaptogenic proteins in the coculture assay using custom-made cDNA libraries. Reisolation of NGL-3/LRRC4B and neuroligin-2 accounts for a minority of positive clones, indicating that current understanding of mammalian synaptogenic proteins is incomplete. We identify LRRTM1 as a transmembrane protein that induces presynaptic differentiation in contacting axons. All four LRRTM family members exhibit synaptogenic activity, LRRTMs localize to excitatory synapses, and artificially induced clustering of LRRTMs mediates postsynaptic differentiation. We generate LRRTM1(-/-) mice and reveal altered distribution of the vesicular glutamate transporter VGLUT1, confirming an in vivo synaptic function. These results suggest a prevalence of LRR domain proteins in trans-synaptic signaling and provide a cellular basis for the reported linkage of LRRTM1 to handedness and schizophrenia.

  17. Monoubiquitination of Tob/BTG family proteins competes with degradation-targeting polyubiquitination

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Toru, E-mail: toru@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Kim, Minsoo [Division of Bacterial Infection, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Kozuka-Hata, Hiroko [Medical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Watanabe, Masato [Department of Medical Genome Science, School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa 277-8562 (Japan); Oyama, Masaaki [Medical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Tsumoto, Kouhei [Medical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Department of Medical Genome Science, School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa 277-8562 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Cell Signal Unit, Okinawa Institute of Science and Technology, 1919-1 Onna-son, Kunigami, Okinawa 904-0412 (Japan)

    2011-05-27

    Highlights: {yields} Tob/BTG family proteins are monoubiquitinated in the absence of E3s in vitro. {yields} Monoubiquitination sites of Tob are identified by mass spectrometry. {yields} The monoubiquitination event correlates with lower levels of polyubiquitination. -- Abstract: Tob belongs to the anti-proliferative Tob/BTG protein family. The expression level of Tob family proteins is strictly regulated both transcriptionally and through post-translational modification. Ubiquitin (Ub)/proteosome-dependent degradation of Tob family proteins is critical in controlling cell cycle progression and DNA damage responses. Various Ub ligases (E3s) are responsible for degradation of Tob protein. Here, we show that Tob family proteins undergo monoubiquitination even in the absence of E3s in vitro. Determination of the ubiquitination site(s) in Tob by mass spectrometric analysis revealed that two lysine residues (Lys48 and Lys63) located in Tob/BTG homology domain are ubiquitinated. A mutant Tob, in which both Lys48 and Lys63 are substituted with alanine, is more strongly polyubiquitinated than wild-type Tob in vivo. These data suggest that monoubiquitination of Tob family proteins confers resistance against polyubiquitination, which targets proteins for degradation. The strategy for regulating the stability of Tob family proteins suggests a novel role for monoubiquitination.

  18. Monoubiquitination of Tob/BTG family proteins competes with degradation-targeting polyubiquitination

    International Nuclear Information System (INIS)

    Suzuki, Toru; Kim, Minsoo; Kozuka-Hata, Hiroko; Watanabe, Masato; Oyama, Masaaki; Tsumoto, Kouhei; Yamamoto, Tadashi

    2011-01-01

    Highlights: → Tob/BTG family proteins are monoubiquitinated in the absence of E3s in vitro. → Monoubiquitination sites of Tob are identified by mass spectrometry. → The monoubiquitination event correlates with lower levels of polyubiquitination. -- Abstract: Tob belongs to the anti-proliferative Tob/BTG protein family. The expression level of Tob family proteins is strictly regulated both transcriptionally and through post-translational modification. Ubiquitin (Ub)/proteosome-dependent degradation of Tob family proteins is critical in controlling cell cycle progression and DNA damage responses. Various Ub ligases (E3s) are responsible for degradation of Tob protein. Here, we show that Tob family proteins undergo monoubiquitination even in the absence of E3s in vitro. Determination of the ubiquitination site(s) in Tob by mass spectrometric analysis revealed that two lysine residues (Lys48 and Lys63) located in Tob/BTG homology domain are ubiquitinated. A mutant Tob, in which both Lys48 and Lys63 are substituted with alanine, is more strongly polyubiquitinated than wild-type Tob in vivo. These data suggest that monoubiquitination of Tob family proteins confers resistance against polyubiquitination, which targets proteins for degradation. The strategy for regulating the stability of Tob family proteins suggests a novel role for monoubiquitination.

  19. Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis

    NARCIS (Netherlands)

    Douma, K.F.L.; Aaronson, N.K.; Vasen, H.F.A.; Verhoef, S.; Gundy, C.M.; Bleiker, E.M.A.

    2010-01-01

    Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA

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

    Science.gov (United States)

    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.

  1. Using Förster-Resonance Energy Transfer to Measure Protein Interactions Between Bcl-2 Family Proteins on Mitochondrial Membranes.

    Science.gov (United States)

    Pogmore, Justin P; Pemberton, James M; Chi, Xiaoke; Andrews, David W

    2016-01-01

    The Bcl-2 family of proteins regulates the process of mitochondrial outer membrane permeabilization, causing the release of cytochrome c and committing a cell to apoptosis. The majority of the functional interactions between these proteins occur at, on, or within the mitochondrial outer membrane, complicating structural studies of the proteins and complexes. As a result most in vitro studies of these protein-protein interactions use truncated proteins and/or detergents which can cause artificial interactions. Herein, we describe a detergent-free, fluorescence-based, in vitro technique to study binding between full-length recombinant Bcl-2 family proteins, particularly cleaved BID (cBID) and BCL-XL, on the membranes of purified mitochondria.

  2. The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids

    Directory of Open Access Journals (Sweden)

    Ngai John

    2006-12-01

    Full Text Available Abstract Background Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs: the OR, V1R, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. Results Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact "V2R-like" olfactory C family GPCRs in the zebrafish. Phylogenetic analysis – which also included a set of 34 C family GPCRs from fugu – places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, T1R taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. Conclusion Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s, these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.

  3. Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family

    Directory of Open Access Journals (Sweden)

    Sonnhammer Erik L

    2008-01-01

    Full Text Available Abstract Background Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extra-cellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection. Results We have combined phylogenetic and function shift analyses to study the evolution of the RIFIN proteins, which are antigenically variant and are encoded by the largest multicopy gene family in Plasmodium falciparum. We show that this family can be subdivided into two major groups that we named A- and B-RIFIN proteins. This suggested sub-grouping is supported by a recently published study that showed that, despite the presence of the Plasmodium export (PEXEL motif in all RIFIN variants, proteins from each group have different cellular localizations during the intraerythrocytic life cycle of the parasite. In the present study we show that function shift analysis, a novel technique to predict functional divergence between sub-groups of a protein family, indicates that RIFINs have undergone neo- or sub-functionalization. Conclusion These results question the general trend of clustering large antigenically variant protein groups into homogenous families. Assigning functions to protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. Using phylogenetic and function shift analysis methods, we identify new directions for the investigation of this broad and complex group of proteins.

  4. Utilization of family planning services by married Sudanese women of reproductive age.

    Science.gov (United States)

    Ibnouf, A H; van den Borne, H W; Maarse, J A M

    2007-01-01

    To explore differences in utilization of family planning services and predisposing factors, we surveyed 601 women from urban and rural areas of Khartoum state. About half were using modern family planning techniques; there were no significant differences in utilization rates between urban and rural settings. Contraceptive pills were the most frequently used modern method (47.7%) followed by intrauterine devices (10.2%) and injections (7.5%). Breastfeeding was used by around 33% of both groups. The rhythm method and withdrawal were more often used by urban women (22.2% and 8.6% respectively) than rural women (16.1% and 3.6% respectively). Use of male methods (condom; sterilization) was extremely low. Socioeconomic status, knowledge and education level were the most important determinants of using modern methods.

  5. The Resignation of the Governor-General: Family Drama and National Reproduction

    Directory of Open Access Journals (Sweden)

    Barbara Baird

    2011-04-01

    Full Text Available This article tells the story of the 2003 resignation of Peter Hollingworth as Governor-General as part of an ongoing hyper-anxiety in Australia about the state and status of ‘the child’. The sexually abused child sits at the centre of this story and carries a heavy burden with respect to the past and future of the white Australian nation. The recuperation of that child to a state of innocence, repeatedly, as stories of its abuse keep returning to our front pages and political agendas, is necessary for the reproduction of the white nation. This article shows that the Hollingworth drama is entwined with the current politics of motherhood and fatherhood and the carriage of national feeling and temporality through the performances of these always racialised identities. Attending to the politics of the historical construction of the child, and the idealised parents who abuse or protect it (but never allow this child a voice or a sexuality of her or his own, thus becomes a part of the project of accountability to the past which has also occupied public life in Australia over recent years.

  6. Two novel heat-soluble protein families abundantly expressed in an anhydrobiotic tardigrade.

    Directory of Open Access Journals (Sweden)

    Ayami Yamaguchi

    Full Text Available Tardigrades are able to tolerate almost complete dehydration by reversibly switching to an ametabolic state. This ability is called anhydrobiosis. In the anhydrobiotic state, tardigrades can withstand various extreme environments including space, but their molecular basis remains largely unknown. Late embryogenesis abundant (LEA proteins are heat-soluble proteins and can prevent protein-aggregation in dehydrated conditions in other anhydrobiotic organisms, but their relevance to tardigrade anhydrobiosis is not clarified. In this study, we focused on the heat-soluble property characteristic of LEA proteins and conducted heat-soluble proteomics using an anhydrobiotic tardigrade. Our heat-soluble proteomics identified five abundant heat-soluble proteins. All of them showed no sequence similarity with LEA proteins and formed two novel protein families with distinct subcellular localizations. We named them Cytoplasmic Abundant Heat Soluble (CAHS and Secretory Abundant Heat Soluble (SAHS protein families, according to their localization. Both protein families were conserved among tardigrades, but not found in other phyla. Although CAHS protein was intrinsically unstructured and SAHS protein was rich in β-structure in the hydrated condition, proteins in both families changed their conformation to an α-helical structure in water-deficient conditions as LEA proteins do. Two conserved repeats of 19-mer motifs in CAHS proteins were capable to form amphiphilic stripes in α-helices, suggesting their roles as molecular shield in water-deficient condition, though charge distribution pattern in α-helices were different between CAHS and LEA proteins. Tardigrades might have evolved novel protein families with a heat-soluble property and this study revealed a novel repertoire of major heat-soluble proteins in these anhydrobiotic animals.

  7. The Sorcerer II Global Ocean Sampling Expedition: Expanding theUniverse of Protein Families

    Energy Technology Data Exchange (ETDEWEB)

    Yooseph, Shibu; Sutton, Granger; Rusch, Douglas B.; Halpern,Aaron L.; Williamson, Shannon J.; Remington, Karin; Eisen, Jonathan A.; Heidelberg, Karla B.; Manning, Gerard; Li, Weizhong; Jaroszewski, Lukasz; Cieplak, Piotr; Miller, Christopher S.; Li, Huiying; Mashiyama, Susan T.; Joachimiak, Marcin P.; van Belle, Christopher; Chandonia, John-Marc; Soergel, David A.; Zhai, Yufeng; Natarajan, Kannan; Lee, Shaun; Raphael,Benjamin J.; Bafna, Vineet; Friedman, Robert; Brenner, Steven E.; Godzik,Adam; Eisenberg, David; Dixon, Jack E.; Taylor, Susan S.; Strausberg,Robert L.; Frazier, Marvin; Venter, J.Craig

    2006-03-23

    Metagenomics projects based on shotgun sequencing of populations of micro-organisms yield insight into protein families. We used sequence similarity clustering to explore proteins with a comprehensive dataset consisting of sequences from available databases together with 6.12 million proteins predicted from an assembly of 7.7 million Global Ocean Sampling (GOS) sequences. The GOS dataset covers nearly all known prokaryotic protein families. A total of 3,995 medium- and large-sized clusters consisting of only GOS sequences are identified, out of which 1,700 have no detectable homology to known families. The GOS-only clusters contain a higher than expected proportion of sequences of viral origin, thus reflecting a poor sampling of viral diversity until now. Protein domain distributions in the GOS dataset and current protein databases show distinct biases. Several protein domains that were previously categorized as kingdom specific are shown to have GOS examples in other kingdoms. About 6,000 sequences (ORFans) from the literature that heretofore lacked similarity to known proteins have matches in the GOS data. The GOS dataset is also used to improve remote homology detection. Overall, besides nearly doubling the number of current proteins, the predicted GOS proteins also add a great deal of diversity to known protein families and shed light on their evolution. These observations are illustrated using several protein families, including phosphatases, proteases, ultraviolet-irradiation DNA damage repair enzymes, glutamine synthetase, and RuBisCO. The diversity added by GOS data has implications for choosing targets for experimental structure characterization as part of structural genomics efforts. Our analysis indicates that new families are being discovered at a rate that is linear or almost linear with the addition of new sequences, implying that we are still far from discovering all protein families in nature.

  8. The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families.

    Science.gov (United States)

    Yooseph, Shibu; Sutton, Granger; Rusch, Douglas B; Halpern, Aaron L; Williamson, Shannon J; Remington, Karin; Eisen, Jonathan A; Heidelberg, Karla B; Manning, Gerard; Li, Weizhong; Jaroszewski, Lukasz; Cieplak, Piotr; Miller, Christopher S; Li, Huiying; Mashiyama, Susan T; Joachimiak, Marcin P; van Belle, Christopher; Chandonia, John-Marc; Soergel, David A; Zhai, Yufeng; Natarajan, Kannan; Lee, Shaun; Raphael, Benjamin J; Bafna, Vineet; Friedman, Robert; Brenner, Steven E; Godzik, Adam; Eisenberg, David; Dixon, Jack E; Taylor, Susan S; Strausberg, Robert L; Frazier, Marvin; Venter, J Craig

    2007-03-01

    Metagenomics projects based on shotgun sequencing of populations of micro-organisms yield insight into protein families. We used sequence similarity clustering to explore proteins with a comprehensive dataset consisting of sequences from available databases together with 6.12 million proteins predicted from an assembly of 7.7 million Global Ocean Sampling (GOS) sequences. The GOS dataset covers nearly all known prokaryotic protein families. A total of 3,995 medium- and large-sized clusters consisting of only GOS sequences are identified, out of which 1,700 have no detectable homology to known families. The GOS-only clusters contain a higher than expected proportion of sequences of viral origin, thus reflecting a poor sampling of viral diversity until now. Protein domain distributions in the GOS dataset and current protein databases show distinct biases. Several protein domains that were previously categorized as kingdom specific are shown to have GOS examples in other kingdoms. About 6,000 sequences (ORFans) from the literature that heretofore lacked similarity to known proteins have matches in the GOS data. The GOS dataset is also used to improve remote homology detection. Overall, besides nearly doubling the number of current proteins, the predicted GOS proteins also add a great deal of diversity to known protein families and shed light on their evolution. These observations are illustrated using several protein families, including phosphatases, proteases, ultraviolet-irradiation DNA damage repair enzymes, glutamine synthetase, and RuBisCO. The diversity added by GOS data has implications for choosing targets for experimental structure characterization as part of structural genomics efforts. Our analysis indicates that new families are being discovered at a rate that is linear or almost linear with the addition of new sequences, implying that we are still far from discovering all protein families in nature.

  9. The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families.

    Directory of Open Access Journals (Sweden)

    Shibu Yooseph

    2007-03-01

    Full Text Available Metagenomics projects based on shotgun sequencing of populations of micro-organisms yield insight into protein families. We used sequence similarity clustering to explore proteins with a comprehensive dataset consisting of sequences from available databases together with 6.12 million proteins predicted from an assembly of 7.7 million Global Ocean Sampling (GOS sequences. The GOS dataset covers nearly all known prokaryotic protein families. A total of 3,995 medium- and large-sized clusters consisting of only GOS sequences are identified, out of which 1,700 have no detectable homology to known families. The GOS-only clusters contain a higher than expected proportion of sequences of viral origin, thus reflecting a poor sampling of viral diversity until now. Protein domain distributions in the GOS dataset and current protein databases show distinct biases. Several protein domains that were previously categorized as kingdom specific are shown to have GOS examples in other kingdoms. About 6,000 sequences (ORFans from the literature that heretofore lacked similarity to known proteins have matches in the GOS data. The GOS dataset is also used to improve remote homology detection. Overall, besides nearly doubling the number of current proteins, the predicted GOS proteins also add a great deal of diversity to known protein families and shed light on their evolution. These observations are illustrated using several protein families, including phosphatases, proteases, ultraviolet-irradiation DNA damage repair enzymes, glutamine synthetase, and RuBisCO. The diversity added by GOS data has implications for choosing targets for experimental structure characterization as part of structural genomics efforts. Our analysis indicates that new families are being discovered at a rate that is linear or almost linear with the addition of new sequences, implying that we are still far from discovering all protein families in nature.

  10. REPRODUCTIVE AND METABOLIC RESPONSES IN EWES TO DIETARY PROTEIN SUPPLEMENT DURING MATING PERIOD IN DRY SEASON OF NORTHEAST BRAZIL

    Directory of Open Access Journals (Sweden)

    Magda Rodrigues

    2015-01-01

    Full Text Available This study evaluated the effect of food supplements with different levels of protein on reproductive and metabolic response of ewes during the mating period. Forty-one ewes were supplemented during 43 days with amount protein to meet 1.0 (diet I; n = 14, 1.7 (diet II; n = 13 and 2.1 (diet III; n = 14 times the maintenance requirements. Dry matter (DM intake was higher (P < 0.01 in diet III when compared to diets I and II. Orts were lesser in diets II and III (P < 0.05 when compared to diet I. Intake of organic matter (OM, crude protein (CP and ether extract (EE was higher in diet III (P < 0.05, but NDF and ADF intake was superior in diet I (P < 0.05. In diet III, a higher frequency of female mated was observed (P < 0.05. The prolificity and twinning rate was higher in ewes of diet II (P < 0.05. Greater birth weight of lambs (P < 0.05 was verified in diet III. The progesterone levels were affected by diets II and III (P < 0.05. In conclusion, the supplementation of ewes with intermediate level of protein improves their reproductive response.

  11. Comparative and functional analysis of the widely occurring family of Nep1-like proteins

    NARCIS (Netherlands)

    Oome, Stan; van den Ackerveken, Guido

    2014-01-01

    Nep1-like proteins (NLP) are best known for their cytotoxic activity in dicot plants. NLP are taxonomically widespread among microbes with very different lifestyles. To learn more about this enigmatic protein family, we analyzed more than 500 available NLP protein sequences from fungi, oomycetes,

  12. Regulation and Selectivity of Exchange Factors for G-proteins of the Ras-family

    NARCIS (Netherlands)

    Popovic, M.

    2013-01-01

    Small G-proteins are important regulators of the cellular signaling pathways. Among them, members of the Ras family of small G-proteins regulate processes such as cell differentiation, growth, migration, transport and adhesion, and their deregulation may lead to various diseases. Small G-proteins

  13. The Protein Kinase RSK Family - Roles in Prostate Cancer

    National Research Council Canada - National Science Library

    Lannigan, Deborah

    2006-01-01

    The Ser/Thr protein kinase p90-kDa ribosomal S6 kinase (RSK) is an important downstream effector of mitogen-activated protein kinase but its roles in prostate cancer have not been previously examined...

  14. Racial Differences in Pregnancy Intention, Reproductive Coercion, and Partner Violence among Family Planning Clients: A Qualitative Exploration.

    Science.gov (United States)

    Holliday, Charvonne N; Miller, Elizabeth; Decker, Michele R; Burke, Jessica G; Documet, Patricia I; Borrero, Sonya B; Silverman, Jay G; Tancredi, Daniel J; Ricci, Edmund; McCauley, Heather L

    Unintended pregnancy (UIP) is a persistent public health concern in the United States disproportionately experienced by racial/ethnic minorities and women of low socioeconomic status. UIP often occurs with experiences of reproductive coercion (RC) and intimate partner violence (IPV). The purpose of the study was to qualitatively describe and compare contexts for UIP risk between low-income Black and White women with histories of IPV/RC. Semistructured interviews were conducted with low-income Black and White women with histories of IPV or RC, ages 18 to 29 years, recruited from family planning clinics in Pittsburgh, Pennsylvania. Interviews with 10 non-Hispanic Black women and 34 non-Hispanic White women (N = 44) were included in the analysis. Differences between White and Black women emerged regarding IPV/RC experiences, gender roles in intimate relationships, and trauma histories, including childhood adversity. Fatal threats and IPV related to childbearing were most influential among White women. Among Black women, pregnancy was greatly influenced by RC related to impending incarceration, subfertility, and condom nonuse, and decisions about contraception were often dependent on the male. Sexual abuse, including childhood sexual assault, in the context of sexual/reproductive health was more prominent among White women. Childhood experiences of neglect impacted pregnancy intention and love-seeking behaviors among Black women. Racial differences exist in experiences of IPV/RC with regard to UIP even among women with similar economic resources and health care access. These findings provide much-needed context to the persistent racial/ethnic disparities in UIP and illustrate influences beyond differential access to care and socioeconomic status. Copyright © 2018 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  15. FEATURES OF REPRODUCTION OF THE HUMAN CAPITAL IN THE SOCIAL INSTITUTION OF THE FAMILY

    Directory of Open Access Journals (Sweden)

    Dar'ya G. Bykova

    2015-01-01

    Full Text Available  Subject / topic. The article deals with the problem of increasing the qualitytion of human capital on the basis of enhancing the role of the social institution of the family. The issues of socialization of young people and involving them in a motivated work.Purpose. The main purpose of the presentation material in this article we conclude, is to find methods to increase efficiency chelovechesky potential on the basis of family relationships.Methodology. In this paper, the methods used: abstractstion, analysis and synthesis, analogy, dialectic method of induction and deduction, observation, generalization, objectivism, compare.Conclusions / relevance. In the context of the trends of aging and reduction of the country's population, the reform of the pension system creates a number of conditions on the one hand, contribute to the solution of the demographic problem, but on the other – has a multifactorial effect on the quality of human capital as a result of parental work. The article presents the possible approaches to solving this problem. Practical application of the results of this work will allow to rethink the approach to the concept of human resources, improving the socio-economic development of theRussian Federation. 

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

    Science.gov (United States)

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

    2011-11-25

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

  17. Programming the body, planning reproduction, governing life: the '(ir-) rationality' of family planning and the embodiment of social inequalities in Salvador da Bahia (Brazil).

    Science.gov (United States)

    De Zordo, Silvia

    2012-01-01

    This paper examines family planning in Brazil as biopolitics and explores how the democratization of the State and of reproductive health services after two decades of military dictatorship (1964-1984) has influenced health professionals' and family planning users' discourses and practices. Do health professionals envisage family planning as a 'right' or do they conceive it, following the old neo-Malthusian rationale, as a 'moral duty' of poor people, whose 'irrational' reproduction jeopardizes the family's and the nation's well being? And how do their patients conceptualize and embody family planning? To answer these questions, this paper draws on 13 months of multi-sited ethnographic research undertaken between 2003 and 2005 in two public family planning services in Salvador da Bahia, where participant observation was undertaken and unstructured interviews were conducted with 11 health professionals and 70 family planning users, mostly low income black women. The paper examines how different bio-political rationalities operate in these services and argues that the old neo-Malthusian rationale and the current, dominant discourse on reproductive rights, gender equality and citizenship coexist. The coalescence of different biopolitical rationalities leads to the double stigmatization of family planning users as 'victims' of social and gender inequalities and as 'irrational' patients, 'irresponsible' mothers and 'bad' citizens if they do not embody the neo-Malthusian and biomedical rationales shaping medical practice. However, these women do not behave as 'docile bodies': they tactically use medical and non-medical contraceptives not only to be good mothers and citizens, but also to enhance themselves and to attain their own goals.

  18. Família: maternidade e procriação assistida Family: maternity and assisted reproduction

    Directory of Open Access Journals (Sweden)

    Maria da Graça Reis Braga

    2005-04-01

    Full Text Available O presente trabalho trata das transformações que se operam na idéia de família que desenvolvemos no Ocidente. Tais mudanças se devem, entre outros fatores, aos diferentes lugares que a mulher passou a ocupar na família e na sociedade e à constituição de sua identidade pela via da maternidade. Isso também é acompanhado pela decadência do modelo patriarcal, o que gera intensas discussões a respeito de um possível fator de feminilização da cultura e declínio da função paterna. A essas questões somam-se os avanços tecnológicos no campo da medicina da reprodução e as intervenções sobre o corpo feminino, o que tem proporcionado tanto mudanças quanto reforços no modelo de família tradicional ocidental.The present article discusses the transformations within the concepts of family in the Western society. These changes are due to (among others reasons the social position that women have assumed, and to the constitution of a feminine identity based on the fact of becoming a mother. These matters follow the decadence of a patriarchal pattern, which generates discussions regarding a supposed rising of a femininization of culture and the failure of the father role. To these questions recent development of reproductive medicine technologies, and medical interventions upon feminine body can be added, which has provide changes as well as reinforcements to a traditional family model.

  19. Computing a new family of shape descriptors for protein structures

    DEFF Research Database (Denmark)

    Røgen, Peter; Sinclair, Robert

    2003-01-01

    The large-scale 3D structure of a protein can be represented by the polygonal curve through the carbon a atoms of the protein backbone. We introduce an algorithm for computing the average number of times that a given configuration of crossings on such polygonal curves is seen, the average being...

  20. Structural insights and ab initio sequencing within the DING proteins family

    International Nuclear Information System (INIS)

    Elias, Mikael; Liebschner, Dorothee; Gotthard, Guillaume; Chabriere, Eric

    2011-01-01

    DING proteins constitute a recently discovered protein family that is ubiquitous in eukaryotes. The structural insights and the physiological involvements of these intriguing proteins are hereby deciphered. DING proteins constitute an intriguing family of phosphate-binding proteins that was identified in a wide range of organisms, from prokaryotes and archae to eukaryotes. Despite their seemingly ubiquitous occurrence in eukaryotes, their encoding genes are missing from sequenced genomes. Such a lack has considerably hampered functional studies. In humans, these proteins have been related to several diseases, like atherosclerosis, kidney stones, inflammation processes and HIV inhibition. The human phosphate binding protein is a human representative of the DING family that was serendipitously discovered from human plasma. An original approach was developed to determine ab initio the complete and exact sequence of this 38 kDa protein by utilizing mass spectrometry and X-ray data in tandem. Taking advantage of this first complete eukaryotic DING sequence, a immunohistochemistry study was undertaken to check the presence of DING proteins in various mice tissues, revealing that these proteins are widely expressed. Finally, the structure of a bacterial representative from Pseudomonas fluorescens was solved at sub-angstrom resolution, allowing the molecular mechanism of the phosphate binding in these high-affinity proteins to be elucidated

  1. Structural insights and ab initio sequencing within the DING proteins family

    Energy Technology Data Exchange (ETDEWEB)

    Elias, Mikael, E-mail: mikael.elias@weizmann.ac.il [Weizmann Institute of Science, Rehovot (Israel); Liebschner, Dorothee [CRM2, Nancy Université (France); Gotthard, Guillaume; Chabriere, Eric [AFMB, Université Aix-Marseille II (France)

    2011-01-01

    DING proteins constitute a recently discovered protein family that is ubiquitous in eukaryotes. The structural insights and the physiological involvements of these intriguing proteins are hereby deciphered. DING proteins constitute an intriguing family of phosphate-binding proteins that was identified in a wide range of organisms, from prokaryotes and archae to eukaryotes. Despite their seemingly ubiquitous occurrence in eukaryotes, their encoding genes are missing from sequenced genomes. Such a lack has considerably hampered functional studies. In humans, these proteins have been related to several diseases, like atherosclerosis, kidney stones, inflammation processes and HIV inhibition. The human phosphate binding protein is a human representative of the DING family that was serendipitously discovered from human plasma. An original approach was developed to determine ab initio the complete and exact sequence of this 38 kDa protein by utilizing mass spectrometry and X-ray data in tandem. Taking advantage of this first complete eukaryotic DING sequence, a immunohistochemistry study was undertaken to check the presence of DING proteins in various mice tissues, revealing that these proteins are widely expressed. Finally, the structure of a bacterial representative from Pseudomonas fluorescens was solved at sub-angstrom resolution, allowing the molecular mechanism of the phosphate binding in these high-affinity proteins to be elucidated.

  2. FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

    NARCIS (Netherlands)

    Koole, Koos; Clausen, Martijn J. A. M.; van Es, Robert J. J.; van Kempen, Pauline M. W.; Melchers, Lieuwe J.; Koole, Ron; Langendijk, Johannes A.; van Diest, Paul J.; Roodenburg, Jan L. N.; Schuuring, Ed; Willems, Stefan M.

    Introduction Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member

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

    International Nuclear Information System (INIS)

    Mistry, Jaina; Kloppmann, Edda; Rost, Burkhard; Punta, Marco

    2013-01-01

    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 acquired 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

  4. Structure-function correlations of pulmonary surfactant protein SP-B and the saposin-like family of proteins.

    Science.gov (United States)

    Olmeda, Bárbara; García-Álvarez, Begoña; Pérez-Gil, Jesús

    2013-03-01

    Pulmonary surfactant is a lipid-protein complex secreted by the respiratory epithelium of mammalian lungs, which plays an essential role in stabilising the alveolar surface and so reducing the work of breathing. The surfactant protein SP-B is part of this complex, and is strictly required for the assembly of pulmonary surfactant and its extracellular development to form stable surface-active films at the air-liquid alveolar interface, making the lack of SP-B incompatible with life. In spite of its physiological importance, a model for the structure and the mechanism of action of SP-B is still needed. The sequence of SP-B is homologous to that of the saposin-like family of proteins, which are membrane-interacting polypeptides with apparently diverging activities, from the co-lipase action of saposins to facilitate the degradation of sphingolipids in the lysosomes to the cytolytic actions of some antibiotic proteins, such as NK-lysin and granulysin or the amoebapore of Entamoeba histolytica. Numerous studies on the interactions of these proteins with membranes have still not explained how a similar sequence and a potentially related fold can sustain such apparently different activities. In the present review, we have summarised the most relevant features of the structure, lipid-protein and protein-protein interactions of SP-B and the saposin-like family of proteins, as a basis to propose an integrated model and a common mechanistic framework of the apparent functional versatility of the saposin fold.

  5. Fundamental Characteristics of AAA+ Protein Family Structure and Function.

    Science.gov (United States)

    Miller, Justin M; Enemark, Eric J

    2016-01-01

    Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

  6. Adaptor Protein Complex 2–Mediated Endocytosis Is Crucial for Male Reproductive Organ Development in Arabidopsis[W

    Science.gov (United States)

    Kim, Soo Youn; Xu, Zheng-Yi; Song, Kyungyoung; Kim, Dae Heon; Kang, Hyangju; Reichardt, Ilka; Sohn, Eun Ju; Friml, Jiří; Juergens, Gerd; Hwang, Inhwan

    2013-01-01

    Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2–dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs. PMID:23975898

  7. Enhancing the prediction of protein pairings between interacting families using orthology information

    Directory of Open Access Journals (Sweden)

    Pazos Florencio

    2008-01-01

    Full Text Available Abstract Background It has repeatedly been shown that interacting protein families tend to have similar phylogenetic trees. These similarities can be used to predicting the mapping between two families of interacting proteins (i.e. which proteins from one family interact with which members of the other. The correct mapping will be that which maximizes the similarity between the trees. The two families may eventually comprise orthologs and paralogs, if members of the two families are present in more than one organism. This fact can be exploited to restrict the possible mappings, simply by impeding links between proteins of different organisms. We present here an algorithm to predict the mapping between families of interacting proteins which is able to incorporate information regarding orthologues, or any other assignment of proteins to "classes" that may restrict possible mappings. Results For the first time in methods for predicting mappings, we have tested this new approach on a large number of interacting protein domains in order to statistically assess its performance. The method accurately predicts around 80% in the most favourable cases. We also analysed in detail the results of the method for a well defined case of interacting families, the sensor and kinase components of the Ntr-type two-component system, for which up to 98% of the pairings predicted by the method were correct. Conclusion Based on the well established relationship between tree similarity and interactions we developed a method for predicting the mapping between two interacting families using genomic information alone. The program is available through a web interface.

  8. A family of related proteins is encoded by the major Drosophila heat shock gene family

    International Nuclear Information System (INIS)

    Wadsworth, S.C.

    1982-01-01

    At least four proteins of 70,000 to 75,000 molecular weight (70-75K) were synthesized from mRNA which hybridized with a cloned heat shock gene previously shown to be localized to the 87A and 87C heat shock puff sites. These in vitro-synthesized proteins were indistinguishable from in vivo-synthesized heat shock-induced proteins when analyzed on sodium dodecyl sulfate-polyacrylamide gels. A comparison of the pattern of this group of proteins synthesized in vivo during a 5-min pulse or during continuous labeling indicates that the 72-75K proteins are probably not kinetic precursors to the major 70K heat shock protein. Partial digestion products generated with V8 protease indicated that the 70-75K heat shock proteins are closely related, but that there are clear differences between them. The partial digestion patterns obtained from heat shock proteins from the Kc cell line and from the Oregon R strain of Drosophila melanogaster are very similar. Genetic analysis of the patterns of 70-75K heat shock protein synthesis indicated that the genes encoding at least two of the three 72-75K heat shock proteins are located outside of the major 87A and 87C puff sites

  9. The impact of social franchising on the use of reproductive health and family planning services at public commune health stations in Vietnam

    OpenAIRE

    Pham Van; Alden Dana L; Ngo Anh D; Phan Ha

    2010-01-01

    Abstract Background Service franchising is a business model that involves building a network of outlets (franchisees) that are locally owned, but act in coordinated manner with the guidance of a central headquarters (franchisor). The franchisor maintains quality standards, provides managerial training, conducts centralized purchasing and promotes a common brand. Research indicates that franchising private reproductive health and family planning (RHFP) services in developing countries improves...

  10. Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides

    DEFF Research Database (Denmark)

    Safavi-Hemami, Helena; Li, Qing; Jackson, Ronneshia L.

    2016-01-01

    Formation of correct disulfide bonds in the endoplasmic reticulum is a crucial step for folding proteins destined for secretion. Protein disulfide isomerases (PDIs) play a central role in this process. We report a previously unidentified, hypervariable family of PDIs that represents the most...... diverse gene family of oxidoreductases described in a single genus to date. These enzymes are highly expressed specifically in the venom glands of predatory cone snails, animals that synthesize a remarkably diverse set of cysteine-rich peptide toxins (conotoxins). Enzymes in this PDI family, termed...

  11. Characterization of a DUF820 family protein Alr3200 of the ...

    Indian Academy of Sciences (India)

    The hypothetical protein 'Alr3200' of Anabaena sp. strain PCC7120 is highly conserved among cyanobacterialspecies. It is a member of the DUF820 (Domain of Unknown Function) protein family, and is predicted to have aDNase domain. Biochemical analysis revealed a Mg(II)-dependent DNase activity for Alr3200 with a ...

  12. Role of the MAGUK protein family in synapse formation and function.

    Science.gov (United States)

    Oliva, Carlos; Escobedo, Pía; Astorga, César; Molina, Claudia; Sierralta, Jimena

    2012-01-01

    Synaptic function is crucially dependent on the spatial organization of the presynaptic and postsynaptic apparatuses and the juxtaposition of both membrane compartments. This precise arrangement is achieved by a protein network at the submembrane region of each cell that is built around scaffold proteins. The membrane-associated guanylate kinase (MAGUK) family of proteins is a widely expressed and well-conserved group of proteins that plays an essential role in the formation and regulation of this scaffolding. Here, we review general features of this protein family, focusing on the discs large and calcium/calmodulin-dependent serine protein kinase subfamilies of MAGUKs in the formation, function, and plasticity of synapses. Copyright © 2011 Wiley Periodicals, Inc.

  13. Nonlinear analysis of sequence symmetry of beta-trefoil family proteins

    Energy Technology Data Exchange (ETDEWEB)

    Li Mingfeng [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Huang Yanzhao [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Xu Ruizhen [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Xiao Yi [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China)]. E-mail: yxiao@mail.hust.edu.cn

    2005-07-01

    The tertiary structures of proteins of beta-trefoil family have three-fold quasi-symmetry while their amino acid sequences appear almost at random. In the present paper we show that these amino acid sequences have hidden symmetries in fact and furthermore the degrees of these hidden symmetries are the same as those of their tertiary structures. We shall present a modified recurrence plot to reveal hidden symmetries in protein sequences. Our results can explain the contradiction in sequence-structure relations of proteins of beta-trefoil family.

  14. The Wor1-like protein Fgp1 regulates pathogenicity, toxin synthesis and reproduction in the phytopathogenic fungus Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Wilfried Jonkers

    Full Text Available WOR1 is a gene for a conserved fungal regulatory protein controlling the dimorphic switch and pathogenicity determents in Candida albicans and its ortholog in the plant pathogen Fusarium oxysporum, called SGE1, is required for pathogenicity and expression of key plant effector proteins. F. graminearum, an important pathogen of cereals, is not known to employ switching and no effector proteins from F. graminearum have been found to date that are required for infection. In this study, the potential role of the WOR1-like gene in pathogenesis was tested in this toxigenic fungus. Deletion of the WOR1 ortholog (called FGP1 in F. graminearum results in greatly reduced pathogenicity and loss of trichothecene toxin accumulation in infected wheat plants and in vitro. The loss of toxin accumulation alone may be sufficient to explain the loss of pathogenicity to wheat. Under toxin-inducing conditions, expression of genes for trichothecene biosynthesis and many other genes are not detected or detected at lower levels in Δfgp1 strains. FGP1 is also involved in the developmental processes of conidium formation and sexual reproduction and modulates a morphological change that accompanies mycotoxin production in vitro. The Wor1-like proteins in Fusarium species have highly conserved N-terminal regions and remarkably divergent C-termini. Interchanging the N- and C- terminal portions of proteins from F. oxysporum and F. graminearum resulted in partial to complete loss of function. Wor1-like proteins are conserved but have evolved to regulate pathogenicity in a range of fungi, likely by adaptations to the C-terminal portion of the protein.

  15. Peptide domains involved in the localization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus

    International Nuclear Information System (INIS)

    Rowland, Raymond R.R.; Schneider, Paula; Fang Ying; Wootton, Sarah; Yoo, Dongwan; Benfield, David A.

    2003-01-01

    The nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is the principal component of the viral nucleocapsid and localizes to the nucleolus. Peptide sequence analysis of the N protein of several North American isolates identified two potential nuclear localization signal (NLS) sequences located at amino acids 10-13 and 41-42, which were labeled NLS-1 and NLS-2, respectively. Peptides containing NLS-1 or NLS-2 were sufficient to accumulate enhanced green fluorescent protein (EGFP) in the nucleus. The inactivation of NLS-1 by site-directed mutagenesis or the deletion of the first 14 amino acids did not affect N protein localization to the nucleolus. The substitution of key lysine residues with uncharged amino acids in NLS-2 blocked nuclear/nucleolar localization. Site-directed mutagenesis within NLS-2 identified the sequence, KKNKK, as forming the core localization domain within NLS-2. Using an in vitro pull-down assay, the N protein was able to bind importin-α, importin-β nuclear transport proteins. The localization pattern of N-EGFP fusion peptides represented by a series of deletions from the C- and N-terminal ends of the N protein identified a region covering amino acids 41-72, which contained a nucleolar localization signal (NoLS) sequence. The 41-72 N peptide when fused to EGFP mimicked the nucleolar-cytoplasmic distribution of native N. These results identify a single NLS involved in the transport of N from the cytoplasm and into nucleus. An additional peptide sequence, overlapping NLS-2, is involved in the further targeting of N to the nucleolus

  16. A not-so-grim tale: how childhood family structure influences reproductive and risk-taking outcomes in a historical U.S. Population.

    Science.gov (United States)

    Sheppard, Paula; Garcia, Justin R; Sear, Rebecca

    2014-01-01

    Childhood family structure has been shown to play an important role in shaping a child's life course development, especially in industrialised societies. One hypothesis which could explain such findings is that parental investment is likely to be diluted in families without both natural parents. Most empirical studies have examined the influence of only one type of family disruption or composition (e.g. father absence) making it difficult to simultaneously compare the effects of different kinds of family structure on children's future outcomes. Here we use a large, rich data source (n=16,207) collected by Alfred Kinsey and colleagues in the United States from 1938 to 1963, to examine the effects of particular childhood family compositions and compare between them. The dataset further allows us to look at the effects of family structure on an array of traits relating to sexual maturity, reproduction, and risk-taking. Our results show that, for both sexes, living with a single mother or mother and stepfather during childhood was often associated with faster progression to life history events and greater propensity for risk-taking behaviours. However, living with a single father or father and stepmother was typically not significantly different to having both natural parents for these outcomes. Our results withstand adjustment for socioeconomic status, age, ethnicity, age at puberty (where applicable), and sibling configuration. While these results support the hypothesis that early family environment influences subsequent reproductive strategy, the different responses to the presence or absence of different parental figures in the household rearing environment suggests that particular family constructions exert independent influences on childhood outcomes. Our results suggest that father-absent households (i.e. single mothers or mothers and stepfathers) are most highly associated with subsequent fast life history progressions, compared with mother-absent households

  17. A not-so-grim tale: how childhood family structure influences reproductive and risk-taking outcomes in a historical U.S. Population.

    Directory of Open Access Journals (Sweden)

    Paula Sheppard

    Full Text Available Childhood family structure has been shown to play an important role in shaping a child's life course development, especially in industrialised societies. One hypothesis which could explain such findings is that parental investment is likely to be diluted in families without both natural parents. Most empirical studies have examined the influence of only one type of family disruption or composition (e.g. father absence making it difficult to simultaneously compare the effects of different kinds of family structure on children's future outcomes. Here we use a large, rich data source (n=16,207 collected by Alfred Kinsey and colleagues in the United States from 1938 to 1963, to examine the effects of particular childhood family compositions and compare between them. The dataset further allows us to look at the effects of family structure on an array of traits relating to sexual maturity, reproduction, and risk-taking. Our results show that, for both sexes, living with a single mother or mother and stepfather during childhood was often associated with faster progression to life history events and greater propensity for risk-taking behaviours. However, living with a single father or father and stepmother was typically not significantly different to having both natural parents for these outcomes. Our results withstand adjustment for socioeconomic status, age, ethnicity, age at puberty (where applicable, and sibling configuration. While these results support the hypothesis that early family environment influences subsequent reproductive strategy, the different responses to the presence or absence of different parental figures in the household rearing environment suggests that particular family constructions exert independent influences on childhood outcomes. Our results suggest that father-absent households (i.e. single mothers or mothers and stepfathers are most highly associated with subsequent fast life history progressions, compared with mother

  18. Progranulin, a glycoprotein deficient in frontotemporal dementia, is a novel substrate of several protein disulfide isomerase family proteins.

    Directory of Open Access Journals (Sweden)

    Sandra Almeida

    Full Text Available The reduced production or activity of the cysteine-rich glycoprotein progranulin is responsible for about 20% of cases of familial frontotemporal dementia. However, little is known about the molecular mechanisms that govern the level and secretion of progranulin. Here we show that progranulin is expressed in mouse cortical neurons and more prominently in mouse microglia in culture and is abundant in the endoplasmic reticulum (ER and Golgi. Using chemical crosslinking, immunoprecipitation, and mass spectrometry, we found that progranulin is bound to a network of ER Ca(2+-binding chaperones including BiP, calreticulin, GRP94, and four members of the protein disulfide isomerase (PDI family. Loss of ERp57 inhibits progranulin secretion. Thus, progranulin is a novel substrate of several PDI family proteins and modulation of the ER chaperone network may be a therapeutic target for controlling progranulin secretion.

  19. Evolutionary gradient of predicted nuclear localization signals (NLS)-bearing proteins in genomes of family Planctomycetaceae.

    Science.gov (United States)

    Guo, Min; Yang, Ruifu; Huang, Chen; Liao, Qiwen; Fan, Guangyi; Sun, Chenghang; Lee, Simon Ming-Yuen

    2017-04-04

    The nuclear envelope is considered a key classification marker that distinguishes prokaryotes from eukaryotes. However, this marker does not apply to the family Planctomycetaceae, which has intracellular spaces divided by lipidic intracytoplasmic membranes (ICMs). Nuclear localization signal (NLS), a short stretch of amino acid sequence, destines to transport proteins from cytoplasm into nucleus, and is also associated with the development of nuclear envelope. We attempted to investigate the NLS motifs in Planctomycetaceae genomes to demonstrate the potential molecular transition in the development of intracellular membrane system. In this study, we identified NLS-like motifs that have the same amino acid compositions as experimentally identified NLSs in genomes of 11 representative species of family Planctomycetaceae. A total of 15 NLS types and 170 NLS-bearing proteins were detected in the 11 strains. To determine the molecular transformation, we compared NLS-bearing protein abundances in the 11 representative Planctomycetaceae genomes with them in genomes of 16 taxonomically varied microorganisms: nine bacteria, two archaea and five fungi. In the 27 strains, 29 NLS types and 1101 NLS-bearing proteins were identified, principal component analysis showed a significant transitional gradient from bacteria to Planctomycetaceae to fungi on their NLS-bearing protein abundance profiles. Then, we clustered the 993 non-redundant NLS-bearing proteins into 181 families and annotated their involved metabolic pathways. Afterwards, we aligned the ten types of NLS motifs from the 13 families containing NLS-bearing proteins among bacteria, Planctomycetaceae or fungi, considering their diversity, length and origin. A transition towards increased complexity from non-planctomycete bacteria to Planctomycetaceae to archaea and fungi was detected based on the complexity of the 10 types of NLS-like motifs in the 13 NLS-bearing proteins families. The results of this study reveal that

  20. Selecting protein families for environmental features based on manifold regularization.

    Science.gov (United States)

    Jiang, Xingpeng; Xu, Weiwei; Park, E K; Li, Guangrong

    2014-06-01

    Recently, statistics and machine learning have been developed to identify functional or taxonomic features of environmental features or physiological status. Important proteins (or other functional and taxonomic entities) to environmental features can be potentially used as biosensors. A major challenge is how the distribution of protein and gene functions embodies the adaption of microbial communities across environments and host habitats. In this paper, we propose a novel regularization method for linear regression to adapt the challenge. The approach is inspired by local linear embedding (LLE) and we call it a manifold-constrained regularization for linear regression (McRe). The novel regularization procedure also has potential to be used in solving other linear systems. We demonstrate the efficiency and the performance of the approach in both simulation and real data.

  1. Effect of supplementation of concentrates or selenium on production and reproduction in cows grazing pastures of high protein degradability

    Energy Technology Data Exchange (ETDEWEB)

    Mongiardino, M E; Humaran, M; Corbellini, C N; Baldan, A M; Cuneo, M; Balbiani, G [Instituto Nacional de Tecnologia Agropecuaria, Moron, Provincia de Buenos Aires (Argentina). Inst. de Patobiologia

    1996-05-01

    Two experiments were carried out to determine whether the deleterious effects of high amounts of degradable protein on reproduction and production of dairy cows could be minimized by a supplemental source of undergradable protein, or grain supplementation while grazing; and to study the effect of selenium supplementation before calving on the incidence of stillbirths, mastitis, puerperal and metabolic disorders. In a first experiment, 24 Holstein cows fed on red and white clover pasture, paired by previous milk production, calving data and body condition, were supplemented with corn silage and one of two concentrates differing only in the proportion of degradable protein (Group H: 71.5% and Group L: 51.5%). The degradable protein intake from pasture supplied 93% of the requirements in both groups. The addition of undergradable protein in the concentrate of Group L did not improve reproductive performance nor milk, butterfat or solids non-fat production. In a second experiment, 132 Holstein cows and heifers were paired likewise. Both animals in each pair were fed similar forage resources, but each one was supplemented with 2 kg/cow corn grain four times a day (Herd 1) or 4 kg/cow tow times a day (Herd 2). One animal in each pair was randomly assigned to receive a barium selenate injection before calving. Rumen ammonia was higher in Herd 1 in both sampling dates (17 vs 4.2 mg/100 ml and 12 vs 9 mg/100 ml), as well as serum urea up to 50 days post-partum (26 vs 19 mg/100 ml, P<0.02). Body condition scores were similar at calving but significantly lower in Herd 1 during the lactation period (P<0.05). Total milk and butterfat production were higher in Herd 2 (6406.2 vs 6893.8 kg and 190.4 vs 203.5 kg, respectively). Selenium improved pregnancy rate to first artificial insemination in Herd 2 (71 vs 50%), and decreased the frequency of downer cows in both herds (5 vs 0%), but had not effect regarding the Wisconsin Mastitis Test results. (author). 36 refs, 4 figs, 3 tabs.

  2. Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes.

    Directory of Open Access Journals (Sweden)

    Todd J Treangen

    2011-01-01

    Full Text Available Gene duplication followed by neo- or sub-functionalization deeply impacts the evolution of protein families and is regarded as the main source of adaptive functional novelty in eukaryotes. While there is ample evidence of adaptive gene duplication in prokaryotes, it is not clear whether duplication outweighs the contribution of horizontal gene transfer in the expansion of protein families. We analyzed closely related prokaryote strains or species with small genomes (Helicobacter, Neisseria, Streptococcus, Sulfolobus, average-sized genomes (Bacillus, Enterobacteriaceae, and large genomes (Pseudomonas, Bradyrhizobiaceae to untangle the effects of duplication and horizontal transfer. After removing the effects of transposable elements and phages, we show that the vast majority of expansions of protein families are due to transfer, even among large genomes. Transferred genes--xenologs--persist longer in prokaryotic lineages possibly due to a higher/longer adaptive role. On the other hand, duplicated genes--paralogs--are expressed more, and, when persistent, they evolve slower. This suggests that gene transfer and gene duplication have very different roles in shaping the evolution of biological systems: transfer allows the acquisition of new functions and duplication leads to higher gene dosage. Accordingly, we show that paralogs share most protein-protein interactions and genetic regulators, whereas xenologs share very few of them. Prokaryotes invented most of life's biochemical diversity. Therefore, the study of the evolution of biology systems should explicitly account for the predominant role of horizontal gene transfer in the diversification of protein families.

  3. Chicken genome analysis reveals novel genes encoding biotin-binding proteins related to avidin family

    Directory of Open Access Journals (Sweden)

    Nordlund Henri R

    2005-03-01

    Full Text Available Abstract Background A chicken egg contains several biotin-binding proteins (BBPs, whose complete DNA and amino acid sequences are not known. In order to identify and characterise these genes and proteins we studied chicken cDNAs and genes available in the NCBI database and chicken genome database using the reported N-terminal amino acid sequences of chicken egg-yolk BBPs as search strings. Results Two separate hits showing significant homology for these N-terminal sequences were discovered. For one of these hits, the chromosomal location in the immediate proximity of the avidin gene family was found. Both of these hits encode proteins having high sequence similarity with avidin suggesting that chicken BBPs are paralogous to avidin family. In particular, almost all residues corresponding to biotin binding in avidin are conserved in these putative BBP proteins. One of the found DNA sequences, however, seems to encode a carboxy-terminal extension not present in avidin. Conclusion We describe here the predicted properties of the putative BBP genes and proteins. Our present observations link BBP genes together with avidin gene family and shed more light on the genetic arrangement and variability of this family. In addition, comparative modelling revealed the potential structural elements important for the functional and structural properties of the putative BBP proteins.

  4. Protein and glucogenic precursor supplementation: a nutritional strategy to increase reproductive and economic output.

    Science.gov (United States)

    Mulliniks, J T; Cox, S H; Kemp, M E; Endecott, R L; Waterman, R C; Vanleeuwen, D M; Torell, L A; Petersen, M K

    2011-10-01

    Reproductive performance in young beef cows is often compromised due to a mismatch of physiological demands and suboptimal environmental conditions. Studies conducted at the Corona Range and Livestock Research Center from 2000 to 2007 evaluated 3 postpartum supplement strategies that varied in the amount of glucogenic potential (GP) supplied. Reproductive variables, milk production, and serum metabolites were used to assess supplement effectiveness and economics associated with 2- and 3-yr-old beef cows (n = 379) grazing native range. Supplements were individually fed twice/week at 1,135 g/d (2003 to 2004) or 908 g/d (all other years) and provided 1) 327 g of CP, 109 to 118 g of RUP (CON); 2) 327 to 341 g of CP, 142 to 157 g of RUP (RUP); or 3) 327 g of CP, 151 to 173 g of RUP + 40 to 100 g of propionate salt (PS; RUP+PS). Ultimately, total GP for CON, RUP, and RUP+PS was 44 to 47, 57 to 70, and 93 to 141 g, respectively. Blood samples were collected once/week (2000) or twice/week (2001 to 2007) for progesterone analysis to estimate days to resumption of estrus. Cows were exposed to bulls for 60 d or less, and pregnancy was confirmed by rectal palpation at weaning. Days to resumption of estrus after calving decreased linearly (P = 0.02), resulting in an increased pregnancy rate (P = 0.03) with increasing GP. Milk production exhibited a quadratic (P = 0.04) response to increasing GP, with cows fed RUP producing the most amount of milk. However, a linear decrease (P = 0.07) in days from BW nadir to estrus was found with increasing GP. Total kilograms of calf weaned per cow exposed for the supplemental year and subsequent year was increased linearly (P = 0.07) with increased GP. The improvement in pregnancy rate by supplementing RUP+PS resulted in an increase in total revenue of 18% compared with CON-fed cows and 9.5% compared with RUP-fed cows in the subsequent year after supplementation. These data suggest feeding young cows additional GP in the form of PS allows

  5. A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging

    International Nuclear Information System (INIS)

    You, Jae-Hwan; Howell, Gareth; Pattnaik, Asit K.; Osorio, Fernando A.; Hiscox, Julian A.

    2008-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus

  6. Orthology prediction methods: a quality assessment using curated protein families.

    Science.gov (United States)

    Trachana, Kalliopi; Larsson, Tomas A; Powell, Sean; Chen, Wei-Hua; Doerks, Tobias; Muller, Jean; Bork, Peer

    2011-10-01

    The increasing number of sequenced genomes has prompted the development of several automated orthology prediction methods. Tests to evaluate the accuracy of predictions and to explore biases caused by biological and technical factors are therefore required. We used 70 manually curated families to analyze the performance of five public methods in Metazoa. We analyzed the strengths and weaknesses of the methods and quantified the impact of biological and technical challenges. From the latter part of the analysis, genome annotation emerged as the largest single influencer, affecting up to 30% of the performance. Generally, most methods did well in assigning orthologous group but they failed to assign the exact number of genes for half of the groups. The publicly available benchmark set (http://eggnog.embl.de/orthobench/) should facilitate the improvement of current orthology assignment protocols, which is of utmost importance for many fields of biology and should be tackled by a broad scientific community. Copyright © 2011 WILEY Periodicals, Inc.

  7. Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility.

    Directory of Open Access Journals (Sweden)

    Melissa R van Dijk

    2010-04-01

    Full Text Available The process of fertilization is critically dependent on the mutual recognition of gametes and in Plasmodium, the male gamete surface protein P48/45 is vital to this process. This protein belongs to a family of 10 structurally related proteins, the so called 6-cys family. To identify the role of additional members of this family in Plasmodium fertilisation, we performed genetic and functional analysis on the five members of the 6-cys family that are transcribed during the gametocyte stage of P. berghei. This analysis revealed that in addition to P48/45, two members (P230 and P47 also play an essential role in the process of parasite fertilization. Mating studies between parasites lacking P230, P48/45 or P47 demonstrate that P230, like P48/45, is a male fertility factor, consistent with the previous demonstration of a protein complex containing both P48/45 and P230. In contrast, disruption of P47 results in a strong reduction of female fertility, while males remain unaffected. Further analysis revealed that gametes of mutants lacking expression of p48/45 or p230 or p47 are unable to either recognise or attach to each other. Disruption of the paralog of p230, p230p, also specifically expressed in gametocytes, had no observable effect on fertilization. These results indicate that the P. berghei 6-cys family contains a number of proteins that are either male or female specific ligands that play an important role in gamete recognition and/or attachment. The implications of low levels of fertilisation that exist even in the absence of these proteins, indicating alternative pathways of fertilisation, as well as positive selection acting on these proteins, are discussed in the context of targeting these proteins as transmission blocking vaccine candidates.

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

    Science.gov (United States)

    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.

  9. Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication

    International Nuclear Information System (INIS)

    Lee, Changhee; Hodgins, Douglas; Calvert, Jay G.; Welch, Siao-Kun W.; Jolie, Rika; Yoo, Dongwan

    2006-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus replicating in the cytoplasm, but the nucleocapsid (N) protein is specifically localized to the nucleus and nucleolus in virus-infected cells. A 'pat7' motif of 41-PGKK(N/S)KK has previously been identified in the N protein as the functional nuclear localization signal (NLS); however, the biological consequences of N protein nuclear localization are unknown. In the present study, the role of N protein nuclear localization during infection was investigated in pigs using an NLS-null mutant virus. When two lysines at 43 and 44 at the NLS locus were substituted to glycines, the modified NLS with 41-PGGGNKK restricted the N protein to the cytoplasm. This NLS-null mutation was introduced into a full-length infectious cDNA clone of PRRSV. Upon transfection of cells, the NLS-null full-length clone induced cytopathic effects and produced infectious progeny. The NLS-null virus grew to a titer 100-fold lower than that of wild-type virus. To examine the response to NLS-null PRRSV in the natural host, three groups of pigs, consisting of seven animals per group, were intranasally inoculated with wild-type, placebo, or NLS-null virus, and the animals were maintained for 4 weeks. The NLS-null-infected pigs had a significantly shorter mean duration of viremia than wild-type-infected pigs but developed significantly higher titers of neutralizing antibodies. Mutations occurred at the NLS locus in one pig during viremia, and four types of mutations were identified: 41-PGRGNKK, 41-PGGRNKK, and 41-PGRRNKK, and 41-PGKKSKK. Both wild-type and NLS-null viruses persisted in the tonsils for at least 4 weeks, and the NLS-null virus persisting in the tonsils was found to be mutated to either 41-PGRGNKK or 41-PGGRNKK in all pigs. No other mutation was found in the N gene. All types of reversions which occurred during viremia and persistence were able to translocate the mutated N proteins to the nucleus, indicating a

  10. Yolk proteins in the male reproductive system of the fruit fly Drosophila melanogaster: spatial and temporal patterns of expression.

    Science.gov (United States)

    Majewska, Magdalena M; Suszczynska, Agnieszka; Kotwica-Rolinska, Joanna; Czerwik, Tomasz; Paterczyk, Bohdan; Polanska, Marta A; Bernatowicz, Piotr; Bebas, Piotr

    2014-04-01

    yolk proteins in the male reproductive system of D. melanogaster under physiological conditions, and show that somatic cells of the testes are the source of these proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Identification of cytosolic peroxisome proliferator binding protein as a member of the heat shock protein HSP70 family.

    Science.gov (United States)

    Alvares, K; Carrillo, A; Yuan, P M; Kawano, H; Morimoto, R I; Reddy, J K

    1990-01-01

    Clofibrate and many of its structural analogues induce proliferation of peroxisomes in the hepatic parenchymal cells of rodents and certain nonrodent species including primates. This induction is tissue specific, occurring mainly in the liver parenchymal cells and to a lesser extent in the kidney cortical epithelium. The induction of peroxisomes is associated with a predictable pleiotropic response, characterized by hepatomegaly, and increased activities and mRNA levels of certain peroxisomal enzymes. Using affinity chromatography, we had previously isolated a protein that binds to clofibric acid. We now show that this protein is homologous with the heat shock protein HSP70 family by analysis of amino acid sequences of isolated peptides from trypsin-treated clofibric acid binding protein and by cross-reactivity with a monoclonal antibody raised against the conserved region of the 70-kDa heat shock proteins. The clofibric acid-Sepharose column could bind HSP70 proteins isolated from various species, which could then be eluted with either clofibric acid or ATP. Conversely, when a rat liver cytosol containing multiple members of the HSP70 family was passed through an ATP-agarose column, and eluted with clofibric acid, only P72 (HSC70) was eluted. These results suggest that clofibric acid, a peroxisome proliferator, preferentially interacts with P72 at or near the ATP binding site. Images PMID:2371272

  12. Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms

    DEFF Research Database (Denmark)

    Rohde, Mikkel; Daugaard, Mads; Jensen, Mette Hartvig

    2005-01-01

    Whereas the stress-inducible heat-shock protein 70 (Hsp70) has gained plenty of attention as a putative target for tumor therapy, little is known about the role of other Hsp70 proteins in cancer. Here we present the first thorough analysis of the expression and function of the cytosolic Hsp70...... proteins in human cancer cells and identify Hsp70-2, a protein essential for spermatogenesis, as an important regulator of cancer cell growth. Targeted knock-down of the individual family members by RNA interference revealed that both Hsp70 and Hsp70-2 were required for cancer cell growth, whereas...

  13. The Strong Family Program: an innovative model to engage Aboriginal and Torres Strait Islander youth and Elders with reproductive and sexual health community education.

    Science.gov (United States)

    Duley, P; Botfield, J R; Ritter, T; Wicks, J; Brassil, A

    2017-08-01

    Issue addressed Aboriginal youth in Australia often experience high rates of intimate partner violence (family violence) and poorer reproductive and sexual health than their non-Aboriginal counterparts. To address some of the disparities, the Strong Family Program was developed to deliver reproductive and sexual health education to Aboriginal communities in New South Wales. Methods Development of the program was based on an extensive consultation process with Aboriginal communities. It was implemented in three communities, with two groups from each hosting Aboriginal youth and Elders in a yarning circle within the culturally respectful frameworks of 'men and boys'' and 'women and girls'' business. An evaluation was conducted to measure reproductive and sexual health knowledge and attitude changes upon program completion, using pre- and post-program surveys and yarning (focus group discussions). Results Program participants comprised 48 females and 28 males. Overall, mean knowledge and attitude scores improved upon completion of the program (from 77% to 82% and from 4.15 to 4.32 out of 5, respectively). Among participants aged 20 years and under (the youngest participant was 13 years), there was an increase in knowledge (P=0.034); among participants aged over 20 years (the oldest participant was 78 years), there was an increase in positive attitudes (P=0.001). Participants perceived the information provided to be useful and relevant, with many reporting improved knowledge and attitudes around rights and respectful relationships. Conclusions Reproductive and sexual health education in Aboriginal communities should be based on community consultations and carried out within a culturally appropriate framework to promote greater success. Continued implementation of the Strong Family Program will promote increased understanding of respectful relationships and improved health outcomes for Aboriginal young people. So what? The Strong Family Program was based on an extensive

  14. The effect of dietary protein on reproduction in the mare. VI. Serum progestagen concentrations during pregnancy

    Directory of Open Access Journals (Sweden)

    F.E. Van Niekerk

    1998-07-01

    Full Text Available Sixty-four Thoroughbred and Anglo-Arab mares aged 6-12 years were used, of which 40 were non-lactating and 24 lactating. Foals from these 24 mares were weaned at the age of 6 months. Non-lactating and lactating mares were divided into 4 dietary groups each. The total daily protein intake and the protein quality (essential amino-acid content differed in the 4 groups of non-lactating and 4 groups of lactating mares. The mares were covered and the effect of the quantity and quality of dietary protein on serum progestagen concentrations during pregnancy was studied. A sharp decline in serum progestagen concentrations was recorded in all dietary groups from Days 18 to 40 of pregnancy, with some individual mares reaching values of less than 4 ng/mℓ. Serum progestagen concentrations recorded in some of the non-lactating mares on the low-quality protein diet increased to higher values (p<0.05 than those of mares in the other 3 dietary groups at 35-140 days of pregnancy. A similar trend was observed for the lactating mares on a low-quality protein diet at 30-84 days of pregnancy. No such trends were observed in any of the other dietary groups. High-quality protein supplementation increased serum progestagen concentrations during the 1st 30 days of pregnancy. Lactation depressed serum progestagen concentrations until after the foals were weaned.

  15. Sifting through genomes with iterative-sequence clustering produces a large, phylogenetically diverse protein-family resource.

    Science.gov (United States)

    Sharpton, Thomas J; Jospin, Guillaume; Wu, Dongying; Langille, Morgan G I; Pollard, Katherine S; Eisen, Jonathan A

    2012-10-13

    New computational resources are needed to manage the increasing volume of biological data from genome sequencing projects. One fundamental challenge is the ability to maintain a complete and current catalog of protein diversity. We developed a new approach for the identification of protein families that focuses on the rapid discovery of homologous protein sequences. We implemented fully automated and high-throughput procedures to de novo cluster proteins into families based upon global alignment similarity. Our approach employs an iterative clustering strategy in which homologs of known families are sifted out of the search for new families. The resulting reduction in computational complexity enables us to rapidly identify novel protein families found in new genomes and to perform efficient, automated updates that keep pace with genome sequencing. We refer to protein families identified through this approach as "Sifting Families," or SFams. Our analysis of ~10.5 million protein sequences from 2,928 genomes identified 436,360 SFams, many of which are not represented in other protein family databases. We validated the quality of SFam clustering through statistical as well as network topology-based analyses. We describe the rapid identification of SFams and demonstrate how they can be used to annotate genomes and metagenomes. The SFam database catalogs protein-family quality metrics, multiple sequence alignments, hidden Markov models, and phylogenetic trees. Our source code and database are publicly available and will be subject to frequent updates (http://edhar.genomecenter.ucdavis.edu/sifting_families/).

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

    Science.gov (United States)

    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.

  17. Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases.

    Science.gov (United States)

    Kauffman, Karlina J; Yu, Shenliang; Jin, Jiaxin; Mugo, Brian; Nguyen, Nathan; O'Brien, Aidan; Nag, Shanta; Lystad, Alf Håkon; Melia, Thomas J

    2018-04-10

    During macroautophagy/autophagy, mammalian Atg8-family proteins undergo 2 proteolytic processing events. The first exposes a COOH-terminal glycine used in the conjugation of these proteins to lipids on the phagophore, the precursor to the autophagosome, whereas the second releases the lipid. The ATG4 family of proteases drives both cleavages, but how ATG4 proteins distinguish between soluble and lipid-anchored Atg8 proteins is not well understood. In a fully reconstituted delipidation assay, we establish that the physical anchoring of mammalian Atg8-family proteins in the membrane dramatically shifts the way ATG4 proteases recognize these substrates. Thus, while ATG4B is orders of magnitude faster at processing a soluble unprimed protein, all 4 ATG4 proteases can be activated to similar enzymatic activities on lipid-attached substrates. The recognition of lipidated but not soluble substrates is sensitive to a COOH-terminal LIR motif both in vitro and in cells. We suggest a model whereby ATG4B drives very fast priming of mammalian Atg8 proteins, whereas delipidation is inherently slow and regulated by all ATG4 homologs.

  18. Endeavour to simplify the frustrated concept of protein-ammonium family ionic liquid interactions.

    Science.gov (United States)

    Jha, Indrani; Venkatesu, Pannuru

    2015-08-28

    The large amount of attention earned by ionic liquids (ILs) in the various physical and chemical sciences has been attributed to their unique, designer nature. In the past few years, the role of ILs in protein folding/unfolding has been rapidly growing. In light of the increasing importance of ILs, it is desirable to systematize the ion effects on protein properties such as structure stability, activity and enantioselectivity. Various studies available in the literature show ILs as a potential solvent medium for many enzymatic reactions, as well as in various protein folding/unfolding studies. Various reviews by many researchers focus on the synthesis, application and general properties of the ILs, however a review focussing on the effect of various ILs on the activity, structure and stability of proteins is still missing. Also, according to the best of our knowledge there is no single review available throughout the literature that focuses on the effect of the same family of ILs on different proteins. Therefore, it is a priority to obtain complete knowledge of the biomolecules, particularly amino acids (AAs) and proteins in a particular IL family. The focus of the present perspective is to investigate the performance of a list of proteins and protein model compounds in the presence of ammonium-based ILs. This perspective presents a survey of all the key developments from the available reports and also our past and present experience related to proteins and ammonium-based ILs. Additionally, we have tried to put the available information in chronological order in most of the cases. The use of ammonium family ILs as a co-solvent for various proteins model compounds and proteins has been outlined. This perspective can act as a barometer for reckoning the various advancements made in this field and can also galvanize further investigation of various untouched aspects of this research area.

  19. Ubiquitin-Mediated Regulation of Endocytosis by Proteins of the Arrestin Family

    Directory of Open Access Journals (Sweden)

    Michel Becuwe

    2012-01-01

    Full Text Available In metazoans, proteins of the arrestin family are key players of G-protein-coupled receptors (GPCRS signaling and trafficking. Following stimulation, activated receptors are phosphorylated, thus allowing the binding of arrestins and hence an “arrest” of receptor signaling. Arrestins act by uncoupling receptors from G proteins and contribute to the recruitment of endocytic proteins, such as clathrin, to direct receptor trafficking into the endocytic pathway. Arrestins also serve as adaptor proteins by promoting the recruitment of ubiquitin ligases and participate in the agonist-induced ubiquitylation of receptors, known to have impact on their subcellular localization and stability. Recently, the arrestin family has expanded following the discovery of arrestin-related proteins in other eukaryotes such as yeasts or fungi. Surprisingly, most of these proteins are also involved in the ubiquitylation and endocytosis of plasma membrane proteins, thus suggesting that the role of arrestins as ubiquitin ligase adaptors is at the core of these proteins' functions. Importantly, arrestins are themselves ubiquitylated, and this modification is crucial for their function. In this paper, we discuss recent data on the intricate connections between arrestins and the ubiquitin pathway in the control of endocytosis.

  20. Incorporation of radioactive leucine as an evidence for protein synthesis in Lizard epididymis. Studies during the reproductive cycle and after testoterone administration to intact and castrated animals

    International Nuclear Information System (INIS)

    Gigon, Annie; Dufaure, J.-P.

    1975-01-01

    Lizard epididymis activity during the reproductive cycle and after testosterone administration results in a marked increase of radioactive leucine incorporation in vivo and in vitro. The electrophoretic distribution of soluble proteins shows different peaks of radioactivity. Comparison between histological response and pattern of electrophoresis suggests that one of these peaks may correspond to an activity of secretion [fr

  1. Protein profile of seminal plasma and functionality of spermatozoa during the reproductive season in the common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss)

    Czech Academy of Sciences Publication Activity Database

    Shaliutina-Kolešová, A.; Kotas, P.; Štěrba, Ján; Rodina, M.; Dzyuba, B.; Cosson, J.; Linhart, O.

    2016-01-01

    Roč. 83, č. 11 (2016), s. 968-982 ISSN 1040-452X R&D Projects: GA ČR GA15-03044S; GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : reproductive season * spermatozoon motility * seminal plasma proteins * carp * rainbow trout * protein identification Subject RIV: EE - Microbiology, Virology Impact factor: 2.316, year: 2016

  2. Nature of protein family signatures: insights from singular value analysis of position-specific scoring matrices.

    Directory of Open Access Journals (Sweden)

    Akira R Kinjo

    Full Text Available Position-specific scoring matrices (PSSMs are useful for detecting weak homology in protein sequence analysis, and they are thought to contain some essential signatures of the protein families. In order to elucidate what kind of ingredients constitute such family-specific signatures, we apply singular value decomposition to a set of PSSMs and examine the properties of dominant right and left singular vectors. The first right singular vectors were correlated with various amino acid indices including relative mutability, amino acid composition in protein interior, hydropathy, or turn propensity, depending on proteins. A significant correlation between the first left singular vector and a measure of site conservation was observed. It is shown that the contribution of the first singular component to the PSSMs act to disfavor potentially but falsely functionally important residues at conserved sites. The second right singular vectors were highly correlated with hydrophobicity scales, and the corresponding left singular vectors with contact numbers of protein structures. It is suggested that sequence alignment with a PSSM is essentially equivalent to threading supplemented with functional information. In addition, singular vectors may be useful for analyzing and annotating the characteristics of conserved sites in protein families.

  3. FAM20: an evolutionarily conserved family of secreted proteins expressed in hematopoietic cells

    Directory of Open Access Journals (Sweden)

    Cobos Everardo

    2005-01-01

    Full Text Available Abstract Background Hematopoiesis is a complex developmental process controlled by a large number of factors that regulate stem cell renewal, lineage commitment and differentiation. Secreted proteins, including the hematopoietic growth factors, play critical roles in these processes and have important biological and clinical significance. We have employed representational difference analysis to identify genes that are differentially expressed during experimentally induced myeloid differentiation in the murine EML hematopoietic stem cell line. Results One identified clone encoded a previously unidentified protein of 541 amino acids that contains an amino terminal signal sequence but no other characterized domains. This protein is a member of family of related proteins that has been named family with sequence similarity 20 (FAM20 with three members (FAM20A, FAM20B and FAM20C in mammals. Evolutionary comparisons revealed the existence of a single FAM20 gene in the simple vertebrate Ciona intestinalis and the invertebrate worm Caenorhabditis elegans and two genes in two insect species, Drosophila melanogaster and Anopheles gambiae. Six FAM20 family members were identified in the genome of the pufferfish, Fugu rubripes and five members in the zebrafish, Danio rerio. The mouse Fam20a protein was ectopically expressed in a mammalian cell line and found to be a bona fide secreted protein and efficient secretion was dependent on the integrity of the signal sequence. Expression analysis revealed that the Fam20a gene was indeed differentially expressed during hematopoietic differentiation and that the other two family members (Fam20b and Fam20c were also expressed during hematcpoiesis but that their mRNA levels did not vary significantly. Likewise FAM20A was expressed in more limited set of human tissues than the other two family members. Conclusions The FAM20 family represents a new family of secreted proteins with potential functions in regulating

  4. The 'tubulin-like' S1 protein of Spirochaeta is a member of the hsp65 stress protein family

    Science.gov (United States)

    Munson, D.; Obar, R.; Tzertzinis, G.; Margulis, L.

    1993-01-01

    A 65-kDa protein (called S1) from Spirochaeta bajacaliforniensis was identified as 'tubulin-like' because it cross-reacted with at least four different antisera raised against tubulin and was isolated, with a co-polymerizing 45-kDa protein, by warm-cold cycling procedures used to purify tubulin from mammalian brain. Furthermore, at least three genera of non-cultivable symbiotic spirochetes (Pillotina, Diplocalyx, and Hollandina) that contain conspicuous 24-nm cytoplasmic tubules displayed a strong fluorescence in situ when treated with polyclonal antisera raised against tubulin. Here we summarize results that lead to the conclusion that this 65-kDa protein has no homology to tubulin. S1 is an hsp65 stress protein homologue. Hsp65 is a highly immunogenic family of hsp60 proteins which includes the 65-kDa antigens of Mycobacterium tuberculosis (an active component of Freund's complete adjuvant), Borrelia, Treponema, Chlamydia, Legionella, and Salmonella. The hsp60s, also known as chaperonins, include E. coli GroEL, mitochondrial and chloroplast chaperonins, the pea aphid 'symbionin' and many other proteins involved in protein folding and the stress response.

  5. Marked variability in the extent of protein disorder within and between viral families.

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    Ravindra Pushker

    Full Text Available Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues, and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively. Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses, except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel

  6. Fast and simple protein-alignment-guided assembly of orthologous gene families from microbiome sequencing reads.

    Science.gov (United States)

    Huson, Daniel H; Tappu, Rewati; Bazinet, Adam L; Xie, Chao; Cummings, Michael P; Nieselt, Kay; Williams, Rohan

    2017-01-25

    Microbiome sequencing projects typically collect tens of millions of short reads per sample. Depending on the goals of the project, the short reads can either be subjected to direct sequence analysis or be assembled into longer contigs. The assembly of whole genomes from metagenomic sequencing reads is a very difficult problem. However, for some questions, only specific genes of interest need to be assembled. This is then a gene-centric assembly where the goal is to assemble reads into contigs for a family of orthologous genes. We present a new method for performing gene-centric assembly, called protein-alignment-guided assembly, and provide an implementation in our metagenome analysis tool MEGAN. Genes are assembled on the fly, based on the alignment of all reads against a protein reference database such as NCBI-nr. Specifically, the user selects a gene family based on a classification such as KEGG and all reads binned to that gene family are assembled. Using published synthetic community metagenome sequencing reads and a set of 41 gene families, we show that the performance of this approach compares favorably with that of full-featured assemblers and that of a recently published HMM-based gene-centric assembler, both in terms of the number of reference genes detected and of the percentage of reference sequence covered. Protein-alignment-guided assembly of orthologous gene families complements whole-metagenome assembly in a new and very useful way.

  7. PANTHER: A Library of Protein Families and Subfamilies Indexed by Function

    OpenAIRE

    Thomas, Paul D.; Campbell, Michael J.; Kejariwal, Anish; Mi, Huaiyu; Karlak, Brian; Daverman, Robin; Diemer, Karen; Muruganujan, Anushya; Narechania, Apurva

    2003-01-01

    In the genomic era, one of the fundamental goals is to characterize the function of proteins on a large scale. We describe a method, PANTHER, for relating protein sequence relationships to function relationships in a robust and accurate way. PANTHER is composed of two main components: the PANTHER library (PANTHER/LIB) and the PANTHER index (PANTHER/X). PANTHER/LIB is a collection of “books,” each representing a protein family as a multiple sequence alignment, a Hidden Markov Model (HMM)...

  8. Diversity and dispersal of a ubiquitous protein family: acyl-CoA dehydrogenases.

    Science.gov (United States)

    Shen, Yao-Qing; Lang, B Franz; Burger, Gertraud

    2009-09-01

    Acyl-CoA dehydrogenases (ACADs), which are key enzymes in fatty acid and amino acid catabolism, form a large, pan-taxonomic protein family with at least 13 distinct subfamilies. Yet most reported ACAD members have no subfamily assigned, and little is known about the taxonomic distribution and evolution of the subfamilies. In completely sequenced genomes from approximately 210 species (eukaryotes, bacteria and archaea), we detect ACAD subfamilies by rigorous ortholog identification combining sequence similarity search with phylogeny. We then construct taxonomic subfamily-distribution profiles and build phylogenetic trees with orthologous proteins. Subfamily profiles provide unparalleled insight into the organisms' energy sources based on genome sequence alone and further predict enzyme substrate specificity, thus generating explicit working hypotheses for targeted biochemical experimentation. Eukaryotic ACAD subfamilies are traditionally considered as mitochondrial proteins, but we found evidence that in fungi one subfamily is located in peroxisomes and participates in a distinct beta-oxidation pathway. Finally, we discern horizontal transfer, duplication, loss and secondary acquisition of ACAD genes during evolution of this family. Through these unorthodox expansion strategies, the ACAD family is proficient in utilizing a large range of fatty acids and amino acids-strategies that could have shaped the evolutionary history of many other ancient protein families.

  9. Reticulomics: Protein-Protein Interaction Studies with Two Plasmodesmata-Localized Reticulon Family Proteins Identify Binding Partners Enriched at Plasmodesmata, Endoplasmic Reticulum, and the Plasma Membrane.

    Science.gov (United States)

    Kriechbaumer, Verena; Botchway, Stanley W; Slade, Susan E; Knox, Kirsten; Frigerio, Lorenzo; Oparka, Karl; Hawes, Chris

    2015-11-01

    The endoplasmic reticulum (ER) is a ubiquitous organelle that plays roles in secretory protein production, folding, quality control, and lipid biosynthesis. The cortical ER in plants is pleomorphic and structured as a tubular network capable of morphing into flat cisternae, mainly at three-way junctions, and back to tubules. Plant reticulon family proteins (RTNLB) tubulate the ER by dimerization and oligomerization, creating localized ER membrane tensions that result in membrane curvature. Some RTNLB ER-shaping proteins are present in the plasmodesmata (PD) proteome and may contribute to the formation of the desmotubule, the axial ER-derived structure that traverses primary PD. Here, we investigate the binding partners of two PD-resident reticulon proteins, RTNLB3 and RTNLB6, that are located in primary PD at cytokinesis in tobacco (Nicotiana tabacum). Coimmunoprecipitation of green fluorescent protein-tagged RTNLB3 and RTNLB6 followed by mass spectrometry detected a high percentage of known PD-localized proteins as well as plasma membrane proteins with putative membrane-anchoring roles. Förster resonance energy transfer by fluorescence lifetime imaging microscopy assays revealed a highly significant interaction of the detected PD proteins with the bait RTNLB proteins. Our data suggest that RTNLB proteins, in addition to a role in ER modeling, may play important roles in linking the cortical ER to the plasma membrane. © 2015 American Society of Plant Biologists. All Rights Reserved.

  10. Delineation of the Pasteurellaceae-specific GbpA-family of glutathione-binding proteins

    Directory of Open Access Journals (Sweden)

    Vergauwen Bjorn

    2011-11-01

    Full Text Available Abstract Background The Gram-negative bacterium Haemophilus influenzae is a glutathione auxotroph and acquires the redox-active tripeptide by import. The dedicated glutathione transporter belongs to the ATP-binding cassette (ABC-transporter superfamily and displays more than 60% overall sequence identity with the well-studied dipeptide (Dpp permease of Escherichia coli. The solute binding protein (SBP that mediates glutathione transport in H. influenzae is a lipoprotein termed GbpA and is 54% identical to E. coli DppA, a well-studied member of family 5 SBP's. The discovery linking GbpA to glutathione import came rather unexpectedly as this import-priming SBP was previously annotated as a heme-binding protein (HbpA, and was thought to mediate heme acquisition. Nonetheless, although many SBP's have been implicated in more than one function, a prominent physiological role for GbpA and its partner permease in heme acquisition appears to be very unlikely. Here, we sought to characterize five representative GbpA homologs in an effort to delineate the novel GbpA-family of glutathione-specific family 5 SBPs and to further clarify their functional role in terms of ligand preferences. Results Lipoprotein and non-lipoprotein GbpA homologs were expressed in soluble form and substrate specificity was evaluated via a number of ligand binding assays. A physiologically insignificant affinity for hemin was observed for all five GbpA homologous test proteins. Three out of five test proteins were found to bind glutathione and some of its physiologically relevant derivatives with low- or submicromolar affinity. None of the tested SBP family 5 allocrites interacted with the remaining two GbpA test proteins. Structure-based sequence alignments and phylogenetic analysis show that the two binding-inert GbpA homologs clearly form a separate phylogenetic cluster. To elucidate a structure-function rationale for this phylogenetic differentiation, we determined the crystal

  11. Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families

    Science.gov (United States)

    Defelipe, Lucas A.; Lanzarotti, Esteban; Gauto, Diego; Marti, Marcelo A.; Turjanski, Adrián G.

    2015-01-01

    Cysteine residues have a rich chemistry and play a critical role in the catalytic activity of a plethora of enzymes. However, cysteines are susceptible to oxidation by Reactive Oxygen and Nitrogen Species, leading to a loss of their catalytic function. Therefore, cysteine oxidation is emerging as a relevant physiological regulatory mechanism. Formation of a cyclic sulfenyl amide residue at the active site of redox-regulated proteins has been proposed as a protection mechanism against irreversible oxidation as the sulfenyl amide intermediate has been identified in several proteins. However, how and why only some specific cysteine residues in particular proteins react to form this intermediate is still unknown. In the present work using in-silico based tools, we have identified a constrained conformation that accelerates sulfenyl amide formation. By means of combined MD and QM/MM calculation we show that this conformation positions the NH backbone towards the sulfenic acid and promotes the reaction to yield the sulfenyl amide intermediate, in one step with the concomitant release of a water molecule. Moreover, in a large subset of the proteins we found a conserved beta sheet-loop-helix motif, which is present across different protein folds, that is key for sulfenyl amide production as it promotes the previous formation of sulfenic acid. For catalytic activity, in several cases, proteins need the Cysteine to be in the cysteinate form, i.e. a low pKa Cys. We found that the conserved motif stabilizes the cysteinate by hydrogen bonding to several NH backbone moieties. As cysteinate is also more reactive toward ROS we propose that the sheet-loop-helix motif and the constraint conformation have been selected by evolution for proteins that need a reactive Cys protected from irreversible oxidation. Our results also highlight how fold conservation can be correlated to redox chemistry regulation of protein function. PMID:25741692

  12. TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine.

    Directory of Open Access Journals (Sweden)

    Stephanie Jemielity

    2013-03-01

    Full Text Available Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4 specifically bind phosphatidylserine (PS. TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies.

  13. Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis.

    Science.gov (United States)

    Oldereid, N B; Angelis, P D; Wiger, R; Clausen, O P

    2001-05-01

    We investigated the frequency of spontaneous apoptosis and expression of the Bcl-2 family of proteins during normal spermatogenesis in man. Testicular tissue with both normal morphology and DNA content was obtained from necro-donors and fixed in Bouin's solution. A TdT-mediated dUTP end-labelling method (TUNEL) was used for the detection of apoptotic cells. Expression of apoptosis regulatory Bcl-2 family proteins and of p53 and p21(Waf1) was assessed by immunohistochemistry. Germ cell apoptosis was detected in all testes and was mainly seen in primary spermatocytes and spermatids and in a few spermatogonia. Bcl-2 and Bak were preferentially expressed in the compartments of spermatocytes and differentiating spermatids, while Bcl-x was preferentially expressed in spermatogonia. Bax showed a preferential expression in nuclei of round spermatids, whereas Bad was only seen in the acrosome region of various stages of spermatids. Mcl-1 staining was weak without a particular pattern, whereas expression of Bcl-w, p53 and p21(Waf1) proteins was not detected by immunohistochemistry. The results show that spontaneous apoptosis occurs in all male germ cell compartments in humans. Bcl-2 family proteins are distributed preferentially within distinct germ cell compartments suggesting a specific role for these proteins in the processes of differentiation and maturation during human spermatogenesis.

  14. Variability and action mechanism of a family of anticomplement proteins in Ixodes ricinus.

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    Bernard Couvreur

    Full Text Available BACKGROUND: Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. METHODOLOGY/PRINCIPAL FINDINGS: We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in Ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical or functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. CONCLUSIONS/SIGNIFICANCE: Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway. Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods.

  15. The Social Mechanisms of the Reproduction of the Cultural Capital of Families in a Provincial Russian City

    Science.gov (United States)

    Ochkina, A. V.

    2011-01-01

    Research on the reproduction of cultural capital in Russia shows that it requires not only appropriate motivation on the part of parents, close association between parents and children, but also institutional and material support. Inadequate financial resources, breakdowns in the functioning of the system of education and culture, and conflicts in…

  16. Reproductive health characteristics of marijuana and cocaine users: results from the 2002 National Survey of Family Growth

    NARCIS (Netherlands)

    Gelder, M.M.H.J. van; Reefhuis, J.; Herron, A.M.; Williams, M.L.; Roeleveld, N.

    2011-01-01

    CONTEXT: Illicit drug use is associated with risky sexual behaviors in adolescents and young adults. However, few studies have examined these associations among drug users of all reproductive ages, using a control group of nonusers. METHODS: Associations between marijuana and cocaine use, and

  17. Characterization of the Pichia pastoris protein-O-mannosyltransferase gene family.

    Directory of Open Access Journals (Sweden)

    Juergen H Nett

    Full Text Available The methylotrophic yeast, Pichiapastoris, is an important organism used for the production of therapeutic proteins. However, the presence of fungal-like glycans, either N-linked or O-linked, can elicit an immune response or enable the expressed protein to bind to mannose receptors, thus reducing their efficacy. Previously we have reported the elimination of β-linked glycans in this organism. In the current report we have focused on reducing the O-linked mannose content of proteins produced in P. pastoris, thereby reducing the potential to bind to mannose receptors. The initial step in the synthesis of O-linked glycans in P. pastoris is the transfer of mannose from dolichol-phosphomannose to a target protein in the yeast secretory pathway by members of the protein-O-mannosyltransferase (PMT family. In this report we identify and characterize the members of the P. pastoris PMT family. Like Candida albicans, P. pastoris has five PMT genes. Based on sequence homology, these PMTs can be grouped into three sub-families, with both PMT1 and PMT2 sub-families possessing two members each (PMT1 and PMT5, and PMT2 and PMT6, respectively. The remaining sub-family, PMT4, has only one member (PMT4. Through gene knockouts we show that PMT1 and PMT2 each play a significant role in O-glycosylation. Both, by gene knockouts and the use of Pmt inhibitors we were able to significantly reduce not only the degree of O-mannosylation, but also the chain-length of these glycans. Taken together, this reduction of O-glycosylation represents an important step forward in developing the P. pastoris platform as a suitable system for the production of therapeutic glycoproteins.

  18. A hybrid clustering approach to recognition of protein families in 114 microbial genomes

    Directory of Open Access Journals (Sweden)

    Gogarten J Peter

    2004-04-01

    Full Text Available Abstract Background Grouping proteins into sequence-based clusters is a fundamental step in many bioinformatic analyses (e.g., homology-based prediction of structure or function. Standard clustering methods such as single-linkage clustering capture a history of cluster topologies as a function of threshold, but in practice their usefulness is limited because unrelated sequences join clusters before biologically meaningful families are fully constituted, e.g. as the result of matches to so-called promiscuous domains. Use of the Markov Cluster algorithm avoids this non-specificity, but does not preserve topological or threshold information about protein families. Results We describe a hybrid approach to sequence-based clustering of proteins that combines the advantages of standard and Markov clustering. We have implemented this hybrid approach over a relational database environment, and describe its application to clustering a large subset of PDB, and to 328577 proteins from 114 fully sequenced microbial genomes. To demonstrate utility with difficult problems, we show that hybrid clustering allows us to constitute the paralogous family of ATP synthase F1 rotary motor subunits into a single, biologically interpretable hierarchical grouping that was not accessible using either single-linkage or Markov clustering alone. We describe validation of this method by hybrid clustering of PDB and mapping SCOP families and domains onto the resulting clusters. Conclusion Hybrid (Markov followed by single-linkage clustering combines the advantages of the Markov Cluster algorithm (avoidance of non-specific clusters resulting from matches to promiscuous domains and single-linkage clustering (preservation of topological information as a function of threshold. Within the individual Markov clusters, single-linkage clustering is a more-precise instrument, discerning sub-clusters of biological relevance. Our hybrid approach thus provides a computationally efficient

  19. A comprehensive software suite for protein family construction and functional site prediction.

    Directory of Open Access Journals (Sweden)

    David Renfrew Haft

    Full Text Available In functionally diverse protein families, conservation in short signature regions may outperform full-length sequence comparisons for identifying proteins that belong to a subgroup within which one specific aspect of their function is conserved. The SIMBAL workflow (Sites Inferred by Metabolic Background Assertion Labeling is a data-mining procedure for finding such signature regions. It begins by using clues from genomic context, such as co-occurrence or conserved gene neighborhoods, to build a useful training set from a large number of uncharacterized but mutually homologous proteins. When training set construction is successful, the YES partition is enriched in proteins that share function with the user's query sequence, while the NO partition is depleted. A selected query sequence is then mined for short signature regions whose closest matches overwhelmingly favor proteins from the YES partition. High-scoring signature regions typically contain key residues critical to functional specificity, so proteins with the highest sequence similarity across these regions tend to share the same function. The SIMBAL algorithm was described previously, but significant manual effort, expertise, and a supporting software infrastructure were required to prepare the requisite training sets. Here, we describe a new, distributable software suite that speeds up and simplifies the process for using SIMBAL, most notably by providing tools that automate training set construction. These tools have broad utility for comparative genomics, allowing for flexible collection of proteins or protein domains based on genomic context as well as homology, a capability that can greatly assist in protein family construction. Armed with this new software suite, SIMBAL can serve as a fast and powerful in silico alternative to direct experimentation for characterizing proteins and their functional interactions.

  20. Chromophore photophysics and dynamics in fluorescent proteins of the GFP family

    International Nuclear Information System (INIS)

    Nienhaus, Karin; Nienhaus, G Ulrich

    2016-01-01

    Proteins of the green fluorescent protein (GFP) family are indispensable for fluorescence imaging experiments in the life sciences, particularly of living specimens. Their essential role as genetically encoded fluorescence markers has motivated many researchers over the last 20 years to further advance and optimize these proteins by using protein engineering. Amino acids can be exchanged by site-specific mutagenesis, starting with naturally occurring proteins as templates. Optical properties of the fluorescent chromophore are strongly tuned by the surrounding protein environment, and a targeted modification of chromophore-protein interactions requires a profound knowledge of the underlying photophysics and photochemistry, which has by now been well established from a large number of structural and spectroscopic experiments and molecular-mechanical and quantum-mechanical computations on many variants of fluorescent proteins. Nevertheless, such rational engineering often does not meet with success and thus is complemented by random mutagenesis and selection based on the optical properties. In this topical review, we present an overview of the key structural and spectroscopic properties of fluorescent proteins. We address protein-chromophore interactions that govern ground state optical properties as well as processes occurring in the electronically excited state. Special emphasis is placed on photoactivation of fluorescent proteins. These light-induced reactions result in large structural changes that drastically alter the fluorescence properties of the protein, which enables some of the most exciting applications, including single particle tracking, pulse chase imaging and super-resolution imaging. We also present a few examples of fluorescent protein application in live-cell imaging experiments. (topical review)

  1. Chromophore photophysics and dynamics in fluorescent proteins of the GFP family

    Science.gov (United States)

    Nienhaus, Karin; Nienhaus, G. Ulrich

    2016-11-01

    Proteins of the green fluorescent protein (GFP) family are indispensable for fluorescence imaging experiments in the life sciences, particularly of living specimens. Their essential role as genetically encoded fluorescence markers has motivated many researchers over the last 20 years to further advance and optimize these proteins by using protein engineering. Amino acids can be exchanged by site-specific mutagenesis, starting with naturally occurring proteins as templates. Optical properties of the fluorescent chromophore are strongly tuned by the surrounding protein environment, and a targeted modification of chromophore-protein interactions requires a profound knowledge of the underlying photophysics and photochemistry, which has by now been well established from a large number of structural and spectroscopic experiments and molecular-mechanical and quantum-mechanical computations on many variants of fluorescent proteins. Nevertheless, such rational engineering often does not meet with success and thus is complemented by random mutagenesis and selection based on the optical properties. In this topical review, we present an overview of the key structural and spectroscopic properties of fluorescent proteins. We address protein-chromophore interactions that govern ground state optical properties as well as processes occurring in the electronically excited state. Special emphasis is placed on photoactivation of fluorescent proteins. These light-induced reactions result in large structural changes that drastically alter the fluorescence properties of the protein, which enables some of the most exciting applications, including single particle tracking, pulse chase imaging and super-resolution imaging. We also present a few examples of fluorescent protein application in live-cell imaging experiments.

  2. Analysis of odorant-binding protein gene family members in the polyembryonic wasp, Copidosoma floridanum: evidence for caste bias and host interaction.

    Science.gov (United States)

    Donnell, David M

    2014-01-01

    The polyembryonic wasp Copidosoma floridanum produces two larval castes, soldiers and reproductives, during development within its caterpillar host. Primary structures were determined for 6 odorant-binding protein (OBP) gene family members in Copidosoma and then analyzed alongside two formerly sequenced OBP genes from this wasp. The genes were examined for caste-bias in expression patterns using reverse transcription-polymerase chain reaction (RT-PCR) and in situ expression studies. Six of the 8 genes show a clear bias in gene expression towards one or the other larval caste. Of the 3 distinct in situ probe hybridization patterns observed in this study, none lie in tissues with clear chemosensory functions. Two of the patterns suggest the majority of the Copidosoma OBP gene family members discovered thus far come into contact with host hemolymph. Most of these OBPs are expressed exclusively in the serosal membrane encompassing each of the reproductive larvae. The absence of expression in the membrane surrounding soldier larvae strongly suggests these OBPs are performing caste-specific functions in the host. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Vitellogenin in the honey bee brain: Atypical localization of a reproductive protein that promotes longevity.

    Science.gov (United States)

    Münch, Daniel; Ihle, Kate E; Salmela, Heli; Amdam, Gro V

    2015-11-01

    In comparative gerontology, highly social insects such as honey bees (Apis mellifera) receive much attention due to very different and flexible aging patterns among closely related siblings. While experimental strategies that manipulate socio-environmental factors suggest a causative link between aging and social signals and behaviors, the molecular underpinnings of this linkage are less well understood. Here we study the atypical localization of the egg-yolk protein vitellogenin (Vg) in the brain of the honey bee. Vg is known to influence honey bee social regulation and aging rate. Our findings suggest that Vg immunoreactivity in the brain is specifically localized within the class of non-neuronal glial cells. We discuss how these results can help explain the socially-dependent aging rate of honey bees. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-04-24

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

  5. Impediments to media communication of social change in family planning and reproductive health: experiences from East Africa.

    Science.gov (United States)

    Kagurusi, Patrick T

    2013-09-01

    The media has been employed to increase uptake of Family Planning through behaviour change communication (BCC). Understanding the barriers encountered in effectively undertaking this function would increase the strategy's effectiveness. Sixty journalists from East Africa participated in trainings to enhance their BCC skills for Family Planning in which a qualitative study was nested to identify barriers to effective Family Planning BCC in the region's media. The barriers were observed to be insufficient BCC skills, journalists' conflict of interest, interests of media houses, inaccessible sources of family planning information, editorial ideologies and absence of commercially beneficial demand. Coupled with the historical ideologies of the media in the region, the observed barriers have precipitated ineffective family planning BCC in the regions media. Effective BCC for family planning in the regions media requires capacity building among practitioners and alignment of the concept to the media's and consumers' aspirations.

  6. Upregulation of human heme oxygenase gene expression by Ets-family proteins.

    Science.gov (United States)

    Deramaudt, B M; Remy, P; Abraham, N G

    1999-03-01

    Overexpression of human heme oxygenase-1 has been shown to have the potential to promote EC proliferation and angiogenesis. Since Ets-family proteins have been shown to play an important role in angiogenesis, we investigated the presence of ETS binding sites (EBS), GGAA/T, and ETS protein contributing to human HO-1 gene expression. Several chloramphenicol acetyltransferase constructs were examined in order to analyze the effect of ETS family proteins on the transduction of HO-1 in Xenopus oocytes and in microvessel endothelial cells. Heme oxygenase promoter activity was up-regulated by FLI-1ERGETS-1 protein(s). Chloramphenicol acetyltransferase (CAT) assays demonstrated that the promoter region (-1500 to +19) contains positive and negative control elements and that all three members of the ETS protein family were responsible for the up-regulation of HHO-1. Electrophoretic mobility shift assays (EMSA), performed with nuclear extracts from endothelial cells overexpressing HHO-1 gene, and specific HHO-1 oligonucleotides probes containing putative EBS resulted in a specific and marked bandshift. Synergistic binding was observed in EMSA between AP-1 on the one hand, FLI-1, ERG, and ETS-1 protein on the other. Moreover, 5'-deletion analysis demonstrated the existence of a negative control element of HHO-1 expression located between positions -1500 and -120 on the HHO-1 promoter. The presence of regulatory sequences for transcription factors such as ETS-1, FLI-1, or ERG, whose activity is associated with cell proliferation, endothelial cell differentiation, and matrix metalloproteinase transduction, may be an indication of the important role that HO-1 may play in coronary collateral circulation, tumor growth, angiogenesis, and hemoglobin-induced endothelial cell injuries.

  7. Slipins: ancient origin, duplication and diversification of the stomatin protein family

    Directory of Open Access Journals (Sweden)

    Young J Peter W

    2008-02-01

    Full Text Available Abstract Background Stomatin is a membrane protein that was first isolated from human red blood cells. Since then, a number of stomatin-like proteins have been identified in all three domains of life. The conservation among these proteins is remarkable, with bacterial and human homologs sharing 50 % identity. Despite being associated with a variety of diseases such as cancer, kidney failure and anaemia, precise functions of these proteins remain unclear. Results We have constructed a comprehensive phylogeny of all 'stomatin-like' sequences that share a 150 amino acid domain. We show these proteins comprise an ancient family that arose early in prokaryotic evolution, and we propose a new nomenclature that reflects their phylogeny, based on the name "slipin" (stomatin-like protein. Within prokaryotes there are two distinct subfamilies that account for the two different origins of the eight eukaryotic stomatin subfamilies, one of which gave rise to eukaryotic SLP-2, renamed here "paraslipin". This was apparently acquired through the mitochondrial endosymbiosis and is widely distributed amongst the major kingdoms. The other prokaryotic subfamily gave rise to the ancestor of the remaining seven eukaryotic subfamilies. The highly diverged "alloslipin" subfamily is represented only by fungal, viral and ciliate sequences. The remaining six subfamilies, collectively termed "slipins", are confined to metazoa. Protostome stomatin, as well as a newly reported arthropod subfamily slipin-4, are restricted to invertebrate groups, whilst slipin-1 (previously SLP-1 is present in nematodes and higher metazoa. In vertebrates, the stomatin family expanded considerably, with at least two duplication events giving rise to podocin and slipin-3 subfamilies (previously SLP-3, with the retained ancestral sequence giving rise to vertebrate stomatin. Conclusion Stomatin-like proteins have their origin in an ancient duplication event that occurred early on in the evolution

  8. A Drosophila protein family implicated in pheromone perception is related to Tay-Sachs GM2-activator protein.

    Science.gov (United States)

    Starostina, Elena; Xu, Aiguo; Lin, Heping; Pikielny, Claudio W

    2009-01-02

    Low volatility, lipid-like cuticular hydrocarbon pheromones produced by Drosophila melanogaster females play an essential role in triggering and modulating mating behavior, but the chemosensory mechanisms involved remain poorly understood. Recently, we showed that the CheB42a protein, which is expressed in only 10 pheromone-sensing taste hairs on the front legs of males, modulates progression to late stages of male courtship behavior in response to female-specific cuticular hydrocarbons. Here we report that expression of all 12 genes in the CheB gene family is predominantly or exclusively gustatory-specific, and occurs in many different, often non-overlapping patterns. Only the Gr family of gustatory receptor genes displays a comparable variety of gustatory-specific expression patterns. Unlike Grs, however, expression of all but one CheB gene is sexually dimorphic. Like CheB42a, other CheBs may therefore function specifically in gustatory perception of pheromones. We also show that CheBs belong to the ML superfamily of lipid-binding proteins, and are most similar to human GM2-activator protein (GM2-AP). In particular, GM2-AP residues involved in ligand binding are conserved in CheBs but not in other ML proteins. Finally, CheB42a is specifically secreted into the inner lumen of pheromone-sensing taste hairs, where pheromones interact with membrane-bound receptors. We propose that CheB proteins interact directly with lipid-like Drosophila pheromones and modulate their detection by the gustatory signal transduction machinery. Furthermore, as loss of GM2-AP in Tay-Sachs disease prevents degradation of GM2 gangliosides and results in neurodegeneration, the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons.

  9. A Drosophila Protein Family Implicated in Pheromone Perception Is Related to Tay-Sachs GM2-Activator Protein*

    Science.gov (United States)

    Starostina, Elena; Xu, Aiguo; Lin, Heping; Pikielny, Claudio W.

    2009-01-01

    Low volatility, lipid-like cuticular hydrocarbon pheromones produced by Drosophila melanogaster females play an essential role in triggering and modulating mating behavior, but the chemosensory mechanisms involved remain poorly understood. Recently, we showed that the CheB42a protein, which is expressed in only 10 pheromone-sensing taste hairs on the front legs of males, modulates progression to late stages of male courtship behavior in response to female-specific cuticular hydrocarbons. Here we report that expression of all 12 genes in the CheB gene family is predominantly or exclusively gustatory-specific, and occurs in many different, often non-overlapping patterns. Only the Gr family of gustatory receptor genes displays a comparable variety of gustatory-specific expression patterns. Unlike Grs, however, expression of all but one CheB gene is sexually dimorphic. Like CheB42a, other CheBs may therefore function specifically in gustatory perception of pheromones. We also show that CheBs belong to the ML superfamily of lipid-binding proteins, and are most similar to human GM2-activator protein (GM2-AP). In particular, GM2-AP residues involved in ligand binding are conserved in CheBs but not in other ML proteins. Finally, CheB42a is specifically secreted into the inner lumen of pheromone-sensing taste hairs, where pheromones interact with membrane-bound receptors. We propose that CheB proteins interact directly with lipid-like Drosophila pheromones and modulate their detection by the gustatory signal transduction machinery. Furthermore, as loss of GM2-AP in Tay-Sachs disease prevents degradation of GM2 gangliosides and results in neurodegeneration, the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons. PMID:18952610

  10. Stealth proteins: in silico identification of a novel protein family rendering bacterial pathogens invisible to host immune defense.

    Directory of Open Access Journals (Sweden)

    Peter Sperisen

    2005-11-01

    Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

  11. Stealth Proteins: In Silico Identification of a Novel Protein Family Rendering Bacterial Pathogens Invisible to Host Immune Defense.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

  12. Golgi coiled-coil proteins contain multiple binding sites for Rab family G proteins

    NARCIS (Netherlands)

    Sinka, Rita; Gillingham, Alison K.; Kondylis, Vangelis; Munro, Sean

    2008-01-01

    Vesicles and other carriers destined for the Golgi apparatus must be guided to the correct cisternae. Golgins, long coiled-coil proteins that localize to particular Golgi subdomains via their C termini, are candidate regulators of vesicle sorting. In this study, we report that the GRIP domain

  13. Pu-Erh Tea Extract Induces the Degradation of FET Family Proteins Involved in the Pathogenesis of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Yang Yu

    2014-01-01

    Full Text Available FET family proteins consist of fused in sarcoma/translocated in liposarcoma (FUS/TLS, Ewing's sarcoma (EWS, and TATA-binding protein-associated factor 15 (TAF15. Mutations in the copper/zinc superoxide dismutase (SOD1, TAR DNA-binding protein 43 (TDP-43, and FET family proteins are associated with the development of amyotrophic lateral sclerosis (ALS, a fatal neurodegenerative disease. There is currently no cure for this disease and few effective treatments are available. Epidemiological studies indicate that the consumption of tea is associated with a reduced risk of developing neurodegenerative diseases. The results of this study revealed that components of a pu-erh tea extract (PTE interacted with FET family proteins but not with TDP-43 or SOD1. PTE induced the degradation of FET family proteins but had no effects on TDP-43 or SOD1. The most frequently occurring ALS-linked FUS/TLS mutant protein, R521C FUS/TLS, was also degraded in the presence of PTE. Furthermore, ammonium chloride, a lysosome inhibitor, but not lactacystin, a proteasome inhibitor, reduced the degradation of FUS/TLS protein by PTE. PTE significantly reduced the incorporation of R521C FUS/TLS into stress granules under stress conditions. These findings suggest that PTE may have beneficial health effects, including preventing the onset of FET family protein-associated neurodegenerative diseases and delaying the progression of ALS by inhibiting the cytoplasmic aggregation of FET family proteins.

  14. Modern contraceptive use, unmet need, and demand satisfied among women of reproductive age who are married or in a union in the focus countries of the Family Planning 2020 initiative: a systematic analysis using the Family Planning Estimation Tool.

    Science.gov (United States)

    Cahill, Niamh; Sonneveldt, Emily; Stover, John; Weinberger, Michelle; Williamson, Jessica; Wei, Chuchu; Brown, Win; Alkema, Leontine

    2018-03-03

    The London Summit on Family Planning in 2012 inspired the Family Planning 2020 (FP2020) initiative and the 120×20 goal of having an additional 120 million women and adolescent girls become users of modern contraceptives in 69 of the world's poorest countries by the year 2020. Working towards achieving 120 × 20 is crucial for ultimately achieving the Sustainable Development Goals of universal access and satisfying demand for reproductive health. Thus, a performance assessment is required to determine countries' progress. An updated version of the Family Planning Estimation Tool (FPET) was used to construct estimates and projections of the modern contraceptive prevalence rate (mCPR), unmet need for, and demand satisfied with modern methods of contraception among women of reproductive age who are married or in a union in the focus countries of the FP2020 initiative. We assessed current levels of family planning indicators and changes between 2012 and 2017. A counterfactual analysis was used to assess if recent levels of mCPR exceeded pre-FP2020 expectations. In 2017, the mCPR among women of reproductive age who are married or in a union in the FP2020 focus countries was 45·7% (95% uncertainty interval [UI] 42·4-49·1), unmet need for modern methods was 21·6% (19·7-23·9), and the demand satisfied with modern methods was 67·9% (64·4-71·1). Between 2012 and 2017 the number of women of reproductive age who are married or in a union who use modern methods increased by 28·8 million (95% UI 5·8-52·5). At the regional level, Asia has seen the mCPR among women of reproductive age who are married or in a union grow from 51·0% (95% UI 48·5-53·4) to 51·8% (47·3-56·5) between 2012 and 2017, which is slow growth, particularly when compared with a change from 23·9% (22·9-25·0) to 28·5% (26·8-30·2) across Africa. At the country level, based on a counterfactual analysis, we found that 61% of the countries that have made a commitment to FP2020 exceeded pre

  15. Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

    Science.gov (United States)

    Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

    2018-01-04

    Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Ixodes ticks belonging to the Ixodes ricinus complex encode a family of anticomplement proteins.

    Science.gov (United States)

    Daix, V; Schroeder, H; Praet, N; Georgin, J-P; Chiappino, I; Gillet, L; de Fays, K; Decrem, Y; Leboulle, G; Godfroid, E; Bollen, A; Pastoret, P-P; Gern, L; Sharp, P M; Vanderplasschen, A

    2007-04-01

    The alternative pathway of complement is an important innate defence against pathogens including ticks. This component of the immune system has selected for pathogens that have evolved countermeasures. Recently, a salivary protein able to inhibit the alternative pathway was cloned from the American tick Ixodes scapularis (Valenzuela et al., 2000; J. Biol. Chem. 275, 18717-18723). Here, we isolated two different sequences, similar to Isac, from the transcriptome of I. ricinus salivary glands. Expression of these sequences revealed that they both encode secreted proteins able to inhibit the complement alternative pathway. These proteins, called I. ricinus anticomplement (IRAC) protein I and II, are coexpressed constitutively in I. ricinus salivary glands and are upregulated during blood feeding. Also, we demonstrated that they are the products of different genes and not of alleles of the same locus. Finally, phylogenetic analyses demonstrate that ticks belonging to the Ixodes ricinus complex encode a family of relatively small anticomplement molecules undergoing diversification by positive Darwinian selection.

  17. Orphan Nuclear Receptor NR4A1 Binds a Novel Protein Interaction Site on Anti-apoptotic B Cell Lymphoma Gene 2 Family Proteins.

    Science.gov (United States)

    Godoi, Paulo H C; Wilkie-Grantham, Rachel P; Hishiki, Asami; Sano, Renata; Matsuzawa, Yasuko; Yanagi, Hiroko; Munte, Claudia E; Chen, Ya; Yao, Yong; Marassi, Francesca M; Kalbitzer, Hans R; Matsuzawa, Shu-Ichi; Reed, John C

    2016-07-01

    B cell lymphoma gene 2 (Bcl-2) family proteins are key regulators of programmed cell death and important targets for drug discovery. Pro-apoptotic and anti-apoptotic Bcl-2 family proteins reciprocally modulate their activities in large part through protein interactions involving a motif known as BH3 (Bcl-2 homology 3). Nur77 is an orphan member of the nuclear receptor family that lacks a BH3 domain but nevertheless binds certain anti-apoptotic Bcl-2 family proteins (Bcl-2, Bfl-1, and Bcl-B), modulating their effects on apoptosis and autophagy. We used a combination of NMR spectroscopy-based methods, mutagenesis, and functional studies to define the interaction site of a Nur77 peptide on anti-apoptotic Bcl-2 family proteins and reveal a novel interaction surface. Nur77 binds adjacent to the BH3 peptide-binding crevice, suggesting the possibility of cross-talk between these discrete binding sites. Mutagenesis of residues lining the identified interaction site on Bcl-B negated the interaction with Nur77 protein in cells and prevented Nur77-mediated modulation of apoptosis and autophagy. The findings establish a new protein interaction site with the potential to modulate the apoptosis and autophagy mechanisms governed by Bcl-2 family proteins. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.

    Science.gov (United States)

    Touré, B Barry; Miller-Moslin, Karen; Yusuff, Naeem; Perez, Lawrence; Doré, Michael; Joud, Carol; Michael, Walter; DiPietro, Lucian; van der Plas, Simon; McEwan, Michael; Lenoir, Francois; Hoe, Madelene; Karki, Rajesh; Springer, Clayton; Sullivan, John; Levine, Kymberly; Fiorilla, Catherine; Xie, Xiaoling; Kulathila, Raviraj; Herlihy, Kara; Porter, Dale; Visser, Michael

    2013-02-14

    Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

  19. Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative protein folding.

    Science.gov (United States)

    Sato, Yoshimi; Kojima, Rieko; Okumura, Masaki; Hagiwara, Masatoshi; Masui, Shoji; Maegawa, Ken-ichi; Saiki, Masatoshi; Horibe, Tomohisa; Suzuki, Mamoru; Inaba, Kenji

    2013-01-01

    The mammalian endoplasmic reticulum (ER) harbors disulfide bond-generating enzymes, including Ero1α and peroxiredoxin 4 (Prx4), and nearly 20 members of the protein disulfide isomerase family (PDIs), which together constitute a suitable environment for oxidative protein folding. Here, we clarified the Prx4 preferential recognition of two PDI family proteins, P5 and ERp46, and the mode of interaction between Prx4 and P5 thioredoxin domain. Detailed analyses of oxidative folding catalyzed by the reconstituted Prx4-PDIs pathways demonstrated that, while P5 and ERp46 are dedicated to rapid, but promiscuous, disulfide introduction, PDI is an efficient proofreader of non-native disulfides. Remarkably, the Prx4-dependent formation of native disulfide bonds was accelerated when PDI was combined with ERp46 or P5, suggesting that PDIs work synergistically to increase the rate and fidelity of oxidative protein folding. Thus, the mammalian ER seems to contain highly systematized oxidative networks for the efficient production of large quantities of secretory proteins.

  20. A combinatorial approach to detect coevolved amino acid networks in protein families of variable divergence.

    Directory of Open Access Journals (Sweden)

    Julie Baussand

    2009-09-01

    Full Text Available Communication between distant sites often defines the biological role of a protein: amino acid long-range interactions are as important in binding specificity, allosteric regulation and conformational change as residues directly contacting the substrate. The maintaining of functional and structural coupling of long-range interacting residues requires coevolution of these residues. Networks of interaction between coevolved residues can be reconstructed, and from the networks, one can possibly derive insights into functional mechanisms for the protein family. We propose a combinatorial method for mapping conserved networks of amino acid interactions in a protein which is based on the analysis of a set of aligned sequences, the associated distance tree and the combinatorics of its subtrees. The degree of coevolution of all pairs of coevolved residues is identified numerically, and networks are reconstructed with a dedicated clustering algorithm. The method drops the constraints on high sequence divergence limiting the range of applicability of the statistical approaches previously proposed. We apply the method to four protein families where we show an accurate detection of functional networks and the possibility to treat sets of protein sequences of variable divergence.

  1. MARS: A protein family involved in the formation of vertical skeletal elements.

    Science.gov (United States)

    Abehsera, Shai; Peles, Shani; Tynyakov, Jenny; Bentov, Shmuel; Aflalo, Eliahu D; Li, Shihao; Li, Fuhua; Xiang, Jianhai; Sagi, Amir

    2017-05-01

    Vertical organizations of skeletal elements are found in various vertebrate teeth and invertebrate exoskeletons. The molecular mechanism behind the development of such structural organizations is poorly known, although it is generally held that organic matrix proteins play an essential role. While most crustacean cuticular organizations exhibit horizontal chitinous layering, a typical vertical organization is found towards the surface of the teeth in the mandibles of the crayfish Cherax quadricarinatus. Candidate genes encoding for mandible-forming structural proteins were mined in C. quadricarinatus molt-related transcriptomic libraries by using a binary patterning approach. A new protein family, termed the Mandible Alanine Rich Structural (MARS) protein family, with a modular sequence design predicted to form fibers, was found. Investigations of spatial and temporal expression of the different MARS genes suggested specific expression in the mandibular teeth-forming epithelium, particularly during the formation of the chitinous vertical organization. MARS loss-of-function RNAi experiments resulted in the collapse of the organization of the chitin fibers oriented vertically to the surface of the crayfish mandibular incisor tooth. A general search of transcriptomic libraries suggested conservation of MARS proteins across a wide array of crustaceans. Our results provide a first look into the molecular mechanism used to build the complex crustacean mandible and into the specialized vertical structural solution that has evolved in skeletal elements. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors

    Directory of Open Access Journals (Sweden)

    Kelly J Culhane

    2015-11-01

    Full Text Available Although family B G protein-coupled receptors (GPCRs contain only 15 members, they play key roles in transmembrane signal transduction of hormones. Family B GPCRs are drug targets for developing therapeutics for diseases ranging from metabolic to neurological disorders. Despite their importance, the molecular mechanism of activation of family B GPCRs remains largely unexplored due to the challenges in expression and purification of functional receptors to the quantity for biophysical characterization. Currently, there is no crystal structure available of a full-length family B GPCR. However, structures of key domains, including the extracellular ligand binding regions and seven-helical transmembrane regions, have been solved by X-ray crystallography and NMR, providing insights into the mechanisms of ligand recognition and selectivity, and helical arrangements within the cell membrane. Moreover, biophysical and biochemical methods have been used to explore functions, key residues for signaling, and the kinetics and dynamics of signaling processes. This review summarizes the current knowledge of the signal transduction mechanism of family B GPCRs at the molecular level and comments on the challenges and outlook for mechanistic studies of family B GPCRs.

  3. iPfam: a database of protein family and domain interactions found in the Protein Data Bank.

    Science.gov (United States)

    Finn, Robert D; Miller, Benjamin L; Clements, Jody; Bateman, Alex

    2014-01-01

    The database iPfam, available at http://ipfam.org, catalogues Pfam domain interactions based on known 3D structures that are found in the Protein Data Bank, providing interaction data at the molecular level. Previously, the iPfam domain-domain interaction data was integrated within the Pfam database and website, but it has now been migrated to a separate database. This allows for independent development, improving data access and giving clearer separation between the protein family and interactions datasets. In addition to domain-domain interactions, iPfam has been expanded to include interaction data for domain bound small molecule ligands. Functional annotations are provided from source databases, supplemented by the incorporation of Wikipedia articles where available. iPfam (version 1.0) contains >9500 domain-domain and 15 500 domain-ligand interactions. The new website provides access to this data in a variety of ways, including interactive visualizations of the interaction data.

  4. Choosing Pre-conception Planning for Women/Families: Counselling and Informed Consent (Part 2) - Pre-conception Reproductive Planning, Lifestyle, Immunization, and Psychosocial Issues.

    Science.gov (United States)

    Wilson, R Douglas

    2017-12-06

    To inform reproductive and other health care providers about pre-conception evaluation, including considerations for reproductive planning, lifestyle modification, immunization status and attitudes, and psychosocial issues. This counselling information can be used for patient education and planning and possible pre-conception and/or prenatal testing. This information may allow for improved risk assessment when pre-conception counselling for individual patients and their families is used. CONSIDERATIONS FOR PRE-CONCEPTION CARE (PART 2) REGARDING PRE-CONCEPTION REPRODUCTIVE PLANNING, LIFESTYLE, IMMUNIZATIONS, AND PSYCHOSOCIAL ISSUES: CONSIDERATION FOR CARE STATEMENTS: For this review article, the Consideration for Care Statements use the Grading of Recommendations, Assessment, Development and Evaluations strength and quality principles because they are comparable for the clinician and the patient/public user. For example, "Strong" for clinicians is defined as "the recommendation would apply to most individuals. Formal discussion aids are not likely to be needed to help individuals make decisions consistent with their values and preferences." For patients/the public, "Strong" is defined as, "we believe most people in this situation would want the recommended course of actions and only a small number would not." Quality of evidence (High, Moderate, Low) is based on the confidence that the true effect lies close to that of the estimate of the effect. In addition, the Canadian Task Force on Preventive Health Care key to evidence statements and grading of recommendations are included. PubMed, Medline, and the Cochrane Database were searched until May 2017, using appropriate key words (i.e., preconception, reproductive planning, lifestyle modification, immunization risks and benefits, psychosocial pregnancy factors/issues). Grey (unpublished) literature was identified through searching websites of health technology assessment and health technology assessment

  5. The CREC family, a novel family of multiple EF-hand, low-affinity Ca(2+)-binding proteins localised to the secretory pathway of mammalian cells

    DEFF Research Database (Denmark)

    Honoré, B; Vorum, H

    2000-01-01

    The CREC family consists of a number of recently discovered multiple (up to seven) EF-hand proteins that localise to the secretory pathway of mammalian cells. At present, the family includes reticulocalbin, ERC-55/TCBP-49/E6BP, Cab45, calumenin and crocalbin/CBP-50. Similar proteins are found......(2+)-regulated activities. Recent evidence has been obtained that some CREC family members are involved in pathological activities such as malignant cell transformation, mediation of the toxic effects of snake venom toxins and putative participation in amyloid formation. Udgivelsesdato: 2000-Jan-21...

  6. Sifting through genomes with iterative-sequence clustering produces a large, phylogenetically diverse protein-family resource

    Directory of Open Access Journals (Sweden)

    Sharpton Thomas J

    2012-10-01

    Full Text Available Abstract Background New computational resources are needed to manage the increasing volume of biological data from genome sequencing projects. One fundamental challenge is the ability to maintain a complete and current catalog of protein diversity. We developed a new approach for the identification of protein families that focuses on the rapid discovery of homologous protein sequences. Results We implemented fully automated and high-throughput procedures to de novo cluster proteins into families based upon global alignment similarity. Our approach employs an iterative clustering strategy in which homologs of known families are sifted out of the search for new families. The resulting reduction in computational complexity enables us to rapidly identify novel protein families found in new genomes and to perform efficient, automated updates that keep pace with genome sequencing. We refer to protein families identified through this approach as “Sifting Families,” or SFams. Our analysis of ~10.5 million protein sequences from 2,928 genomes identified 436,360 SFams, many of which are not represented in other protein family databases. We validated the quality of SFam clustering through statistical as well as network topology–based analyses. Conclusions We describe the rapid identification of SFams and demonstrate how they can be used to annotate genomes and metagenomes. The SFam database catalogs protein-family quality metrics, multiple sequence alignments, hidden Markov models, and phylogenetic trees. Our source code and database are publicly available and will be subject to frequent updates (http://edhar.genomecenter.ucdavis.edu/sifting_families/.

  7. On the Power and Limits of Sequence Similarity Based Clustering of Proteins Into Families

    DEFF Research Database (Denmark)

    Wiwie, Christian; Röttger, Richard

    2017-01-01

    Over the last decades, we have observed an ongoing tremendous growth of available sequencing data fueled by the advancements in wet-lab technology. The sequencing information is only the beginning of the actual understanding of how organisms survive and prosper. It is, for instance, equally...... important to also unravel the proteomic repertoire of an organism. A classical computational approach for detecting protein families is a sequence-based similarity calculation coupled with a subsequent cluster analysis. In this work we have intensively analyzed various clustering tools on a large scale. We...... used the data to investigate the behavior of the tools' parameters underlining the diversity of the protein families. Furthermore, we trained regression models for predicting the expected performance of a clustering tool for an unknown data set and aimed to also suggest optimal parameters...

  8. The non-structural protein 5 and matrix protein are antigenic targets of T cell immunity to genotype 1 porcine reproductive and respiratory syndrome viruses

    Directory of Open Access Journals (Sweden)

    Helen eMokhtar

    2016-02-01

    Full Text Available The porcine reproductive and respiratory syndrome virus (PRRSV is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focussed on envelope glycoproteins to target virus-neutralising antibody responses. However, these approaches have failed to demonstrate the necessary efficacy to progress towards market. T cells are crucial to the control of many viruses through cytolysis and cytokine secretion. Since control of PRRSV infection is not dependent on the development of neutralising antibodies, it has been proposed that T cell mediated immunity plays a key role. We therefore hypothesised that conserved T cell antigens represent prime candidates for the development a novel PRRS vaccine. Antigens were identified by screening a proteome-wide synthetic peptide library with T cells from cohorts of pigs rendered immune by experimental infections with a closely-related (subtype 1 or divergent (subtype 3 PRRSV-1 strain. Dominant T cell IFN-γ responses were directed against the non-structural protein 5 (NSP5, and to a lesser extent, the matrix (M protein. The majority of NSP5-specific CD8 T cells and M-specific CD4 T cells expressed a putative effector memory phenotype and were polyfunctional as assessed by co-expression of TNF-α and mobilisation of the cytotoxic degranulation marker CD107a. Both antigens were generally well conserved amongst strains of both PRRSV genotypes. Thus M and NSP5 represent attractive vaccine candidate T cell antigens which should be evaluated further in the context of PRRSV vaccine development.

  9. BH3-only protein Bim inhibits activity of antiapoptotic members of Bcl-2 family when expressed in yeast.

    Science.gov (United States)

    Juhásová, Barbora; Mentel, Marek; Bhatia-Kiššová, Ingrid; Zeman, Igor; Kolarov, Jordan; Forte, Michael; Polčic, Peter

    2011-09-02

    Proteins of the Bcl-2 family regulate programmed cell death in mammals by promoting the release of cytochrome c from mitochondria in response to various proapoptotic stimuli. The mechanism by which BH3-only members of the family activate multidomain proapoptotic proteins Bax and Bak to form a pore in mitochondrial membranes remains under dispute. We report that cell death promoting activity of BH3-only protein Bim can be reconstituted in yeast when both Bax and antiapoptotic protein Bcl-X(L) are present, suggesting that Bim likely activates Bax indirectly by inhibiting antiapoptotic proteins. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Characterization of the deleted in autism 1 protein family: implications for studying cognitive disorders.

    Science.gov (United States)

    Aziz, Azhari; Harrop, Sean P; Bishop, Naomi E

    2011-01-19

    Autism spectrum disorders (ASDs) are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1) and cXorf36 or Deleted in Autism-1 Related (DIA1R) are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L), lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental retardation.

  11. Characterization of the deleted in autism 1 protein family: implications for studying cognitive disorders.

    Directory of Open Access Journals (Sweden)

    Azhari Aziz

    2011-01-01

    Full Text Available Autism spectrum disorders (ASDs are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1 and cXorf36 or Deleted in Autism-1 Related (DIA1R are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L, lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental

  12. Phylogeny of the Vitamin K 2,3-Epoxide Reductase (VKOR) Family and Evolutionary Relationship to the Disulfide Bond Formation Protein B (DsbB) Family.

    Science.gov (United States)

    Bevans, Carville G; Krettler, Christoph; Reinhart, Christoph; Watzka, Matthias; Oldenburg, Johannes

    2015-07-29

    In humans and other vertebrate animals, vitamin K 2,3-epoxide reductase (VKOR) family enzymes are the gatekeepers between nutritionally acquired K vitamins and the vitamin K cycle responsible for posttranslational modifications that confer biological activity upon vitamin K-dependent proteins with crucial roles in hemostasis, bone development and homeostasis, hormonal carbohydrate regulation and fertility. We report a phylogenetic analysis of the VKOR family that identifies five major clades. Combined phylogenetic and site-specific conservation analyses point to clade-specific similarities and differences in structure and function. We discovered a single-site determinant uniquely identifying VKOR homologs belonging to human pathogenic, obligate intracellular prokaryotes and protists. Building on previous work by Sevier et al. (Protein Science 14:1630), we analyzed structural data from both VKOR and prokaryotic disulfide bond formation protein B (DsbB) families and hypothesize an ancient evolutionary relationship between the two families where one family arose from the other through a gene duplication/deletion event. This has resulted in circular permutation of primary sequence threading through the four-helical bundle protein folds of both families. This is the first report of circular permutation relating distant a-helical membrane protein sequences and folds. In conclusion, we suggest a chronology for the evolution of the five extant VKOR clades.

  13. Functional characterization of fidgetin, an AAA-family protein mutated in fidget mice

    International Nuclear Information System (INIS)

    Yang Yan; Mahaffey, Connie L.; Berube, Nathalie; Nystuen, Arne; Frankel, Wayne N.

    2005-01-01

    The mouse fidget mutation is an autosomal recessive mutation that renders reduced or absent semicircular canals, microphthalmia, and various skeletal abnormalities to affected mice. We previously identified the defective gene which encodes fidgetin, a new member of the ATPases associated with diverse cellular activities (AAA proteins). Here, we report on the subcellular localization of fidgetin as well as that of two closely related proteins, fidgetin-like 1 and fidgetin-like 2. Epitope-tagging and immunostaining revealed that both fidgetin and fidgetin-like 2 were predominantly localized to the nucleus, whereas fidgetin-like 1 was both nuclear and cytoplasmic. Furthermore, deletion studies identified a putative bipartite nuclear localization signal in the middle portion of the fidgetin protein. Since AAA proteins are known to form functional hetero- or homo-hexamers, we used reciprocal immunoprecipitation to examine the potential interaction among these proteins. We found that fidgetin interacted with itself and this specific interaction was abolished when either the N- or C-terminus of the protein was truncated. Taken together, our results suggest that fidgetin is a nuclear AAA-family protein with the potential to form homo-oligomers, thus representing the first step towards the elucidation of fidgetin's cellular function and the disease mechanism in fidget mutant mice

  14. Turnover of amyloid precursor protein family members determines their nuclear signaling capability.

    Science.gov (United States)

    Gersbacher, Manuel T; Goodger, Zoë V; Trutzel, Annette; Bundschuh, Diana; Nitsch, Roger M; Konietzko, Uwe

    2013-01-01

    The amyloid precursor protein (APP) as well as its homologues, APP-like protein 1 and 2 (APLP1 and APLP2), are cleaved by α-, β-, and γ-secretases, resulting in the release of their intracellular domains (ICDs). We have shown that the APP intracellular domain (AICD) is transported to the nucleus by Fe65 where they jointly bind the histone acetyltransferase Tip60 and localize to spherical nuclear complexes (AFT complexes), which are thought to be sites of transcription. We have now analyzed the subcellular localization and turnover of the APP family members. Similarly to AICD, the ICD of APLP2 localizes to spherical nuclear complexes together with Fe65 and Tip60. In contrast, the ICD of APLP1, despite binding to Fe65, does not translocate to the nucleus. In addition, APLP1 predominantly localizes to the plasma membrane, whereas APP and APLP2 are detected in vesicular structures. APLP1 also demonstrates a much slower turnover of the full-length protein compared to APP and APLP2. We further show that the ICDs of all APP family members are degraded by the proteasome and that the N-terminal amino acids of ICDs determine ICD degradation rate. Together, our results suggest that different nuclear signaling capabilities of APP family members are due to different rates of full-length protein processing and ICD proteasomal degradation. Our results provide evidence in support of a common nuclear signaling function for APP and APLP2 that is absent in APLP1, but suggest that APLP1 has a regulatory role in the nuclear translocation of APP family ICDs due to the sequestration of Fe65.

  15. Receptor oligomerization in family B1 of G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

    2012-01-01

    , the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

  16. Structural and functional diversification in the teleost S100 family of calcium-binding proteins

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    Korsching Sigrun I

    2008-02-01

    Full Text Available Abstract Background Among the EF-Hand calcium-binding proteins the subgroup of S100 proteins constitute a large family with numerous and diverse functions in calcium-mediated signaling. The evolutionary origin of this family is still uncertain and most studies have examined mammalian family members. Results We have performed an extensive search in several teleost genomes to establish the s100 gene family in fish. We report that the teleost S100 repertoire comprises fourteen different subfamilies which show remarkable similarity across six divergent teleost species. Individual species feature distinctive subsets of thirteen to fourteen genes that result from local gene duplications and gene losses. Eight of the fourteen S100 subfamilies are unique for teleosts, while six are shared with mammalian species and three of those even with cartilaginous fish. Several S100 family members are found in jawless fish already, but none of them are clear orthologs of cartilaginous or bony fish s100 genes. All teleost s100 genes show the expected structural features and are subject to strong negative selection. Many aspects of the genomic arrangement and location of mammalian s100 genes are retained in the teleost s100 gene family, including a completely conserved intron/exon border between the two EF hands. Zebrafish s100 genes exhibit highly specific and characteristic expression patterns, showing both redundancy and divergence in their cellular expression. In larval tissue expression is often restricted to specific cell types like keratinocytes, hair cells, ionocytes and olfactory receptor neurons as demonstrated by in situ hybridization. Conclusion The origin of the S100 family predates at least the segregation of jawed from jawless fish and some extant family members predate the divergence of bony from cartilaginous fish. Despite a complex pattern of gene gains and losses the total repertoire size is remarkably constant between species. On the expression

  17. Protein thermostability prediction within homologous families using temperature-dependent statistical potentials.

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    Fabrizio Pucci

    Full Text Available The ability to rationally modify targeted physical and biological features of a protein of interest holds promise in numerous academic and industrial applications and paves the way towards de novo protein design. In particular, bioprocesses that utilize the remarkable properties of enzymes would often benefit from mutants that remain active at temperatures that are either higher or lower than the physiological temperature, while maintaining the biological activity. Many in silico methods have been developed in recent years for predicting the thermodynamic stability of mutant proteins, but very few have focused on thermostability. To bridge this gap, we developed an algorithm for predicting the best descriptor of thermostability, namely the melting temperature Tm, from the protein's sequence and structure. Our method is applicable when the Tm of proteins homologous to the target protein are known. It is based on the design of several temperature-dependent statistical potentials, derived from datasets consisting of either mesostable or thermostable proteins. Linear combinations of these potentials have been shown to yield an estimation of the protein folding free energies at low and high temperatures, and the difference of these energies, a prediction of the melting temperature. This particular construction, that distinguishes between the interactions that contribute more than others to the stability at high temperatures and those that are more stabilizing at low T, gives better performances compared to the standard approach based on T-independent potentials which predict the thermal resistance from the thermodynamic stability. Our method has been tested on 45 proteins of known Tm that belong to 11 homologous families. The standard deviation between experimental and predicted Tm's is equal to 13.6°C in cross validation, and decreases to 8.3°C if the 6 worst predicted proteins are excluded. Possible extensions of our approach are discussed.

  18. GH32 family activity: a topological approach through protein contact networks.

    Science.gov (United States)

    Cimini, Sara; Di Paola, Luisa; Giuliani, Alessandro; Ridolfi, Alessandra; De Gara, Laura

    2016-11-01

    The application of Protein Contact Networks methodology allowed to highlight a novel response of border region between the two domains to substrate binding. Glycoside hydrolases (GH) are enzymes that mainly hydrolyze the glycosidic bond between two carbohydrates or a carbohydrate and a non-carbohydrate moiety. These enzymes are involved in many fundamental and diverse biological processes in plants. We have focused on the GH32 family, including enzymes very similar in both sequence and structure, each having however clear specificities of substrate preferences and kinetic properties. Structural and topological differences among proteins of the GH32 family have been here identified by means of an emerging approach (Protein Contact network, PCN) based on the formalization of 3D structures as contact networks among amino-acid residues. The PCN approach proved successful in both reconstructing the already known functional domains and in identifying the structural counterpart of the properties of GH32 enzymes, which remain uncertain, like their allosteric character. The main outcome of the study was the discovery of the activation upon binding of the border (cleft) region between the two domains. This reveals the allosteric nature of the enzymatic activity for all the analyzed forms in the GH32 family, a character yet to be highlighted in biochemical studies. Furthermore, we have been able to recognize a topological signature (graph energy) of the different affinity of the enzymes towards small and large substrates.

  19. Conserved binding of GCAC motifs by MEC-8, couch potato, and the RBPMS protein family

    Science.gov (United States)

    Soufari, Heddy

    2017-01-01

    Precise regulation of mRNA processing, translation, localization, and stability relies on specific interactions with RNA-binding proteins whose biological function and target preference are dictated by their preferred RNA motifs. The RBPMS family of RNA-binding proteins is defined by a conserved RNA recognition motif (RRM) domain found in metazoan RBPMS/Hermes and RBPMS2, Drosophila couch potato, and MEC-8 from Caenorhabditis elegans. In order to determine the parameters of RNA sequence recognition by the RBPMS family, we have first used the N-terminal domain from MEC-8 in binding assays and have demonstrated a preference for two GCAC motifs optimally separated by >6 nucleotides (nt). We have also determined the crystal structure of the dimeric N-terminal RRM domain from MEC-8 in the unbound form, and in complex with an oligonucleotide harboring two copies of the optimal GCAC motif. The atomic details reveal the molecular network that provides specificity to all four bases in the motif, including multiple hydrogen bonds to the initial guanine. Further studies with human RBPMS, as well as Drosophila couch potato, confirm a general preference for this double GCAC motif by other members of the protein family and the presence of this motif in known targets. PMID:28003515

  20. Community-based educational intervention on necklace method as a natural family planning amongst reproductive age group women in India

    Directory of Open Access Journals (Sweden)

    Jyothi Ramesh

    2018-01-01

    Conclusions: Nurses play a vital role in educating women and creating awareness regarding modern and safe family planning methods. These methods are effective and essential to avoid unwanted pregnancy and thus greatly impact the health of women.

  1. The impact of social franchising on the use of reproductive health and family planning services at public commune health stations in Vietnam.

    Science.gov (United States)

    Ngo, Anh D; Alden, Dana L; Pham, Van; Phan, Ha

    2010-02-28

    Service franchising is a business model that involves building a network of outlets (franchisees) that are locally owned, but act in coordinated manner with the guidance of a central headquarters (franchisor). The franchisor maintains quality standards, provides managerial training, conducts centralized purchasing and promotes a common brand. Research indicates that franchising private reproductive health and family planning (RHFP) services in developing countries improves quality and utilization. However, there is very little evidence that franchising improves RHFP services delivered through community-based public health clinics. This study evaluates behavioral outcomes associated with a new approach - the Government Social Franchise (GSF) model - developed to improve RHFP service quality and capacity in Vietnam's commune health stations (CHSs). The project involved networking and branding 36 commune health station (CHS) clinics in two central provinces of Da Nang and Khanh Hoa, Vietnam. A quasi-experimental design with 36 control CHSs assessed GSF model effects on client use as measured by: 1) clinic-reported client volume; 2) the proportion of self-reported RHFP service users at participating CHS clinics over the total sample of respondents; and 3) self-reported RHFP service use frequency. Monthly clinic records were analyzed. In addition, household surveys of 1,181 CHS users and potential users were conducted prior to launch and then 6 and 12 months after implementing the GSF network. Regression analyses controlled for baseline differences between intervention and control groups. CHS franchise membership was significantly associated with a 40% plus increase in clinic-reported client volumes for both reproductive and general health services. A 45% increase in clinic-reported family planning service clients related to GSF membership was marginally significant (p = 0.05). Self-reported frequency of RHFP service use increased by 20% from the baseline survey to the

  2. The impact of social franchising on the use of reproductive health and family planning services at public commune health stations in Vietnam

    Science.gov (United States)

    2010-01-01

    Background Service franchising is a business model that involves building a network of outlets (franchisees) that are locally owned, but act in coordinated manner with the guidance of a central headquarters (franchisor). The franchisor maintains quality standards, provides managerial training, conducts centralized purchasing and promotes a common brand. Research indicates that franchising private reproductive health and family planning (RHFP) services in developing countries improves quality and utilization. However, there is very little evidence that franchising improves RHFP services delivered through community-based public health clinics. This study evaluates behavioral outcomes associated with a new approach - the Government Social Franchise (GSF) model - developed to improve RHFP service quality and capacity in Vietnam's commune health stations (CHSs). Methods The project involved networking and branding 36 commune health station (CHS) clinics in two central provinces of Da Nang and Khanh Hoa, Vietnam. A quasi-experimental design with 36 control CHSs assessed GSF model effects on client use as measured by: 1) clinic-reported client volume; 2) the proportion of self-reported RHFP service users at participating CHS clinics over the total sample of respondents; and 3) self-reported RHFP service use frequency. Monthly clinic records were analyzed. In addition, household surveys of 1,181 CHS users and potential users were conducted prior to launch and then 6 and 12 months after implementing the GSF network. Regression analyses controlled for baseline differences between intervention and control groups. Results CHS franchise membership was significantly associated with a 40% plus increase in clinic-reported client volumes for both reproductive and general health services. A 45% increase in clinic-reported family planning service clients related to GSF membership was marginally significant (p = 0.05). Self-reported frequency of RHFP service use increased by 20% from

  3. The impact of social franchising on the use of reproductive health and family planning services at public commune health stations in Vietnam

    Directory of Open Access Journals (Sweden)

    Pham Van

    2010-02-01

    Full Text Available Abstract Background Service franchising is a business model that involves building a network of outlets (franchisees that are locally owned, but act in coordinated manner with the guidance of a central headquarters (franchisor. The franchisor maintains quality standards, provides managerial training, conducts centralized purchasing and promotes a common brand. Research indicates that franchising private reproductive health and family planning (RHFP services in developing countries improves quality and utilization. However, there is very little evidence that franchising improves RHFP services delivered through community-based public health clinics. This study evaluates behavioral outcomes associated with a new approach - the Government Social Franchise (GSF model - developed to improve RHFP service quality and capacity in Vietnam's commune health stations (CHSs. Methods The project involved networking and branding 36 commune health station (CHS clinics in two central provinces of Da Nang and Khanh Hoa, Vietnam. A quasi-experimental design with 36 control CHSs assessed GSF model effects on client use as measured by: 1 clinic-reported client volume; 2 the proportion of self-reported RHFP service users at participating CHS clinics over the total sample of respondents; and 3 self-reported RHFP service use frequency. Monthly clinic records were analyzed. In addition, household surveys of 1,181 CHS users and potential users were conducted prior to launch and then 6 and 12 months after implementing the GSF network. Regression analyses controlled for baseline differences between intervention and control groups. Results CHS franchise membership was significantly associated with a 40% plus increase in clinic-reported client volumes for both reproductive and general health services. A 45% increase in clinic-reported family planning service clients related to GSF membership was marginally significant (p = 0.05. Self-reported frequency of RHFP service use

  4. Co-ordinate regulation of cytokinin gene family members during flag leaf and reproductive development in wheat.

    Science.gov (United States)

    Song, Jiancheng; Jiang, Lijun; Jameson, Paula Elizabeth

    2012-06-06

    As the global population continues to expand, increasing yield in bread wheat is of critical importance as 20% of the world's food supply is sourced from this cereal. Several recent studies of the molecular basis of grain yield indicate that the cytokinins are a key factor in determining grain yield. In this study, cytokinin gene family members in bread wheat were isolated from four multigene families which regulate cytokinin synthesis and metabolism, the isopentenyl transferases (IPT), cytokinin oxidases (CKX), zeatin O-glucosyltransferases (ZOG), and β-glucosidases (GLU). As bread wheat is hexaploid, each gene family is also likely to be represented on the A, B and D genomes. By using a novel strategy of qRT-PCR with locus-specific primers shared among the three homoeologues of each family member, detailed expression profiles are provided of family members of these multigene families expressed during leaf, spike and seed development. The expression patterns of individual members of the IPT, CKX, ZOG, and GLU multigene families in wheat are shown to be tissue- and developmentally-specific. For instance, TaIPT2 and TaCKX1 were the most highly expressed family members during early seed development, with relative expression levels of up to 90- and 900-fold higher, respectively, than those in the lowest expressed samples. The expression of two cis-ZOG genes was sharply increased in older leaves, while an extremely high mRNA level of TaGLU1-1 was detected in young leaves. Key genes with tissue- and developmentally-specific expression have been identified which would be prime targets for genetic manipulation towards yield improvement in bread wheat breeding programmes, utilising TILLING and MAS strategies.

  5. Protein homology network families reveal step-wise diversification of Type III and Type IV secretion systems.

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    Duccio Medini

    2006-12-01

    Full Text Available From the analysis of 251 prokaryotic genomes stored in public databases, the 761,260 deduced proteins were used to reconstruct a complete set of bacterial proteic families. Using the new Overlap algorithm, we have partitioned the Protein Homology Network (PHN, where the proteins are the nodes and the links represent homology relationships. The algorithm identifies the densely connected regions of the PHN that define the families of homologous proteins, here called PHN-Families, recognizing the phylogenetic relationships embedded in the network. By direct comparison with a manually curated dataset, we assessed that this classification algorithm generates data of quality similar to a human expert. Then, we explored the network to identify families involved in the assembly of Type III and Type IV secretion systems (T3SS and T4SS. We noticed that, beside a core of conserved functions (eight proteins for T3SS, seven for T4SS, a variable set of accessory components is always present (one to nine for T3SS, one to five for T4SS. Each member of the core corresponds to a single PHN-Family, while accessory proteins are distributed among different pure families. The PHN-Family classification suggests that T3SS and T4SS have been assembled through a step-wise, discontinuous process, by complementing the conserved core with subgroups of nonconserved proteins. Such genetic modules, independently recruited and probably tuned on specific effectors, contribute to the functional specialization of these organelles to different microenvironments.

  6. Using hierarchical clustering of secreted protein families to classify and rank candidate effectors of rust fungi.

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    Diane G O Saunders

    Full Text Available Rust fungi are obligate biotrophic pathogens that cause considerable damage on crop plants. Puccinia graminis f. sp. tritici, the causal agent of wheat stem rust, and Melampsora larici-populina, the poplar leaf rust pathogen, have strong deleterious impacts on wheat and poplar wood production, respectively. Filamentous pathogens such as rust fungi secrete molecules called disease effectors that act as modulators of host cell physiology and can suppress or trigger host immunity. Current knowledge on effectors from other filamentous plant pathogens can be exploited for the characterisation of effectors in the genome of recently sequenced rust fungi. We designed a comprehensive in silico analysis pipeline to identify the putative effector repertoire from the genome of two plant pathogenic rust fungi. The pipeline is based on the observation that known effector proteins from filamentous pathogens have at least one of the following properties: (i contain a secretion signal, (ii are encoded by in planta induced genes, (iii have similarity to haustorial proteins, (iv are small and cysteine rich, (v contain a known effector motif or a nuclear localization signal, (vi are encoded by genes with long intergenic regions, (vii contain internal repeats, and (viii do not contain PFAM domains, except those associated with pathogenicity. We used Markov clustering and hierarchical clustering to classify protein families of rust pathogens and rank them according to their likelihood of being effectors. Using this approach, we identified eight families of candidate effectors that we consider of high value for functional characterization. This study revealed a diverse set of candidate effectors, including families of haustorial expressed secreted proteins and small cysteine-rich proteins. This comprehensive classification of candidate effectors from these devastating rust pathogens is an initial step towards probing plant germplasm for novel resistance components.

  7. TGF-β mimic proteins form an extended gene family in the murine parasite Heligmosomoides polygyrus.

    Science.gov (United States)

    Smyth, Danielle J; Harcus, Yvonne; White, Madeleine P J; Gregory, William F; Nahler, Janina; Stephens, Ian; Toke-Bjolgerud, Edward; Hewitson, James P; Ivens, Alasdair; McSorley, Henry J; Maizels, Rick M

    2018-04-01

    We recently reported the discovery of a new parasite-derived protein that functionally mimics the immunosuppressive cytokine transforming growth factor (TGF)-β. The Heligmosomoides polygyrus TGF-β Mimic (Hp-TGM) shares no homology to any TGF-β family member, however it binds the mammalian TGF-β receptor and induces expression of Foxp3, the canonical transcription factor of both mouse and human regulatory T cells. Hp-TGM consists of five atypical Complement Control Protein (CCP, Pfam 00084) domains, each lacking certain conserved residues and 12-15 amino acids longer than the 60-70 amino acids consensus domain, but with a recognizable 3-cysteine, tryptophan, cysteine motif. We now report on the identification of a family of nine related Hp-TGM homologues represented in the secreted proteome and transcriptome of H. polygyrus. Recombinant proteins from five of the nine new TGM members were tested for TGF-β activity, but only two were functionally active in an MFB-F11 reporter assay, and by the induction of T cell Foxp3 expression. Sequence comparisons reveal that proteins with functional activity are similar or identical to Hp-TGM across the first three CCP domains, but more variable in domains 4 and 5. Inactive proteins diverged in all domains, or lacked some domains entirely. Testing truncated versions of Hp-TGM confirmed that domains 1-3 are essential for full activity in vitro, while domains 4 and 5 are not required. Further studies will elucidate whether these latter domains fulfill other functions in promoting host immune regulation during infection and if the more divergent family members play other roles in immunomodulation. Copyright © 2018. Published by Elsevier Ltd.

  8. Reproductive Health of Women in Rural Areas of East Azerbaijan – Iran, before and after Implementation of rural Family Physician Program: an Ecologic Study

    Science.gov (United States)

    Alizadeh, Mahasti; Jabbari Birami, Hossein; Moradi, Siavash

    2015-01-01

    Introduction: Implementation of rural family physician program in Iran in 2005 has been evaluated and shown that this program has been led to some improvements in health indicators. In this study, some reproductive health (RH) indicators were compared before and after implementation of this program in rural areas of East Azerbaijan, Iran. Methods: In this ecologic- time trend study, the data of 191075 births of rural women of East Azerbaijan from 2001 to 2010 was extracted from vital horoscope (ZIJ) and used for calculation of 20 important RH indicators. The paired t-test and correlation analysis wear used for data analysis. Results: Some indicators such as adolescent marriage rate, adolescent birth and over 35 year olds birth rate were increased after rural family physician program implementation in 2005. Also stillbirth rate and unsafe delivery were decreased during this period. There was a significant correlation between increasing adolescent birth rate and increasing low birth weight deliveries (r= 0.911, P= 0.031) and also between increasing over 35 year olds birth rate and increasing neonatal mortality rate in term of prematurity and congenital malformations (r= 0.912, P= 0.031) after program implementation. Conclusion: Perinatal care and safe delivery even for pregnancies outside the typical child-bearing ages are promoting after implementation of rural family physician program in East Azerbaijan. Also decreasing unsafe delivery and stillbirth rate can be considered as achievements of running this program in this province. PMID:26744731

  9. Reproductive Health of Women in Rural Areas of East Azerbaijan – Iran, before and after Implementation of rural Family Physician Program: an Ecologic Study

    Directory of Open Access Journals (Sweden)

    Mahasti Alizadeh

    2015-12-01

    Full Text Available Introduction: Implementation of rural family physician program in Iran in 2005 has been evaluated and shown that this program has been led to some improvements in health indicators. In this study, some reproductive health (RH indicators were compared before and after implementation of this program in rural areas of East Azerbaijan, Iran. Methods: In this ecologic- time trend study, the data of 191075 births of rural women of East Azerbaijan from 2001 to 2010 was extracted from vital horoscope (ZIJ and used for calculation of 20 important RH indicators. The paired t-test and correlation analysis wear used for data analysis. Results: Some indicators such as adolescent marriage rate, adolescent birth and over 35 year olds birth rate were increased after rural family physician program implementation in 2005. Also stillbirth rate and unsafe delivery were decreased during this period. There was a significant correlation between increasing adolescent birth rate and increasing low birth weight deliveries (r= 0.911, P= 0.031 and also between increasing over 35 year olds birth rate and increasing neonatal mortality rate in term of prematurity and congenital malformations (r= 0.912, P= 0.031 after program implementation. Conclusion: Perinatal care and safe delivery even for pregnancies outside the typical child-bearing ages are promoting after implementation of rural family physician program in East Azerbaijan. Also decreasing unsafe delivery and stillbirth rate can be considered as achievements of running this program in this province.

  10. The actin family protein ARP6 contributes to the structure and the function of the nucleolus

    International Nuclear Information System (INIS)

    Kitamura, Hiroshi; Matsumori, Haruka; Kalendova, Alzbeta; Hozak, Pavel; Goldberg, Ilya G.; Nakao, Mitsuyoshi; Saitoh, Noriko; Harata, Masahiko

    2015-01-01

    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. - 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

  11. The actin family protein ARP6 contributes to the structure and the function of the nucleolus

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Hiroshi [Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoka-ku, Sendai 981-8555 (Japan); Matsumori, Haruka [Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 (Japan); Kalendova, Alzbeta; Hozak, Pavel [Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20 Prague (Czech Republic); Goldberg, Ilya G. [Image Informatics and Computational Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224 (United States); Nakao, Mitsuyoshi [Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 (Japan); Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 102-0076 (Japan); Saitoh, Noriko [Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 (Japan); Harata, Masahiko, E-mail: mharata@biochem.tohoku.ac.jp [Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoka-ku, Sendai 981-8555 (Japan)

    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. - 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.

  12. Hormone signaling linked to silkmoth sex pheromone biosynthesis involves Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of the insect PAT family protein Bombyx mori lipid storage droplet protein-1(BmLsd)

    Science.gov (United States)

    The structurally-related members of the PAT family of proteins, which are so name based on similarity amongst perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), and tail-interacting protein of 47 kilodaltons (TIP47), are cytoplasmic lipid droplet (LD)-associated proteins charac...

  13. Phytoplasma protein effector SAP11 enhances insect vector reproduction by manipulating plant development and defense hormone biosynthesis.

    Science.gov (United States)

    Sugio, Akiko; Kingdom, Heather N; MacLean, Allyson M; Grieve, Victoria M; Hogenhout, Saskia A

    2011-11-29

    Phytoplasmas are insect-transmitted phytopathogenic bacteria that can alter plant morphology and the longevity and reproduction rates and behavior of their insect vectors. There are various examples of animal and plant parasites that alter the host phenotype to attract insect vectors, but it is unclear how these parasites accomplish this. We hypothesized that phytoplasmas produce effectors that modulate specific targets in their hosts leading to the changes in plant development and insect performance. Previously, we sequenced and mined the genome of Aster Yellows phytoplasma strain Witches' Broom (AY-WB) and identified 56 candidate effectors. Here, we report that the secreted AY-WB protein 11 (SAP11) effector modulates plant defense responses to the advantage of the AY-WB insect vector Macrosteles quadrilineatus. SAP11 binds and destabilizes Arabidopsis CINCINNATA (CIN)-related TEOSINTE BRANCHED1, CYCLOIDEA, PROLIFERATING CELL FACTORS 1 and 2 (TCP) transcription factors, which control plant development and promote the expression of lipoxygenase (LOX) genes involved in jasmonate (JA) synthesis. Both the Arabidopsis SAP11 lines and AY-WB-infected plants produce less JA on wounding. Furthermore, the AY-WB insect vector produces more offspring on AY-WB-infected plants, SAP11 transgenic lines, and plants impaired in CIN-TCP and JA synthesis. Thus, SAP11-mediated destabilization of CIN-TCPs leads to the down-regulation of LOX2 expression and JA synthesis and an increase in M. quadrilineatus progeny. Phytoplasmas are obligate inhabitants of their plant host and insect vectors, in which the latter transmits AY-WB to a diverse range of plant species. This finding demonstrates that pathogen effectors can reach beyond the pathogen-host interface to modulate a third organism in the biological interaction.

  14. Identification of an evolutionary conserved SURF-6 domain in a family of nucleolar proteins extending from human to yeast

    International Nuclear Information System (INIS)

    Polzikov, Mikhail; Zatsepina, Olga; Magoulas, Charalambos

    2005-01-01

    The mammalian SURF-6 protein is localized in the nucleolus, yet its function remains elusive in the recently characterized nucleolar proteome. We discovered by searching the Protein families database that a unique evolutionary conserved SURF-6 domain is present in the carboxy-terminal of a novel family of eukaryotic proteins extending from human to yeast. By using the enhanced green fluorescent protein as a fusion protein marker in mammalian cells, we show that proteins from distantly related taxonomic groups containing the SURF-6 domain are localized in the nucleolus. Deletion sequence analysis shows that multiple regions of the SURF-6 protein are capable of nucleolar targeting independently of the evolutionary conserved domain. We identified that the Saccharomyces cerevisiae member of the SURF-6 family, named rrp14 or ykl082c, has been categorized in yeast databases to interact with proteins involved in ribosomal biogenesis and cell polarity. These results classify SURF-6 as a new family of nucleolar proteins in the eukaryotic kingdom and point out that SURF-6 has a distinct domain within the known nucleolar proteome that may mediate complex protein-protein interactions for analogous processes between yeast and mammalian cells

  15. SMAD family proteins: the current knowledge on their expression and potential role in neoplastic diseases

    Directory of Open Access Journals (Sweden)

    Magdalena Witkowska

    2014-03-01

    Full Text Available Transforming growth factor beta (TGF-β plays a crucial role and takes part in many processes in the human body both in physiology and pathology. This cytokine is involved in angiogenesis, regulates apoptosis and stimulates divisions of cells, such as hepatocytes, lymphocytes or hematopoietic cells. SMAD proteins family is a unique group of particles responsible for transducting the signal induced by TGF-β into the nucleus. This molecules, after receiving a signal from activated TGF-β, act on transcription factors in the nucleus, leading directly to the expression of the corresponding genes. According to current knowledge, disturbances in the functioning of SMAD proteins are present in a number of diseases. The reduced expression was observed, for example in cardiovascular diseases such as primary pulmonary hypertension or myocardial infarction, autoimmune diseases for instance systemic lupus erythematosus and multiple sclerosis, Alzheimer’s disease or osteoporosis. The latest clinical data showed the presence of mutations in SMAD proteins in cancerogenesis. Mutation of SMAD-4 protein can be detected in half of the patients with pancreatic cancer, 20% of patients with colorectal cancer and 10% of patients with lung cancer. However, mutation in SMAD-2 protein was observed in 7% of both patients with colorectal cancer and lung cancer. On the basis of numerous works, SMAD protein expression would be valuable prognostic factor in some of neoplastic diseases.

  16. INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions.

    Science.gov (United States)

    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.

  17. Financing Maternal Health and Family Planning: Are We on the Right Track? Evidence from the Reproductive Health Subaccounts in Mexico, 2003-2012.

    Directory of Open Access Journals (Sweden)

    Leticia Avila-Burgos

    Full Text Available To analyze whether the changes observed in the level and distribution of resources for maternal health and family planning (MHFP programs from 2003 to 2012 were consistent with the financial goals of the related policies.A longitudinal descriptive analysis of the Mexican Reproductive Health Subaccounts 2003-2012 was performed by financing scheme and health function. Financing schemes included social security, government schemes, household out-of-pocket (OOP payments, and private insurance plans. Functions were preventive care, including family planning, antenatal and puerperium health services, normal and cesarean deliveries, and treatment of complications. Changes in the financial imbalance indicators covered by MHFP policy were tracked: (a public and OOP expenditures as percentages of total MHFP spending; (b public expenditure per woman of reproductive age (WoRA, 15-49 years by financing scheme; (c public expenditure on treating complications as a percentage of preventive care; and (d public expenditure on WoRA at state level. Statistical analyses of trends and distributions were performed.Public expenditure on government schemes grew by approximately 300%, and the financial imbalance between populations covered by social security and government schemes decreased. The financial burden on households declined, particularly among households without social security. Expenditure on preventive care grew by 16%, narrowing the financing gap between treatment of complications and preventive care. Finally, public expenditure per WoRA for government schemes nearly doubled at the state level, although considerable disparities persist.Changes in the level and distribution of MHFP funding from 2003 to 2012 were consistent with the relevant policy goals. However, improving efficiency requires further analysis to ascertain the impact of investments on health outcomes. This, in turn, will require better financial data systems as a precondition for improving

  18. Financing Maternal Health and Family Planning: Are We on the Right Track? Evidence from the Reproductive Health Subaccounts in Mexico, 2003-2012.

    Science.gov (United States)

    Avila-Burgos, Leticia; Cahuana-Hurtado, Lucero; Montañez-Hernandez, Julio; Servan-Mori, Edson; Aracena-Genao, Belkis; Del Río-Zolezzi, Aurora

    2016-01-01

    To analyze whether the changes observed in the level and distribution of resources for maternal health and family planning (MHFP) programs from 2003 to 2012 were consistent with the financial goals of the related policies. A longitudinal descriptive analysis of the Mexican Reproductive Health Subaccounts 2003-2012 was performed by financing scheme and health function. Financing schemes included social security, government schemes, household out-of-pocket (OOP) payments, and private insurance plans. Functions were preventive care, including family planning, antenatal and puerperium health services, normal and cesarean deliveries, and treatment of complications. Changes in the financial imbalance indicators covered by MHFP policy were tracked: (a) public and OOP expenditures as percentages of total MHFP spending; (b) public expenditure per woman of reproductive age (WoRA, 15-49 years) by financing scheme; (c) public expenditure on treating complications as a percentage of preventive care; and (d) public expenditure on WoRA at state level. Statistical analyses of trends and distributions were performed. Public expenditure on government schemes grew by approximately 300%, and the financial imbalance between populations covered by social security and government schemes decreased. The financial burden on households declined, particularly among households without social security. Expenditure on preventive care grew by 16%, narrowing the financing gap between treatment of complications and preventive care. Finally, public expenditure per WoRA for government schemes nearly doubled at the state level, although considerable disparities persist. Changes in the level and distribution of MHFP funding from 2003 to 2012 were consistent with the relevant policy goals. However, improving efficiency requires further analysis to ascertain the impact of investments on health outcomes. This, in turn, will require better financial data systems as a precondition for improving the

  19. Phylogenetic distribution and membrane topology of the LytR-CpsA-Psr protein family

    Directory of Open Access Journals (Sweden)

    Berger-Bächi Brigitte

    2008-12-01

    Full Text Available Abstract Background The bacterial cell wall is the target of many antibiotics and cell envelope constituents are critical to host-pathogen interactions. To combat resistance development and virulence, a detailed knowledge of the individual factors involved is essential. Members of the LytR-CpsA-Psr family of cell envelope-associated attenuators are relevant for β-lactam resistance, biofilm formation, and stress tolerance, and they are suggested to play a role in cell wall maintenance. However, their precise function is still unknown. This study addresses the occurrence as well as sequence-based characteristics of the LytR-CpsA-Psr proteins. Results A comprehensive list of LytR-CpsA-Psr proteins was established, and their phylogenetic distribution and clustering into subgroups was determined. LytR-CpsA-Psr proteins were present in all Gram-positive organisms, except for the cell wall-deficient Mollicutes and one strain of the Clostridiales. In contrast, the majority of Gram-negatives did not contain LytR-CpsA-Psr family members. Despite high sequence divergence, the LytR-CpsA-Psr domains of different subclusters shared a highly similar, predicted mixed a/β-structure, and conserved charged residues. PhoA fusion experiments, using MsrR of Staphylococcus aureus, confirmed membrane topology predictions and extracellular location of its LytR-CpsA-Psr domain. Conclusion The LytR-CpsA-Psr domain is unique to bacteria. The presence of diverse subgroups within the LytR-CpsA-Psr family might indicate functional differences, and could explain variations in phenotypes of respective mutants reported. The identified conserved structural elements and amino acids are likely to be important for the function of the domain and will help to guide future studies of the LytR-CpsA-Psr proteins.

  20. Porcine reproductive and respiratory syndrome virus nonstructural protein 2 (nsp2) topology and selective isoform integration in artificial membranes

    Science.gov (United States)

    Membrane modification of host subcellular compartments is critical to the replication of many RNA viruses. Enveloped viruses additionally require the ability to requisition cellular membranes during egress for the development of infectious progeny. Porcine reproductive and respiratory syndrome virus...

  1. PfEMP1 – A Parasite Protein Family of Key Importance in Plasmodium falciparum Malaria Immunity and Pathogenesis

    DEFF Research Database (Denmark)

    Hviid, Lars; Jensen, Anja T R

    2015-01-01

    to be a central element in the pathogenesis of the disease. It is mediated by the interaction of parasite ligands on the erythrocyte surface and a range of host receptor molecules in many organs and tissues. Among several proteins and protein families implicated in this process, the P. falciparum erythrocyte...... membrane protein 1 (PfEMP1) family of high-molecular weight and highly variable antigens appears to be the most prominent. In this chapter, we aim to provide a systematic overview of the current knowledge about these proteins, their structure, their function, how they are presented on the erythrocyte...

  2. Family planning as part of reproductive health, including the HIV / AIDS aspects, in Zimbabwe and Southern Africa

    NARCIS (Netherlands)

    Verkuyl, Douwe Arie Anne

    2003-01-01

    This thesis explores the demand for family planning (FP) in the region and demonstrates that just at the time that demand takes off the brain drain and economic situation make it unlikely that the required services will be provided. This, increasingly, results in unsafe abortions. FP in Zimbabwe is

  3. Plant, animal, and fungal micronutrient queuosine is salvaged by members of the DUF2419 protein family.

    Science.gov (United States)

    Zallot, Rémi; Brochier-Armanet, Céline; Gaston, Kirk W; Forouhar, Farhad; Limbach, Patrick A; Hunt, John F; de Crécy-Lagard, Valérie

    2014-08-15

    Queuosine (Q) is a modification found at the wobble position of tRNAs with GUN anticodons. Although Q is present in most eukaryotes and bacteria, only bacteria can synthesize Q de novo. Eukaryotes acquire queuine (q), the free base of Q, from diet and/or microflora, making q an important but under-recognized micronutrient for plants, animals, and fungi. Eukaryotic type tRNA-guanine transglycosylases (eTGTs) are composed of a catalytic subunit (QTRT1) and a homologous accessory subunit (QTRTD1) forming a complex that catalyzes q insertion into target tRNAs. Phylogenetic analysis of eTGT subunits revealed a patchy distribution pattern in which gene losses occurred independently in different clades. Searches for genes co-distributing with eTGT family members identified DUF2419 as a potential Q salvage protein family. This prediction was experimentally validated in Schizosaccharomyces pombe by confirming that Q was present by analyzing tRNA(Asp) with anticodon GUC purified from wild-type cells and by showing that Q was absent from strains carrying deletions in the QTRT1 or DUF2419 encoding genes. DUF2419 proteins occur in most Eukarya with a few possible cases of horizontal gene transfer to bacteria. The universality of the DUF2419 function was confirmed by complementing the S. pombe mutant with the Zea mays (maize), human, and Sphaerobacter thermophilus homologues. The enzymatic function of this family is yet to be determined, but structural similarity with DNA glycosidases suggests a ribonucleoside hydrolase activity.

  4. Glis family proteins are differentially implicated in the cellular reprogramming of human somatic cells.

    Science.gov (United States)

    Lee, Seo-Young; Noh, Hye Bin; Kim, Hyeong-Taek; Lee, Kang-In; Hwang, Dong-Youn

    2017-09-29

    The ground-breaking discovery of the reprogramming of somatic cells into pluripotent cells, termed induced pluripotent stem cells (iPSCs), was accomplished by delivering 4 transcription factors, Oct4, Sox2, Klf4, and c-Myc, into fibroblasts. Since then, several efforts have attempted to unveil other factors that are directly implicated in or might enhance reprogramming. Importantly, a number of transcription factors are reported to retain reprogramming activity. A previous study suggested Gli-similar 1 (Glis1) as a factor that enhances the reprogramming of fibroblasts during iPSC generation. However, the implication of other Glis members, including Glis2 and Glis3 (variants 1 and 2), in cellular reprogramming remains unknown. In this study, we investigated the potential involvement of human Glis family proteins, including hGlis1-3, in cellular reprogramming. Our results demonstrate that hGlis1, which is reported to reprogram human fibroblasts, promotes the reprogramming of human adipose-derived stromal cells (hADSCs), indicating that the reprogramming activity of Glis1 is not cell type-specific. Strikingly, hGlis3 promoted the reprogramming of hADSCs as efficiently as hGlis1. On the contrary, hGlis2 showed a strong negative effect on reprogramming. Together, our results reveal clear differences in the cellular reprogramming activity among Glis family members and provide valuable insight into the development of a new reprogramming strategy using Glis family proteins.

  5. Trends in global warming and evolution of matrix protein 2 family from influenza A virus.

    Science.gov (United States)

    Yan, Shao-Min; Wu, Guang

    2009-12-01

    The global warming is an important factor affecting the biological evolution, and the influenza is an important disease that threatens humans with possible epidemics or pandemics. In this study, we attempted to analyze the trends in global warming and evolution of matrix protein 2 family from influenza A virus, because this protein is a target of anti-flu drug, and its mutation would have significant effect on the resistance to anti-flu drugs. The evolution of matrix protein 2 of influenza A virus from 1959 to 2008 was defined using the unpredictable portion of amino-acid pair predictability. Then the trend in this evolution was compared with the trend in the global temperature, the temperature in north and south hemispheres, and the temperature in influenza A virus sampling site, and species carrying influenza A virus. The results showed the similar trends in global warming and in evolution of M2 proteins although we could not correlate them at this stage of study. The study suggested the potential impact of global warming on the evolution of proteins from influenza A virus.

  6. Regulation of cellulase expression, sporulation, and morphogenesis by velvet family proteins in Trichoderma reesei.

    Science.gov (United States)

    Liu, Kuimei; Dong, Yanmei; Wang, Fangzhong; Jiang, Baojie; Wang, Mingyu; Fang, Xu

    2016-01-01

    Homologs of the velvet protein family are encoded by the ve1, vel2, and vel3 genes in Trichoderma reesei. To test their regulatory functions, the velvet protein-coding genes were disrupted, generating Δve1, Δvel2, and Δvel3 strains. The phenotypic features of these strains were examined to identify their functions in morphogenesis, sporulation, and cellulase expression. The three velvet-deficient strains produced more hyphal branches, indicating that velvet family proteins participate in the morphogenesis in T. reesei. Deletion of ve1 and vel3 did not affect biomass accumulation, while deletion of vel2 led to a significantly hampered growth when cellulose was used as the sole carbon source in the medium. The deletion of either ve1 or vel2 led to the sharp decrease of sporulation as well as a global downregulation of cellulase-coding genes. In contrast, although the expression of cellulase-coding genes of the ∆vel3 strain was downregulated in the dark, their expression in light condition was unaffected. Sporulation was hampered in the ∆vel3 strain. These results suggest that Ve1 and Vel2 play major roles, whereas Vel3 plays a minor role in sporulation, morphogenesis, and cellulase expression.

  7. Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family proteins

    Energy Technology Data Exchange (ETDEWEB)

    Tee, Thiam-Tsui, E-mail: thiamtsu@yahoo.com [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia); Cheah, Yew-Hoong [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia); Bioassay Unit, Herbal Medicine Research Center, Institute for Medical Research, Jalan Pahang, Kuala Lumpur (Malaysia); Meenakshii, Nallappan [Biology Department, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Mohd Sharom, Mohd Yusof; Azimahtol Hawariah, Lope Pihie [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer We isolated xanthorrhizol, a sesquiterpenoid compound from Curcuma xanthorrhiza. Black-Right-Pointing-Pointer Xanthorrhizol induced apoptosis in HepG2 cells as observed using SEM. Black-Right-Pointing-Pointer Apoptosis in xanthorrhizol-treated HepG2 cells involved Bcl-2 family proteins. Black-Right-Pointing-Pointer DNA fragmentation was observed in xanthorrhizol-treated HepG2 cells. Black-Right-Pointing-Pointer DNA fragmentation maybe due to cleavage of PARP and DFF45/ICAD proteins. -- Abstract: Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid compound isolated from Curcuma xanthorrhiza. Previously, we have reported that xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by inducing apoptotic cell death via caspase activation. Here, we attempt to further elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated HepG2 cells as observed by scanning electron microscopy was accompanied by truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-X{sub L} expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken together, these results suggest xanthorrhizol as a potent antiproliferative agent on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed that xanthorrhizol could be used as an anti-liver cancer drug for future studies.

  8. The function of yeast CAP family proteins in lipid export, mating, and pathogen defense.

    Science.gov (United States)

    Darwiche, Rabih; El Atab, Ola; Cottier, Stéphanie; Schneiter, Roger

    2018-04-01

    In their natural habitat, yeast cells are constantly challenged by changing environmental conditions and a fierce competition for limiting resources. To thrive under such conditions, cells need to adapt and divide quickly, and be able to neutralize the toxic compounds secreted by their neighbors. Proteins like the pathogen-related yeast, Pry proteins, which belong to the large CAP/SCP/TAPS superfamily, may have an important role in this function. CAP proteins are conserved from yeast to man and are characterized by a unique αβα sandwich fold. They are mostly secreted glycoproteins and have been implicated in many different physiological processes including pathogen defense, virulence, venom toxicity, and sperm maturation. Yeast members of this family bind and export sterols as well as fatty acids, and they render cells resistant to eugenol, an antimicrobial compound present in clove oil. CAP family members might thus exert their various physiological functions through binding, sequestration, and neutralization of such small hydrophobic compounds. © 2017 Federation of European Biochemical Societies.

  9. Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family proteins

    International Nuclear Information System (INIS)

    Tee, Thiam-Tsui; Cheah, Yew-Hoong; Meenakshii, Nallappan; Mohd Sharom, Mohd Yusof; Azimahtol Hawariah, Lope Pihie

    2012-01-01

    Highlights: ► We isolated xanthorrhizol, a sesquiterpenoid compound from Curcuma xanthorrhiza. ► Xanthorrhizol induced apoptosis in HepG2 cells as observed using SEM. ► Apoptosis in xanthorrhizol-treated HepG2 cells involved Bcl-2 family proteins. ► DNA fragmentation was observed in xanthorrhizol-treated HepG2 cells. ► DNA fragmentation maybe due to cleavage of PARP and DFF45/ICAD proteins. -- Abstract: Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid compound isolated from Curcuma xanthorrhiza. Previously, we have reported that xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by inducing apoptotic cell death via caspase activation. Here, we attempt to further elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated HepG2 cells as observed by scanning electron microscopy was accompanied by truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-X L expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken together, these results suggest xanthorrhizol as a potent antiproliferative agent on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed that xanthorrhizol could be used as an anti-liver cancer drug for future studies.

  10. The actin family protein ARP6 contributes to the structure and the function of the nucleolus.

    Science.gov (United States)

    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.

  11. The PIN family of proteins in potato and their putative role in tuberisation

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    Efstathios eRoumeliotis

    2013-12-01

    Full Text Available The PIN family of trans-membrane proteins mediates auxin efflux throughout the plant and during various phases of plant development. In Arabidopsis thaliana, the PIN family comprised of 8 members, divided into ‘short’ and ‘long’ PINs according to the length of the hydrophilic domain of the protein. Based on sequence homology using the recently published potato genome sequence (Solanum tuberosum group Phureja we identified ten annotated potato StPIN genes. Mining the publicly available gene expression data, we constructed a catalogue tissue specificity of StPIN gene expression, focusing on the process of tuberization. A total of four StPIN genes exhibited increased expression four days after tuber induction, prior to the onset of stolon swelling. For two PIN genes, StPIN4 and StPIN2, promoter sequences were cloned and fused to the GUS reporter protein to study tissue specificity in more detail. StPIN4 promoter driven GUS staining was detected in the flower stigma, in the flower style, below the ovary and petals, in the root tips, in the vascular tissue of the stolons and in the tuber parenchyma cells. StPIN2 promoter driven GUS staining was detected in flower buds, in the vascular tissue of the swelling stolons and in the storage parenchyma of the growing tubers. Based on our results, we postulate a role for the StPINs in redistributing auxin in the swelling stolon during early events in tuber development.

  12. Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins

    OpenAIRE

    Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan

    2015-01-01

    Productive viral replication requires overcoming many barriers posed by the host innate immune system. Human sterile alpha motif domain-containing 9 (SAMD9) is a newly identified antiviral factor that is specifically targeted by poxvirus proteins belonging to the C7 family of host-range factors. Here we provide the first, to our knowledge, atomic view of two functionally divergent proteins from the C7 family and determine the molecular basis that dictates whether they can target SAMD9 effecti...

  13. Comparative genome analysis reveals a conserved family of actin-like proteins in apicomplexan parasites

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    Sibley L David

    2005-12-01

    Full Text Available Abstract Background The phylum Apicomplexa is an early-branching eukaryotic lineage that contains a number of important human and animal pathogens. Their complex life cycles and unique cytoskeletal features distinguish them from other model eukaryotes. Apicomplexans rely on actin-based motility for cell invasion, yet the regulation of this system remains largely unknown. Consequently, we focused our efforts on identifying actin-related proteins in the recently completed genomes of Toxoplasma gondii, Plasmodium spp., Cryptosporidium spp., and Theileria spp. Results Comparative genomic and phylogenetic studies of apicomplexan genomes reveals that most contain only a single conventional actin and yet they each have 8–10 additional actin-related proteins. Among these are a highly conserved Arp1 protein (likely part of a conserved dynactin complex, and Arp4 and Arp6 homologues (subunits of the chromatin-remodeling machinery. In contrast, apicomplexans lack canonical Arp2 or Arp3 proteins, suggesting they lost the Arp2/3 actin polymerization complex on their evolutionary path towards intracellular parasitism. Seven of these actin-like proteins (ALPs are novel to apicomplexans. They show no phylogenetic associations to the known Arp groups and likely serve functions specific to this important group of intracellular parasites. Conclusion The large diversity of actin-like proteins in apicomplexans suggests that the actin protein family has diverged to fulfill various roles in the unique biology of intracellular parasites. Conserved Arps likely participate in vesicular transport and gene expression, while apicomplexan-specific ALPs may control unique biological traits such as actin-based gliding motility.

  14. Functions and regulation of the multitasking FANCM family of DNA motor proteins.

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    Xue, Xiaoyu; Sung, Patrick; Zhao, Xiaolan

    2015-09-01

    Members of the conserved FANCM family of DNA motor proteins play key roles in genome maintenance processes. FANCM supports genome duplication and repair under different circumstances and also functions in the ATR-mediated DNA damage checkpoint. Some of these roles are shared among lower eukaryotic family members. Human FANCM has been linked to Fanconi anemia, a syndrome characterized by cancer predisposition, developmental disorder, and bone marrow failure. Recent studies on human FANCM and its orthologs from other organisms have provided insights into their biological functions, regulation, and collaboration with other genome maintenance factors. This review summarizes the progress made, with the goal of providing an integrated view of the functions and regulation of these enzymes in humans and model organisms and how they advance our understanding of genome maintenance processes. © 2015 Xue et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

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    Shi-qi An

    2014-10-01

    Full Text Available Bis-(3',5' cyclic di-guanylate (cyclic di-GMP is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc. This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d∼2 µM. Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

  16. Molecular evolution of a chordate specific family of G protein-coupled receptors

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    Leese Florian

    2011-08-01

    Full Text Available Abstract Background Chordate evolution is a history of innovations that is marked by physical and behavioral specializations, which led to the development of a variety of forms from a single ancestral group. Among other important characteristics, vertebrates obtained a well developed brain, anterior sensory structures, a closed circulatory system and gills or lungs as blood oxygenation systems. The duplication of pre-existing genes had profound evolutionary implications for the developmental complexity in vertebrates, since mutations modifying the function of a duplicated protein can lead to novel functions, improving the evolutionary success. Results We analyzed here the evolution of the GPRC5 family of G protein-coupled receptors by comprehensive similarity searches and found that the receptors are only present in chordates and that the size of the receptor family expanded, likely due to genome duplication events in the early history of vertebrate evolution. We propose that a single GPRC5 receptor coding gene originated in a stem chordate ancestor and gave rise by duplication events to a gene family comprising three receptor types (GPRC5A-C in vertebrates, and a fourth homologue present only in mammals (GPRC5D. Additional duplications of GPRC5B and GPRC5C sequences occurred in teleost fishes. The finding that the expression patterns of the receptors are evolutionarily conserved indicates an important biological function of these receptors. Moreover, we found that expression of GPRC5B is regulated by vitamin A in vivo, confirming previous findings that linked receptor expression to retinoic acid levels in tumor cell lines and strengthening the link between the receptor expression and the development of a complex nervous system in chordates, known to be dependent on retinoic acid signaling. Conclusions GPRC5 receptors, a class of G protein-coupled receptors with unique sequence characteristics, may represent a molecular novelty that helped non

  17. Community-level effect of the reproductive health vouchers program on out-of-pocket spending on family planning and safe motherhood services in Kenya.

    Science.gov (United States)

    Obare, Francis; Warren, Charlotte; Kanya, Lucy; Abuya, Timothy; Bellows, Ben

    2015-08-25

    Although vouchers can protect individuals in low-income countries from financial catastrophe and impoverishment arising from out-of-pocket expenditures on healthcare, their effectiveness in achieving this goal depends on whether both service and transport costs are subsidized as well as other factors such as service availability in a given locality and community perceptions about the quality of care. This paper examines the community-level effect of the reproductive health vouchers program on out-of-pocket expenditure on family planning, antenatal, delivery and postnatal care services in Kenya. Data are from two rounds of cross-sectional household surveys in voucher and non-voucher sites. The first survey was conducted between May 2010 and July 2011 among 2,933 women aged 15-49 years while the second survey took place between July and October 2012 among 3,094 women of similar age groups. The effect of the program on out-of-pocket expenditure is determined by difference-in-differences estimation. Analysis entails comparison of changes in proportions, means and medians as well as estimation of multivariate linear regression models with interaction terms between indicators for study site (voucher or non-voucher) and period of study (2010-2011 or 2012). There were significantly greater declines in the proportions of women from voucher sites that paid for antenatal, delivery and postnatal care services at health facilities compared to those from non-voucher sites. The changes were also consistent with increased uptake of the safe motherhood voucher in intervention sites over time. There was, however, no significant difference in changes in the proportions of women from voucher and non-voucher sites that paid for family planning services. The results further show that there were significant differences in changes in the amount paid for family planning and antenatal care services by women from voucher compared to those from non-voucher sites. Although there were greater

  18. Testing for adaptive evolution of the female reproductive protein ZPC in mammals, birds and fishes reveals problems with the M7-M8 likelihood ratio test.

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    Berlin, Sofia; Smith, Nick G C

    2005-11-10

    Adaptive evolution appears to be a common feature of reproductive proteins across a very wide range of organisms. A promising way of addressing the evolutionary forces responsible for this general phenomenon is to test for adaptive evolution in the same gene but among groups of species, which differ in their reproductive biology. One can then test evolutionary hypotheses by asking whether the variation in adaptive evolution is consistent with the variation in reproductive biology. We have attempted to apply this approach to the study of a female reproductive protein, zona pellucida C (ZPC), which has been previously shown by the use of likelihood ratio tests (LRTs) to be under positive selection in mammals. We tested for evidence of adaptive evolution of ZPC in 15 mammalian species, in 11 avian species and in six fish species using three different LRTs (M1a-M2a, M7-M8, and M8a-M8). The only significant findings of adaptive evolution came from the M7-M8 test in mammals and fishes. Since LRTs of adaptive evolution may yield false positives in some situations, we examined the properties of the LRTs by several different simulation methods. When we simulated data to test the robustness of the LRTs, we found that the pattern of evolution in ZPC generates an excess of false positives for the M7-M8 LRT but not for the M1a-M2a or M8a-M8 LRTs. This bias is strong enough to have generated the significant M7-M8 results for mammals and fishes. We conclude that there is no strong evidence for adaptive evolution of ZPC in any of the vertebrate groups we studied, and that the M7-M8 LRT can be biased towards false inference of adaptive evolution by certain patterns of non-adaptive evolution.

  19. Hydrogen bond networks determine emergent mechanical and thermodynamic properties across a protein family

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    Dallakyan Sargis

    2008-08-01

    Full Text Available Abstract Background Gram-negative bacteria use periplasmic-binding proteins (bPBP to transport nutrients through the periplasm. Despite immense diversity within the recognized substrates, all members of the family share a common fold that includes two domains that are separated by a conserved hinge. The hinge allows the protein to cycle between open (apo and closed (ligated conformations. Conformational changes within the proteins depend on a complex interplay of mechanical and thermodynamic response, which is manifested as an increase in thermal stability and decrease of flexibility upon ligand binding. Results We use a distance constraint model (DCM to quantify the give and take between thermodynamic stability and mechanical flexibility across the bPBP family. Quantitative stability/flexibility relationships (QSFR are readily evaluated because the DCM links mechanical and thermodynamic properties. We have previously demonstrated that QSFR is moderately conserved across a mesophilic/thermophilic RNase H pair, whereas the observed variance indicated that different enthalpy-entropy mechanisms allow similar mechanical response at their respective melting temperatures. Our predictions of heat capacity and free energy show marked diversity across the bPBP family. While backbone flexibility metrics are mostly conserved, cooperativity correlation (long-range couplings also demonstrate considerable amount of variation. Upon ligand removal, heat capacity, melting point, and mechanical rigidity are, as expected, lowered. Nevertheless, significant differences are found in molecular cooperativity correlations that can be explained by the detailed nature of the hydrogen bond network. Conclusion Non-trivial mechanical and thermodynamic variation across the family is explained by differences within the underlying H-bond networks. The mechanism is simple; variation within the H-bond networks result in altered mechanical linkage properties that directly affect

  20. Studying the co-evolution of protein families with the Mirrortree web server.

    Science.gov (United States)

    Ochoa, David; Pazos, Florencio

    2010-05-15

    The Mirrortree server allows to graphically and interactively study the co-evolution of two protein families, and investigate their possible interactions and functional relationships in a taxonomic context. The server includes the possibility of starting from single sequences and hence it can be used by non-expert users. The web server is freely available at http://csbg.cnb.csic.es/mtserver. It was tested in the main web browsers. Adobe Flash Player is required at the client side to perform the interactive assessment of co-evolution. pazos@cnb.csic.es Supplementary data are available at Bioinformatics online.

  1. Serum retinol binding protein 4 in patients with familial partial lipodystrophy.

    Science.gov (United States)

    Godoy-Matos, Amélio F; Moreira, Rodrigo O; MacDowell, Renata; Bendet, Izidro; Mory, Patrícia B; Moises, Regina S

    2009-07-01

    To determine Retinol Binding Protein 4 (RBP4) levels in patients with Familial Partial Lipodystrophy (FPLD). Ten patients with FPLD and a control group (9 patients) were selected to participate in the study. RBP4-log levels were lower in patients with FPLD in comparison to control group (1.52 +/- 0.32 vs 1.84+/-0.25, p=0.029). A statistical trend was observed between Waist-to-Hip Ratio and RBP4-log (r=-0.44, p=0.054). RBP4 levels are decreased in FPLD.

  2. Xanthurenic acid translocates proapoptotic Bcl-2 family proteins into mitochondria and impairs mitochondrial function

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    Hess Otto M

    2004-04-01

    Full Text Available Abstract Background Xanthurenic acid is an endogenous molecule produced by tryptophan degradation, produced in the cytoplasm and mitochondria. Its accumulation can be observed in aging-related diseases, e.g. senile cataract and infectious disease. We previously reported that xanthurenic acid provokes apoptosis, and now present a study of the response of mitochondria to xanthurenic acid. Results Xanthurenic acid at 10 or 20 μM in culture media of human aortic smooth muscle cells induces translocation of the proteins Bax, Bak, Bclxs, and Bad into mitochondria. In 20 μM xanthurenic acid, Bax is also translocated to the nucleus. In isolated mitochondria xanthurenic acid leads to Bax and Bclxs oligomerization, accumulation of Ca2+, and increased oxygen consumption. Conclusion Xanthurenic acid interacts directly with Bcl-2 family proteins, inducing mitochondrial pathways of apoptosis and impairing mitochondrial functions.

  3. Franchising reproductive health services.

    Science.gov (United States)

    Stephenson, Rob; Tsui, Amy Ong; Sulzbach, Sara; Bardsley, Phil; Bekele, Getachew; Giday, Tilahun; Ahmed, Rehana; Gopalkrishnan, Gopi; Feyesitan, Bamikale

    2004-12-01

    Networks of franchised health establishments, providing a standardized set of services, are being implemented in developing countries. This article examines associations between franchise membership and family planning and reproductive health outcomes for both the member provider and the client. Regression models are fitted examining associations between franchise membership and family planning and reproductive health outcomes at the service provider and client levels in three settings. Franchising has a positive association with both general and family planning client volumes, and the number of family planning brands available. Similar associations with franchise membership are not found for reproductive health service outcomes. In some settings, client satisfaction is higher at franchised than other types of health establishments, although the association between franchise membership and client outcomes varies across the settings. Franchise membership has apparent benefits for both the provider and the client, providing an opportunity to expand access to reproductive health services, although greater attention is needed to shift the focus from family planning to a broader reproductive health context.

  4. Franchising Reproductive Health Services

    Science.gov (United States)

    Stephenson, Rob; Tsui, Amy Ong; Sulzbach, Sara; Bardsley, Phil; Bekele, Getachew; Giday, Tilahun; Ahmed, Rehana; Gopalkrishnan, Gopi; Feyesitan, Bamikale

    2004-01-01

    Objectives Networks of franchised health establishments, providing a standardized set of services, are being implemented in developing countries. This article examines associations between franchise membership and family planning and reproductive health outcomes for both the member provider and the client. Methods Regression models are fitted examining associations between franchise membership and family planning and reproductive health outcomes at the service provider and client levels in three settings. Results Franchising has a positive association with both general and family planning client volumes, and the number of family planning brands available. Similar associations with franchise membership are not found for reproductive health service outcomes. In some settings, client satisfaction is higher at franchised than other types of health establishments, although the association between franchise membership and client outcomes varies across the settings. Conclusions Franchise membership has apparent benefits for both the provider and the client, providing an opportunity to expand access to reproductive health services, although greater attention is needed to shift the focus from family planning to a broader reproductive health context. PMID:15544644

  5. The Aspergillus fumigatus Damage Resistance Protein Family Coordinately Regulates Ergosterol Biosynthesis and Azole Susceptibility

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    Jinxing Song

    2016-02-01

    Full Text Available Ergosterol is a major and specific component of the fungal plasma membrane, and thus, the cytochrome P450 enzymes (Erg proteins that catalyze ergosterol synthesis have been selected as valuable targets of azole antifungals. However, the opportunistic pathogen Aspergillus fumigatus has developed worldwide resistance to azoles largely through mutations in the cytochrome P450 enzyme Cyp51 (Erg11. In this study, we demonstrate that a cytochrome b5-like heme-binding damage resistance protein (Dap family, comprised of DapA, DapB, and DapC, coordinately regulates the functionality of cytochrome P450 enzymes Erg5 and Erg11 and oppositely affects susceptibility to azoles. The expression of all three genes is induced in an azole concentration-dependent way, and the decreased susceptibility to azoles requires DapA stabilization of cytochrome P450 protein activity. In contrast, overexpression of DapB and DapC causes dysfunction of Erg5 and Erg11, resulting in abnormal accumulation of sterol intermediates and further accentuating the sensitivity of ΔdapA strains to azoles. The results of exogenous-hemin rescue and heme-binding-site mutagenesis experiments demonstrate that the heme binding of DapA contributes the decreased azole susceptibility, while DapB and -C are capable of reducing the activities of Erg5 and Erg11 through depletion of heme. In vivo data demonstrate that inactivated DapA combined with activated DapB yields an A. fumigatus mutant that is easily treatable with azoles in an immunocompromised mouse model of invasive pulmonary aspergillosis. Compared to the single Dap proteins found in Saccharomyces cerevisiae and Schizosaccharomyces pombe, we suggest that this complex Dap family regulatory system emerged during the evolution of fungi as an adaptive means to regulate ergosterol synthesis in response to environmental stimuli.

  6. Overview of OVATE FAMILY PROTEINS, a novel class of plant-specific growth regulators

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    Shucai eWang

    2016-03-01

    Full Text Available OVATE FAMILY PROTEINS (OFPs are a class of proteins with a conserved OVATE domain. OVATE protein was first identified in tomato as a key regulator of fruit shape. OFPs are plant-specific proteins that are widely distributed in the plant kingdom including mosses and lycophytes. Transcriptional activity analysis of Arabidopsis OFPs (AtOFPs in protoplasts suggests that they act as transcription repressors. Functional characterization of OFPs from different plant species including Arabidopsis, rice, tomato, pepper and banana suggests that OFPs regulate multiple aspects of plant growth and development, which is likely achieved by interacting with different types of transcription factors including the KNOX and BELL classes, and/or directly regulating the expression of target genes such as Gibberellin 20 oxidase (GA20ox. Here, we examine how OVATE was originally identified, summarize recent progress in elucidation of the roles of OFPs in regulating plant growth and development, and describe possible mechanisms underpinning this regulation. Finally, we review potential new research directions that could shed additional light on the functional biology of OFPs in plants.

  7. First characterization of three cyclophilin family proteins in the oyster, Crassostrea ariakensis Gould.

    Science.gov (United States)

    Xu, Ting; Xie, Jiasong; Yang, Shoubao; Ye, Shigen; Luo, Ming; Wu, Xinzhong

    2016-08-01

    Cyclophilins (CyPs) are a family of proteins that bind the immunosuppressive agent cyclosporin A (CsA) with high-affinity and belong to one of the three superfamilies of peptidyl-prolyl cis-trans isomerases (PPIase). In this report, three cyclophilin genes (Ca-CyPs), including Ca-CyPA, Ca-CyPB and Ca-PPIL3, were identified from oyster, Crassostrea ariakensis Gould in which Ca-CyPA encodes a protein with 165 amino acid sequences, Ca-CyPB encodes a protein with 217 amino acid sequences and Ca-PPIL3 encodes a protein with 162 amino acid sequences. All of the three Ca-CyPs genes contain a typical CyP-PPIase domain with its signature sequences and Ca-CyPB contains an N-signal peptide sequences. Tissue distribution study revealed that Ca-CyPs were ubiquitously expressed in all examined tissues and the highest levels were observed in hemocytes. RLO incubation upregulated the mRNA expression levels of Ca-CyPs, indicating that three Ca-CyPs might be involved in oyster immune response against RLO infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Characterisation of protein families in spider digestive fluids and their role in extra-oral digestion.

    Science.gov (United States)

    Walter, André; Bechsgaard, Jesper; Scavenius, Carsten; Dyrlund, Thomas S; Sanggaard, Kristian W; Enghild, Jan J; Bilde, Trine

    2017-08-10

    Spiders are predaceous arthropods that are capable of subduing and consuming relatively large prey items compared to their own body size. For this purpose, spiders have evolved potent venoms to immobilise prey and digestive fluids that break down nutrients inside the prey's body by means of extra-oral digestion (EOD). Both secretions contain an array of active proteins, and an overlap of some components has been anecdotally reported, but not quantified. We systematically investigated the extent of such protein overlap. As venom injection and EOD succeed each other, we further infer functional explanations, and, by comparing two spider species belonging to different clades, assess its adaptive significance for spider EOD in general. We describe the protein composition of the digestive fluids of the mygalomorph Acanthoscurria geniculata and the araneomorph Stegodyphus mimosarum, in comparison with previously published data on a third spider species. We found a number of similar hydrolases being highly abundant in all three species. Among them, members of the family of astacin-like metalloproteases were particularly abundant. While the importance of these proteases in spider venom and digestive fluid was previously noted, we now highlight their widespread use across different spider taxa. Finally, we found species specific differences in the protein overlap between venom and digestive fluid, with the difference being significantly greater in S. mimosarum compared to A. geniculata. The injection of venom precedes the injection with digestive fluid, and the overlap of proteins between venom and digestive fluid suggests an early involvement in EOD. Species specific differences in the overlap may reflect differences in ecology between our two study species. The protein composition of the digestive fluid of all the three species we compared is highly similar, suggesting that the cocktail of enzymes is highly conserved and adapted to spider EOD.

  9. Identification of group specific motifs in Beta-lactamase family of proteins

    Directory of Open Access Journals (Sweden)

    Saxena Akansha

    2009-12-01

    Full Text Available Abstract Background Beta-lactamases are one of the most serious threats to public health. In order to combat this threat we need to study the molecular and functional diversity of these enzymes and identify signatures specific to these enzymes. These signatures will enable us to develop inhibitors and diagnostic probes specific to lactamases. The existing classification of beta-lactamases was developed nearly 30 years ago when few lactamases were available. DLact database contain more than 2000 beta-lactamase, which can be used to study the molecular diversity and to identify signatures specific to this family. Methods A set of 2020 beta-lactamase proteins available in the DLact database http://59.160.102.202/DLact were classified using graph-based clustering of Best Bi-Directional Hits. Non-redundant (> 90 percent identical protein sequences from each group were aligned using T-Coffee and annotated using information available in literature. Motifs specific to each group were predicted using PRATT program. Results The graph-based classification of beta-lactamase proteins resulted in the formation of six groups (Four major groups containing 191, 726, 774 and 73 proteins while two minor groups containing 50 and 8 proteins. Based on the information available in literature, we found that each of the four major groups correspond to the four classes proposed by Ambler. The two minor groups were novel and do not contain molecular signatures of beta-lactamase proteins reported in literature. The group-specific motifs showed high sensitivity (> 70% and very high specificity (> 90%. The motifs from three groups (corresponding to class A, C and D had a high level of conservation at DNA as well as protein level whereas the motifs from the fourth group (corresponding to class B showed conservation at only protein level. Conclusion The graph-based classification of beta-lactamase proteins corresponds with the classification proposed by Ambler, thus there is

  10. New kids on the block: The Popeye domain containing (POPDC) protein family acting as a novel class of cAMP effector proteins in striated muscle.

    Science.gov (United States)

    Brand, Thomas; Schindler, Roland

    2017-12-01

    The cyclic 3',5'-adenosine monophosphate (cAMP) signalling pathway constitutes an ancient signal transduction pathway present in prokaryotes and eukaryotes. Previously, it was thought that in eukaryotes three effector proteins mediate cAMP signalling, namely protein kinase A (PKA), exchange factor directly activated by cAMP (EPAC) and the cyclic-nucleotide gated channels. However, recently a novel family of cAMP effector proteins emerged and was termed the Popeye domain containing (POPDC) family, which consists of three members POPDC1, POPDC2 and POPDC3. POPDC proteins are transmembrane proteins, which are abundantly present in striated and smooth muscle cells. POPDC proteins bind cAMP with high affinity comparable to PKA. Presently, their biochemical activity is poorly understood. However, mutational analysis in animal models as well as the disease phenotype observed in patients carrying missense mutations suggests that POPDC proteins are acting by modulating membrane trafficking of interacting proteins. In this review, we will describe the current knowledge about this gene family and also outline the apparent gaps in our understanding of their role in cAMP signalling and beyond. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. ST proteins, a new family of plant tandem repeat proteins with a DUF2775 domain mainly found in Fabaceae and Asteraceae.

    Science.gov (United States)

    Albornos, Lucía; Martín, Ignacio; Iglesias, Rebeca; Jiménez, Teresa; Labrador, Emilia; Dopico, Berta

    2012-11-07

    Many proteins with tandem repeats in their sequence have been described and classified according to the length of the repeats: I) Repeats of short oligopeptides (from 2 to 20 amino acids), including structural cell wall proteins and arabinogalactan proteins. II) Repeats that range in length from 20 to 40 residues, including proteins with a well-established three-dimensional structure often involved in mediating protein-protein interactions. (III) Longer repeats in the order of 100 amino acids that constitute structurally and functionally independent units. Here we analyse ShooT specific (ST) proteins, a family of proteins with tandem repeats of unknown function that were first found in Leguminosae, and their possible similarities to other proteins with tandem repeats. ST protein sequences were only found in dicotyledonous plants, limited to several plant families, mainly the Fabaceae and the Asteraceae. ST mRNAs accumulate mainly in the roots and under biotic interactions. Most ST proteins have one or several Domain(s) of Unknown Function 2775 (DUF2775). All deduced ST proteins have a signal peptide, indicating that these proteins enter the secretory pathway, and the mature proteins have tandem repeat oligopeptides that share a hexapeptide (E/D)FEPRP followed by 4 partially conserved amino acids, which could determine a putative N-glycosylation signal, and a fully conserved tyrosine. In a phylogenetic tree, the sequences clade according to taxonomic group. A possible involvement in symbiosis and abiotic stress as well as in plant cell elongation is suggested, although different STs could play different roles in plant development. We describe a new family of proteins called ST whose presence is limited to the plant kingdom, specifically to a few families of dicotyledonous plants. They present 20 to 40 amino acid tandem repeat sequences with different characteristics (signal peptide, DUF2775 domain, conservative repeat regions) from the described group of 20 to 40

  12. Rice Ovate Family Protein 2 (OFP2) alters hormonal homeostasis and vasculature development.

    Science.gov (United States)

    Schmitz, Aaron J; Begcy, Kevin; Sarath, Gautam; Walia, Harkamal

    2015-12-01

    OFP (Ovate Family Protein) is a transcription factor family found only in plants. In dicots, OFPs control fruit shape and secondary cell wall biosynthesis. OFPs are also thought to function through interactions with KNOX and BELL transcription factors. Here, we have functionally characterized OsOFP2, a member of the OFP subgroup associated with regulating fruit shape. OsOFP2 was found to localize to the nucleus and to the cytosol. A putative nuclear export signal was identified within the OVATE domain and was required for the localization of OsOFP2 to distinct cytosolic spots. Rice plants overexpressing OsOFP2 were reduced in height and exhibited altered leaf morphology, seed shape, and positioning of vascular bundles in stems. Transcriptome analysis indicated disruptions of genes associated with vasculature development, lignin biosynthesis, and hormone homeostasis. Reduced expression of the gibberellin biosynthesis gene GA 20-oxidase 7 coincided with lower gibberellin content in OsOFP2 overexpression lines. Also, we found that OsOFP2 was expressed in plant vasculature and determined that putative vascular development KNOX and BELL proteins interact with OsOFP2. KNOX and BELL genes are known to suppress gibberellin biosynthesis through GA20ox gene regulation and can restrict lignin biosynthesis. We propose that OsOFP2 could modulate KNOX-BELL function to control diverse aspects of development including vasculature development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview

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    Soichi Takeda

    2016-05-01

    Full Text Available A disintegrin and metalloproteinase (ADAM family proteins constitute a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell-surface protein ectodomains, including the latent forms of growth factors, cytokines, receptors and other molecules. Snake venom metalloproteinases (SVMPs are major components in most viper venoms. SVMPs are primarily responsible for hemorrhagic activity and may also interfere with the hemostatic system in envenomed animals. SVMPs are phylogenetically most closely related to ADAMs and, together with ADAMs and related ADAM with thrombospondin motifs (ADAMTS family proteinases, constitute adamalysins/reprolysins or the M12B clan (MEROPS database of metalloproteinases. Although the catalytic domain structure is topologically similar to that of other metalloproteinases such as matrix metalloproteinases, the M12B proteinases have a modular structure with multiple non-catalytic ancillary domains that are not found in other proteinases. Notably, crystallographic studies revealed that, in addition to the conserved metalloproteinase domain, M12B members share a hallmark cysteine-rich domain designated as the “ADAM_CR” domain. Despite their name, ADAMTSs lack disintegrin-like structures and instead comprise two ADAM_CR domains. This review highlights the current state of our knowledge on the three-dimensional structures of M12B proteinases, focusing on their unique domains that may collaboratively participate in directing these proteinases to specific substrates.

  14. The Plasmodium PHIST and RESA-Like Protein Families of Human and Rodent Malaria Parasites

    Science.gov (United States)

    Moreira, Cristina K.; Naissant, Bernina; Coppi, Alida; Bennett, Brandy L.; Aime, Elena; Franke-Fayard, Blandine; Janse, Chris J.; Coppens, Isabelle; Sinnis, Photini; Templeton, Thomas J.

    2016-01-01

    The phist gene family has members identified across the Plasmodium genus, defined by the presence of a domain of roughly 150 amino acids having conserved aromatic residues and an all alpha-helical structure. The family is highly amplified in P. falciparum, with 65 predicted genes in the genome of the 3D7 isolate. In contrast, in the rodent malaria parasite P. berghei 3 genes are identified, one of which is an apparent pseudogene. Transcripts of the P. berghei phist genes are predominant in schizonts, whereas in P. falciparum transcript profiles span different asexual blood stages and gametocytes. We pursued targeted disruption of P. berghei phist genes in order to characterize a simplistic model for the expanded phist gene repertoire in P. falciparum. Unsuccessful attempts to disrupt P. berghei PBANKA_114540 suggest that this phist gene is essential, while knockout of phist PBANKA_122900 shows an apparent normal progression and non-essential function throughout the life cycle. Epitope-tagging of P. falciparum and P. berghei phist genes confirmed protein export to the erythrocyte cytoplasm and localization with a punctate pattern. Three P. berghei PEXEL/HT-positive exported proteins exhibit at least partial co-localization, in support of a common vesicular compartment in the cytoplasm of erythrocytes infected with rodent malaria parasites. PMID:27022937

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

    Science.gov (United States)

    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

  16. Identification of Heat Shock Protein families and J-protein types by incorporating Dipeptide Composition into Chou's general PseAAC.

    Science.gov (United States)

    Ahmad, Saeed; Kabir, Muhammad; Hayat, Maqsood

    2015-11-01

    Heat Shock Proteins (HSPs) are the substantial ingredients for cell growth and viability, which are found in all living organisms. HSPs manage the process of folding and unfolding of proteins, the quality of newly synthesized proteins and protecting cellular homeostatic processes from environmental stress. On the basis of functionality, HSPs are categorized into six major families namely: (i) HSP20 or sHSP (ii) HSP40 or J-proteins types (iii) HSP60 or GroEL/ES (iv) HSP70 (v) HSP90 and (vi) HSP100. Identification of HSPs family and sub-family through conventional approaches is expensive and laborious. It is therefore, highly desired to establish an automatic, robust and accurate computational method for prediction of HSPs quickly and reliably. Regard, a computational model is developed for the prediction of HSPs family. In this model, protein sequences are formulated using three discrete methods namely: Split Amino Acid Composition, Pseudo Amino Acid Composition, and Dipeptide Composition. Several learning algorithms are utilized to choice the best one for high throughput computational model. Leave one out test is applied to assess the performance of the proposed model. The empirical results showed that support vector machine achieved quite promising results using Dipeptide Composition feature space. The predicted outcomes of proposed model are 90.7% accuracy for HSPs dataset and 97.04% accuracy for J-protein types, which are higher than existing methods in the literature so far. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. A conserved function in phosphatidylinositol metabolism for mammalian Vps13 family proteins.

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    Jae-Sook Park

    Full Text Available The Vps13 protein family is highly conserved in eukaryotic cells. In humans, mutations in the gene encoding the family member VPS13A lead to the neurodegenerative disorder chorea-acanthocytosis. In the yeast Saccharomyces cerevisiae, there is just a single version of VPS13, thereby simplifying the task of unraveling its molecular function(s. While VPS13 was originally identified in yeast by its role in vacuolar sorting, recent studies have revealed a completely different function for VPS13 in sporulation, where VPS13 regulates phosphatidylinositol-4-phosphate (PtdIns(4P levels in the prospore membrane. This discovery raises the possibility that the disease phenotype associated with vps13A mutants in humans is due to misregulation of PtdIns(4P in membranes. To determine whether VPS13A affects PtdIns(4P in membranes from mammalian neuronal cells, phosphatidylinositol phosphate pools were compared in PC12 tissue culture cells in the absence or presence of VPS13A. Consistent with the yeast results, the localization of PtdIns(4P is specifically altered in VPS13A knockdown cells while other phosphatidylinositol phosphates appear unaffected. In addition, VPS13A is necessary to prevent the premature degeneration of neurites that develop in response to Nerve Growth Factor. The regulation of PtdIns(4P is therefore a conserved function of the Vps13 family and may play a role in the maintenance of neuronal processes in mammals.

  18. The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins

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    Ning Li

    2015-12-01

    Full Text Available Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers.

  19. Methyl-CpG-Binding Protein (MBD) Family: Epigenomic Read-Outs Functions and Roles in Tumorigenesis and Psychiatric Diseases.

    Science.gov (United States)

    Gigek, Carolina Oliveira; Chen, Elizabeth Suchi; Smith, Marilia Arruda Cardoso

    2016-01-01

    Epigenetics is the study of the heritable changes on gene expression that are responsible for the regulation of development and that have an impact on several diseases. However, it is of equal importance to understand how epigenetic machinery works. DNA methylation is the most studied epigenetic mark and is generally associated with the regulation of gene expression through the repression of promoter activity and by affecting genome stability. Therefore, the ability of the cell to interpret correct methylation marks and/or the correct interpretation of methylation plays a role in many diseases. The major family of proteins that bind methylated DNA is the methyl-CpG binding domain proteins, or the MBDs. Here, we discuss the structure that makes these proteins a family, the main functions and interactions of all protein family members and their role in human disease such as psychiatric disorders and cancer. © 2015 Wiley Periodicals, Inc.

  20. Family Resemblances: Human Reproductive Cloning as an Example for Reconsidering the Mutual Relationships between Bioethics and Science Fiction.

    Science.gov (United States)

    Hansen, Solveig L

    2018-03-08

    In the traditions of narrative ethics and casuistry, stories have a well-established role. Specifically, illness narratives provide insight into patients' perspectives and histories. However, because they tend to see fiction as an aesthetic endeavour, practitioners in these traditions often do not realize that fictional stories are valuable moral sources of their own. In this paper I employ two arguments to show the mutual relationship between bioethics and fiction, specifically, science fiction. First, both discourses use imagination to set a scene and determine a perspective. Second, bioethics and science fiction share the family resemblance of expressing moral beliefs. I then consider how understanding bioethics and science fiction as interrelated discourses can be the basis of a methodology for inquiry into relational autonomy in the context of biotechnologies and medicine. As an example of this methodology, I analyse Fay Weldon's novel The Cloning of Joanna May (1989).

  1. Expression of activator protein-1 (AP-1) family members in breast cancer

    International Nuclear Information System (INIS)

    Kharman-Biz, Amirhossein; Gao, Hui; Ghiasvand, Reza; Zhao, Chunyan; Zendehdel, Kazem; Dahlman-Wright, Karin

    2013-01-01

    The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer. We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses. We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01). Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer

  2. The C1q family of proteins: insights into the emerging non-traditional functions

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    Berhane eGhebrehiwet

    2012-04-01

    Full Text Available Research conducted over the past 20 years have helped us unravel not only the hidden structural and functional subtleties of human C1q, but also has catapulted the molecule from a mere recognition unit of the classical pathway to a well-recognized molecular sensor of damage modified self or non-self antigens. Thus, C1q is involved in a rapidly expanding list of pathological disorders—including autoimmunity, trophoblast migration, preeclampsia and cancer. The results of two recent reports are provided to underscore the critical role C1q plays in health and disease. First is the observation by Singh and colleagues showing that pregnant C1q-/- mice recapitulate the key features of human preeclampsia that correlate with increased fetal death. Treatment of the C1q-/- mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of preeclampsia. Second is the report by Hong et al., which showed that C1q can induce apoptosis of prostate cancer cells by activating the tumor suppressor molecule WW-domain containing oxydoreductase (WWOX or WOX1 and destabilizing cell adhesion. Downregulation of C1q on the other hand enhanced prostate hyperplasia and cancer formation due to failure of WOX1 activation. Recent evidence also shows that C1q belongs to a family of structurally and functionally related TNFα-like family of proteins that may have arisen from a common ancestral gene. Therefore C1q not only shares the diverse functions with the TNF family of proteins, but also explains why C1q has retained some of its ancestral cytokine-like activities. This review is intended to highlight some of the structural and functional aspects of C1q by underscoring the growing list of its non-traditional functions.

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

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    Shchelkunov Sergei N

    2010-10-01

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

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

    Science.gov (United States)

    Antonets, Denis V; Nepomnyashchikh, Tatyana S; Shchelkunov, Sergei N

    2010-10-27

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

  5. Amino acid sequences of ribosomal proteins S11 from Bacillus stearothermophilus and S19 from Halobacterium marismortui. Comparison of the ribosomal protein S11 family.

    Science.gov (United States)

    Kimura, M; Kimura, J; Hatakeyama, T

    1988-11-21

    The complete amino acid sequences of ribosomal proteins S11 from the Gram-positive eubacterium Bacillus stearothermophilus and of S19 from the archaebacterium Halobacterium marismortui have been determined. A search for homologous sequences of these proteins revealed that they belong to the ribosomal protein S11 family. Homologous proteins have previously been sequenced from Escherichia coli as well as from chloroplast, yeast and mammalian ribosomes. A pairwise comparison of the amino acid sequences showed that Bacillus protein S11 shares 68% identical residues with S11 from Escherichia coli and a slightly lower homology (52%) with the homologous chloroplast protein. The halophilic protein S19 is more related to the eukaryotic (45-49%) than to the eubacterial counterparts (35%).

  6. Genome-wide identification of mitogen-activated protein kinase gene family in Gossypium raimondii and the function of their corresponding orthologs in tetraploid cultivated cotton.

    Science.gov (United States)

    Zhang, Xueying; Wang, Liman; Xu, Xiaoyang; Cai, Caiping; Guo, Wangzhen

    2014-12-10

    Mitogen-activated protein kinase (MAPK) cascades play a crucial role in plant growth and development as well as biotic and abiotic stress responses. Knowledge about the MAPK gene family in cotton is limited, and systematic investigation of MAPK family proteins has not been reported. By performing a bioinformatics homology search, we identified 28 putative MAPK genes in the Gossypium raimondii genome. These MAPK members were anchored onto 11 chromosomes in G. raimondii, with uneven distribution. Phylogenetic analysis showed that the MAPK candidates could be classified into the four known A, B, C and D groups, with more MAPKs containing the TEY phosphorylation site (18 members) than the TDY motif (10 members). Furthermore, 21 cDNA sequences of MAPKs with complete open reading frames (ORFs) were identified in G. hirsutum via PCR-based approaches, including 13 novel MAPKs and eight with homologs reported previously in tetraploid cotton. The expression patterns of 23 MAPK genes reveal their important roles in diverse functions in cotton, in both various developmental stages of vegetative and reproductive growth and in the stress response. Using a reverse genetics approach based on tobacco rattle virus-induced gene silencing (TRV-VIGS), we further verified that MPK9, MPK13 and MPK25 confer resistance to defoliating isolates of Verticillium dahliae in cotton. Silencing of MPK9, MPK13 and MPK25 can significantly enhance cotton susceptibility to this pathogen. This study presents a comprehensive identification of 28 mitogen-activated protein kinase genes in G. raimondii. Their phylogenetic relationships, transcript expression patterns and responses to various stressors were verified. This study provides the first systematic analysis of MAPKs in cotton, improving our understanding of defense responses in general and laying the foundation for future crop improvement using MAPKs.

  7. The Coat Protein and NIa Protease of Two Potyviridae Family Members Independently Confer Superinfection Exclusion

    Science.gov (United States)

    French, Roy

    2016-01-01

    ABSTRACT Superinfection exclusion (SIE) is an antagonistic virus-virus interaction whereby initial infection by one virus prevents subsequent infection by closely related viruses. Although SIE has been described in diverse viruses infecting plants, humans, and animals, its mechanisms, including involvement of specific viral determinants, are just beginning to be elucidated. In this study, SIE determinants encoded by two economically important wheat viruses, Wheat streak mosaic virus (WSMV; genus Tritimovirus, family Potyviridae) and Triticum mosaic virus (TriMV; genus Poacevirus, family Potyviridae), were identified in gain-of-function experiments that used heterologous viruses to express individual virus-encoded proteins in wheat. Wheat plants infected with TriMV expressing WSMV P1, HC-Pro, P3, 6K1, CI, 6K2, NIa-VPg, or NIb cistrons permitted efficient superinfection by WSMV expressing green fluorescent protein (WSMV-GFP). In contrast, wheat infected with TriMV expressing WSMV NIa-Pro or coat protein (CP) substantially excluded superinfection by WSMV-GFP, suggesting that both of these cistrons are SIE effectors encoded by WSMV. Importantly, SIE is due to functional WSMV NIa-Pro or CP rather than their encoding RNAs, as altering the coded protein products by minimally changing RNA sequences led to abolishment of SIE. Deletion mutagenesis further revealed that elicitation of SIE by NIa-Pro requires the entire protein while CP requires only a 200-amino-acid (aa) middle fragment (aa 101 to 300) of the 349 aa. Strikingly, reciprocal experiments with WSMV-mediated expression of TriMV proteins showed that TriMV CP, and TriMV NIa-Pro to a lesser extent, likewise excluded superinfection by TriMV-GFP. Collectively, these data demonstrate that WSMV- and TriMV-encoded CP and NIa-Pro proteins are effectors of SIE and that these two proteins trigger SIE independently of each other. IMPORTANCE Superinfection exclusion (SIE) is an antagonistic virus-virus interaction that

  8. Expression analysis of the Theileria parva subtelomere-encoded variable secreted protein gene family.

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    Jacqueline Schmuckli-Maurer

    Full Text Available The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm.We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals.Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic

  9. Potential costs of bacterial infection on storage protein gene expression and reproduction in queenless Apis mellifera worker bees on distinct dietary regimes.

    Science.gov (United States)

    Lourenço, Anete Pedro; Martins, Juliana Ramos; Guidugli-Lazzarini, Karina Rosa; Macedo, Liliane Maria Fróes; Bitondi, Márcia Maria Gentile; Simões, Zilá Luz Paulino

    2012-09-01

    Insects are able to combat infection by initiating an efficient immune response that involves synthesizing antimicrobial peptides and a range of other defense molecules. These responses may be costly to the organism, resulting in it exploiting endogenous resources to maintain homeostasis or support defense to the detriment of other physiological needs. We used queenless worker bees on distinct dietary regimes that may alter hemolymph protein storage and ovary activation to investigate the physiological costs of infection with Serratia marcescens. The expression of the genes encoding the storage proteins vitellogenin and hexamerin 70a, the vitellogenin receptor, and vasa (which has a putative role in reproduction), was impaired in the infected bees. This impairment was mainly evident in the bees fed beebread, which caused significantly higher expression of these genes than did royal jelly or syrup, and this was confirmed at the vitellogenin and hexamerin 70a protein levels. Beebread was also the only diet that promoted ovary activation in the queenless bees, but this activation was significantly impaired by the infection. The expression of the genes encoding the storage proteins apolipophorins-I and -III and the lipophorin receptor was not altered by infection regardless the diet provided to the bees. Similarly, the storage of apolipophorin-I in the hemolymph was only slightly impaired by the infection, independently of the supplied diet. Taken together these results indicate that, infection demands a physiological cost from the transcription of specific protein storage-related genes and from the reproductive capacity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Genotypic variability in faba bean (vicia faba L.) for seed yield and protein content under drought stress during vegetative and Reproductive Stages

    International Nuclear Information System (INIS)

    Abdelmula, A. A.; Gasim, S. M.; Link, W.; Mohamed, A. A.; Khalifa, J. E.

    2012-01-01

    Faba bean (viciafaba L.) is subjected to drought stress during different growth stages. In this study, variability in seed yield and protein content was investigated when drought occurred during the vegetative and reproductive stages. Twenty two genotypes of faba bean were field evaluated under three levels of drought stress at two locations in the Sudan. The three levels of drought were normal watering (non-stress), drought during the vegetative stage and drought during the reproductive stage. Data were collected on yield and vegetative traits and protein content. The results showed that yield, as well as other traits, were reduced by drought. The genotypes exhibited significant differences for 100 seed weight, plant height and protein content. The interaction between the genotypes and drought was significant for yield/plant. Some genotypes were more sensitive when drought occurred during the vegetative stage, some when drought occurred during the vegetative stage, and others were more stable under the three levels of drought. yield/plant showed significant covariance with pods/plant and plant height. The association between different characters varied according to trait and the time of drought incidence. The correlation of yield/plant with protein content was negative under all drought levels, and the average correlation coefficient was 0.32. It could be concluded that the specific adaptation and the wide adaptation have great implication for improving faba bean under drought. To select for high seed yield under drought, secondary characters, such as pods/plant and plant height could be of great importance. Drought could reduce protein content and affect its association with yield/plant.(Author)

  11. Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members.

    Science.gov (United States)

    Deneka, Alexander; Korobeynikov, Vladislav; Golemis, Erica A

    2015-10-01

    The CAS (Crk-associated substrate) adaptor protein family consists of four members: CASS1/BCAR1/p130Cas, CASS2/NEDD9/HEF1/Cas-L, CASS3/EFS/Sin and CASS4/HEPL. While CAS proteins lack enzymatic activity, they contain specific recognition and binding sites for assembly of larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes. All family members are intermediates in integrin-dependent signaling pathways mediated at focal adhesions, and associate with FAK and SRC family kinases to activate downstream effectors regulating the actin cytoskeleton. Most studies of CAS proteins to date have been focused on the first two members, BCAR1 and NEDD9, with altered expression of these proteins now appreciated as influencing disease development and prognosis for cancer and other serious pathological conditions. For these family members, additional mechanisms of action have been defined in receptor tyrosine kinase (RTK) signaling, estrogen receptor signaling or cell cycle progression, involving discrete partner proteins such as SHC, NSP proteins, or AURKA. By contrast, EFS and CASS4 have been less studied, although structure-function analyses indicate they conserve many elements with the better-known family members. Intriguingly, a number of recent studies have implicated these proteins in immune system function, and the pathogenesis of developmental disorders, autoimmune disorders including Crohn's disease, Alzheimer's disease, cancer and other diseases. In this review, we summarize the current understanding of EFS and CASS4 protein function in the context of the larger CAS family group. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. The Drosophila DOCK family protein Sponge is required for development of the air sac primordium

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    Morishita, Kazushge; Anh Suong, Dang Ngoc; Yoshida, Hideki; Yamaguchi, Masamitsu, E-mail: myamaguc@kit.ac.jp

    2017-05-15

    Dedicator of cytokinesis (DOCK) family genes are known as DOCK1-DOCK11 in mammals. DOCK family proteins mainly regulate actin filament polymerization and/or depolymerization and are GEF proteins, which contribute to cellular signaling events by activating small G proteins. Sponge (Spg) is a Drosophila counterpart to mammalian DOCK3/DOCK4, and plays a role in embryonic central nervous system development, R7 photoreceptor cell differentiation, and adult thorax development. In order to conduct further functional analyses on Spg in vivo, we examined its localization in third instar larval wing imaginal discs. Immunostaining with purified anti-Spg IgG revealed that Spg mainly localized in the air sac primordium (ASP) in wing imaginal discs. Spg is therefore predicted to play an important role in the ASP. The specific knockdown of Spg by the breathless-GAL4 driver in tracheal cells induced lethality accompanied with a defect in ASP development and the induction of apoptosis. The monitoring of ERK signaling activity in wing imaginal discs by immunostaining with anti-diphospho-ERK IgG revealed reductions in the ERK signal cascade in Spg knockdown clones. Furthermore, the overexpression of D-raf suppressed defects in survival and the proliferation of cells in the ASP induced by the knockdown of Spg. Collectively, these results indicate that Spg plays a critical role in ASP development and tracheal cell viability that is mediated by the ERK signaling pathway. - Highlights: • Spg mainly localizes in the air sac primordium in wing imaginal discs. • Spg plays a critical role in air sac primordium development. • Spg positively regulates the ERK signal cascade.

  13. Evolutionary mechanisms driving the evolution of a large polydnavirus gene family coding for protein tyrosine phosphatases

    Directory of Open Access Journals (Sweden)

    Serbielle Céline

    2012-12-01

    Full Text Available Abstract Background Gene duplications have been proposed to be the main mechanism involved in genome evolution and in acquisition of new functions. Polydnaviruses (PDVs, symbiotic viruses associated with parasitoid wasps, are ideal model systems to study mechanisms of gene duplications given that PDV genomes consist of virulence genes organized into multigene families. In these systems the viral genome is integrated in a wasp chromosome as a provirus and virus particles containing circular double-stranded DNA are injected into the parasitoids’ hosts and are essential for parasitism success. The viral virulence factors, organized in gene families, are required collectively to induce host immune suppression and developmental arrest. The gene family which encodes protein tyrosine phosphatases (PTPs has undergone spectacular expansion in several PDV genomes with up to 42 genes. Results Here, we present strong indications that PTP gene family expansion occurred via classical mechanisms: by duplication of large segments of the chromosomally integrated form of the virus sequences (segmental duplication, by tandem duplications within this form and by dispersed duplications. We also propose a novel duplication mechanism specific to PDVs that involves viral circle reintegration into the wasp genome. The PTP copies produced were shown to undergo conservative evolution along with episodes of adaptive evolution. In particular recently produced copies have undergone positive selection in sites most likely involved in defining substrate selectivity. Conclusion The results provide evidence about the dynamic nature of polydnavirus proviral genomes. Classical and PDV-specific duplication mechanisms have been involved in the production of new gene copies. Selection pressures associated with antagonistic interactions with parasitized hosts have shaped these genes used to manipulate lepidopteran physiology with evidence for positive selection involved in

  14. A DOUBLE KNOCKOUT; A NOVEL APPROACH TO UNDERSTANDING STRESS-INDUCIBLE 70 KDA HEAT SHOCK PROTEINS (HSP70S) ON DEVELOPMENT AND REPRODUCTION

    Science.gov (United States)

    Heat and chemical toxicants which disrupt spermatogenesis and cause male infertility are thought to induce the expression of Hsp70-1 and 70-3, the major inducible heat shock proteins of the 70kDa family. Previous studies from several laboratories including our own have characteri...

  15. Distinct roles of the RasGAP family proteins in C. elegans associative learning and memory.

    Science.gov (United States)

    Gyurkó, M Dávid; Csermely, Péter; Sőti, Csaba; Steták, Attila

    2015-10-15

    The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans.

  16. A bipolar clamp mechanism for activation of Jak-family protein tyrosine kinases.

    Directory of Open Access Journals (Sweden)

    Dipak Barua

    2009-04-01

    Full Text Available Most cell surface receptors for growth factors and cytokines dimerize in order to mediate signal transduction. For many such receptors, the Janus kinase (Jak family of non-receptor protein tyrosine kinases are recruited in pairs and juxtaposed by dimerized receptor complexes in order to activate one another by trans-phosphorylation. An alternative mechanism for Jak trans-phosphorylation has been proposed in which the phosphorylated kinase interacts with the Src homology 2 (SH2 domain of SH2-B, a unique adaptor protein with the capacity to homo-dimerize. Building on a rule-based kinetic modeling approach that considers the concerted nature and combinatorial complexity of modular protein domain interactions, we examine these mechanisms in detail, focusing on the growth hormone (GH receptor/Jak2/SH2-Bbeta system. The modeling results suggest that, whereas Jak2-(SH2-Bbeta(2-Jak2 heterotetramers are scarcely expected to affect Jak2 phosphorylation, SH2-Bbeta and dimerized receptors synergistically promote Jak2 trans-activation in the context of intracellular signaling. Analysis of the results revealed a unique mechanism whereby SH2-B and receptor dimers constitute a bipolar 'clamp' that stabilizes the active configuration of two Jak2 molecules in the same macro-complex.

  17. Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Interacts with Nsp9 and Cellular DHX9 To Regulate Viral RNA Synthesis.

    Science.gov (United States)

    Liu, Long; Tian, Jiao; Nan, Hao; Tian, Mengmeng; Li, Yuan; Xu, Xiaodong; Huang, Baicheng; Zhou, Enmin; Hiscox, Julian A; Chen, Hongying

    2016-06-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid (N) protein is the main component of the viral capsid to encapsulate viral RNA, and it is also a multifunctional protein involved in the regulation of host cell processes. Nonstructural protein 9 (Nsp9) is the RNA-dependent RNA polymerase that plays a critical role in viral RNA transcription and replication. In this study, we demonstrate that PRRSV N protein is bound to Nsp9 by protein-protein interaction and that the contacting surface on Nsp9 is located in the two predicted α-helixes formed by 48 residues at the C-terminal end of the protein. Mutagenesis analyses identified E646, E608, and E611 on Nsp9 and Q85 on the N protein as the pivotal residues participating in the N-Nsp9 interaction. By overexpressing the N protein binding fragment of Nsp9 in infected Marc-145 cells, the synthesis of viral RNAs, as well as the production of infectious progeny viruses, was dramatically inhibited, suggesting that Nsp9-N protein association is involved in the process of viral RNA production. In addition, we show that PRRSV N interacts with cellular RNA helicase DHX9 and redistributes the protein into the cytoplasm. Knockdown of DHX9 increased the ratio of short subgenomic mRNAs (sgmRNAs); in contrast, DHX9 overexpression benefited the synthesis of longer sgmRNAs and the viral genomic RNA (gRNA). These results imply that DHX9 is recruited by the N protein in PRRSV infection to regulate viral RNA synthesis. We postulate that N and DHX9 may act as antiattenuation factors for the continuous elongation of nascent transcript during negative-strand RNA synthesis. It is unclear whether the N protein of PRRSV is involved in regulation of the viral RNA production process. In this report, we demonstrate that the N protein of the arterivirus PRRSV participates in viral RNA replication and transcription through interacting with Nsp9 and its RdRp and recruiting cellular RNA helicase to promote the production of

  18. EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome

    Science.gov (United States)

    Bertsias, G K; Agmon-Levin, N; Brown, S; Cervera, R; Costedoat-Chalumeau, N; Doria, A; Fischer-Betz, R; Forger, F; Moraes-Fontes, M F; Khamashta, M; King, J; Lojacono, A; Marchiori, F; Meroni, P L; Mosca, M; Motta, M; Ostensen, M; Pamfil, C; Raio, L; Schneider, M; Svenungsson, E; Tektonidou, M; Yavuz, S; Boumpas, D; Tincani, A

    2017-01-01

    Objectives Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Methods Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. Results Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. Conclusions Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus. PMID:27457513

  19. Is the faculty of family planning and reproductive health care guidance on emergency contraception being followed in general practice? An audit in the West Midlands, UK.

    Science.gov (United States)

    Bannister, Lisa; Macve, Joanna; Pinkey, Benjamin; Webberley, Helen

    2007-07-01

    In 2003, the Faculty of Family Planning and Reproductive Health Care (FFPRHC) of the Royal College of Obstetricians and Gynaecologists published guidance on emergency contraception (EC). A literature search revealed no published work describing doctors' actions when prescribing EC. In order to assess the extent to which the FFPRHC Guidance is being followed in general practice, an audit of the medical notes of women requesting EC between January 2003 and December 2004 in six general practice surgeries located in the West Midlands, UK was conducted. From the medical notes, discussions between health care professionals and patients requesting EC regarding ongoing contraceptive needs, the risk of sexually transmitted infections (STIs) and the availability of the emergency intrauterine device (IUD) were recorded. A total of 718 emergency contraceptive pill consultations were analysed. The median age for presentation was 24 years. The 20-24 years age group accounted for the most consultations (30.9%). In 40% of consultations there was no evidence of future contraceptive needs having been discussed. Only 20 (2.8%) consultation notes contained evidence that STIs had been discussed. Chlamydia tests were undertaken in only 15/718 (1.7%) consultations. In only 10 (1.4%) of the consultations was the IUD discussed with the patient as an alternative form of EC. This audit suggests that the FFPRHC Guidance on EC is not being followed in general practice, and therefore patients requesting EC may not be receiving the highest standard of care.

  20. Student perceptions of reproductive health education in US medical schools: a qualitative analysis of students taking family planning electives

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    Kathryn Veazey

    2015-11-01

    Full Text Available Background: Abortion services will be sought by an estimated one in three US women before they reach age 45. Despite the importance of family planning (FP care, many medical schools do not currently offer formal education in this area, and students are unable to meet associated competency standards prior to graduation. Purpose: The purpose of this study was to explore students’ motivations in pursuing FP electives throughout the United States, their experiences during these courses, and any impact of these rotations on their plans for future practice. Method: We conducted a qualitative study consisting of semi-structured interviews with medical students upon completing fourth-year FP electives at US medical schools. Thirty-seven LCME-accredited US medical schools offered fourth-year FP electives. Course directors at 21 of these institutions recruited study participants between June 2012 and June 2013. Interviews were transcribed, coded, and analyzed with ATLAS/ti software to identify salient themes. Results: We interviewed 29 students representing 14 institutions from all regions of the United States (East Coast, Midwest, South, and West Coast. Five central themes emerged. Medical students are using FP electives to fill gaps in the standard curriculum. Elective participation did not change students’ pre-elective stance on abortion. Many students intend to provide abortion in the future but identified possible limiting factors. Proficiency in contraception and options counseling were top competencies desired and gained. Students reported excellent satisfaction with FP electives and would recommend it to their peers, regardless of their personal beliefs. Conclusions: Interview data revealed that students are using FP electives to fill gaps within preclinical and clinical medical school curriculum. Future physicians will be unable to provide comprehensive care for their female patients if they are not provided with this education. Research

  1. Student perceptions of reproductive health education in US medical schools: a qualitative analysis of students taking family planning electives.

    Science.gov (United States)

    Veazey, Kathryn; Nieuwoudt, Claudia; Gavito, Christina; Tocce, Kristina

    2015-01-01

    Abortion services will be sought by an estimated one in three US women before they reach age 45. Despite the importance of family planning (FP) care, many medical schools do not currently offer formal education in this area, and students are unable to meet associated competency standards prior to graduation. The purpose of this study was to explore students' motivations in pursuing FP electives throughout the United States, their experiences during these courses, and any impact of these rotations on their plans for future practice. We conducted a qualitative study consisting of semi-structured interviews with medical students upon completing fourth-year FP electives at US medical schools. Thirty-seven LCME-accredited US medical schools offered fourth-year FP electives. Course directors at 21 of these institutions recruited study participants between June 2012 and June 2013. Interviews were transcribed, coded, and analyzed with ATLAS/ti software to identify salient themes. We interviewed 29 students representing 14 institutions from all regions of the United States (East Coast, Midwest, South, and West Coast). Five central themes emerged. Medical students are using FP electives to fill gaps in the standard curriculum. Elective participation did not change students' pre-elective stance on abortion. Many students intend to provide abortion in the future but identified possible limiting factors. Proficiency in contraception and options counseling were top competencies desired and gained. Students reported excellent satisfaction with FP electives and would recommend it to their peers, regardless of their personal beliefs. Interview data revealed that students are using FP electives to fill gaps within preclinical and clinical medical school curriculum. Future physicians will be unable to provide comprehensive care for their female patients if they are not provided with this education. Research should be directed at development and analysis of comprehensive FP curricula

  2. Effects of short light regimes and lower dietary protein content on the reproductive performance of White Roman geese in an environment-controlled house.

    Science.gov (United States)

    Chang, Shen-Chang; Chiang, Hsin-I; Lin, Min-Jung; Jea, Yu-Shine; Chen, Lih-Ren; Fan, Yang-Kwang; Lee, Tzu-Tai

    2016-07-01

    The objective of this study is to investigate the effects of short light regimes and lower dietary protein content on the reproductive performance of White Roman geese in an environment- controlled house. Thirty-two ganders and 80 geese during the third laying period were allotted into 16 pens, randomly assigned into a split-plot design with two different lighting regimes: (1) short light regimes (SL) with 6.5h of light and 17.5h of dark (6.5L:17.5D), and (2) long light regimes (LL) with 19L:5D during the 6-wk prelaying period, followed by two different levels of protein diets (Low CP: 15% vs. High CP: 18%) for the laying period. The results showed that birds treated with the SL light regime had a heavier body weight compared to those treated with LL at the arrival of the peak period of egg production (6.19 vs. 5.87kg, Pvs. 175day, Pvs. 12.6%, Plight regime during the prelaying period and on the low CP diet during the laying period found conditions sufficient to sustain their regular reproduction performance, which would benefit geese farmers in the perspectives of energy saving and prolonged laying period. Copyright © 2016. Published by Elsevier B.V.

  3. Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins.

    Science.gov (United States)

    Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan

    2015-12-01

    Human sterile alpha motif domain-containing 9 (SAMD9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus C7 protein. To understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of C7 and myxoma virus M64, a C7 family member that is unable to antagonize SAMD9. Despite their different functions and only 23% sequence identity, the two proteins have very similar overall structures, displaying a previously unidentified fold comprised of a compact 12-stranded antiparallel β-sandwich wrapped in two short α helices. Extensive structure-guided mutagenesis of C7 identified three loops clustered on one edge of the β sandwich as critical for viral replication and binding with SAMD9. The loops are characterized with functionally important negatively charged, positively charged, and hydrophobic residues, respectively, together forming a unique "three-fingered molecular claw." The key residues of the claw are not conserved in two C7 family members that do not antagonize SAMD9 but are conserved in distantly related C7 family members from four poxvirus genera that infect diverse mammalian species. Indeed, we found that all in the latter group of proteins bind SAMD9. Taken together, our data indicate that diverse mammalian poxviruses use a conserved molecular claw in a C7-like protein to target SAMD9 and overcome host restriction.

  4. Phytoplasma protein effector SAP11 enhances insect vector reproduction by manipulating plant development and defense hormone biosynthesis

    OpenAIRE

    Sugio, Akiko; Kingdom, Heather N.; MacLean, Allyson M.; Grieve, Victoria M.; Hogenhout, Saskia A.

    2011-01-01

    Phytoplasmas are insect-transmitted phytopathogenic bacteria that can alter plant morphology and the longevity and reproduction rates and behavior of their insect vectors. There are various examples of animal and plant parasites that alter the host phenotype to attract insect vectors, but it is unclear how these parasites accomplish this. We hypothesized that phytoplasmas produce effectors that modulate specific targets in their hosts leading to the changes in plant development and insect per...

  5. Six subgroups and extensive recent duplications characterize the evolution of the eukaryotic tubulin protein family.

    Science.gov (United States)

    Findeisen, Peggy; Mühlhausen, Stefanie; Dempewolf, Silke; Hertzog, Jonny; Zietlow, Alexander; Carlomagno, Teresa; Kollmar, Martin

    2014-08-27

    Tubulins belong to the most abundant proteins in eukaryotes providing the backbone for many cellular substructures like the mitotic and meiotic spindles, the intracellular cytoskeletal network, and the axonemes of cilia and flagella. Homologs have even been reported for archaea and bacteria. However, a taxonomically broad and whole-genome-based analysis of the tubulin protein family has never been performed, and thus, the number of subfamilies, their taxonomic distribution, and the exact grouping of the supposed archaeal and bacterial homologs are unknown. Here, we present the analysis of 3,524 tubulins from 504 species. The tubulins formed six major subfamilies, α to ζ. Species of all major kingdoms of the eukaryotes encode members of these subfamilies implying that they must have already been present in the last common eukaryotic ancestor. The proposed archaeal homologs grouped together with the bacterial TubZ proteins as sister clade to the FtsZ proteins indicating that tubulins are unique to eukaryotes. Most species contained α- and/or β-tubulin gene duplicates resulting from recent branch- and species-specific duplication events. This shows that tubulins cannot be used for constructing species phylogenies without resolving their ortholog-paralog relationships. The many gene duplicates and also the independent loss of the δ-, ε-, or ζ-tubulins, which have been shown to be part of the triplet microtubules in basal bodies, suggest that tubulins can functionally substitute each other. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Chitosanases from Family 46 of Glycoside Hydrolases: From Proteins to Phenotypes

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    Pascal Viens

    2015-10-01

    Full Text Available Chitosanases, enzymes that catalyze the endo-hydrolysis of glycolytic links in chitosan, are the subject of numerous studies as biotechnological tools to generate low molecular weight chitosan (LMWC or chitosan oligosaccharides (CHOS from native, high molecular weight chitosan. Glycoside hydrolases belonging to family GH46 are among the best-studied chitosanases, with four crystallography-derived structures available and more than forty enzymes studied at the biochemical level. They were also subjected to numerous site-directed mutagenesis studies, unraveling the molecular mechanisms of hydrolysis. This review is focused on the taxonomic distribution of GH46 proteins, their multi-modular character, the structure-function relationships and their biological functions in the host organisms.

  7. The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

    Science.gov (United States)

    Garces de los Fayos Alonso, Ines; Lagger, Sabine; Merkel, Olaf; Kenner, Lukas

    2018-01-01

    The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer development has been extensively analysed. Multiple in vitro and in vivo studies have highlighted the complexity of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization resulting in diverse transcriptional response profiles. However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies. In this review, we focus on the impact of deregulated expression of AP-1 TFs in CD30-positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma. PMID:29597249

  8. Protein phosphatase 2A mediates JS-K-induced apoptosis by affecting Bcl-2 family proteins in human hepatocellular carcinoma HepG2 cells.

    Science.gov (United States)

    Liu, Ling; Huang, Zile; Chen, Jingjing; Wang, Jiangang; Wang, Shuying

    2018-04-25

    Protein phosphatase 2A (PP2A) is an important enzyme within various signal transduction pathways. The present study was investigated PP2A mediates JS-K-induced apoptosis by affecting Bcl-2 family protein. JS-K showed diverse inhibitory effects in five HCC cell lines, especially HepG2 cells. JS-K caused a dose- and time-dependent reduction in cell viability and increased in levels of LDH release. Meanwhile, JS-K- induced apoptosis was characterized by mitochondrial membrane potential reduction, Hoechst 33342 + /PI + dual staining, release of cytochrome c (Cyt c), and activation of cleaved caspase-9/3. Moreover, JS-K-treatment could lead to the activation of protein phosphatase 2A-C (PP2A-C), decrease of anti-apoptotic Bcl-2 family-protein expression including p-Bcl-2 (Ser70), Bcl-2, Bcl-xL, and Mcl-1 as well as the increase of pro-apoptosis Bcl-2 family-protein including Bim, Bad, Bax, and Bak. Furthermore, JS-K caused a marked increase of intracellular NO levels while pre-treatment with Carboxy-PTIO (a NO scavenger) reduced the cytotoxicity effects and the apoptosis rate. Meanwhile, pre-treatment with Carboxy-PTIO attenuated the JS-K-induced up-regulation of PP2A, Cyt c, and cleaved-caspase-9/3 activation. The silencing PP2A-C by siRNA could abolish the activation of PP2A-C, down-regulation of anti-apoptotic Bcl-2 family-protein (p-Bcl-2, Bcl-2, Bcl-xL, and Mcl-1), increase of pro-apoptosis Bcl-2 family-protein (Bim, Bad, Bax, and Bak) and apoptotic-related protein (Cyt c, cleaved caspase-9/3) that were caused by JS-K in HepG2 cells. In addition, pre-treatment with OA (a PP2A inhibitor) also attenuated the above effects induced by JS-K. In summary, NO release from JS-K induces apoptosis through PP2A activation, which contributed to the regulation of Bcl-2 family proteins. © 2018 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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

  10. A novel germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene in an Italian family with gigantism.

    Science.gov (United States)

    Urbani, C; Russo, D; Raggi, F; Lombardi, M; Sardella, C; Scattina, I; Lupi, I; Manetti, L; Tomisti, L; Marcocci, C; Martino, E; Bogazzi, F

    2014-10-01

    Acromegaly usually occurs as a sporadic disease, but it may be a part of familial pituitary tumor syndromes in rare cases. Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been associated with a predisposition to familial isolated pituitary adenoma. The aim of the present study was to evaluate the AIP gene in a patient with gigantism and in her relatives. Direct sequencing of AIP gene was performed in fourteen members of the family, spanning among three generations. The index case was an 18-year-old woman with gigantism due to an invasive GH-secreting pituitary adenoma and a concomitant tall-cell variant of papillary thyroid carcinoma. A novel germline mutation in the AIP gene (c.685C>T, p.Q229X) was identified in the proband and in two members of her family, who did not present clinical features of acromegaly or other pituitary disorders. Eleven subjects had no mutation in the AIP gene. Two members of the family with clinical features of acromegaly refused either the genetic or the biochemical evaluation. The Q229X mutation was predicted to generate a truncated AIP protein, lacking the last two tetratricopeptide repeat domains and the final C-terminal α-7 helix. We identified a new AIP germline mutation predicted to produce a truncated AIP protein, lacking its biological properties due to the disruption of the C-terminus binding sites for both the chaperones and the client proteins of AIP.

  11. Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway

    DEFF Research Database (Denmark)

    Leffers, H; Madsen, Peder; Rasmussen, H H

    1993-01-01

    tissues showed that polypeptides comigrating with proteins 9124, 9125 and 9126 are ubiquitous and highly expressed in the brain. Stratifin, however, was present only in cultured epithelial cells and was most abundant in fetal and adult human tissues enriched in stratified squamous keratinising epithelium......We have identified a family of abundant acidic human keratinocyte proteins with apparent molecular masses ranging between 30,000 and 31,100 (isoelectric focussing sample spot proteins 9109 (epithelial marker stratifin), 9124, 9125, 9126 and 9231 in the master two-dimensional gel database of human...

  12. Identification and characterization of a chitin-binding protein purified from coelomic fluid of the lugworm Arenicola marina defining a novel protein sequence family

    DEFF Research Database (Denmark)

    Vitashenkova, Nina; Moeller, Jesper Bonnet; Leth-Larsen, Rikke

    2012-01-01

    by coelomocytes, in the nephridium and in round cells in epidermis and in eggs. Moreover, AML-1 expression was up-regulated in response to a parasitic infection. We conclude that AML-1 purified from coelomic fluid is encoded by AML-1b and represents a novel type of protein family that binds acetylated components....

  13. Molecular cloning of a Candida albicans gene (SSB1) coding for a protein related to the Hsp70 family.

    Science.gov (United States)

    Maneu, V; Cervera, A M; Martinez, J P; Gozalbo, D

    1997-06-15

    We have cloned and sequenced a Candida albicans gene (SSB1) encoding a potential member of the heat-shock protein seventy (hsp70) family. The protein encoded by this gene contains 613 amino acids and shows a high degree (85%) of sequence identity to the ssb subfamily (ssb1 and ssb2) of the Saccharomyces cerevisiae hsp70 family. The transcribed mRNA (2.1 kb) is present in similar amounts both in yeast and germ tube cells of C. albicans.

  14. Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity.

    Directory of Open Access Journals (Sweden)

    Gonçalo da Costa

    Full Text Available Familial amyloidotic polyneuropathy (FAP is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR. This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease.

  15. Macrophage inflammatory protein-1alpha: a link between innate immunity and familial Mediterranean fever?

    Science.gov (United States)

    Dizdar, Omer; Kalyoncu, Umut; Karadag, Omer; Akdogan, Ali; Kiraz, Sedat; Ertenli, Ihsan; Barista, Ibrahim; Calguneri, Meral

    2007-01-01

    The aim of this study is to investigate the relationship between chemokines and the inflammation in Familial Mediterranean Fever (FMF). Forty-nine patients with FMF (41 in remission and 8 in acute attack period) and 20 healthy controls were included in the study. Serum levels of macrophage inflammatory protein-1alpha (MIP-1alpha) were assessed in the patients and the controls, along with other parameters of disease activity, i.e., fibrinogen, C-reactive protein and erythrocyte sedimentation rate. Serum MIP-1alpha levels of the patients with FMF in acute attack period were significantly higher than the patients in remission and healthy controls (p=0.02 and p=0.038, respectively). MIP-1alpha levels were weakly correlated with CRP (r=0.32, p=0.032) levels. MIP-1alpha may have a role in the pathogenesis of FMF attacks. MIP-1alpha and other chemokines may constitute a link between the innate immune system and FMF.

  16. Automatic discovery of cross-family sequence features associated with protein function

    Directory of Open Access Journals (Sweden)

    Krings Andrea

    2006-01-01

    Full Text Available Abstract Background Methods for predicting protein function directly from amino acid sequences are useful tools in the study of uncharacterised protein families and in comparative genomics. Until now, this problem has been approached using machine learning techniques that attempt to predict membership, or otherwise, to predefined functional categories or subcellular locations. A potential drawback of this approach is that the human-designated functional classes may not accurately reflect the underlying biology, and consequently important sequence-to-function relationships may be missed. Results We show that a self-supervised data mining approach is able to find relationships between sequence features and functional annotations. No preconceived ideas about functional categories are required, and the training data is simply a set of protein sequences and their UniProt/Swiss-Prot annotations. The main technical aspect of the approach is the co-evolution of amino acid-based regular expressions and keyword-based logical expressions with genetic programming. Our experiments on a strictly non-redundant set of eukaryotic proteins reveal that the strongest and most easily detected sequence-to-function relationships are concerned with targeting to various cellular compartments, which is an area already well studied both experimentally and computationally. Of more interest are a number of broad functional roles which can also be correlated with sequence features. These include inhibition, biosynthesis, transcription and defence against bacteria. Despite substantial overlaps between these functions and their corresponding cellular compartments, we find clear differences in the sequence motifs used to predict some of these functions. For example, the presence of polyglutamine repeats appears to be linked more strongly to the "transcription" function than to the general "nuclear" function/location. Conclusion We have developed a novel and useful approach for

  17. Expanded microbial genome coverage and improved protein family annotation in the COG database.

    Science.gov (United States)

    Galperin, Michael Y; Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

    2015-01-01

    Microbial genome sequencing projects produce numerous sequences of deduced proteins, only a small fraction of which have been or will ever be studied experimentally. This leaves sequence analysis as the only feasible way to annotate these proteins and assign to them tentative functions. The Clusters of Orthologous Groups of proteins (COGs) database (http://www.ncbi.nlm.nih.gov/COG/), first created in 1997, has been a popular tool for functional annotation. Its success was largely based on (i) its reliance on complete microbial genomes, which allowed reliable assignment of orthologs and paralogs for most genes; (ii) orthology-based approach, which used the function(s) of the characterized member(s) of the protein family (COG) to assign function(s) to the entire set of carefully identified orthologs and describe the range of potential functions when there were more than one; and (iii) careful manual curation of the annotation of the COGs, aimed at detailed prediction of the biological function(s) for each COG while avoiding annotation errors and overprediction. Here we present an update of the COGs, the first since 2003, and a comprehensive revision of the COG annotations and expansion of the genome coverage to include representative complete genomes from all bacterial and archaeal lineages down to the genus level. This re-analysis of the COGs shows that the original COG assignments had an error rate below 0.5% and allows an assessment of the progress in functional genomics in the past 12 years. During this time, functions of many previously uncharacterized COGs have been elucidated and tentative functional assignments of many COGs have been validated, either by targeted experiments or through the use of high-throughput methods. A particularly important development is the assignment of functions to several widespread, conserved proteins many of which turned out to participate in translation, in particular rRNA maturation and tRNA modification. The new version of the

  18. Assisted human reproduction: psychological and ethical dilemmas

    National Research Council Canada - National Science Library

    Singer, Dani; Hunter, Myra

    2003-01-01

    ... Psychological therapy and counselling with individuals and families after donor conception Sharon A Pettle Chapter 9 182 Policy development in third party reproduction: an international perspective...

  19. Conservation and divergence of ADAM family proteins in the Xenopus genome

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    Shah Anoop

    2010-07-01

    Full Text Available Abstract Background Members of the disintegrin metalloproteinase (ADAM family play important roles in cellular and developmental processes through their functions as proteases and/or binding partners for other proteins. The amphibian Xenopus has long been used as a model for early vertebrate development, but genome-wide analyses for large gene families were not possible until the recent completion of the X. tropicalis genome sequence and the availability of large scale expression sequence tag (EST databases. In this study we carried out a systematic analysis of the X. tropicalis genome and uncovered several interesting features of ADAM genes in this species. Results Based on the X. tropicalis genome sequence and EST databases, we identified Xenopus orthologues of mammalian ADAMs and obtained full-length cDNA clones for these genes. The deduced protein sequences, synteny and exon-intron boundaries are conserved between most human and X. tropicalis orthologues. The alternative splicing patterns of certain Xenopus ADAM genes, such as adams 22 and 28, are similar to those of their mammalian orthologues. However, we were unable to identify an orthologue for ADAM7 or 8. The Xenopus orthologue of ADAM15, an active metalloproteinase in mammals, does not contain the conserved zinc-binding motif and is hence considered proteolytically inactive. We also found evidence for gain of ADAM genes in Xenopus as compared to other species. There is a homologue of ADAM10 in Xenopus that is missing in most mammals. Furthermore, a single scaffold of X. tropicalis genome contains four genes encoding ADAM28 homologues, suggesting genome duplication in this region. Conclusions Our genome-wide analysis of ADAM genes in X. tropicalis revealed both conservation and evolutionary divergence of these genes in this amphibian species. On the one hand, all ADAMs implicated in normal development and health in other species are conserved in X. tropicalis. On the other hand, some

  20. The family of light-harvesting-related proteins (LHCs, ELIPs, HLIPs): was the harvesting of light their primary function?

    Science.gov (United States)

    Montané, M H; Kloppstech, K

    2000-11-27

    Light-harvesting complex proteins (LHCs) and early light-induced proteins (ELIPs) are essential pigment-binding components of the thylakoid membrane and are encoded by one of the largest and most complex higher plant gene families. The functional diversification of these proteins corresponded to the transition from extrinsic (phycobilisome-based) to intrinsic (LHC-based) light-harvesting antenna systems during the evolution of chloroplasts from cyanobacteria, yet the functional basis of this diversification has been elusive. Here, we propose that the original function of LHCs and ELIPs was not to collect light and to transfer its energy content to the reaction centers but to disperse the absorbed energy of light in the form of heat or fluorescence. These energy-dispersing proteins are believed to have originated in cyanobacteria as one-helix, highly light-inducible proteins (HLIPs) that later acquired four helices through two successive gene duplication steps. We suggest that the ELIPs arose first in this succession, with a primary function in energy dispersion for protection of photosynthetic pigments from photo-oxidation. We consider the LHC I and II families as more recent and very successful evolutionary additions to this family that ultimately attained a new function, thereby replacing the ancestral extrinsic light-harvesting system. Our model accounts for the non-photochemical quenching role recently shown for higher plant psbS proteins.

  1. Chimeric viruses containing the N-terminal ectodomains of GP5 and M proteins of porcine reproductive and respiratory syndrome do not change the cellular tropism of equine arteritis virus

    Science.gov (United States)

    Equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV) are members of family Arteriviridae; they share many biological properties but differ significantly in cellular tropism. Using an infectious cDNA clone of EAV, we engineered a panel of six chimeric viruses b...

  2. A guild of 45 CRISPR-associated (Cas protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes.

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    Daniel H Haft

    2005-11-01

    Full Text Available Clustered regularly interspaced short palindromic repeats (CRISPRs are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer "immunity" against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated.

  3. Functional studies of ssDNA binding ability of MarR family protein TcaR from Staphylococcus epidermidis.

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    Yu-Ming Chang

    Full Text Available The negative transcription regulator of the ica locus, TcaR, regulates proteins involved in the biosynthesis of poly-N-acetylglucosamine (PNAG. Absence of TcaR increases PNAG production and promotes biofilm formation in Staphylococci. Previously, the 3D structure of TcaR in its apo form and its complex structure with several antibiotics have been analyzed. However, the detailed mechanism of multiple antibiotic resistance regulator (MarR family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA. Here we show by electrophoretic mobility shift assay (EMSA, electron microscopy (EM, circular dichroism (CD, and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA, thereby identifying a new role in MarR family proteins. Moreover, we show that TcaR preferentially binds 33-mer ssDNA over double-stranded DNA and inhibits viral ssDNA replication. In contrast, such ssDNA binding properties were not observed for other MarR family protein and TetR family protein, suggesting that the results from our studies are not an artifact due to simple charge interactions between TcaR and ssDNA. Overall, these results suggest a novel role for TcaR in regulation of DNA replication. We anticipate that the results of this work will extend our understanding of MarR family protein and broaden the development of new therapeutic strategies for Staphylococci.

  4. Expression of GIMAP1, a GTPase of the immunity-associated protein family, is not up-regulated in malaria

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    Carter Christine

    2009-04-01

    Full Text Available Abstract Background GIMAP (GTPase of the immunity-associated protein family proteins are a family of putative GTPases believed to be regulators of cell death in lymphomyeloid cells. GIMAP1 was the first reported member of this gene family, identified as a gene up-regulated at the RNA level in the spleens of mice infected with the malarial parasite, Plasmodium chabaudi. Methods A monoclonal antibody against mouse GIMAP1 was developed and was used to analyse the expression of the endogenous protein in tissues of normal mice and in defined sub-populations of cells prepared from lymphoid tissues using flow cytometry. It was also used to assess the expression of GIMAP1 protein after infection and/or immunization of mice with P. chabaudi. Real-time PCR analysis was employed to measure the expression of GIMAP1 for comparison with the protein level analysis. Results GIMAP1 protein expression was detected in all lineages of lymphocytes (T, B, NK, in F4/80+ splenic macrophages and in some lymphoid cell lines. Additional evidence is presented suggesting that the strong expression by mature B cells of GIMAP1 and other GIMAP genes and proteins seen in mice may be a species-dependent characteristic. Unexpectedly, no increase was found in the expression of GIMAP1 in P. chabaudi infected mice at either the mRNA or protein level, and this remained so despite applying a number of variations to the protocol. Conclusion The model of up-regulation of GIMAP1 in response to infection/immunization with P. chabaudi is not a robustly reproducible experimental system. The GIMAP1 protein is widely expressed in lymphoid cells, with an interesting increase in expression in the later stages of B cell development. Alternative approaches will be required to define the functional role of this GTPase in immune cells.

  5. Molecular Characterization of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL Gene Family in Betula luminifera

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    Xiu-Yun Li

    2018-05-01

    Full Text Available As a major family of plant-specific transcription factors, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL genes play vital regulatory roles in plant growth, development and stress responses. In this study, 18 SPL genes were identified and cloned from Betula luminifera. Two zinc finger-like structures and a nuclear location signal (NLS segments were existed in the SBP domains of all BlSPLs. Phylogenetic analysis showed that these genes were clustered into nine groups (group I-IX. The intron/exon structure and motif composition were highly conserved within the same group. 12 of the 18 BlSPLs were experimentally verified as the targets of miR156, and two cleavage sites were detected in these miR156-targeted BlSPL genes. Many putative cis-elements, associated with light, stresses and phytohormones response, were identified in the promoter regions of BlSPLs, suggesting that BlSPL genes are probably involved in important physiological processes and developmental events. Tissue-specific expression analysis showed that miR156-targeted BlSPLs exhibited a more differential expression pattern, while most miR156-nontargeted BlSPLs tended to be constitutively expressed, suggesting the distinct roles of miR156-targeted and nontargeted BlSPLs in development and growth of B. luminifera. Further expression analysis revealed that miR156-targeted BlSPLs were dramatically up-regulated with age, whereas mature BlmiR156 level was apparently declined with age, indicating that miR156/SPL module plays important roles in vegetative phase change of B. luminifera. Moreover, yeast two-hybrid assay indicated that several miR156-targeted and nontargeted BlSPLs could interact with two DELLA proteins (BlRGA and BlRGL, which suggests that certain BlSPLs take part in the GA regulated processes through protein interaction with DELLA proteins. All these results provide an important basis for further exploring the biological functions of BlSPLs in B. luminifera.

  6. The Non-structural Protein 5 and Matrix Protein Are Antigenic Targets of T Cell Immunity to Genotype 1 Porcine Reproductive and Respiratory Syndrome Viruses

    DEFF Research Database (Denmark)

    Mokhtar, Helen; Pedrera, Miriam; Frossard, Jean-Pierre

    2016-01-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focused on envelope glycoproteins to target virus-neutralizing antibody responses...... proposed that T cell-mediated immunity plays a key role. Therefore, we hypothesized that conserved T cell antigens represent prime candidates for the development a novel PRRS vaccine. Antigens were identified by screening a proteome-wide synthetic peptide library with T cells from cohorts of pigs rendered...... attractive vaccine candidate T cell antigens, which should be evaluated further in the context of PRRSV vaccine development....

  7. Interconversion of two GDP-bound conformations and their selection in an Arf-family small G protein.

    Science.gov (United States)

    Okamura, Hideyasu; Nishikiori, Masaki; Xiang, Hongyu; Ishikawa, Masayuki; Katoh, Etsuko

    2011-07-13

    ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate in many cellular functions via their characteristic GTP/GDP conformational cycles, during which a nucleotide(∗)Mg(2+)-binding site communicates with a remote N-terminal helix. However, the conformational interplay between the nucleotides, the helix, the protein core, and Mg(2+) has not been fully delineated. Herein, we report a study of the dynamics of an Arf-family protein, Arl8, under various conditions by means of NMR relaxation spectroscopy. The data indicated that, when GDP is bound, the protein core, which does not include the N-terminal helix, reversibly transition between an Arf-family GDP form and another conformation that resembles the Arf-family GTP form. Additionally, we found that the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned former and latter conformations in a population-shift manner. Given the dynamics of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of an energy diagram. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth.

    Science.gov (United States)

    Viloria, Katrina; Munasinghe, Amanda; Asher, Sharan; Bogyere, Roberto; Jones, Lucy; Hill, Natasha J

    2016-11-25

    SPARC is a matricellular protein that is involved in both pancreatic cancer and diabetes. It belongs to a wider family of proteins that share structural and functional similarities. Relatively little is known about this extended family, but evidence of regulatory interactions suggests the importance of a holistic approach to their study. We show that Hevin, SPOCKs, and SMOCs are strongly expressed within islets, ducts, and blood vessels, suggesting important roles for these proteins in the normal pancreas, while FSTL-1 expression is localised to the stromal compartment reminiscent of SPARC. In direct contrast to SPARC, however, FSTL-1 expression is reduced in pancreatic cancer. Consistent with this, FSTL-1 inhibited pancreatic cancer cell proliferation. The complexity of SPARC family proteins is further revealed by the detection of multiple cell-type specific isoforms that arise due to a combination of post-translational modification and alternative splicing. Identification of splice variants lacking a signal peptide suggests the existence of novel intracellular isoforms. This study underlines the importance of addressing the complexity of the SPARC family and provides a new framework to explain their controversial and contradictory effects. We also demonstrate for the first time that FSTL-1 suppresses pancreatic cancer cell growth.

  9. Putative midkine family protein up-regulation in Patella caerulea (Mollusca, Gastropoda) exposed to sublethal concentrations of cadmium

    International Nuclear Information System (INIS)

    Vanucci, Silvana; Minerdi, Daniela; Kadomatsu, Kenji; Mengoni, Alessio; Bazzicalupo, Marco

    2005-01-01

    A cDNA sequence of a putative midkine (MK) family protein was identified and characterised in the mollusc Patella caerulea. The midkine family consists of two members, midkine and pleiotrophin (PTN), and it is one of the recently discovered cytokines. Our results show that this putative midkine protein is up-regulated in specimens of P. caerulea exposed to sublethal cadmium concentrations (i.e. 0.5 and 1 mg l -1 Cd) over a 10-day exposure period. Semiquantitative RT-PCR and quantitative Real time RT-PCR estimations indicate elevated expression of midkine mRNA in exposed specimens compared to controls. Moreover, RT-PCR Real time values were higher in the viscera (here defined as the part of the soft tissue including digestive gland plus gills) than in the foot (i.e. foot plus head plus heart) of the limpets. At present, information on the functional signalling significance of the midkine family proteins suggests that the up-regulation of P. caerulea putative midkine family protein is a distress signal likely with informative value on health status of the organism and with potential prognostic capability

  10. Molecular characterization of two sub-family specific monoclonal antibodies to meningococcal Factor H binding protein

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    C. Lo Passo

    2018-04-01

    Full Text Available Factor H binding protein (FHbp is a component of two licensed vaccines for prevention of sepsis and meningitis caused by serogroup B meningococci. FHbp binds human Factor H (FH, which contributes to evasion of host immunity and FHbp sequence variants can be classified into two sub-families. Antibodies against FHbp elicit complement-mediated killing and can inhibit recruitment of FH to the bacterial surface. We report epitope mapping studies of two murine IgG mAbs, designated JAR 31 and JAR 36, isolated from a mouse immunized with FHbp in sub-family A, which is present in ∼30–40% of invasive isolates. In the present study, we tested the reactivity of mAbs JAR 31 and JAR 36 with seven natural FHbp sequence variants from different phylogenic groups. We screened bacteriophage-displayed peptide libraries to identify amino acid residues contributing to the JAR 36 epitope. Based on the reactivities of mAbs JAR 31 and JAR 36 with the seven FHbp variants, and the frequent occurrences of aspartate (D and lysine (K residues in the JAR 36-bound phage peptides, we selected six residues in the carboxyl-terminal region of FHbp for replacement with alanine (A. The D201A and K203A substitutions respectively eliminated and decreased binding of mAbs JAR 31 and JAR 36 to FHbp. These substitutions did not affect binding of the control mAb JAR 33 or of human FH. JAR 31 or JAR 36 mediated cooperative complement-mediated bactericidal activity with other anti-FHbp mAbs. The identification of two amino acid residues involved in the epitopes recognized by these anti-FHbp mAbs may contribute to a more complete understanding of the spatial requirements for cooperative anti-FHbp mAb bactericidal activity. Keywords: Biochemistry, Immunology, Microbiology, Molecular biology

  11. New insights on the sialidase protein family revealed by a phylogenetic analysis in metazoa.

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    Edoardo Giacopuzzi

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

  12. Characterization of the heterotrimeric G-protein family and its transmembrane regulator from capsicum (Capsicum annuum L.).

    Science.gov (United States)

    Romero-Castillo, Rafael A; Roy Choudhury, Swarup; León-Félix, Josefina; Pandey, Sona

    2015-05-01

    Throughout evolution, organisms have created numerous mechanisms to sense and respond to their environment. One such highly conserved mechanism involves regulation by heterotrimeric G-protein complex comprised of alpha (Gα), beta (Gβ) and gamma (Gγ) subunits. In plants, these proteins play important roles in signal transduction pathways related to growth and development including response to biotic and abiotic stresses and consequently affect yield. In this work, we have identified and characterized the complete heterotrimeric G-protein repertoire in the Capsicum annuum (Capsicum) genome which consists of one Gα, one Gβ and three Gγ genes. We have also identified one RGS gene in the Capsicum genome that acts as a regulator of the G-protein signaling. Biochemical activities of the proteins were confirmed by assessing the GTP-binding and GTPase activity of the recombinant Gα protein and its regulation by the GTPase acceleration activity of the RGS protein. Interaction between different subunits was established using yeast- and plant-based analyses. Gene and protein expression profiles of specific G-protein components revealed interesting spatial and temporal regulation patterns, especially during root development and during fruit development and maturation. This research thus details the characterization of the first heterotrimeric G-protein family from a domesticated, commercially important vegetable crop. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Effect of crude protein levels and organic selenium supplementation in the diets fed during the breeding season on reproductive parameters of red-winged tinamous (Rhynchotus rufescens

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    L Felipe

    2010-03-01

    Full Text Available There is little information on the nutrition of red-winged tinamous (Rhynchotus rufescens reared in captivity, and their nutritional requirements still need to be determined. This study aimed at determining dietary crude protein requirements and testing four organic selenium supplementation levels in the diet of red-winged tinamous during the breeding season. Birds were housed in a conventional broiler house divided in 16 boxes with one male and three females each. Iso-energy (2800kcal ME/kg pelleted feeds, based on corn and soybean meal, were supplied in tube feeders. In the first experiment, treatments consisted of four different diets containing different crude protein (CP contents (15, 18, 21, or 24% and in the second experiment, the four diets contained equal protein level (22.5% and four different organic selenium levels (0, 0.2, 0.4, or 0.8ppm. Data were analyzed by the least square method. The best egg weight and eggshell thickness were obtained with 22.5% dietary CP. Organic selenium did not influence the studied reproductive traits of red-winged tinamous (Rhynchotus rufescens males or females.

  14. A correspondence between solution-state dynamics of an individual protein and the sequence and conformational diversity of its family.

    Directory of Open Access Journals (Sweden)

    Gregory D Friedland

    2009-05-01

    Full Text Available Conformational ensembles are increasingly recognized as a useful representation to describe fundamental relationships between protein structure, dynamics and function. Here we present an ensemble of ubiquitin in solution that is created by sampling conformational space without experimental information using "Backrub" motions inspired by alternative conformations observed in sub-Angstrom resolution crystal structures. Backrub-generated structures are then selected to produce an ensemble that optimizes agreement with nuclear magnetic resonance (NMR Residual Dipolar Couplings (RDCs. Using this ensemble, we probe two proposed relationships between properties of protein ensembles: (i a link between native-state dynamics and the conformational heterogeneity observed in crystal structures, and (ii a relation between dynamics of an individual protein and the conformational variability explored by its natural family. We show that the Backrub motional mechanism can simultaneously explore protein native-state dynamics measured by RDCs, encompass the conformational variability present in ubiquitin complex structures and facilitate sampling of conformational and sequence variability matching those occurring in the ubiquitin protein family. Our results thus support an overall relation between protein dynamics and conformational changes enabling sequence changes in evolution. More practically, the presented method can be applied to improve protein design predictions by accounting for intrinsic native-state dynamics.

  15. A first-principles model of early evolution: emergence of gene families, species, and preferred protein folds.

    Directory of Open Access Journals (Sweden)

    Konstantin B Zeldovich

    2007-07-01

    Full Text Available In this work we develop a microscopic physical model of early evolution where phenotype--organism life expectancy--is directly related to genotype--the stability of its proteins in their native conformations-which can be determined exactly in the model. Simulating the model on a computer, we consistently observe the "Big Bang" scenario whereby exponential population growth ensues as soon as favorable sequence-structure combinations (precursors of stable proteins are discovered. Upon that, random diversity of the structural space abruptly collapses into a small set of preferred proteins. We observe that protein folds remain stable and abundant in the population at timescales much greater than mutation or organism lifetime, and the distribution of the lifetimes of dominant folds in a population approximately follows a power law. The separation of evolutionary timescales between discovery of new folds and generation of new sequences gives rise to emergence of protein families and superfamilies whose sizes are power-law distributed, closely matching the same distributions for real proteins. On the population level we observe emergence of species--subpopulations that carry similar genomes. Further, we present a simple theory that relates stability of evolving proteins to the sizes of emerging genomes. Together, these results provide a microscopic first-principles picture of how first-gene families developed in the course of early evolution.

  16. 5S rRNA and accompanying proteins in gonads: powerful markers to identify sex and reproductive endocrine disruption in fish.

    Science.gov (United States)

    Diaz de Cerio, Oihane; Rojo-Bartolomé, Iratxe; Bizarro, Cristina; Ortiz-Zarragoitia, Maren; Cancio, Ibon

    2012-07-17

    In anuran ovaries, 5S rDNA is regulated transcriptionally by transcription factor IIIA (TFIIIA), which upon transcription, binds 5S rRNA, forming 7S RNP. 5S rRNA can be stockpiled also in the form of 42S RNP bound to 42sp43. The aim of the present study was to assess the differential transcriptional regulation of 5S rRNA and associated proteins in thicklip gray mullet (Chelon labrosus) gonads. Up to 75% of the total RNA from mullet ovaries was 5S rRNA. qPCR quantification of 5S rRNA expression, in gonads of histologically sexed individuals from different geographical areas, successfully sexed animals. All males had expression levels that were orders of magnitude below expression levels in females, throughout an annual reproductive cycle, with the exception of two individuals: one in November and one in December. Moreover, intersex mullets from a polluted harbor had expression levels between both sexes. TFIIIA and 42sp43 were also very active transcriptionally in gonads of female and intersex mullets, in comparison to males. Nucleocytoplasmatic transport is important in this context and we also analyzed transcriptional levels of importins-α1, -α2, and -β2 and different exportins. Importin-αs behaved similarly to 5S rRNA. Thus, 5S rRNA and associated proteins constitute very powerful molecular markers of sex and effects of xenosterogens in fish gonads, with potential technological applications in the analysis of fish stock dynamics and reproduction as well as in environmental health assessment.

  17. Dr. Jekyll and Mr. Hyde: The Two Faces of the FUS/EWS/TAF15 Protein Family

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    Heinrich Kovar

    2011-01-01

    Full Text Available FUS, EWS, and TAF15 form the FET family of RNA-binding proteins whose genes are found rearranged with various transcription factor genes predominantly in sarcomas and in rare hematopoietic and epithelial cancers. The resulting fusion gene products have attracted considerable interest as diagnostic and promising therapeutic targets. So far, oncogenic FET fusion proteins have been regarded as strong transcription factors that aberrantly activate or repress target genes of their DNA-binding fusion partners. However, the role of the transactivating domain in the context of the normal FET proteins is poorly defined, and, therefore, our knowledge on how FET aberrations impact on tumor biology is incomplete. Since we believe that a full understanding of aberrant FET protein function can only arise from looking at both sides of the coin, the good and the evil, this paper summarizes evidence for the central function of FET proteins in bridging RNA transcription, processing, transport, and DNA repair.

  18. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module

    DEFF Research Database (Denmark)

    Rosenthal, J A; Chen, H; Slepnev, V I

    1999-01-01

    Epsin (epsin 1) is an interacting partner for the EH domain-containing region of Eps15 and has been implicated in conjunction with Eps15 in clathrin-mediated endocytosis. We report here the characterization of a similar protein (epsin 2), which we have cloned from human and rat brain libraries. E...... fluorescent protein-epsin 2 mislocalizes components of the clathrin coat and inhibits clathrin-mediated endocytosis. The epsins define a new protein family implicated in membrane dynamics at the cell surface.......Epsin (epsin 1) is an interacting partner for the EH domain-containing region of Eps15 and has been implicated in conjunction with Eps15 in clathrin-mediated endocytosis. We report here the characterization of a similar protein (epsin 2), which we have cloned from human and rat brain libraries...

  19. CaMKII-MEDIATED PHOSPHORYLATION OF THE BOMBYX MORI LIPID STORAGE DROPLET PROTEIN-1 (BmLsd1), AN INSECT PAT FAMILY PROTEIN, IS ESSENTIAL FOR SILKMOTH SEX PHEROMONE BIOSYNTHESIS

    Science.gov (United States)

    The structurally-related members of the PAT family of proteins, which are so name based on similarity amongst perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), and tail-interacting protein of 47 kilodaltons (TIP47), are cytoplasmic lipid droplet (LD)-associated proteins charac...

  20. A lepidopteran-specific gene family encoding valine-rich midgut proteins.

    Directory of Open Access Journals (Sweden)

    Jothini Odman-Naresh

    Full Text Available Many lepidopteran larvae are serious agricultural pests due to their feeding activity. Digestion of the plant diet occurs mainly in the midgut and is facilitated by the peritrophic matrix (PM, an extracellular sac-like structure, which lines the midgut epithelium and creates different digestive compartments. The PM is attracting increasing attention to control lepidopteran pests by interfering with this vital function. To identify novel PM components and thus potential targets for insecticides, we performed an immunoscreening with anti-PM antibodies using an expression library representing the larval midgut transcriptome of the tobacco hornworm, Manduca sexta. We identified three cDNAs encoding valine-rich midgut proteins of M. sexta (MsVmps, which appear to be loosely associated with the PM. They are members of a lepidopteran-specific family of nine VMP genes, which are exclusively expressed in larval stages in M. sexta. Most of the MsVMP transcripts are detected in the posterior midgut, with the highest levels observed for MsVMP1. To obtain further insight into Vmp function, we expressed MsVMP1 in insect cells and purified the recombinant protein. Lectin staining and glycosidase treatment indicated that MsVmp1 is highly O-glycosylated. In line with results from qPCR, immunoblots revealed that MsVmp1 amounts are highest in feeding larvae, while MsVmp1 is undetectable in starving and molting larvae. Finally using immunocytochemistry, we demonstrated that MsVmp1 localizes to the cytosol of columnar cells, which secrete MsVmp1 into the ectoperitrophic space in feeding larvae. In starving and molting larvae, MsVmp1 is found in the gut lumen, suggesting that the PM has increased its permeability. The present study demonstrates that lepidopteran species including many agricultural pests have evolved a set of unique proteins that are not found in any other taxon and thus may reflect an important adaptation in the highly specialized lepidopteran

  1. Functional evolution in the plant SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL gene family

    Directory of Open Access Journals (Sweden)

    Jill Christine Preston

    2013-04-01

    Full Text Available The SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL family of transcription factors is functionally diverse, controlling a number of fundamental aspects of plant growth and development, including vegetative phase change, flowering time, branching, and leaf initiation rate. In natural plant populations, variation in flowering time and shoot architecture have major consequences for fitness. Likewise, in crop species, variation in branching and developmental rate impact biomass and yield. Thus, studies aimed at dissecting how the various functions are partitioned among different SPL genes in diverse plant lineages are key to providing insight into the genetic basis of local adaptation and have already garnered attention by crop breeders. Here we use phylogenetic reconstruction to reveal nine major SPL gene lineages, each of which is described in terms of function and diversification. To assess evidence for ancestral and derived functions within each SPL gene lineage, we use ancestral character state reconstructions. Our analyses suggest an emerging pattern of sub-functionalization, neo-functionalization, and possible convergent evolution following both ancient and recent gene duplication. Based on these analyses we suggest future avenues of research that may prove fruitful for elucidating the importance of SPL gene evolution in plant growth and development.

  2. Direct Involvement of Retinoblastoma Family Proteins in DNA Repair by Non-homologous End-Joining

    Directory of Open Access Journals (Sweden)

    Rebecca Cook

    2015-03-01

    Full Text Available Deficiencies in DNA double-strand break (DSB repair lead to genetic instability, a recognized cause of cancer initiation and evolution. We report that the retinoblastoma tumor suppressor protein (RB1 is required for DNA DSB repair by canonical non-homologous end-joining (cNHEJ. Support of cNHEJ involves a mechanism independent of RB1’s cell-cycle function and depends on its amino terminal domain with which it binds to NHEJ components XRCC5 and XRCC6. Cells with engineered loss of RB family function as well as cancer-derived cells with mutational RB1 loss show substantially reduced levels of cNHEJ. RB1 variants disabled for the interaction with XRCC5 and XRCC6, including a cancer-associated variant, are unable to support cNHEJ despite being able to confer cell-cycle control. Our data identify RB1 loss as a candidate driver of structural genomic instability and a causative factor for cancer somatic heterogeneity and evolution.

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

    Directory of Open Access Journals (Sweden)

    Daojun Cheng

    2014-01-01

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

  4. The effect of dietary protein on reproduction in the mare. IV. Serum progestagen, FSH, LH and melatonin concentrations during the anovulatory, transitional and ovulatory periods in the non-pregnant mare

    Directory of Open Access Journals (Sweden)

    F.E. Van Niekerk

    1997-07-01

    Full Text Available The effect of total protein intake and protein quality on the serum concentrations of certain reproductive hormones during the anovulatory, transitional and ovulatory periods were studied in 36 Anglo-Arab mares. High-quality protein stimulated FSH and LH production during the late transitional period. Serum progestagen and melatonin concentrations were unaffected by the quality of protein nutrition during the anovulatory period. Mares receiving high-quality protein exhibited a 10-14-day cyclical pattern of FSH release approximately 4-6 weeks earlier than the mares fed the lower-quality protein diet, and also ovulated 3-4 weeks earlier than the mares on the lower-quality protein diet. Progesterone concentrations during the 1st oestrous cycle after the anovulatory period were unaffected by protein quality in the diet.

  5. Cloning and expression of the translocator protein (18 kDa), voltage-dependent anion channel, and diazepam binding inhibitor in the gonad of largemouth bass (Micropterus salmoides) across the reproductive cycle.

    Science.gov (United States)

    Doperalski, Nicholas J; Martyniuk, Christopher J; Prucha, Melinda S; Kroll, Kevin J; Denslow, Nancy D; Barber, David S

    2011-08-01

    Cholesterol transport across the mitochondrial membrane is rate-limiting for steroidogenesis in vertebrates. Previous studies in fish have characterized expression of the steroidogenic acute regulatory protein, however the function and regulation of other genes and proteins involved in piscine cholesterol transport have not been evaluated. In the current study, mRNA sequences of the 18 kDa translocator protein (tspo; formerly peripheral benzodiazepine receptor), voltage-dependent anion channel (vdac), and diazepam binding inhibitor (dbi; also acyl-CoA binding protein) were cloned from largemouth bass. Gonadal expression was examined across reproductive stages to determine if expression is correlated with changes in steroid levels and with indicators of reproductive maturation. In testis, transcript abundance of tspo and dbi increased with reproductive maturation (6- and 23-fold maximal increase, respectively) and expression of tspo and dbi was positively correlated with reproductive stage, gonadosomatic index (GSI), and circulating levels of testosterone. Testis vdac expression was positively correlated with reproductive stage and GSI. In females, gonadal tspo and vdac expression was negatively correlated with GSI and levels of plasma testosterone and 17β-estradiol. Ovarian dbi expression was not correlated with indicators of reproductive maturation. These studies represent the first investigation of the steroidogenic role of tspo, vdac, and dbi in fish. Findings suggest that cholesterol transport in largemouth bass testis, but not in ovary, may be transcriptionally-regulated, however further investigation will be necessary to fully elucidate the role of these genes in largemouth bass steroidogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Peasant reproduction and local knowledge in contexts of social and environmental fragility. Family and community strategies in the mountain range of Tentzo, México

    Directory of Open Access Journals (Sweden)

    Beatriz Martínez Corona

    2016-09-01

    Full Text Available The article presents results of research conducted in the city of San Antonio Juarez, Tzicatlacoyan township, in the state of Puebla, Mexico. The objective was to determine the reproductive strategies of domestic groups peasants, facing adverse environmental conditions that severely restrict the development of agriculture. From qualitative and quantitative techniques, it was found the presence of different reproduction strategies, at the neighborhood level, based on local knowledge, the gender division of labor and domestic level organization and community group.

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

    Science.gov (United States)

    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

  8. A systematic analysis of the early transcribed membrane protein family throughout the life cycle of Plasmodium yoelii.

    Science.gov (United States)

    MacKellar, Drew C; Vaughan, Ashley M; Aly, Ahmed S I; DeLeon, Sasha; Kappe, Stefan H I

    2011-11-01

    The early transcribed membrane proteins (ETRAMPs) are a family of small, highly charged transmembrane proteins unique to malaria parasites. Some members of the ETRAMP family have been localized to the parasitophorous vacuole membrane that separates the intracellular parasite from the host cell and thus presumably have a role in host-parasite interactions. Although it was previously shown that two ETRAMPs are critical for rodent malaria parasite liver-stage development, the importance of most ETRAMPs during the parasite life cycle remains unknown. Here, we comprehensively identify nine new etramps in the genome of the rodent malaria parasite Plasmodium yoelii, and elucidate their conservation in other malaria parasites. etramp expression profiles are diverse throughout the parasite life cycle as measured by RT-PCR. Epitope tagging of two ETRAMPs demonstrates protein expression in blood and liver stages, and reveals differences in both their timing of expression and their subcellular localization. Gene targeting studies of each of the nine uncharacterized etramps show that two are refractory to deletion and thus likely essential for blood-stage replication. Seven etramps are not essential for any life cycle stage. Systematic characterization of the members of the ETRAMP family reveals the diversity in importance of each family member at the interface between host and parasite throughout the developmental cycle of the malaria parasite. © 2011 Blackwell Publishing Ltd.

  9. Differential protein expression, DNA binding and interaction with SV40 large tumour antigen implicate the p63-family of proteins in replicative senescence.

    Science.gov (United States)

    Djelloul, Siham; Tarunina, Marina; Barnouin, Karin; Mackay, Alan; Jat, Parmjit S

    2002-02-07

    P53 activity plays a key role in mammalian cells when they undergo replicative senescence at their Hayflick limit. To determine whether p63 proteins, members of the family of p53-related genes, are also involved in this process, we examined their expression in serially passaged rat embryo fibroblasts. Upon senescence, two truncated DeltaNp63 proteins decreased in abundance whereas two TAp63 isoforms accumulated. 2-D gel analysis showed that the DeltaNp63 proteins underwent post-translational modifications in both proliferating and senescent cells. Direct binding of DeltaNp63 proteins to a p53 consensus motif was greater in proliferating cells than senescent cells. In contrast p63alpha isoforms bound to DNA in a p53 dependent manner and this was higher in senescent cells than proliferating cells. An interaction of p63alpha proteins with SV40 large tumour antigen was also detected and ectopic expression of DeltaNp63alpha can extend the lifespan of rat embryo fibroblasts. Taken together the results indicate that p63 proteins may play a role in replicative senescence either by competition for p53 DNA binding sites or by direct interaction with p53 protein bound to DNA.

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

    Directory of Open Access Journals (Sweden)

    Finan Christopher L

    2005-03-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    kinase SNF1 complex, and an adaptor–regulator related to the SNF1/AMPK family, AKINβγ. CBM20s and CBM48s of amylolytic enzymes occur predominantly in the microbial world, whereas the non-amylolytic proteins containing these modules are mostly of plant and animal origin. Comparison of amino acid sequences...... that they exhibit independent behaviour, i.e. each family forms its own part in an evolutionary tree, with enzyme specificity (protein function) being well represented within each family. The distinction between CBM20 and CBM48 families is not sharp since there are representatives in both CBM families that possess...

  12. Annotation and analysis of a large cuticular protein family with the R&R Consensus in Anopheles gambiae

    Directory of Open Access Journals (Sweden)

    He Ningjia

    2008-01-01

    Full Text Available Abstract Background The most abundant family of insect cuticular proteins, the CPR family, is recognized by the R&R Consensus, a domain of about 64 amino acids that binds to chitin and is present throughout arthropods. Several species have now been shown to have more than 100 CPR genes, inviting speculation as to the functional importance of this large number and diversity. Results We have identified 156 genes in Anopheles gambiae that code for putative cuticular proteins in this CPR family, over 1% of the total number of predicted genes in this species. Annotation was verified using several criteria including identification of TATA boxes, INRs, and DPEs plus support from proteomic and gene expression analyses. Two previously recognized CPR classes, RR-1 and RR-2, form separate, well-supported clades with the exception of a small set of genes with long branches whose relationships are poorly resolved. Several of these outliers have clear orthologs in other species. Although both clades are under purifying selection, the RR-1 variant of the R&R Consensus is evolving at twice the rate of the RR-2 variant and is structurally more labile. In contrast, the regions flanking the R&R Consensus have diversified in amino-acid composition to a much greater extent in RR-2 genes compared with RR-1 genes. Many genes are found in compact tandem arrays that may include similar or dissimilar genes but always include just one of the two classes. Tandem arrays of RR-2 genes frequently contain subsets of genes coding for highly similar proteins (sequence clusters. Properties of the proteins indicated that each cluster may serve a distinct function in the cuticle. Conclusion The complete annotation of this large gene family provides insight on the mechanisms of gene family evolution and clues about the need for so many CPR genes. These data also should assist annotation of other Anopheles genes.

  13. The Puf family of RNA-binding proteins in plants: phylogeny, structural modeling, activity and subcellular localization

    Directory of Open Access Journals (Sweden)

    Tam Michael WC

    2010-03-01

    Full Text Available Abstract Background Puf proteins have important roles in controlling gene expression at the post-transcriptional level by promoting RNA decay and repressing translation. The Pumilio homology domain (PUM-HD is a conserved region within Puf proteins that binds to RNA with sequence specificity. Although Puf proteins have been well characterized in animal and fungal systems, little is known about the structural and functional characteristics of Puf-like proteins in plants. Results The Arabidopsis and rice genomes code for 26 and 19 Puf-like proteins, respectively, each possessing eight or fewer Puf repeats in their PUM-HD. Key amino acids in the PUM-HD of several of these proteins are conserved with those of animal and fungal homologs, whereas other plant Puf proteins demonstrate extensive variability in these amino acids. Three-dimensional modeling revealed that the predicted structure of this domain in plant Puf proteins provides a suitable surface for binding RNA. Electrophoretic gel mobility shift experiments showed that the Arabidopsis AtPum2 PUM-HD binds with high affinity to BoxB of the Drosophila Nanos Response Element I (NRE1 RNA, whereas a point mutation in the core of the NRE1 resulted in a significant reduction in binding affinity. Transient expression of several of the Arabidopsis Puf proteins as fluorescent protein fusions revealed a dynamic, punctate cytoplasmic pattern of localization for most of these proteins. The presence of predicted nuclear export signals and accumulation of AtPuf proteins in the nucleus after treatment of cells with leptomycin B demonstrated that shuttling of these proteins between the cytosol and nucleus is common among these proteins. In addition to the cytoplasmically enriched AtPum proteins, two AtPum proteins showed nuclear targeting with enrichment in the nucleolus. Conclusions The Puf family of RNA-binding proteins in plants consists of a greater number of members than any other model species studied to

  14. Protein kinase inhibitor peptide (PKI): a family of endogenous neuropeptides that modulate neuronal cAMP-dependent protein kinase function.

    Science.gov (United States)

    Dalton, George D; Dewey, William L

    2006-02-01

    Signal transduction cascades involving cAMP-dependent protein kinase are highly conserved among a wide variety of organisms. Given the universal nature of this enzyme it is not surprising that cAMP-dependent protein kinase plays a critical role in numerous cellular processes. This is particularly evident in the nervous system where cAMP-dependent protein kinase is involved in neurotransmitter release, gene transcription, and synaptic plasticity. Protein kinase inhibitor peptide (PKI) is an endogenous thermostable peptide that modulates cAMP-dependent protein kinase function. PKI contains two distinct functional domains within its amino acid sequence that allow it to: (1) potently and specifically inhibit the activity of the free catalytic subunit of cAMP-dependent protein kinase and (2) export the free catalytic subunit of cAMP-dependent protein kinase from the nucleus. Three distinct PKI isoforms (PKIalpha, PKIbeta, PKIgamma) have been identified and each isoform is expressed in the brain. PKI modulates neuronal synaptic activity, while PKI also is involved in morphogenesis and symmetrical left-right axis formation. In addition, PKI also plays a role in regulating gene expression induced by cAMP-dependent protein kinase. Future studies should identify novel physiological functions for endogenous PKI both in the nervous system and throughout the body. Most interesting will be the determination whether functional differences exist between individual PKI isoforms which is an intriguing possibility since these isoforms exhibit: (1) cell-type specific tissue expression patterns, (2) different potencies for the inhibition of cAMP-dependent protein kinase activity, and (3) expression patterns that are hormonally, developmentally and cell-cycle regulated. Finally, synthetic peptide analogs of endogenous PKI will continue to be invaluable tools that are used to elucidate the role of cAMP-dependent protein kinase in a variety of cellular processes throughout the nervous

  15. Phylogenetic Reconstruction Shows Independent Evolutionary Origins of Mitochondrial Transcription Factors from an Ancient Family of RNA Methyltransferase Proteins.

    Science.gov (United States)

    Aj Harris; Goldman, Aaron David

    2018-04-25

    Here, we generate a robust phylogenetic framework for the rRNA adenine N(6)-methyltransferase (RAMTase) protein family that shows a more ancient and complex evolutionary history within the family than previously reported. RAMTases occur universally by descent across the three domains of life, and typical orthologs within the family perform methylation of the small subunits of ribosomal RNA (rRNA). However, within the RAMTase family, two different groups of mitochondrial transcription factors, mtTFB1 and mtTFB2, have evolved in eukaryotes through neofunctionalization. Previous phylogenetic analyses have suggested that mtTFB1 and mtTFB2 comprise sister clades that arose via gene duplication, which occurred sometime following the endosymbiosis event that produced the mitochondrion. Through dense and taxonomically broad sampling of RAMTase family members especially within bacteria, we found that these eukaryotic mitochondrial transcription factors, mtTFB1 and mtTFB2, have independent origins in phylogenetically distant clades such that their divergence most likely predates the last universal common ancestor of life. The clade of mtTFB2s comprises orthologs in Opisthokonts and the clade of mtTFB1s includes orthologs in Amoebozoa and Metazoa. Thus, we clearly demonstrate that the neofunctionalization producing the transcription factor function evolved twice independently within the RAMTase family. These results are consistent with and help to elucidate outcomes from prior experimental studies, which found that some members of mtTFB1 still perform the ancestral rRNA methylation function, and the results have broader implications for understanding the evolution of new protein functions. Our phylogenetic reconstruction is also in agreement with prior studies showing two independent origins of plastid RAMTases in Viridiplantae and other photosynthetic autotrophs. We believe that this updated phylogeny of RAMTases should provide a robust evolutionary framework for ongoing

  16. Genome-wide identification and characterization of stress-associated protein (SAP gene family encoding A20/AN1 zinc-finger proteins in Medicago truncatula

    Directory of Open Access Journals (Sweden)

    Zhou Yong

    2018-01-01

    Full Text Available Stress associated proteins (SAPs play important roles in developmental processes, responses to various stresses and hormone stimulation in plants. However, little is known about the SAP gene family in Medicago truncatula. In this study, a total of 17 MtSAP genes encoding A20/AN1 zinc-finger proteins were characterized. Out of these 17 genes, 15 were distributed over all 8 chromosomes at different densities, and two segmental duplication events were detected. The phylogenetic analysis of these proteins and their orthologs from Arabidopsis and rice suggested that they could be classified into five out of the seven groups of SAP family genes, with genes in the same group showing similar structures and conserved domains. The cis-elements of the MtSAP promoters were studied, and many cis-elements related to stress and plant hormone responses were identified. We also investigated the stress-responsive expression patterns of the MtSAP genes under various stresses, including drought, exposure to NaCl and cold. The qRT-PCR results showed that numerous MtSAP genes exhibited transcriptional responses to multiple abiotic stresses. These results lay the foundation for further functional characterization of SAP genes. To the best of our knowledge, this is the first report of a genome-wide analysis of the SAP gene family in M. truncatula.

  17. A novel firefly luciferase biosensor enhances the detection of apoptosis induced by ESAT-6 family proteins of Mycobacterium tuberculosis

    International Nuclear Information System (INIS)

    Shi, Junwei; Zhang, Huan; Fang, Liurong; Xi, Yongqiang; Zhou, Yanrong; Luo, Rui; Wang, Dang; Xiao, Shaobo; Chen, Huanchun

    2014-01-01

    Highlights: • We developed a novel firefly luciferase based biosensor to detect apoptosis. • The novel biosensor 233-DnaE-DEVDG was reliable, sensitive and convenient. • 233-DnaE-DEVDG faithfully indicated ESAT-6 family proteins of Mycobacterium tuberculosis induced apoptosis. • EsxA, esxT and esxL in ESAT-6 family proteins induced apoptosis. • Activation of nuclear factor-κB (NF-κB) participated in esxT-induced apoptosis. - Abstract: The activation of caspase-3 is a key surrogate marker for detecting apoptosis. To quantitate caspase-3 activity, we constructed a biosensor comprising a recombinant firefly luciferase containing a caspase-3 cleavage site. When apoptosis was induced, caspase-3 cleavage of the biosensor activated firefly luciferase by a factor greater than 25. The assay conveniently detected apoptosis in real time, indicating that it will facilitate drug discovery. We screened ESAT-6 family proteins of Mycobacterium tuberculosis and found that esxA, esxT and esxL induced apoptosis. Further, activation of nuclear factor-κB (NF-κB) and the NF-κB-regulated genes encoding tumor necrosis factor-α (TNF-α) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) participated in esxT-induced apoptosis. We conclude that this assay is useful for high-throughput screening to identify and characterize proteins and drugs that regulate apoptosis

  18. A novel firefly luciferase biosensor enhances the detection of apoptosis induced by ESAT-6 family proteins of Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Junwei; Zhang, Huan; Fang, Liurong; Xi, Yongqiang; Zhou, Yanrong; Luo, Rui; Wang, Dang, E-mail: wangdang511@126.com; Xiao, Shaobo; Chen, Huanchun

    2014-10-03

    Highlights: • We developed a novel firefly luciferase based biosensor to detect apoptosis. • The novel biosensor 233-DnaE-DEVDG was reliable, sensitive and convenient. • 233-DnaE-DEVDG faithfully indicated ESAT-6 family proteins of Mycobacterium tuberculosis induced apoptosis. • EsxA, esxT and esxL in ESAT-6 family proteins induced apoptosis. • Activation of nuclear factor-κB (NF-κB) participated in esxT-induced apoptosis. - Abstract: The activation of caspase-3 is a key surrogate marker for detecting apoptosis. To quantitate caspase-3 activity, we constructed a biosensor comprising a recombinant firefly luciferase containing a caspase-3 cleavage site. When apoptosis was induced, caspase-3 cleavage of the biosensor activated firefly luciferase by a factor greater than 25. The assay conveniently detected apoptosis in real time, indicating that it will facilitate drug discovery. We screened ESAT-6 family proteins of Mycobacterium tuberculosis and found that esxA, esxT and esxL induced apoptosis. Further, activation of nuclear factor-κB (NF-κB) and the NF-κB-regulated genes encoding tumor necrosis factor-α (TNF-α) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) participated in esxT-induced apoptosis. We conclude that this assay is useful for high-throughput screening to identify and characterize proteins and drugs that regulate apoptosis.

  19. Variant Exported Blood-Stage Proteins Encoded by Plasmodium Multigene Families Are Expressed in Liver Stages Where They Are Exported into the Parasitophorous Vacuole.

    Directory of Open Access Journals (Sweden)

    Aurélie Fougère

    2016-11-01

    Full Text Available Many variant proteins encoded by Plasmodium-specific multigene families are exported into red blood cells (RBC. P. falciparum-specific variant proteins encoded by the var, stevor and rifin multigene families are exported onto the surface of infected red blood cells (iRBC and mediate interactions between iRBC and host cells resulting in tissue sequestration and rosetting. However, the precise function of most other Plasmodium multigene families encoding exported proteins is unknown. To understand the role of RBC-exported proteins of rodent malaria parasites (RMP we analysed the expression and cellular location by fluorescent-tagging of members of the pir, fam-a and fam-b multigene families. Furthermore, we performed phylogenetic analyses of the fam-a and fam-b multigene families, which indicate that both families have a history of functional differentiation unique to RMP. We demonstrate for all three families that expression of family members in iRBC is not mutually exclusive. Most tagged proteins were transported into the iRBC cytoplasm but not onto the iRBC plasma membrane, indicating that they are unlikely to play a direct role in iRBC-host cell interactions. Unexpectedly, most family members are also expressed during the liver stage, where they are transported into the parasitophorous vacuole. This suggests that these protein families promote parasite development in both the liver and blood, either by supporting parasite development within hepatocytes and erythrocytes and/or by manipulating the host immune response. Indeed, in the case of Fam-A, which have a steroidogenic acute regulatory-related lipid transfer (START domain, we found that several family members can transfer phosphatidylcholine in vitro. These observations indicate that these proteins may transport (host phosphatidylcholine for membrane synthesis. This is the first demonstration of a biological function of any exported variant protein family of rodent malaria parasites.

  20. Fish reproduction

    National Research Council Canada - National Science Library

    Rocha, Maria João; Arukwe, Augustine; Kapoor, B. G

    2008-01-01

    ... of reproductive systems is essential for such studies. Fishes comprise over 28,000 species, with a remarkable variability in morphology, physiology and environmental adaptation. Knowledge on fish reproduction is scattered across numerous sources that shows a dynamic research field. The Editors believe it to be an opportune moment for a...

  1. Identification of two auto-cleavage products of nonstructural protein 1 (nsp1) in porcine reproductive and respiratory syndrome virus infected cells: nsp1 function as interferon antagonist

    International Nuclear Information System (INIS)

    Chen, Z.; Lawson, S.; Sun, Z.; Zhou, X.; Guan, X.; Christopher-Hennings, J.; Nelson, E.A.; Fang, Y.

    2010-01-01

    The porcine reproductive and respiratory syndrome virus nsp1 is predicted to be auto-cleaved from the replicase polyprotein into nsp1α and nsp1β subunits. In infected cells, we detected the actual existence of nsp1α and nsp1β. Cleavage sites between nsp1α/nsp1β and nsp1β/nsp2 were identified by protein microsequencing analysis. Time course study showed that nsp1α and nsp1β mainly localize into the cell nucleus after 10 h post infection. Further analysis revealed that both proteins dramatically inhibited IFN-β expression. The nsp1β was observed to significantly inhibit expression from an interferon-stimulated response element promoter after Sendai virus infection or interferon treatment. It was further determined to inhibit nuclear translocation of STAT1 in the JAK-STAT signaling pathway. These results demonstrated that nsp1β has ability to inhibit both interferon synthesis and signaling, while nsp1α alone strongly inhibits interferon synthesis. These findings provide important insights into mechanisms of nsp1 in PRRSV pathogenesis and its impact in vaccine development.

  2. Characterization of cDNA encoding human placental anticoagulant protein (PP4): Homology with the lipocortin family

    International Nuclear Information System (INIS)

    Grundmann, U.; Abel, K.J.; Bohn, H.; Loebermann, H.; Lottspeich, F.; Kuepper, H.

    1988-01-01

    A cDNA library prepared from human placenta was screened for sequences encoding the placental protein 4 (PP4). PP4 is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. Partial amino acid sequence information from PP4-derived cyanogen bromide fragments was used to design three oligonucleotide probes for screening the library. From 10 6 independent recombinants, 18 clones were identified that hybridized to all three probes. These 18 recombinants contained cDNA inserts encoding a protein of 320 amino acid residues. In addition to the PP4 cDNA the authors identified 9 other recombinants encoding a protein with considerable similarity (74%) to PP4, which was termed PP4-X. PP4 and PP4-X belong to the lipocortin family, as judged by their homology to lipocortin I and calpactin I

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

    Science.gov (United States)

    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

  4. Novel multiplexed assay for identifying SH2 domain antagonists of STAT family proteins.

    Science.gov (United States)

    Takakuma, Kazuyuki; Ogo, Naohisa; Uehara, Yutaka; Takahashi, Susumu; Miyoshi, Nao; Asai, Akira

    2013-01-01

    Some of the signal transducer and activator of transcription (STAT) family members are constitutively activated in a wide variety of human tumors. The activity of STAT depends on their Src homology 2 (SH2) domain-mediated binding to sequences containing phosphorylated tyrosine. Thus, antagonizing this binding is a feasible approach to inhibiting STAT activation. We have developed a novel multiplexed assay for STAT3- and STAT5b-SH2 binding, based on amplified luminescent proximity homogeneous assay (Alpha) technology. AlphaLISA and AlphaScreen beads were combined in a single-well assay, which allowed the binding of STAT3- and STAT5b-SH2 to phosphotyrosine peptides to be simultaneously monitored. Biotin-labeled recombinant human STAT proteins were obtained as N- and C-terminal deletion mutants. The spacer length of the DIG-labeled peptide, the reaction time, and the concentration of sodium chloride were optimized to establish a HTS system with Z' values of greater than 0.6 for both STAT3- and STAT5b-SH2 binding. We performed a HTS campaign for chemical libraries using this multiplexed assay and identified hit compounds. A 2-chloro-1,4-naphthalenedione derivative, Compound 1, preferentially inhibited STAT3-SH2 binding in vitro, and the nuclear translocation of STAT3 in HeLa cells. Initial structure activity relationship (SAR) studies using the multiplexed assay showed the 3-substituent effect on both the activity and selectivity of STAT3 and STAT5b inhibition. Therefore, this multiplexed assay is useful for not only searching for potential lead compounds but also obtaining SAR data for developing new STAT3/STAT5b inhibitors.

  5. A Novel Family of Cell Wall-Related Proteins Regulated Differently during the Yeast Life Cycle

    Science.gov (United States)

    Rodríguez-Peña, José Manuel; Cid, Víctor J.; Arroyo, Javier; Nombela, César

    2000-01-01

    The Saccharomyces cerevisiae Ygr189c, Yel040w, and Ylr213c gene products show significant homologies among themselves and with various bacterial β-glucanases and eukaryotic endotransglycosidases. Deletion of the corresponding genes, either individually or in combination, did not produce a lethal phenotype. However, the removal of YGR189c and YEL040w, but not YLR213c, caused additive sensitivity to compounds that interfere with cell wall construction, such as Congo red and Calcofluor White, and overexpression of YEL040w led to resistance to these compounds. These genes were renamed CRH1 and CRH2, respectively, for Congo red hypersensitive. By site-directed mutagenesis we found that the putative glycosidase domain of CRH1 was critical for its function in complementing hypersensitivity to the inhibitors. The involvement of CRH1 and CRH2 in the development of cell wall architecture was clearly shown, since the alkali-soluble glucan fraction in the crh1Δ crh2Δ strain was almost twice the level in the wild-type. Interestingly, the three genes were subject to different patterns of transcriptional regulation. CRH1 and YLR213c (renamed CRR1, for CRH related) were found to be cell cycle regulated and also expressed under sporulation conditions, whereas CRH2 expression did not vary during the mitotic cycle. Crh1 and Crh2 are localized at the cell surface, particularly in chitin-rich areas. Consistent with the observed expression patterns, Crh1–green fluorescent protein was found at the incipient bud site, around the septum area in later stages of budding, and in ascospore envelopes. Crh2 was found to localize mainly at the bud neck throughout the whole budding cycle, in mating projections and zygotes, but not in ascospores. These data suggest that the members of this family of putative glycosidases might exert a common role in cell wall organization at different stages of the yeast life cycle. PMID:10757808

  6. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

    Energy Technology Data Exchange (ETDEWEB)

    Benny Klimek, Margaret E.; Aydogdu, Tufan [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Link, Majik J.; Pons, Marianne [Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Koniaris, Leonidas G. [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States); Zimmers, Teresa A., E-mail: tzimmers@med.miami.edu [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States)

    2010-01-15

    Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is a devastating complication of cancer associated with poor quality of life and increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We tested how myostatin inhibition might influence cancer cachexia using genetic and pharmacological approaches. First, hypermuscular myostatin null mice were injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice were more sensitive to tumor-induced cachexia, losing more absolute mass and proportionately more muscle mass than wild-type mice. Because myostatin null mice lack expression from development, however, we also sought to manipulate myostatin acutely. The histone deacetylase inhibitor Trichostatin A has been shown to increase muscle mass in normal and dystrophic mice by inducing the myostatin inhibitor, follistatin. Although Trichostatin A administration induced muscle growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia. Finally we sought to inhibit myostatin and related ligands by administration of the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic administration of ACVR2B-Fc potently inhibited muscle wasting and protected adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that host-derived myostatin is not the sole mediator of muscle wasting in cancer. More importantly, skeletal muscle preservation with ACVR2B-Fc establishes that targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an important and potent therapeutic avenue in cancer cachexia.

  7. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

    International Nuclear Information System (INIS)

    Benny Klimek, Margaret E.; Aydogdu, Tufan; Link, Majik J.; Pons, Marianne; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2010-01-01

    Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is a devastating complication of cancer associated with poor quality of life and increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We tested how myostatin inhibition might influence cancer cachexia using genetic and pharmacological approaches. First, hypermuscular myostatin null mice were injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice were more sensitive to tumor-induced cachexia, losing more absolute mass and proportionately more muscle mass than wild-type mice. Because myostatin null mice lack expression from development, however, we also sought to manipulate myostatin acutely. The histone deacetylase inhibitor Trichostatin A has been shown to increase muscle mass in normal and dystrophic mice by inducing the myostatin inhibitor, follistatin. Although Trichostatin A administration induced muscle growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia. Finally we sought to inhibit myostatin and related ligands by administration of the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic administration of ACVR2B-Fc potently inhibited muscle wasting and protected adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that host-derived myostatin is not the sole mediator of muscle wasting in cancer. More importantly, skeletal muscle preservation with ACVR2B-Fc establishes that targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an important and potent therapeutic avenue in cancer cachexia.

  8. [From dualism to multiplicity: seeing BCL-2 family proteins and cell death with new eyes].

    Science.gov (United States)

    Aouacheria, Abdel

    2015-01-01

    The concept of cell death has many links to the concept of death itself, defined as the opposite of life. Achievements obtained through research on apoptosis have apparently allowed us to transcend this Manichean view. Death is no longer outside, but rather inside living systems, as a constitutive force at work within the living matter. Whereas the death of cells can be positive and breed "creation" (e.g. during morphogenesis), its dysregulation can also cause or contribute to fatal diseases including cancer. It is tempting to apply this biological discourse to illuminate the relations between life and death, taken in general terms, but does this generalization actually hold? Is this discourse not essentially a metaphor? If cell death is considered as a vital aspect of various biological processes, then are we not faced with some vitalistic conception of death? Are there one or more meanings to the word "death"? Does the power to self-destruct act in opposition to other key features of living entities, or rather in juxtaposition to them? In this article, we first describe how the field of cell death has been developed on the basis of perceived and built dichotomies, mirroring the original opposition between life and death. We detail the limitations of the current paradigm of apoptosis regulation by BCL-2 family proteins, which nicely illustrate the problem of binary thinking in biology. Last, we try to show a way out of this dualistic matrix, by drawing on the notions of multiplicity, complexity, diversity, evolution and contingency. © Société de Biologie, 2016.

  9. Effects of propylene glycol supplementation on blood indicators of hepatic function, body condition score, milk fat-protein concentration and reproductive performance of dairy cows

    Directory of Open Access Journals (Sweden)

    Silviu Ionuţ Borş

    2014-01-01

    Full Text Available The aim of the present study was to determine the effects of propylene glycol on metabolic variables of hepatic function, body condition score, milk fat-protein concentration and reproductive performance of dairy cows after ending administration. Postparturient dairy cows (n = 200 of Holstein Friesian breed were divided into two groups of 100 individuals. The experimental group received during days 0-7 post partum an oral daily dose of 600 ml of propylene glycol; the control group was without any supplement. The hepatic enzymes, glucose, cholesterol and serum albumin were measured on days 10-15, 45-50 and 70 post partum. Reproduction indicators of dairy cows were calculated from the farm recording data and the milk data record from a regular dairy control (days 10, 20, 30, and 50 post partum. Animals that received propylene glycol in the first 7 days post partum had reduced activities of aspartate transaminase and gamma-glutamyl transferase, elevated cholesterol concentration (P 0.05 and low milk fat percentage (P P 0.05. Our results suggest that some blood indicators of hepatic function, milk fat concentration and calving to first oestrus interval can be improved for 70 days post partum by the use of propylene glycol drenching in the first 7 days post partum. The beneficial effect of this treatment could be evaluated by easily available data, which can be used by practitioners in the field to analyze fertility problems in dairy herds and more exactly to examine whether metabolic stress, among other factors, is involved in the fertility problem.

  10. Reproductive performance and oviductal expression of avidin and avidin-related protein-2 in young and old broiler breeder hens orally exposed to supplementary biotin.

    Science.gov (United States)

    Daryabari, H; Akhlaghi, A; Zamiri, M J; Mianji, G Rahimi; Pirsaraei, Z Ansari; Deldar, H; Eghbalian, A N

    2014-09-01

    Published data on the probable involvement of avidin and avidin-related protein-2 (AVR2) in sustaining sperm viability in sperm storage tubules in 38-wk-old turkeys, and the high affinity of avidin or its analogs to biotin suggest that supplementary biotin may increase oviductal avidin and AVR2 expression, thereby attenuating the adverse effect of aging on hen reproductive performance. Broiler breeder hens (n = 120) were randomly assigned to receive 0 (T0), 0.30 (T1), or 0.45 (T2) mg of biotin/L of drinking water from 30 to 33 (young) and 53 to 56 (old) wk of age, and artificially inseminated to determine their reproductive performance. At the end of each period of biotin administration, 8 hens from each treatment group were killed for RNA extraction from the uterovaginal junction. Egg production was lower in the old hens (44%) compared with the young ones (82%), and biotin supplementation increased egg production only in the latter. Administering supplementary biotin to young hens increased their oviductal expression of AVR2, which was much higher in the old hens (1.0 and 4.6 for young and old groups, respectively). Fertility rate was not different between young and old hens, and was increased (4.4%) at the higher level of biotin supplementation. Hatchability and hatchling quality were not affected by biotin supplementation. Embryonic mortality between 17 to 21 d of incubation was higher in young (5.2%) compared with old (1.4%) birds. Egg fertility rate showed a moderate correlation (P biotin supplementation on AVR2 expression, and the relationship between biotin administration and oviductal expression of avidin and AVR2 was dependent on the hen's age, being higher in the young hens. © 2014 Poultry Science Association Inc.

  11. Identification and characterization of a novel Cut family cDNA that encodes human copper transporter protein CutC

    International Nuclear Information System (INIS)

    Li Jixi; Ji Chaoneng; Chen Jinzhong; Yang Zhenxing; Wang Yijing; Fei, Xiangwei; Zheng Mei; Gu Xing; Wen Ge; Xie Yi; Mao Yumin

    2005-01-01

    Copper is an essential heavy metal trace element that plays important roles in cell physiology. The Cut family was associated with the copper homeostasis and involved in several important metabolisms, such as uptake, storage, delivery, and efflux of copper. In this study, a novel Cut family cDNA was isolated from the human fetal brain library, which encodes a 273 amino acid protein with a molecular mass of about 29.3 kDa and a calculated pI of 8.17. It was named hCutC (human copper transporter protein CutC). The ORF of hCutC gene was cloned into pQE30 vector and expressed in Escherichia coli M15. The secreted hCutC protein was purified to a homogenicity of 95% by using the Ni-NTA affinity chromatography. RT-PCR analysis showed that the hCutC gene expressed extensively in human tissues. Subcellular location analysis of hCutC-EGFP fusion protein revealed that hCutC was distributed to cytoplasm of COS-7 cells, and both cytoplasm and nucleus of AD293 cells. The results suggest that hCutC may be one shuttle protein and play important roles in intracellular copper trafficking

  12. Ultra-High-Throughput Screening of Natural Product Extracts to Identify Proapoptotic Inhibitors of Bcl-2 Family Proteins.

    Science.gov (United States)

    Hassig, Christian A; Zeng, Fu-Yue; Kung, Paul; Kiankarimi, Mehrak; Kim, Sylvia; Diaz, Paul W; Zhai, Dayong; Welsh, Kate; Morshedian, Shana; Su, Ying; O'Keefe, Barry; Newman, David J; Rusman, Yudi; Kaur, Harneet; Salomon, Christine E; Brown, Susan G; Baire, Beeraiah; Michel, Andrew R; Hoye, Thomas R; Francis, Subhashree; Georg, Gunda I; Walters, Michael A; Divlianska, Daniela B; Roth, Gregory P; Wright, Amy E; Reed, John C

    2014-09-01

    Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally relevant PPIs. The screens were conducted in 1536-well format and displayed satisfactory overall HTS statistics, with Z'-factor values ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied, and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source, and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra-high-throughput screening using natural product sources and highlight some of the challenges associated with this approach. © 2014 Society for Laboratory Automation and Screening.

  13. Functional Amyloids in Reproduction.

    Science.gov (United States)

    Hewetson, Aveline; Do, Hoa Quynh; Myers, Caitlyn; Muthusubramanian, Archana; Sutton, Roger Bryan; Wylie, Benjamin J; Cornwall, Gail A

    2017-06-29

    Amyloids are traditionally considered pathological protein aggregates that play causative roles in neurodegenerative disease, diabetes and prionopathies. However, increasing evidence indicates that in many biological systems nonpathological amyloids are formed for functional purposes. In this review, we will specifically describe amyloids that carry out biological roles in sexual reproduction including the processes of gametogenesis, germline specification, sperm maturation and fertilization. Several of these functional amyloids are evolutionarily conserved across several taxa, including human, emphasizing the critical role amyloids perform in reproduction. Evidence will also be presented suggesting that, if altered, some functional amyloids may become pathological.

  14. Effect of Piper betel leaf stalk extract on protein metabolism in reproductive tissues of male albino rats

    OpenAIRE

    V Vengaiah; A Govardhan Naik; C Changamma

    2015-01-01

    Objective: To know the impact of Piper betel leaf stalk (P. betel) extract on Protein and energy metabolism and its role in male albino rats. Methods: Healthy adult (3-4 months old) male Wistar strain albino rats were administered with betel leaf stalk extract, at the dose of 50 mg/kg/day through oral gavages for 15 days. Twenty four hours after the last dose, the animals were autopsied. In order to assess antifertility effect in testis, epididymis, seminal vesicle and prostate gland, esti...

  15. [The selective participation of brain-specific non-histone proteins of chromatin Np-3,5 during the reproduction of a defensive habit to food in edible snails].

    Science.gov (United States)

    Kozyrev, S A; Nikitin, V P; Sherstnev, V V

    1991-01-01

    The role of brain-specific nonhistone proteins of chromatine Np-3.5 in the processes of reproduction of elaborated defensive habit to food was studied in previously learning snails. It was found, that gamma-globulines to Np-3.5 during tens of minutes inhibited behavioural and neuronal reactions elicited by a definite conditioned stimulus--carrot juice, without changing reactions to other conditioned stimulus--apple juice. gamma-globulines to other nonhistone proteins of chromatine did not influence the reproduction of food rejection habits. It was supposed that brain-specific nonhistone proteins of chromatine Np-3.5 were selectively involved in the molecular processes providing for neurophysiological mechanisms of information extraction from the long-term memory.

  16. The effect of dietary protein on reproduction in the mare. I. The composition and evaluation of the digestibility of dietary protein from different sources

    Directory of Open Access Journals (Sweden)

    F.E. Van Niekerk

    1997-07-01

    Full Text Available Four rations that differed in their crude protein and essential amino-acid content were compiled. Digestibility of the crude protein and essential amino-acid contents were determined biologically in a feeding trial using 4 Anglo-Arab stallions. Their respective daily diets were: Diet 1: 2 kg cubes, 5 kg tef hay (Eragrostis tef; Diet 2: 2 kg cubes, 5 kg lucerne hay (Medicago sativa; Diet 3: 2 kg cubes, 5 kg tef hay, 200 g fishmeal; Diet 4: 2 kg cubes, 5 kg lucerne hay, 200 g fishmeal. The concentrations of the amino-acids threonine, iso-leucine, leucine and arginine were increased in the total ration when lucerne hay replaced the tef hay while fishmeal supplementation increased the methionine and lysine contents, which provided a wide range of concentrations of digestible amino-acids in each of the 4 rations.

  17. Purification of family B G protein-coupled receptors using nanodiscs: Application to human glucagon-like peptide-1 receptor.

    Directory of Open Access Journals (Sweden)

    Yingying Cai

    Full Text Available Family B G protein-coupled receptors (GPCRs play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1 receptor (GLP1R, whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms.

  18. Purification of family B G protein-coupled receptors using nanodiscs: Application to human glucagon-like peptide-1 receptor.

    Science.gov (United States)

    Cai, Yingying; Liu, Yuting; Culhane, Kelly J; DeVree, Brian T; Yang, Yang; Sunahara, Roger K; Yan, Elsa C Y

    2017-01-01

    Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL) particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms.

  19. Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Jane; Hall, William W. [Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); Ratner, Lee [Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, United States of America (United States); Sheehy, Noreen [Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland)

    2016-07-15

    The human T-cell leukaemia virus type 1 and type 2 (HTLV-1/HTLV-2) antisense proteins HBZ and APH-2 play key roles in the HTLV lifecycles and persistence in the host. Nuclear Factors Associated with double-stranded RNA (NFAR) proteins NF90/110 function in the lifecycles of several viruses and participate in host innate immunity against infection and oncogenesis. Using GST pulldown and co-immunoprecipitation assays we demonstrate specific novel interactions between HBZ/APH-2 and NF90/110 and characterised the protein domains involved. Moreover we show that NF90/110 significantly enhance Tax mediated LTR activation, an effect that was abolished by HBZ but enhanced by APH-2. Additionally we found that HBZ and APH-2 modulate the promoter activity of survivin and are capable of antagonising NF110-mediated survivin activation. Thus interactions between HTLV antisense proteins and the NFAR protein family have an overall positive impact on HTLV infection. Hence NFARs may represent potential therapeutic targets in HTLV infected cells. - Highlights: • This study demonstrates for the first time interactions between NF90/110 and the HTLV antisense proteins HBZ and APH-2. • We show that NF90/110 significantly enhance LTR activation by the HTLV Tax protein, an effect that is abolished by HBZ but enhanced by APH-2. • The study shows that even though the HTLV antisense proteins activate survivin expression they antagonize the ability of NF90/110 to do so. • Overall we found that NF90/110 positively regulate HTLV infection and as such might represent a therapeutic target in infected cells.

  20. Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

    International Nuclear Information System (INIS)

    Murphy, Jane; Hall, William W.; Ratner, Lee; Sheehy, Noreen

    2016-01-01

    The human T-cell leukaemia virus type 1 and type 2 (HTLV-1/HTLV-2) antisense proteins HBZ and APH-2 play key roles in the HTLV lifecycles and persistence in the host. Nuclear Factors Associated with double-stranded RNA (NFAR) proteins NF90/110 function in the lifecycles of several viruses and participate in host innate immunity against infection and oncogenesis. Using GST pulldown and co-immunoprecipitation assays we demonstrate specific novel interactions between HBZ/APH-2 and NF90/110 and characterised the protein domains involved. Moreover we show that NF90/110 significantly enhance Tax mediated LTR activation, an effect that was abolished by HBZ but enhanced by APH-2. Additionally we found that HBZ and APH-2 modulate the promoter activity of survivin and are capable of antagonising NF110-mediated survivin activation. Thus interactions between HTLV antisense proteins and the NFAR protein family have an overall positive impact on HTLV infection. Hence NFARs may represent potential therapeutic targets in HTLV infected cells. - Highlights: • This study demonstrates for the first time interactions between NF90/110 and the HTLV antisense proteins HBZ and APH-2. • We show that NF90/110 significantly enhance LTR activation by the HTLV Tax protein, an effect that is abolished by HBZ but enhanced by APH-2. • The study shows that even though the HTLV antisense proteins activate survivin expression they antagonize the ability of NF90/110 to do so. • Overall we found that NF90/110 positively regulate HTLV infection and as such might represent a therapeutic target in infected cells.

  1. SVM-Prot 2016: A Web-Server for Machine Learning Prediction of Protein Functional Families from Sequence Irrespective of Similarity.

    Science.gov (United States)

    Li, Ying Hong; Xu, Jing Yu; Tao, Lin; Li, Xiao Feng; Li, Shuang; Zeng, Xian; Chen, Shang Ying; Zhang, Peng; Qin, Chu; Zhang, Cheng; Chen, Zhe; Zhu, Feng; Chen, Yu Zong

    2016-01-01

    Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at http://bidd2.nus.edu.sg/cgi-bin/svmprot/svmprot.cgi.

  2. Comparative Community Proteomics Demonstrates the Unexpected Importance of Actinobacterial Glycoside Hydrolase Family 12 Protein for Crystalline Cellulose Hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Hiras, Jennifer; Wu, Yu-Wei; Deng, Kai; Nicora, Carrie D.; Aldrich, Joshua T.; Frey, Dario; Kolinko, Sebastian; Robinson, Errol W.; Jacobs, Jon M.; Adams, Paul D.; Northen, Trent R.; Simmons, Blake A.; Singer, Steven W.

    2016-08-23

    ABSTRACT

    Glycoside hydrolases (GHs) are key enzymes in the depolymerization of plant-derived cellulose, a process central to the global carbon cycle and the conversion of plant biomass to fuels and chemicals. A limited number of GH families hydrolyze crystalline cellulose, often by a processive mechanism along the cellulose chain. During cultivation of thermophilic cellulolytic microbial communities, substantial differences were observed in the crystalline cellulose saccharification activities of supernatants recovered from divergent lineages. Comparative community proteomics identifie