WorldWideScience

Sample records for superfamily hominoidea homo

  1. Comparative analyses of quaternary arrangements in homo-oligomeric proteins in superfamilies: Functional implications.

    Science.gov (United States)

    Sudha, Govindarajan; Srinivasan, Narayanaswamy

    2016-09-01

    A comprehensive analysis of the quaternary features of distantly related homo-oligomeric proteins is the focus of the current study. This study has been performed at the levels of quaternary state, symmetry, and quaternary structure. Quaternary state and quaternary structure refers to the number of subunits and spatial arrangements of subunits, respectively. Using a large dataset of available 3D structures of biologically relevant assemblies, we show that only 53% of the distantly related homo-oligomeric proteins have the same quaternary state. Considering these homologous homo-oligomers with the same quaternary state, conservation of quaternary structures is observed only in 38% of the pairs. In 36% of the pairs of distantly related homo-oligomers with different quaternary states the larger assembly in a pair shows high structural similarity with the entire quaternary structure of the related protein with lower quaternary state and it is referred as "Russian doll effect." The differences in quaternary state and structure have been suggested to contribute to the functional diversity. Detailed investigations show that even though the gross functions of many distantly related homo-oligomers are the same, finer level differences in molecular functions are manifested by differences in quaternary states and structures. Comparison of structures of biological assemblies in distantly and closely related homo-oligomeric proteins throughout the study differentiates the effects of sequence divergence on the quaternary structures and function. Knowledge inferred from this study can provide insights for improved protein structure classification and function prediction of homo-oligomers. Proteins 2016; 84:1190-1202. © 2016 Wiley Periodicals, Inc.

  2. Genomas y cromosomas: estudio evolutivo de Hominoidea y Ceboidea

    OpenAIRE

    Nieves, Mariela; Mudry, Marta Dolores

    2009-01-01

    Los Primates comprenden dos grandes grupos: Prosimii y Antropoidea al que pertenecen los simios, los grandes monos y el hombre. Los antropoideos reúnen a los Monos del Viejo Mundo o Catarrhini y a los Primates del Nuevo Mundo o Platyrrhini, también conocidos como Ceboidea. Los primeros comprenden las familias Cercopithecoidea y Hominoidea (chimpancé, orangután, gorila y los humanos). En la actualidad se dispone de una vasta fuente de datos que permiten relacionar estas familias, ya sea desde ...

  3. Cystatin superfamily.

    Science.gov (United States)

    Ochieng, Josiah; Chaudhuri, Gautam

    2010-02-01

    Cystatins, the classical inhibitors of C1 cysteine proteinases, have been extensively studied and reviewed in the literature. Over the last 20 years, however, proteins containing cystatin domains but lacking protease inhibitory activities have been identified, and most likely more will be described in the near future. These proteins together with family 1, 2, and 3 cystatins constitute the cystatin superfamily. Mounting evidence points to the new roles that some members of the superfamily have acquired over the course of their evolution. This review is focused on the roles of cystatins in: 1) tumorigenesis, 2) stabilization of matrix metalloproteinases, 3) glomerular filtration rate, 4) immunomodulation, and 5) neurodegenerative diseases. It is the goal of this review to get as many investigators as possible to take a second look at the cystatin superfamily regarding their potential involvement in serious human ailments.

  4. Homo Iconicus

    Directory of Open Access Journals (Sweden)

    Francisco García García

    2012-04-01

    Full Text Available Lo icónico se ha revelado como la última opción conceptual con la que definir al hombre: Homo icónicus.  Icónico en varios sentidos: en cuanto que el hombre es un creador de imágenes, y en cuanto que es imagen. Por encima de cualquier otra creación material, instrumental, cultural, la mayor obra creativa del hombre es su recreación, la generación de una imagen de sí. Todas las características del hombre como animal humano construyen el homo icónicus: cuando el hombre se construye como imagen, realiza un movimiento, un gran desplazamiento, al menos simbólico, de sí mismo a su representación, pero cuando se representa o representa el mundo, crea imágenes, en definitiva, habla, se expresa, se relaciona con los otros. 

  5. Homo capax

    Directory of Open Access Journals (Sweden)

    Patricio Mena Malet

    2011-01-01

    Full Text Available El presente ensayo intenta reflexionar sobre algunas características estructurales del homo capax tal como ha sido pensado por Ricoeur de modo explícito a partir de su obra de 1990, Soimême comme un autre. Así, lo que interrogaremos no son las capacidades que Ricoeur analiza a partir de 1990, poder actuar, decir, narrar y narrarse, y considerarse imputable de las consecuencias de sus acciones, sino el ser capaz mismo. ¿Qué significa ser capaz? ¿Se trata como lo afirma el propio Ricoeur de un carácter esencial de la humanidad del hombre? ¿Es un a priori por tanto? La tesis que quisiéramos defender son, primero que el trasfondo de la capacidad es su ser en relación y la pasibilidad, y segundo que solo en el encuentro con lo otro el ser capaz estiliza sus poderes con los que se abrirá al mundo.This essay aims to reflect on some structural characteristics of the homo capax as it has been explicitly conceived by Ricoeur since his 1990 work, Soimême comme un autre. What we examine are not the capabilities that Ricoeur analyzes starting in 1990, to be able to act, speak, narrate, and be narrated, and to be regarded as attributable to the consequences of one's actions, but rather the capable human being itself. What does it mean to be capable? Is it, as Ricoeur himself says, part of the essential nature of man's humanity? Is it therefore a priori? The thesis that we would like to defend is that, first, the background of capability is man's being in relation and passibility, and second, only in encounters with the other does the capable human being stylize the powers with which it opens the world.

  6. The Homo floresiensis Controversy

    Directory of Open Access Journals (Sweden)

    COLIN GROVES

    2007-12-01

    Full Text Available A completely new and unexpected quasi human species, Homo floresiensis, nicknamed the Hobbit, was described in 2004 from Liang Bua, a cave in Flores. Like many important new contributions to the human fossil record in the past, many commentators refused to believe that a new species had been discovered, and the type specimen was interpreted as a pathological modern human, usually as a microcephalic dwarf. There is no substance to these claims: close analysis shows that Homo floresiensis is not only a genuinely new species, but that its closest affinities lie with Plio-Pleistocene African species such as Homo habilis, so that it documents an earlier dispersal of hominins from Africa and had hitherto been suspected.

  7. Homo economicus belief inhibits trust.

    Directory of Open Access Journals (Sweden)

    Ziqiang Xin

    Full Text Available As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  8. Homo economicus belief inhibits trust.

    Science.gov (United States)

    Xin, Ziqiang; Liu, Guofang

    2013-01-01

    As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  9. Evolution of the Genus Homo

    Science.gov (United States)

    Tattersall, Ian; Schwartz, Jeffrey H.

    2009-05-01

    Definition of the genus Homo is almost as fraught as the definition of Homo sapiens. We look at the evidence for “early Homo,” finding little morphological basis for extending our genus to any of the 2.5-1.6-myr-old fossil forms assigned to “early Homo” or Homo habilis/rudolfensis. We also point to heterogeneity among “early African Homo erectus,” and the lack of apomorphies linking these fossils to the Asian Homo erectus group, a cohesive regional clade that shows some internal variation, including brain size increase over time. The first truly cosmopolitan Homo species is Homo heidelbergensis, known from Africa, Europe, and China following 600 kyr ago. One species sympatric with it included the >500-kyr-old Sima de los Huesos fossils from Spain, clearly distinct from Homo heidelbergensis and the oldest hominids assignable to the clade additionally containing Homo neanderthalensis. This clade also shows evidence of brain size expansion with time; but although Homo neanderthalensis had a large brain, it left no unequivocal evidence of the symbolic consciousness that makes our species unique. Homo sapiens clearly originated in Africa, where it existed as a physical entity before it began (also in that continent) to show the first stirrings of symbolism. Most likely, the biological underpinnings of symbolic consciousness were exaptively acquired in the radical developmental reorganization that gave rise to the highly characteristic osteological structure of Homo sapiens, but lay fallow for tens of thousands of years before being “discovered” by a cultural stimulus, plausibly the invention of language.

  10. Governing homo economicus

    DEFF Research Database (Denmark)

    Pultz, Sabina

    2016-01-01

    In this article, I examine how young unemployed people deal with the risk of unemployment in the Danish welfare state, focusing on two main issues. I examine the technologies currently being used in the unemployment system to manage youth unemployment and I explore how the young unemployed people...... unemployment fund operated and I used in-depth interviews to explore the ways in which 33 young unemployed Danes interacted with the unemployment fund. Using the conceptual tools provided by the governmentality risk perspective, I analysed the relationship between institutionalised risk management...... unemployment system, young unemployed people were treated not only as homo economicus, that is, rational actors responding to economic incentives but they were also seen as sensitive beings whose feelings and affects could be shaped by technologies empowering and motivating them in order to enable them...

  11. Homo Oeconomicus and Behavioral Economics

    Directory of Open Access Journals (Sweden)

    Justyna Brzezicka

    2014-12-01

    Full Text Available Recent years have witnessed a growing interest in behavioral trends in both economic theory and practical applications. As a science with vast potential for explaining complex market behaviors, behavioral economics is drifting away from the classical model of homo oeconomicus deployed by mainstream economics. This paper discusses the significance and role of the homo oeconomicus model in light of behavioral economics. It analyzes the direction of changes affecting homo oeconomicus, examines the definition of anomalies within the context of behavioral economics and discusses the anomalous status of homo oeconomicus. The paper proposes a hypothesis that the attitude characterizing homo oeconomicus is unique and incidental. The presented interdisciplinary analysis relies on economics, behavioral economics, economic psychology, behavioral finance and the methodology of science to discuss the homo oeconomicus model. The paper reviews change trends in economics, which are largely propelled by advancements in behavioral economics. The key methodological tools deployed in this paper are theoretical analysis and a compilation of extensive research findings. The results were used to formulate new theories advocating the development of a modern approach to the homo oeconomicus model, recognizing its significance and the growing importance of behavioral economics.

  12. In search of Homo economicus.

    Science.gov (United States)

    Yamagishi, Toshio; Li, Yang; Takagishi, Haruto; Matsumoto, Yoshie; Kiyonari, Toko

    2014-09-01

    Homo economicus, a model for humans in neoclassical economics, is a rational maximizer of self-interest. However, many social scientists regard such a person as a mere imaginary creature. We found that 31 of 446 residents of relatively wealthy Tokyo suburbs met the behavioral definition of Homo economicus. In several rounds of economic games, participants whose behavior was consistent with this model always apportioned the money endowed by the experimenter to themselves, leaving no share for their partners. These participants had high IQs and a deliberative decision style. An additional 39 participants showed a similar disregard for other people's welfare, although they were slightly more altruistic than those in the Homo economicus group. The psychological composition of these quasi-Homo economicus participants was distinct from that of participants in the Homo economicus group. Although participants in the latter group behaved selfishly on the basis of rational calculations, those in the former group made selfish choices impulsively. The implications of these findings concerning the two types of extreme noncooperators are discussed.

  13. The Emergence of Homo sapiens.

    Science.gov (United States)

    Rensberger, Boyce

    1980-01-01

    Describes chronologically the evolution of the human race on earth so as to refute Darwin's theory of descent from animals. Skull fragments from sites around the world suggest at least two possible routes toward the emergence of Homo sapiens sapiens. (Author/SK)

  14. Superfamilies of Evolved and Designed Networks

    Science.gov (United States)

    Milo, Ron; Itzkovitz, Shalev; Kashtan, Nadav; Levitt, Reuven; Shen-Orr, Shai; Ayzenshtat, Inbal; Sheffer, Michal; Alon, Uri

    2004-03-01

    Complex biological, technological, and sociological networks can be of very different sizes and connectivities, making it difficult to compare their structures. Here we present an approach to systematically study similarity in the local structure of networks, based on the significance profile (SP) of small subgraphs in the network compared to randomized networks. We find several superfamilies of previously unrelated networks with very similar SPs. One superfamily, including transcription networks of microorganisms, represents ``rate-limited'' information-processing networks strongly constrained by the response time of their components. A distinct superfamily includes protein signaling, developmental genetic networks, and neuronal wiring. Additional superfamilies include power grids, protein-structure networks and geometric networks, World Wide Web links and social networks, and word-adjacency networks from different languages.

  15. Análisis del error de medición y variabilidad interespecífica morfométrica de Fourier en M2 de primates Hominoidea

    OpenAIRE

    Gamarra Rubio, Beatriz; Romero, A.; Martínez Pérez-Pérez, Alejandro; Galbany i Casals, Jordi

    2011-01-01

    Los análisis de Fourier permiten caracterizar el contorno del diente y obtener una serie de parámetros para un posterior análisis multivariante. Sin embargo, la gran complejidad que presentan algunas formas obliga a determinar el error de medición intrínseco que se produce. El objetivo de este trabajo es aplicar y validar los análisis de Fourier en el estudio de la forma dental del segundo molar inferior (M2) de cuatro especies de primates Hominoidea para explorar la variabilidad morfométrica...

  16. The evolution of homo touristicus

    Directory of Open Access Journals (Sweden)

    Duccio Canestrini

    2016-09-01

    Full Text Available This article looks at the evolution of homo touristicus, a concept that originally referred to a person with a decent level of income who travelled for pleasure for short periods of time, taking advantage of the geoeconomic disparity between their habitual residence and the destinations chosen. This category has grown to include new sub-species and varieties that take in a wide range of forms and motivations and goes far beyond the old ways of being a tourist. These days, tourism is constructed according to new tastes and new technologies; it seems genetically modified and as such it promotes itself and consumes. Although there is still a generic demand for escape, the settings have changed. This paper sets out some of these changes, goes on to note the particular obsession with the safety of the tourist and, finally, appeals for a harmonious development of tourist activity.

  17. Homo economicus: van positief naar normatief

    NARCIS (Netherlands)

    Grol, R.F.; Sent, E.-M.

    2016-01-01

    Homo economicus werd in de interpretatie van neoklassieke economen zoals Milton Friedman als basis voor ‘positieve’ voorspellingen gepositioneerd. Dat zijn voorspellingen over wat is. Gedragseconomen zoals Amos Tversky en Daniel Kahneman zetten de homo economicus juist weg als zijnde ‘normatief’. Da

  18. Caracterización morfólogica del M2 de primates Hominoidea a partir de análisis de Fourier

    Directory of Open Access Journals (Sweden)

    Galbany, Jordi

    2011-01-01

    Full Text Available Los análisis de Fourier permiten caracterizar el contorno del diente a partir de un número determinado de puntos y extraer una serie de parámetros para un posterior análisis multivariante. No obstante, la gran complejidad que presentan algunas conformaciones obliga a comprobar cuántos puntos son necesarios para una correcta representación de ésta. El objetivo de este trabajo es aplicar y validar los análisis de Fourier (Polar y Elíptico en el estudio de la forma dental a partir de diferentes puntos de contorno y explorar la variabilidad morfométrica en diferentes géneros. Se obtuvieron fotografías digitales de la superficie oclusal en segundos molares inferiores (M2s de 4 especies de Primates (Hylobates moloch, Gorilla beringei graueri, Pongo pygmaeus pygmaeus y Pan troglodytes schweirfurthii y se definió su contorno con 30, 40, 60, 80, 100 y 120 puntos y su representación formal a 10 armónicos. El análisis de la variabilidad morfométrica se analizó mediante la aplicación de Análisis Discriminantes y un NP-MANOVA a partir de matrices de distancias para determinar la variabilidad y porcentajes de clasificación correcta a nivel metodológico y taxonómico. Los resultados indicaron que los análisis de forma con series de Fourier permiten analizar la variabilidad morfométrica de M2s en géneros de Hominoidea, con independencia del número de puntos de contorno (30 a 120. Los porcentajes de clasificación son más variables e inferiores con el uso de la serie Polar (≈60-90 que con la Elíptica (75-100%. Un número entre 60-100 puntos de contorno mediante el método elíptico garantiza una descripción correcta de la forma del diente.

  19. Independent evolution of four heme peroxidase superfamilies.

    Science.gov (United States)

    Zámocký, Marcel; Hofbauer, Stefan; Schaffner, Irene; Gasselhuber, Bernhard; Nicolussi, Andrea; Soudi, Monika; Pirker, Katharina F; Furtmüller, Paul G; Obinger, Christian

    2015-05-15

    Four heme peroxidase superfamilies (peroxidase-catalase, peroxidase-cyclooxygenase, peroxidase-chlorite dismutase and peroxidase-peroxygenase superfamily) arose independently during evolution, which differ in overall fold, active site architecture and enzymatic activities. The redox cofactor is heme b or posttranslationally modified heme that is ligated by either histidine or cysteine. Heme peroxidases are found in all kingdoms of life and typically catalyze the one- and two-electron oxidation of a myriad of organic and inorganic substrates. In addition to this peroxidatic activity distinct (sub)families show pronounced catalase, cyclooxygenase, chlorite dismutase or peroxygenase activities. Here we describe the phylogeny of these four superfamilies and present the most important sequence signatures and active site architectures. The classification of families is described as well as important turning points in evolution. We show that at least three heme peroxidase superfamilies have ancient prokaryotic roots with several alternative ways of divergent evolution. In later evolutionary steps, they almost always produced highly evolved and specialized clades of peroxidases in eukaryotic kingdoms with a significant portion of such genes involved in coding various fusion proteins with novel physiological functions.

  20. The aldo-keto reductase superfamily homepage.

    Science.gov (United States)

    Hyndman, David; Bauman, David R; Heredia, Vladi V; Penning, Trevor M

    2003-02-01

    The aldo-keto reductases (AKRs) are one of the three enzyme superfamilies that perform oxidoreduction on a wide variety of natural and foreign substrates. A systematic nomenclature for the AKR superfamily was adopted in 1996 and was updated in September 2000 (visit www.med.upenn.edu/akr). Investigators have been diligent in submitting sequences of functional proteins to the Web site. With the new additions, the superfamily contains 114 proteins expressed in prokaryotes and eukaryotes that are distributed over 14 families (AKR1-AKR14). The AKR1 family contains the aldose reductases, the aldehyde reductases, the hydroxysteroid dehydrogenases and steroid 5beta-reductases, and is the largest. Other families of interest include AKR6, which includes potassium channel beta-subunits, and AKR7 the aflatoxin aldehyde reductases. Two new families include AKR13 (yeast aldose reductase) and AKR14 (Escherichia coli aldehyde reductase). Crystal structures of many AKRs and their complexes with ligands are available in the PDB and accessible through the Web site. Each structure has the characteristic (alpha/beta)(8)-barrel motif of the superfamily, a conserved cofactor binding site and a catalytic tetrad, and variable loop structures that define substrate specificity. Although the majority of AKRs are monomeric proteins of about 320 amino acids in length, the AKR2, AKR6 and AKR7 family may form multimers. To expand the nomenclature to accommodate multimers, we recommend that the composition and stoichiometry be listed. For example, AKR7A1:AKR7A4 (1:3) would designate a tetramer of the composition indicated. The current nomenclature is recognized by the Human Genome Project (HUGO) and the Web site provides a link to genomic information including chromosomal localization, gene boundaries, human ESTs and SNPs and much more.

  1. Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa.

    Science.gov (United States)

    Berger, Lee R; Hawks, John; de Ruiter, Darryl J; Churchill, Steven E; Schmid, Peter; Delezene, Lucas K; Kivell, Tracy L; Garvin, Heather M; Williams, Scott A; DeSilva, Jeremy M; Skinner, Matthew M; Musiba, Charles M; Cameron, Noel; Holliday, Trenton W; Harcourt-Smith, William; Ackermann, Rebecca R; Bastir, Markus; Bogin, Barry; Bolter, Debra; Brophy, Juliet; Cofran, Zachary D; Congdon, Kimberly A; Deane, Andrew S; Dembo, Mana; Drapeau, Michelle; Elliott, Marina C; Feuerriegel, Elen M; Garcia-Martinez, Daniel; Green, David J; Gurtov, Alia; Irish, Joel D; Kruger, Ashley; Laird, Myra F; Marchi, Damiano; Meyer, Marc R; Nalla, Shahed; Negash, Enquye W; Orr, Caley M; Radovcic, Davorka; Schroeder, Lauren; Scott, Jill E; Throckmorton, Zachary; Tocheri, Matthew W; VanSickle, Caroline; Walker, Christopher S; Wei, Pianpian; Zipfel, Bernhard

    2015-09-10

    Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa.

  2. Designer TGFβ superfamily ligands with diversified functionality.

    Directory of Open Access Journals (Sweden)

    George P Allendorph

    Full Text Available Transforming Growth Factor--beta (TGFβ superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs, and Bone Morphogenetic Proteins (BMPs, are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer, to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.

  3. Homo homini : [luuletused] / Valeria Ränik

    Index Scriptorium Estoniae

    Ränik, Valeria, 1964-

    2004-01-01

    Sisu: Homo homini ; "Tegelikult on täiuslik kõik..." ; Mõned kõned ; "Vihmadest lekib lagi..." ; "Sündisid siia, et maksta maksu..." ; "Mingis kohas, mingil ajal..." ; "Emajõgi, Amme jõgi..." ; Kaktus ; Eraelamus ; "Minevikule vesi peale..."

  4. Ennäe homo / Feliks Krapp

    Index Scriptorium Estoniae

    Krapp, Feliks

    1999-01-01

    Elisabeth Ohlsoni fotonäitus "Ecce homo" Pärnu Uue Kunsti Muuseumis 14. VII-22. VIII. E. Ohlsoni sõnum: Kristus armastab kõiki ning on olemas ka seksuaalvähemuste jaoks, vaid ühiskond pole seda alati.

  5. Homo homini : [luuletused] / Valeria Ränik

    Index Scriptorium Estoniae

    Ränik, Valeria, 1964-

    2004-01-01

    Sisu: Homo homini ; "Tegelikult on täiuslik kõik..." ; Mõned kõned ; "Vihmadest lekib lagi..." ; "Sündisid siia, et maksta maksu..." ; "Mingis kohas, mingil ajal..." ; "Emajõgi, Amme jõgi..." ; Kaktus ; Eraelamus ; "Minevikule vesi peale..."

  6. Ennäe homo / Feliks Krapp

    Index Scriptorium Estoniae

    Krapp, Feliks

    1999-01-01

    Elisabeth Ohlsoni fotonäitus "Ecce homo" Pärnu Uue Kunsti Muuseumis 14. VII-22. VIII. E. Ohlsoni sõnum: Kristus armastab kõiki ning on olemas ka seksuaalvähemuste jaoks, vaid ühiskond pole seda alati.

  7. Identification, immunolocalization, and characterization analyses of an exopeptidase of papain superfamily, (cathepsin C) from Clonorchis sinensis.

    Science.gov (United States)

    Liang, Pei; He, Lei; Xu, Yanquan; Chen, Xueqing; Huang, Yan; Ren, Mengyu; Liang, Chi; Li, Xuerong; Xu, Jin; Lu, Gang; Yu, Xinbing

    2014-10-01

    Cathepsin C is an important exopeptidase of papain superfamily and plays a number of great important roles during the parasitic life cycle. The amino acid sequence of cathepsin C from Clonorchis sinensis (C. sinensis) showed 54, 53, and 49% identities to that of Schistosoma japonicum, Schistosoma mansoni, and Homo sapiens, respectively. Phylogenetic analysis utilizing the sequences of papain superfamily of C. sinensis demonstrated that cathepsin C and cathepsin Bs came from a common ancestry. Cathepsin C of C. sinensis (Cscathepsin C) was identified as an excretory/secretory product by Western blot analysis. The results of transcriptional level and translational level of Cscathepsin C at metacercaria stage were higher than that at adult worms. Immunolocalization analysis indicated that Cscathepsin C was specifically distributed in the suckers (oral sucker and ventral sucker), eggs, vitellarium, intestines, and testis of adult worms. In the metacercaria, it was mainly detected on the cyst wall and excretory bladder. Combining with the results mentioned above, it implies that Cscathepsin C may be an essential proteolytic enzyme for proteins digestion of hosts, nutrition assimilation, and immune invasion of C. sinensis. Furthermore, it may be a potential diagnostic antigen and drug target against C. sinensis infection.

  8. The Homo Floresiensis Cranium (LB1): Size, Scaling, and Early Homo Affinities

    National Research Council Canada - National Science Library

    Adam D. Gordon; Lisa Nevell; Bernard Wood

    2008-01-01

    The skeletal remains of a diminutive small-brained hominin found in Late Pleistocene cave deposits on the island of Flores, Indonesia were assigned to a new species, Homo floresiensis [Brown P, et al. (2004...

  9. Homo oeconomicus vs. homo academicus - challenges and dilemmas in a globalized world

    OpenAIRE

    Hălăngescu, Constantin I.

    2011-01-01

    Structured as an essay, this workpaper aims to present sui generis one point of view on the relationship between two models of the social-human typology in the context of globalization: homo oeconomicus and homo academicus. Being only a starting point for futher research into a tripartite structure, the paper preliminary presents views on views of MAN’s multivalent positions between vocation and the adaptation to globalization flows, the dilemmas and paradoxes between the oeconomicus and acad...

  10. HOMO OECONOMICUS și HOMO ACADEMICUS: limite și aspecte conceptuale

    OpenAIRE

    Hălăngescu, Constantin I.

    2012-01-01

    The subject of this paper consist in theoretical study on the relationship between two models of the social-human typology in the context of globalization: homo oeconomicus and homo academicus. Reviewing some of the most approved views on theoretical and conceptual aspects and limits of the two human types presented are not exhaustive and is a starting point for further research that can asnswe to questions like: How far can go the convergence between academics and economics? There are constr...

  11. Bioinformatics of the TULIP domain superfamily.

    Science.gov (United States)

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

    2011-08-01

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

  12. Ecospaces occupied by Homo erectus and Homo sapiens in insular Southeast Asia in the Pleistocene

    Science.gov (United States)

    Hertler, Christine; Haupt, Susanne; Volmer, Rebekka; Bruch, Angela

    2014-05-01

    Hominins migrated to the islands of the Sunda Shelf multiple times. At least two immigration events are evident, an early immigration of Homo erectus in the late Early Pleistocene and a second immigration of Homo sapiens during the Late Pleistocene. Regional environments changed considerably in the Pleistocene. Expansion patterns among hominins are at least co-determined by their ecologies and environmental change. We examine these expansion patterns on the basis of habitat reconstructions. Mammalian communities provide a geographically extensive record and permit to assess hominin ecospaces. Although chronological resolution is low, they represent the most complete record of habitat changes associated with hominin expansion patterns. In order to reconstruct and compare hominin ecospaces on a quantitative scale, we set up a reference sample consisting of mammalian communities of 117 national parks in South Asia and Sub-Saharan Africa. The diversity of such communities is assessed by ecological profiling of specialized herbivore taxa. Moreover, datasets on climate and vegetation correlate with the diversity structure of such specialized herbivore communities. Reconstructing the diversity structure of communities at key sites in Pleistocene Southeast Asia permits to infer features of the climatic and vegetation framework associated with different hominin taxa. Our results show that Homo erectus and Homo sapiens did not occupy similar ecospaces. The ecospace of Homo erectus is characterized by comparatively low diversity among frugivorous and folivorous taxa, while obligate grazers are part of the assemblages. Specialized herbivore communities with such a diversity structure occur at present in East Africa, while they are absent in Southeast Asia. In the reference sample, this type of ecospace corresponds to seasonal wetlands. Although Homo sapiens still inhabits this type of environment in Southeast Asia, his ecospace is wider. Homo sapiens is associated with

  13. From Homo Abilis to Homo Rationalis through Analytic Perception and Mathematics

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    Domenico Lenzi

    2017-02-01

    Full Text Available Starting from the stage of “Homo habilis” man has gained - in the course  of about two million years during which he has undergone a gradual evolution from the initial animal stage - its status as “Homo rationalis”. However, not all individuals are able to satisfactorily activate the skill of reasoning. It is undeniable that a fundamental step towards this activation is the development of mathematical skills, which are a common heritage of all human beings. Hence the need for more concrete and better coordinateddidactic approaches, ultimately leading to the basic concepts of this discipline, which has an essential role in the acquisition of rationality.   Dall’Homo Abilis all’Homo Rationalis tramite la Percezione Analitica e la Matematica A partire dall’Homo abilis, l’uomo ha conquistato – nel corso di circa 2 milioni di anni, in cui si è progressivamente allontanato da uno stadio bestiale – il suo status di Homo rationalis. Però non tutti gli individui sono in grado di attivare in modo soddisfacente le abiltà di ragionamento. È innegabile che una tappa fondamentale verso quest’attivazione sia costituita dallo sviluppo delle abilità matematiche, che sono patrimonio di ogni essere umano. Da ciò deriva la necessità di impostazioni didattiche più concrete e meglio coordinate, da cui far scaturire in modo comprensibile i concetti fondamentali di tale disciplina, che ha un ruolo essenziale per l’acquisizione della razionalità.  Paole Chiave: filogenesi; memoria di specie; Homo sapiens sapiens; percezione

  14. Homo floresiensis. Humanos distintos a nosotros.

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    Carlos Alberto Marmelada

    2008-08-01

    Full Text Available Desde su descubrimiento, la polémica en torno al estatus de Homo floresiensis no ha cesado. ¿Son humanos de nuestra propia especie, pero que eran pigmeos que padecieron enanismo, microcefalia y otra serie de patologías, o se trata de miembros de una especie distinta a la nuestra? El hallazgo de restos pertenecientes a 13 individuos y el estudio de varias partes de su esqueleto avalan la segunda hipótesis.

  15. The Hedonistic Paradox: Is Homo Economicus Happier?

    OpenAIRE

    Konow, James; Earley, Joseph

    2007-01-01

    The “Hedonistic Paradox” states that homo economicus, or someone who seeks happiness for him- or herself, will not find it, but the person who helps others will. This study examines two questions in connection with happiness and generosity. First, do more generous people, as identified in dictator experiments, report on average greater happiness, or subjective well-being (SWB), as measured by responses to various questionnaires? Second, if the answer is affirmative, what is the causal relatio...

  16. Comparative analysis of cystatin superfamily in platyhelminths.

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    Aijiang Guo

    Full Text Available The cystatin superfamily is comprised of cysteine proteinase inhibitors and encompasses at least 3 subfamilies: stefins, cystatins and kininogens. In this study, the platyhelminth cystatin superfamily was identified and grouped into stefin and cystatin subfamilies. The conserved domain of stefins (G, QxVxG was observed in all members of platyhelminth stefins. The three characteristics of cystatins, the cystatin-like domain (G, QxVxG, PW, a signal peptide, and one or two conserved disulfide bonds, were observed in platyhelminths, with the exception of cestodes, which lacked the conserved disulfide bond. However, it is noteworthy that cestode cystatins had two tandem repeated domains, although the second tandem repeated domain did not contain a cystatin-like domain, which has not been previously reported. Tertiary structure analysis of Taenia solium cystatin, one of the cestode cystatins, demonstrated that the N-terminus of T. solium cystatin formed a five turn α-helix, a five stranded β-pleated sheet and a hydrophobic edge, similar to the structure of chicken cystatin. Although no conserved disulfide bond was found in T. solium cystatin, the models of T. solium cystatin and chicken cystatin corresponded at the site of the first disulfide bridge of the chicken cystatin. However, the two models were not similar regarding the location of the second disulfide bridge of chicken cystatin. These results showed that T. solium cystatin and chicken cystatin had similarities and differences, suggesting that the biochemistry of T. solium cystatin could be similar to chicken cystatin in its inhibitory function and that it may have further functional roles. The same results were obtained for other cestode cystatins. Phylogenetic analysis showed that cestode cystatins constituted an independent clade and implied that cestode cystatins should be considered to have formed a new clade during evolution.

  17. Comparative analysis of cystatin superfamily in platyhelminths.

    Science.gov (United States)

    Guo, Aijiang

    2015-01-01

    The cystatin superfamily is comprised of cysteine proteinase inhibitors and encompasses at least 3 subfamilies: stefins, cystatins and kininogens. In this study, the platyhelminth cystatin superfamily was identified and grouped into stefin and cystatin subfamilies. The conserved domain of stefins (G, QxVxG) was observed in all members of platyhelminth stefins. The three characteristics of cystatins, the cystatin-like domain (G, QxVxG, PW), a signal peptide, and one or two conserved disulfide bonds, were observed in platyhelminths, with the exception of cestodes, which lacked the conserved disulfide bond. However, it is noteworthy that cestode cystatins had two tandem repeated domains, although the second tandem repeated domain did not contain a cystatin-like domain, which has not been previously reported. Tertiary structure analysis of Taenia solium cystatin, one of the cestode cystatins, demonstrated that the N-terminus of T. solium cystatin formed a five turn α-helix, a five stranded β-pleated sheet and a hydrophobic edge, similar to the structure of chicken cystatin. Although no conserved disulfide bond was found in T. solium cystatin, the models of T. solium cystatin and chicken cystatin corresponded at the site of the first disulfide bridge of the chicken cystatin. However, the two models were not similar regarding the location of the second disulfide bridge of chicken cystatin. These results showed that T. solium cystatin and chicken cystatin had similarities and differences, suggesting that the biochemistry of T. solium cystatin could be similar to chicken cystatin in its inhibitory function and that it may have further functional roles. The same results were obtained for other cestode cystatins. Phylogenetic analysis showed that cestode cystatins constituted an independent clade and implied that cestode cystatins should be considered to have formed a new clade during evolution.

  18. Taxonomic differences in deciduous upper second molar crown outlines of Homo sapiens, Homo neanderthalensis and Homo erectus.

    Science.gov (United States)

    Bailey, Shara E; Benazzi, Stefano; Souday, Caroline; Astorino, Claudia; Paul, Kathleen; Hublin, Jean-Jacques

    2014-07-01

    A significant number of Middle to Late Pleistocene sites contain primarily (and sometimes only) deciduous teeth (e.g., Grotta del Cavallo, Mezmaiskaya, Blombos). Not surprisingly, there has been a recent renewed interest in deciduous dental variation, especially in the context of distinguishing Homo neanderthalensis and Homo sapiens. Most studies of the deciduous dentition of fossil hominins have focused on standard metrical variation but morphological (non-metric and morphometric) variation also promises to shed light on long standing taxonomic questions. This study examines the taxonomic significance of the crown outline of the deciduous upper second molar through principal components analysis and linear discriminant analysis. We examine whether or not the crown shape of the upper deciduous second molar separates H. neanderthalensis from H. sapiens and explore whether it can be used to correctly assign individuals to taxa. It builds on previous studies by focusing on crown rather than cervical outline and by including a large sample of geographically diverse recent human populations. Our samples include 17 H. neanderthalensis, five early H. sapiens, and 12 Upper Paleolithic H. sapiens. In addition, we include two Homo erectus specimens in order to evaluate the polarity of crown shape differences observed between H. neanderthalensis and H. sapiens. Our results show that crown outline shape discriminates H. sapiens and H. neanderthalensis quite well, but does not do well at distinguishing H. erectus from H. sapiens. We conclude that the crown outline shape observed in H. sapiens is a primitive retention and that the skewed shape observed in H. neanderthalensis is a derived condition. Finally, we explore the phylogenetic implications of the results for the H. erectus molars.

  19. Spinal cord evolution in early Homo.

    Science.gov (United States)

    Meyer, Marc R; Haeusler, Martin

    2015-11-01

    The discovery at Nariokotome of the Homo erectus skeleton KNM-WT 15000, with a narrow spinal canal, seemed to show that this relatively large-brained hominin retained the primitive spinal cord size of African apes and that brain size expansion preceded postcranial neurological evolution. Here we compare the size and shape of the KNM-WT 15000 spinal canal with modern and fossil taxa including H. erectus from Dmanisi, Homo antecessor, the European middle Pleistocene hominins from Sima de los Huesos, and Pan troglodytes. In terms of shape and absolute and relative size of the spinal canal, we find all of the Dmanisi and most of the vertebrae of KNM-WT 15000 are within the human range of variation except for the C7, T2, and T3 of KNM-WT 15000, which are constricted, suggesting spinal stenosis. While additional fossils might definitively indicate whether H. erectus had evolved a human-like enlarged spinal canal, the evidence from the Dmanisi spinal canal and the unaffected levels of KNM-WT 15000 show that unlike Australopithecus, H. erectus had a spinal canal size and shape equivalent to that of modern humans. Subadult status is unlikely to affect our results, as spinal canal growth is complete in both individuals. We contest the notion that vertebrae yield information about respiratory control or language evolution, but suggest that, like H. antecessor and European middle Pleistocene hominins from Sima de los Huesos, early Homo possessed a postcranial neurological endowment roughly commensurate to modern humans, with implications for neurological, structural, and vascular improvements over Pan and Australopithecus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Leukotriene signaling in the extinct human subspecies Homo denisovan and Homo neanderthalensis. Structural and functional comparison with Homo sapiens.

    Science.gov (United States)

    Adel, Susan; Kakularam, Kumar Reddy; Horn, Thomas; Reddanna, Pallu; Kuhn, Hartmut; Heydeck, Dagmar

    2015-01-01

    Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies.

  1. Homo Tangens, or Man Touching and Tangible

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    J Mizinska

    2011-09-01

    Full Text Available The article is devoted to the analysis of the concept sense of touch, which is considered in all its aspects and dimensions. The author's aim is to determine what is touch in terms of philosophy, what types it has and what traditional functions (i.e. prior to the emergence of virtual reality each of these functions performed. The conducted research allows the author to make a conclusion about the importance of perceiving the role and significance of man as a homo tangens - man touching and tangible.

  2. Evolutionarily conserved substrate substructures for automated annotation of enzyme superfamilies.

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    Ranyee A Chiang

    Full Text Available The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contexts are often conserved, while those that vary may indicate functions that are more easily changed or that are no longer required. In analogy to the study of conservation patterns in enzyme sequences and structures, we have examined the patterns of conservation and variation in enzyme function by analyzing graph isomorphisms among enzyme substrates of a large number of enzyme superfamilies. This systematic analysis of substrate substructures establishes the conservation patterns that typify individual superfamilies. Specifically, we determined the chemical substructures that are conserved among all known substrates of a superfamily and the substructures that are reacting in these substrates and then examined the relationship between the two. Across the 42 superfamilies that were analyzed, substantial variation was found in how much of the conserved substructure is reacting, suggesting that superfamilies may not be easily grouped into discrete and separable categories. Instead, our results suggest that many superfamilies may need to be treated individually for analyses of evolution, function prediction, and guiding enzyme engineering strategies. Annotating superfamilies with these conserved and reacting substructure patterns provides information that is orthogonal to information provided by studies of conservation in superfamily sequences and structures, thereby improving the precision with which we can predict the functions of enzymes of unknown function and direct studies in enzyme engineering. Because the method is automated, it is suitable for large-scale characterization and comparison of fundamental functional capabilities of both characterized

  3. A NEW PARADIGMA OF THE ECONOMICAL AGENT. FROM ADAM SMITHS HOMO ECONOMICUS TO HOMO GENEROSUS BASED ON SOCIAL RESPONSIBILITY

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    PUP ANCA

    2010-12-01

    Full Text Available Analyzed form outside, many actions of the economical agent seem to be impulse by the self interest. As a prototype of this kind of person we have the Homo economicus as Adam Smith described it. In a blitz portrait we identify some characteristics: he is perfect rational, perfect egoist, perfect free, perfect competitive and perfect social. The aim of this research is to permute the barycentre from Homo economicus based on self interest, to Homo generosus, based on social responsibility. As a support we have used the prison dilemma to illustrate the roll of cooperation instead self interest. This new coordination will be analyzed to the level of ethical system. Homo economicus is identified in ethics of consequences and the homo generosus in ethics of duty. In my vision, the prototype of homo generosus, is delineated under Kant's categorical imperative: respectful, based on principles as subject and sovereign.

  4. Evolution of Enzymatic Activities in the Enolase Superfamily: L-Fuconate Dehydratase from Xanthomonas campestris

    Energy Technology Data Exchange (ETDEWEB)

    Yew,W.; Fedorov, A.; Fedorov, E.; Rakus, J.; Pierce, R.; Almo, S.; Gerlt, J.

    2006-01-01

    Many members of the mechanistically diverse enolase superfamily have unknown functions. In this report the authors use both genome (operon) context and screening of a library of acid sugars to assign the L-fuconate dehydratase (FucD) function to a member of the mandelate racemase (MR) subgroup of the superfamily encoded by the Xanthomonas campestris pv. campestris str. ATCC 33913 genome (GI: 21233491). Orthologues of FucD are found in both bacteria and eukaryotes, the latter including the rTS beta protein in Homo sapiens that has been implicated in regulating thymidylate synthase activity. As suggested by sequence alignments and confirmed by high-resolution structures in the presence of active site ligands, FucD and MR share the same active site motif of functional groups: three carboxylate ligands for the essential Mg2+ located at the ends of th third, fourth, and fifth-strands in the (/)7-barrel domain (Asp 248, Glu 274, and Glu 301, respectively), a Lys-x-Lys motif at the end of the second-strand (Lys 218 and Lys 220), a His-Asp dyad at the end of the seventh and sixth-strands (His 351 and Asp 324, respectively), and a Glue at the end of the eighth-strand (Glu 382). The mechanism of the FucD reaction involves initial abstraction of the 2-proton by Lys 220, acid catalysis of the vinylogous-elimination of the 3-OH group by His 351, and stereospecific ketonization of the resulting 2-keto-3-deoxy-L-fuconate product. Screening of the library of acid sugars revealed substrate and functional promiscuity: In addition to L-fuconate, FucD also catalyzes the dehydration of L-galactonate, D-arabinonate, D-altronate, L-talonate, and D-ribonate. The dehydrations of L-fuconate, L-galactonate, and D-arabinonate are initiated by abstraction of the 2-protons by Lys 220. The dehydrations of L-talonate and D-ribonate are initiated by abstraction of the 2-protons by His 351; however, protonation of the enediolate intermediates by the conjugate acid of Lys 220 yields L

  5. Architect Homo Poeticus, rejoining reality and utopia

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    Franco Purini

    2015-11-01

    Full Text Available Our cities must regenerate beneath the label of a conceived sustainability, in its total and organic meaning. In order to achieve this goal, it is necessary to integrate tradition and technology, preservation and innovation. We need and idea of the future in which, as in the past, realism joins utopia. A similar union must occur between architecture and urbanism, overcoming on one hand, the illusion of a shared planning process with economic and political power and on the other hand, the city as a juxtaposition of isolated interventions and self-referential projects. The merging closeness of architecture and industrial design was a mistake probably caused by a general diffusion of the media within prevailing human expression. Architecture, should instead be an interpretation of a ‘theme of mankind’, how to behave as ‘homo poeticus’.

  6. Homo Novus - A Human Without Illusions

    CERN Document Server

    Frey, Ulrich J; Willführ, Kai P

    2010-01-01

    Converging evidence from disciplines including sociobiology, evolutionary psychology and human biology forces us to adopt a new idea of what it means to be a human. As cherished concepts such as free will, naïve realism, humans as creation's crowning glory fall and our moral roots in ape group dynamics become clearer, we have to take leave of many concepts that have been central to defining our humanness. What emerges is a new human, the homo novus, a human being without illusions. Leading authors from many different fields explore these issues by addressing these illusions and providing evidence for the need to switch to this new idea of man, in spite of understandable reluctance to let go of our most beloved illusions.

  7. The origin and evolution of Homo sapiens.

    Science.gov (United States)

    Stringer, Chris

    2016-07-05

    If we restrict the use of Homo sapiens in the fossil record to specimens which share a significant number of derived features in the skeleton with extant H. sapiens, the origin of our species would be placed in the African late middle Pleistocene, based on fossils such as Omo Kibish 1, Herto 1 and 2, and the Levantine material from Skhul and Qafzeh. However, genetic data suggest that we and our sister species Homo neanderthalensis shared a last common ancestor in the middle Pleistocene approximately 400-700 ka, which is at least 200 000 years earlier than the species origin indicated from the fossils already mentioned. Thus, it is likely that the African fossil record will document early members of the sapiens lineage showing only some of the derived features of late members of the lineage. On that basis, I argue that human fossils such as those from Jebel Irhoud, Florisbad, Eliye Springs and Omo Kibish 2 do represent early members of the species, but variation across the African later middle Pleistocene/early Middle Stone Age fossils shows that there was not a simple linear progression towards later sapiens morphology, and there was chronological overlap between different 'archaic' and 'modern' morphs. Even in the late Pleistocene within and outside Africa, we find H. sapiens specimens which are clearly outside the range of Holocene members of the species, showing the complexity of recent human evolution. The impact on species recognition of late Pleistocene gene flow between the lineages of modern humans, Neanderthals and Denisovans is also discussed, and finally, I reconsider the nature of the middle Pleistocene ancestor of these lineages, based on recent morphological and genetic data.This article is part of the themed issue 'Major transitions in human evolution'.

  8. Genetic, physiologic and ecogeographic factors contributing to variation in Homo sapiens: Homo floresiensis reconsidered.

    Science.gov (United States)

    Richards, Gary D

    2006-11-01

    A new species, Homo floresiensis, was recently named for Pleistocene hominid remains on Flores, Indonesia. Significant controversy has arisen regarding this species. To address controversial issues and refocus investigations, I examine the affinities of these remains with Homo sapiens. Clarification of problematic issues is sought through an integration of genetic and physiological data on brain ontogeny and evolution. Clarification of the taxonomic value of various 'primitive' traits is possible given these data. Based on this evidence and using a H. sapiens morphological template, models are developed to account for the combination of features displayed in the Flores fossils. Given this overview, I find substantial support for the hypothesis that the remains represent a variant of H. sapiens possessing a combined growth hormone-insulin-like growth factor I axis modification and mutation of the MCPH gene family. Further work will be required to determine the extent to which this variant characterized the population.

  9. Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes

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    Turk Vito

    2009-11-01

    Full Text Available Abstract Background The cystatin superfamily comprises cysteine protease inhibitors that play key regulatory roles in protein degradation processes. Although they have been the subject of many studies, little is known about their genesis, evolution and functional diversification. Our aim has been to obtain a comprehensive insight into their origin, distribution, diversity, evolution and classification in Eukaryota, Bacteria and Archaea. Results We have identified in silico the full complement of the cystatin superfamily in more than 2100 prokaryotic and eukaryotic genomes. The analysis of numerous eukaryotic genomes has provided strong evidence for the emergence of this superfamily in the ancestor of eukaryotes. The progenitor of this superfamily was most probably intracellular and lacked a signal peptide and disulfide bridges, much like the extant Giardia cystatin. A primordial gene duplication produced two ancestral eukaryotic lineages, cystatins and stefins. While stefins remain encoded by a single or a small number of genes throughout the eukaryotes, the cystatins have undergone a more complex and dynamic evolution through numerous gene and domain duplications. In the cystatin superfamily we discovered twenty vertebrate-specific and three angiosperm-specific orthologous families, indicating that functional diversification has occurred only in multicellular eukaryotes. In vertebrate orthologous families, the prevailing trends were loss of the ancestral inhibitory activity and acquisition of novel functions in innate immunity. Bacterial cystatins and stefins may be emergency inhibitors that enable survival of bacteria in the host, defending them from the host's proteolytic activity. Conclusion This study challenges the current view on the classification, origin and evolution of the cystatin superfamily and provides valuable insights into their functional diversification. The findings of this comprehensive study provide guides for future

  10. Structure and Function of the LmbE-like Superfamily

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    Shane Viars

    2014-05-01

    Full Text Available The LmbE-like superfamily is comprised of a series of enzymes that use a single catalytic metal ion to catalyze the hydrolysis of various substrates. These substrates are often key metabolites for eukaryotes and prokaryotes, which makes the LmbE-like enzymes important targets for drug development. Herein we review the structure and function of the LmbE-like proteins identified to date. While this is the newest superfamily of metallohydrolases, a growing number of functionally interesting proteins from this superfamily have been characterized. Available crystal structures of LmbE-like proteins reveal a Rossmann fold similar to lactate dehydrogenase, which represented a novel fold for (zinc metallohydrolases at the time the initial structure was solved. The structural diversity of the N-acetylglucosamine containing substrates affords functional diversity for the LmbE-like enzyme superfamily. The majority of enzymes identified to date are metal-dependent deacetylases that catalyze the hydrolysis of a N-acetylglucosamine moiety on substrate using a combination of amino acid side chains and a single bound metal ion, predominantly zinc. The catalytic zinc is coordinated to proteins via His2-Asp-solvent binding site. Additionally, studies indicate that protein dynamics play important roles in regulating access to the active site and facilitating catalysis for at least two members of this protein superfamily.

  11. PELDOR in rotationally symmetric homo-oligomers

    Science.gov (United States)

    Giannoulis, Angeliki; Ward, Richard; Branigan, Emma; Naismith, James H.; Bode, Bela E.

    2013-01-01

    Nanometre distance measurements by pulsed electron–electron double resonance (PELDOR) spectroscopy have become an increasingly important tool in structural biology. The theoretical underpinning of the experiment is well defined for systems containing two nitroxide spin-labels (spin pairs); however, recently experiments have been reported on homo-oligomeric membrane proteins consisting of up to eight spin-labelled monomers. We have explored the theory behind these systems by examining model systems based on multiple spins arranged in rotationally symmetric polygons. The results demonstrate that with a rising number of spins within the test molecule, increasingly strong distortions appear in distance distributions obtained from an analysis based on the simple spin pair approach. These distortions are significant over a range of system sizes and remain so even when random errors are introduced into the symmetry of the model. We present an alternative approach to the extraction of distances on such systems based on a minimisation that properly treats multi-spin correlations. We demonstrate the utility of this approach on a spin-labelled mutant of the heptameric Mechanosensitive Channel of Small Conductance of E. coli. PMID:24954956

  12. Yawn contagion and empathy in Homo sapiens.

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    Ivan Norscia

    Full Text Available The ability to share others' emotions, or empathy, is crucial for complex social interactions. Clinical, psychological, and neurobiological clues suggest a link between yawn contagion and empathy in humans (Homo sapiens. However, no behavioral evidence has been provided so far. We tested the effect of different variables (e.g., country of origin, sex, yawn characteristics on yawn contagion by running mixed models applied to observational data collected over 1 year on adult (>16 years old human subjects. Only social bonding predicted the occurrence, frequency, and latency of yawn contagion. As with other measures of empathy, the rate of contagion was greatest in response to kin, then friends, then acquaintances, and lastly strangers. Related individuals (r≥0.25 showed the greatest contagion, in terms of both occurrence of yawning and frequency of yawns. Strangers and acquaintances showed a longer delay in the yawn response (latency compared to friends and kin. This outcome suggests that the neuronal activation magnitude related to yawn contagion can differ as a function of subject familiarity. In conclusion, our results demonstrate that yawn contagion is primarily driven by the emotional closeness between individuals and not by other variables, such as gender and nationality.

  13. Nuevos modelos productivos desde la perspectiva del anarquismo postizquierda: del homo laborans al homo consumens

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    José Antonio Calzón García

    2011-10-01

    Full Text Available En este ensayo se plantea la progresiva pérdida, en las últimas décadas, de la ubicación en el sistema productivo en cuanto elemento identitario de la ciudadanía, lo que, desde perspectivas más o menos afines a planteamientos libertarios, ha conllevado dos líneas fundamentales de disidencia y protesta social. En primer lugar, a partir del desarrollo de planteamientos ideológicos que rechazan el trabajo asalariado, por su naturaleza alienante y en connivencia con el establishment. Y en segundo lugar, desde las posiciones de quienes ven en el consumo el mecanismo para la transformación social, a través de estrategias, ora cercanas al decrecimiento, ora defensoras de una utilización política de los ingresos. A lo largo del texto se ilustran con ejemplos y propuestas concretas ambas líneas de actuación, que evidencian la evolución del homo laborans al homo consumens.

  14. Brain size of Homo floresiensis and its evolutionary implications

    OpenAIRE

    Kubo, Daisuke; Kono, Reiko T.; Kaifu, Yousuke

    2013-01-01

    The extremely small endocranial volume (ECV) of LB1, the type specimen of Homo floresiensis, poses a challenge in our understanding of human brain evolution. Some researchers hypothesize dramatic dwarfing of relative brain size from Homo erectus presumably without significant decrease in intellectual function, whereas others expect a lesser degree of brain diminution from a more primitive, small-brained form of hominin currently undocumented in eastern Asia. However, inconsistency in the publ...

  15. The Insect Chemoreceptor Superfamily Is Ancient in Animals.

    Science.gov (United States)

    Robertson, Hugh M

    2015-11-01

    The insect chemoreceptor superfamily consists of 2 gene families, the highly diverse gustatory receptors (GRs) found in all arthropods with sequenced genomes and the odorant receptors that evolved from a GR lineage and have been found only in insects to date. Here, I describe relatives of the insect chemoreceptor superfamily, specifically the basal GR family, in diverse other animals, showing that the superfamily dates back at least to early animal evolution. GR-Like (GRL) genes are present in the genomes of the placozoan Trichoplax adhaerens, an anemone Nematostella vectensis, a coral Acropora digitifera, a polychaete Capitella teleta, a leech Helobdella robusta, the nematode Caenorhabditis elegans (and many other nematodes), 3 molluscs (a limpet Lottia gigantea, an oyster Crassostrea gigas, and the sea hare Aplysia californica), the sea urchin Strongylocentrotus purpuratus, and the sea acorn Saccoglossus kowalevskii. While some of these animals contain multiple divergent GRL lineages, GRLs have been lost entirely from other animal lineages such as vertebrates. GRLs are absent from the ctenophore Mnemiopsis leidyi, the demosponge Amphimedon queenslandica, and 2 available chaonoflagellate genomes, so it remains unclear whether this superfamily originated before or during animal evolution. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Repertoire and evolution of TNF superfamily in Crassostrea gigas: implications for expansion and diversification of this superfamily in Mollusca.

    Science.gov (United States)

    Gao, Dahai; Qiu, Limei; Gao, Qiang; Hou, Zhanhui; Wang, Lingling; Song, Linsheng

    2015-08-01

    Tumor necrosis factor superfamily (TNFSF) members represent a group of cytokines participating in diverse immunological, pathological and developmental pathways. However, compared with deuterostomia and cnidaia, the composition and evolution of TNF homologous in protostomia are still not well understood. In the present study, a total of 81 TNF superfamily (TNFSF) genes from 15 mollusk species, including 23 TNFSF genes from Crassostrea gigas, were surveyed by genome-wide bioinformatics analysis. The phylogenetic analysis showed that 14 out of 23 C. gigas TNFSF genes in five clades exhibited orthologous relationships with Pinctada fucata TNFSF genes. Moreover, there were 15 C. gigas TNFSF genes located in oyster-specific clusters, which were contributed by small-scaled tandem and/or segmental duplication events in oyster. By comparing the sequences of duplicated TNFSF pairs, exon loss and variant in exon/intron length were revealed as the major modes of divergence in gene structure. Most of the duplicated C. gigas TNFSF pairs were evolved under purifying selection with consistent tissue expression patterns, implying functional constraint shaped diversification. This study demonstrated the expansion and early divergence of TNF superfamily in C. gigas, which provides potential insight into revealing the evolution and function of this superfamily in mollusk.

  17. LB1 and LB6 Homo floresiensis are not modern human (Homo sapiens) cretins.

    Science.gov (United States)

    Brown, Peter

    2012-02-01

    Excavations in the late Pleistocene deposits at Liang Bua cave, Flores, have uncovered the skeletal remains of several small-bodied and small-brained hominins in association with stone artefacts and the bones of Stegodon. Due to their combination of plesiomorphic, unique and derived traits, they were ascribed to a new species, Homo floresiensis, which, along with Stegodon, appears to have become extinct ∼17 ka (thousand years ago). However, recently it has been argued that several characteristics of H. floresiensis were consistent with dwarfism and evidence of delayed development in modern human (Homo sapiens) myxoedematous endemic (ME) cretins. This research compares the skeletal and dental morphology in H. floresiensis with the clinical and osteological indicators of cretinism, and the traits that have been argued to be associated with ME cretinism in LB1 and LB6. Contrary to published claims, morphological and statistical comparisons did not identify the distinctive skeletal and dental indicators of cretinism in LB1 or LB6 H. floresiensis. Brain mass, skeletal proportions, epiphyseal union, orofacial morphology, dental development, size of the pituitary fossa and development of the paranasal sinuses, vault bone thickness and dimensions of the hands and feet all distinguish H. floresiensis from modern humans with ME cretinism. The research team responsible for the diagnosis of ME cretinism had not examined the original H. floresiensis skeletal materials, and perhaps, as a result, their research confused taphonomic damage with evidence of disease, and thus contained critical errors of fact and interpretation. Behavioural scenarios attempting to explain the presence of cretinous H. sapiens in the Liang Bua Pleistocene deposits, but not unaffected H. sapiens, are both unnecessary and not supported by the available archaeological and geochronological evidence from Flores. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  18. Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases

    Directory of Open Access Journals (Sweden)

    Purta Elzbieta

    2007-03-01

    Full Text Available Abstract Background SPOUT methyltransferases (MTases are a large class of S-adenosyl-L-methionine-dependent enzymes that exhibit an unusual alpha/beta fold with a very deep topological knot. In 2001, when no crystal structures were available for any of these proteins, Anantharaman, Koonin, and Aravind identified homology between SpoU and TrmD MTases and defined the SPOUT superfamily. Since then, multiple crystal structures of knotted MTases have been solved and numerous new homologous sequences appeared in the databases. However, no comprehensive comparative analysis of these proteins has been carried out to classify them based on structural and evolutionary criteria and to guide functional predictions. Results We carried out extensive searches of databases of protein structures and sequences to collect all members of previously identified SPOUT MTases, and to identify previously unknown homologs. Based on sequence clustering, characterization of domain architecture, structure predictions and sequence/structure comparisons, we re-defined families within the SPOUT superfamily and predicted putative active sites and biochemical functions for the so far uncharacterized members. We have also delineated the common core of SPOUT MTases and inferred a multiple sequence alignment for the conserved knot region, from which we calculated the phylogenetic tree of the superfamily. We have also studied phylogenetic distribution of different families, and used this information to infer the evolutionary history of the SPOUT superfamily. Conclusion We present the first phylogenetic tree of the SPOUT superfamily since it was defined, together with a new scheme for its classification, and discussion about conservation of sequence and structure in different families, and their functional implications. We identified four protein families as new members of the SPOUT superfamily. Three of these families are functionally uncharacterized (COG1772, COG1901, and COG4080

  19. Phylogenetic analysis of the kinesin superfamily from Physcomitrella

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    Zhiyuan eShen

    2012-10-01

    Full Text Available Kinesins are an ancient superfamily of microtubule dependent motors. They participate in an ex-tensive and diverse list of essential cellular functions, including mitosis, cytokinesis, cell polari-zation, cell elongation, flagellar development, and intracellular transport. Based on phylogenetic relationships, the kinesin superfamily has been subdivided into 14 families, which are represented in most eukaryotic phyla. The functions of these families are sometimes conserved between species, but important variations in function across species have been observed. Plants possess most kinesin families including a few plant-specific families. With the availability of an ever in-creasing number of genome sequences from plants, it is important to document the complete complement of kinesins present in a given organism. This will help develop a molecular frame-work to explore the function of each family using genetics, biochemistry and cell biology. The moss Physcomitrella patens has emerged as a powerful model organism to study gene function in plants, which makes it a key candidate to explore complex gene families, such as the kinesin superfamily. Here we report a detailed phylogenetic characterization of the 71 kinesins of the kinesin superfamily in Physcomitrella. We found a remarkable conservation of families and sub-family classes with Arabidopsis, which is important for future comparative analysis of function. Some of the families, such as kinesins 14s are composed of fewer members in moss, while other families, such as the kinesin 12s are greatly expanded. To improve the comparison between spe-cies, and to simplify communication between research groups, we propose a classification of subfamilies based on our phylogenetic analysis.

  20. Periplasmic binding proteins: a versatile superfamily for protein engineering.

    Science.gov (United States)

    Dwyer, Mary A; Hellinga, Homme W

    2004-08-01

    The diversity of biological function, ligand binding, conformational changes and structural adaptability of the periplasmic binding protein superfamily have been exploited to engineer biosensors, allosteric control elements, biologically active receptors and enzymes using a combination of techniques, including computational design. Extensively redesigned periplasmic binding proteins have been re-introduced into bacteria to function in synthetic signal transduction pathways that respond to extracellular ligands and as biologically active enzymes.

  1. CD147 Immunoglobulin Superfamily Receptor Function and Role in Pathology

    OpenAIRE

    Iacono, Kathryn T.; Brown, Amy L.; Greene, Mark I.; Saouaf, Sandra J.

    2007-01-01

    The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer’s disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is intr...

  2. The Spell of Homo Informaticus: Two Superstitions and Three Dreams

    Directory of Open Access Journals (Sweden)

    Marius Povilas Saulauskas

    2000-01-01

    Full Text Available Even at the dawn of a full-fledged information society Homo Informaticus as well as its netted counterpart - Homo Irretitus - already carries a handful of badly compatible fears and hopes. First, anxieties about an inevitable desolation of habitual patterns of human interaction and values,as well as an inexorably impending threat of horrifying global control. Second, evergreen optimism of rapidly approaching egalitarian era under the pledge of free universal access to information, cornucopian abundance of all imaginable material and spiritual goods, and unrestricted reign of knowledge once for all overthrowing unjust orders of power and brute force. The article puts under the close scrutiny the key pro et contra arguments involved in the theoretical articulation of these basic attitudes and examines the topical question: why can neither the dreadful fears nor the gay hopes of Homo Irretitus be reasonably sustained in the face of critical inquiry?

  3. Human evolution. Evolution of early Homo: an integrated biological perspective.

    Science.gov (United States)

    Antón, Susan C; Potts, Richard; Aiello, Leslie C

    2014-07-04

    Integration of evidence over the past decade has revised understandings about the major adaptations underlying the origin and early evolution of the genus Homo. Many features associated with Homo sapiens, including our large linear bodies, elongated hind limbs, large energy-expensive brains, reduced sexual dimorphism, increased carnivory, and unique life history traits, were once thought to have evolved near the origin of the genus in response to heightened aridity and open habitats in Africa. However, recent analyses of fossil, archaeological, and environmental data indicate that such traits did not arise as a single package. Instead, some arose substantially earlier and some later than previously thought. From ~2.5 to 1.5 million years ago, three lineages of early Homo evolved in a context of habitat instability and fragmentation on seasonal, intergenerational, and evolutionary time scales. These contexts gave a selective advantage to traits, such as dietary flexibility and larger body size, that facilitated survival in shifting environments.

  4. Rethinking the dispersal of Homo sapiens out of Africa.

    Science.gov (United States)

    Groucutt, Huw S; Petraglia, Michael D; Bailey, Geoff; Scerri, Eleanor M L; Parton, Ash; Clark-Balzan, Laine; Jennings, Richard P; Lewis, Laura; Blinkhorn, James; Drake, Nick A; Breeze, Paul S; Inglis, Robyn H; Devès, Maud H; Meredith-Williams, Matthew; Boivin, Nicole; Thomas, Mark G; Scally, Aylwyn

    2015-01-01

    Current fossil, genetic, and archeological data indicate that Homo sapiens originated in Africa in the late Middle Pleistocene. By the end of the Late Pleistocene, our species was distributed across every continent except Antarctica, setting the foundations for the subsequent demographic and cultural changes of the Holocene. The intervening processes remain intensely debated and a key theme in hominin evolutionary studies. We review archeological, fossil, environmental, and genetic data to evaluate the current state of knowledge on the dispersal of Homo sapiens out of Africa. The emerging picture of the dispersal process suggests dynamic behavioral variability, complex interactions between populations, and an intricate genetic and cultural legacy. This evolutionary and historical complexity challenges simple narratives and suggests that hybrid models and the testing of explicit hypotheses are required to understand the expansion of Homo sapiens into Eurasia. © 2015 Wiley Periodicals, Inc.

  5. The Evolution of the Actin Binding NET Superfamily

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    Tim eHawkins

    2014-06-01

    Full Text Available The arabidopsis Networked protein superfamily are plant-specific actin binding proteins which specifically label different membrane compartments and identify specialized sites of interaction between actin and membranes unique to plants. There are 13 members of the superfamily in arabidopsis which group into 4 distinct clades or subfamilies. NET homologues are absent from the genomes of metazoa and fungi, furthermore in Plantae NET sequences are also absent from the genome of mosses and more ancient extant plant clades. A single subfamily of the NET proteins are found encoded in the club moss genome; an extant species of the earliest vascular plants. Gymnosperms have examples from subfamilies 4 and 3 with a hybrid form of NET1 and 2 which shows characteristics of both NET1 and NET2. In addition to NET3 and 4 subfamilies, the NET1 and pollen-expressed NET2 subfamilies are only found as independent sequences in angiosperms. This is consistent with the divergence of reproductive actin. The four subfamilies are conserved across monocots and eudicots with the numbers of members of each clade expanding at this point due in part to regions of genome duplication. Since the emergence of the NET superfamily at the dawn of vascular plants they have continued to develop and diversify in a manner which has mirrored the divergence and complexity of plant species through evolution in the ‘March of Progress’.

  6. Plasmodium interspersed repeats: the major multigene superfamily of malaria parasites

    Science.gov (United States)

    Janssen, Christoph S.; Phillips, R. Stephen; Turner, C. Michael R.; Barrett, Michael P.

    2004-01-01

    Functionally related homologues of known genes can be difficult to identify in divergent species. In this paper, we show how multi-character analysis can be used to elucidate the relationships among divergent members of gene superfamilies. We used probabilistic modelling in conjunction with protein structural predictions and gene-structure analyses on a whole-genome scale to find gene homologies that are missed by conventional similarity-search strategies and identified a variant gene superfamily in six species of malaria (Plasmodium interspersed repeats, pir). The superfamily includes rif in P.falciparum, vir in P.vivax, a novel family kir in P.knowlesi and the cir/bir/yir family in three rodent malarias. Our data indicate that this is the major multi-gene family in malaria parasites. Protein localization of products from pir members to the infected erythrocyte membrane in the rodent malaria parasite P.chabaudi, demonstrates phenotypic similarity to the products of pir in other malaria species. The results give critical insight into the evolutionary adaptation of malaria parasites to their host and provide important data for comparative immunology between malaria parasites obtained from laboratory models and their human counterparts. PMID:15507685

  7. Ecce homo, a fisio-psicologia de um tipo

    OpenAIRE

    2007-01-01

    No presente estudo, pretendemos realizar uma leitura de Ecce homo balizada pelo procedimento genealógico, pela fisio-psicologia e pela tipologia presentes no pensamento de Nietzsche. Acreditamos que a mudança que se opera no tratamento do humano a partir dessas três noções permite a Nietzsche, em Ecce homo, realizar uma espécie de duplo movimento. Por um lado, o filósofo realiza a máxima afirmação da vida e de si mesmo, dando expressão a uma série de estados afetivos que o constitui. Por outr...

  8. Un Ecce Homo de Antonio del Castillo en Granada

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    Montes González, Francisco

    2012-03-01

    Full Text Available The author presents a previously unknown painting by the Baroque artist from Cordoba, Antonio del Castillo y Saavedra. It is an Ecce Homo, a late work, and located in a private collection in Granada.Este artículo presenta el último aporte en el catálogo del pintor barroco cordobés Antonio del Castillo y Saavedra. Se trata de un lienzo con la iconografía del Ecce Homo, perteneciente a su última etapa artística, localizado en una colección particular de Granada.

  9. Structural Evolution of the Protein Kinase-Like Superfamily.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available The protein kinase family is large and important, but it is only one family in a larger superfamily of homologous kinases that phosphorylate a variety of substrates and play important roles in all three superkingdoms of life. We used a carefully constructed structural alignment of selected kinases as the basis for a study of the structural evolution of the protein kinase-like superfamily. The comparison of structures revealed a "universal core" domain consisting only of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the universal core some kinase structures display notable changes, while still retaining essential activity. Hence, the protein kinase-like superfamily has undergone substantial structural and sequence revision over long evolutionary timescales. We constructed a phylogenetic tree for the superfamily using a novel approach that allowed for the combination of sequence and structure information into a unified quantitative analysis. When considered against the backdrop of species distribution and other metrics, our tree provides a compelling scenario for the development of the various kinase families from a shared common ancestor. We propose that most of the so-called "atypical kinases" are not intermittently derived from protein kinases, but rather diverged early in evolution to form a distinct phyletic group. Within the atypical kinases, the aminoglycoside and choline kinase families appear to share the closest relationship. These two families in turn appear to be the most closely related to the protein kinase family. In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. The two most divergent families, alpha-kinases and phosphatidylinositol phosphate kinases (PIPKs, appear to have distinct evolutionary histories. While the PIPKs probably have an

  10. Length variations amongst protein domain superfamilies and consequences on structure and function.

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    Sankaran Sandhya

    Full Text Available BACKGROUND: Related protein domains of a superfamily can be specified by proteins of diverse lengths. The structural and functional implications of indels in a domain scaffold have been examined. METHODOLOGY: In this study, domain superfamilies with large length variations (more than 30% difference from average domain size, referred as 'length-deviant' superfamilies and 'length-rigid' domain superfamilies (<10% length difference from average domain size were analyzed for the functional impact of such structural differences. Our delineated dataset, derived from an objective algorithm, enables us to address indel roles in the presence of peculiar structural repeats, functional variation, protein-protein interactions and to examine 'domain contexts' of proteins tolerant to large length variations. Amongst the top-10 length-deviant superfamilies analyzed, we found that 80% of length-deviant superfamilies possess distant internal structural repeats and nearly half of them acquired diverse biological functions. In general, length-deviant superfamilies have higher chance, than length-rigid superfamilies, to be engaged in internal structural repeats. We also found that approximately 40% of length-deviant domains exist as multi-domain proteins involving interactions with domains from the same or other superfamilies. Indels, in diverse domain superfamilies, were found to participate in the accretion of structural and functional features amongst related domains. With specific examples, we discuss how indels are involved directly or indirectly in the generation of oligomerization interfaces, introduction of substrate specificity, regulation of protein function and stability. CONCLUSIONS: Our data suggests a multitude of roles for indels that are specialized for domain members of different domain superfamilies. These specialist roles that we observe and trends in the extent of length variation could influence decision making in modeling of new superfamily

  11. Identification of protein superfamily from structure- based sequence motif

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The structure-based sequence motif of the distant proteins in evolution, protein tyrosine phosphatases (PTP) Ⅰ and Ⅱ superfamilies, as an example, has been defined by the structural comparison, structure-based sequence alignment and analyses on substitution patterns of residues in common sequence conserved regions. And the phosphatases Ⅰ and Ⅱ can be correctly identified together by the structure-based PTP sequence motif from SWISS-PROT and TrEBML databases. The results show that the correct rates of identification are over 98%. This is the first time to identify PTP Ⅰ and Ⅱ together by this motif.

  12. Helical assembly in the death domain (DD) superfamily.

    Science.gov (United States)

    Ferrao, Ryan; Wu, Hao

    2012-04-01

    Death domain (DD) superfamily members play a central role in apoptotic and inflammatory signaling through formation of oligomeric molecular scaffolds. These scaffolds promote the activation of proinflammatory and apoptotic initiator caspases, as well as Ser/Thr kinases. Interactions between DDs are facilitated by a conserved set of interaction surfaces, type I, type II, and type III. Recently structural information on a ternary complex containing the DDs of MyD88, IRAK4, and IRAK2 and a binary complex containing Fas and FADD DDs has become available. This review will focus on how the three DD interaction surfaces cooperate to facilitate the assembly of these oligomeric signaling complexes.

  13. Structural advances for the major facilitator superfamily (MFS) transporters.

    Science.gov (United States)

    Yan, Nieng

    2013-03-01

    The major facilitator superfamily (MFS) is one of the largest groups of secondary active transporters conserved from bacteria to humans. MFS proteins selectively transport a wide spectrum of substrates across biomembranes and play a pivotal role in multiple physiological processes. Despite intense investigation, only seven MFS proteins from six subfamilies have been structurally elucidated. These structures were captured in distinct states during a transport cycle involving alternating access to binding sites from either side of the membrane. This review discusses recent progress in MFS structure analysis and focuses on the molecular basis for substrate binding, co-transport coupling, and alternating access.

  14. Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication

    OpenAIRE

    2014-01-01

    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five...

  15. Reflexões sobre a articulação entre o homo faber e o homo sapiens na enfermagem

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    Cecilia Nogueira Valenca

    2013-09-01

    Full Text Available Estudo reflexivo com o objetivo de analisar a articulação entre o enfermeiro-docente (Homo sapiens e o enfermeiro-assistencial (Homo faber no ambiente hospitalar, à luz do pensamento gramsciano. Na Enfermagem, coexistem duas dimensões: a teórica, exemplificada na figura do enfermeiro docente com seus projetos de pesquisa e publicações científicas; e a dimensão prática, com a atuação técnico-assistencial. Evidencia-se o distanciamento do enfermeiro docente em relação aos cenários de prática da graduação, assim como do enfermeiro assistencial, da pesquisa e da prática baseada em evidências científicas. Face ao dilema entre Homo faber e Homo sapiens na Enfermagem, emerge a importância de refletir sobre a dimensão ética subjacente às ações de ambos, centradas no ser humano. Este diálogo não pode ser ignorado, pois dele depende o desbravamento de novos horizontes e o crescimento da Enfermagem enquanto ciência e prática social.

  16. A comparison of tooth structure in Neanderthals and early Homo sapiens sapiens: a radiographic study.

    OpenAIRE

    1992-01-01

    Tooth components of 1st and 2nd erupted permanent molars were measured from standardised radiographs of Homo sapiens sapiens and Homo sapiens neanderthalensis. Enamel height was greater in Homo sapiens sapiens but pulp height and width and the height of the enamel to floor of the pulp chamber were greater in Homo sapiens neanderthalensis. Dentine height, crown width and enamel width showed similar results in the two groups. Unerupted first molars were measured to analyse the influence of func...

  17. Diversity, classification and function of the plant protein kinase superfamily.

    Science.gov (United States)

    Lehti-Shiu, Melissa D; Shiu, Shin-Han

    2012-09-19

    Eukaryotic protein kinases belong to a large superfamily with hundreds to thousands of copies and are components of essentially all cellular functions. The goals of this study are to classify protein kinases from 25 plant species and to assess their evolutionary history in conjunction with consideration of their molecular functions. The protein kinase superfamily has expanded in the flowering plant lineage, in part through recent duplications. As a result, the flowering plant protein kinase repertoire, or kinome, is in general significantly larger than other eukaryotes, ranging in size from 600 to 2500 members. This large variation in kinome size is mainly due to the expansion and contraction of a few families, particularly the receptor-like kinase/Pelle family. A number of protein kinases reside in highly conserved, low copy number families and often play broadly conserved regulatory roles in metabolism and cell division, although functions of plant homologues have often diverged from their metazoan counterparts. Members of expanded plant kinase families often have roles in plant-specific processes and some may have contributed to adaptive evolution. Nonetheless, non-adaptive explanations, such as kinase duplicate subfunctionalization and insufficient time for pseudogenization, may also contribute to the large number of seemingly functional protein kinases in plants.

  18. Structure-Based Phylogenetic Analysis of the Lipocalin Superfamily.

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    Balasubramanian Lakshmi

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

  19. TNF Superfamily: A Growing Saga of Kidney Injury Modulators

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    Maria D. Sanchez-Niño

    2010-01-01

    Full Text Available Members of the TNF superfamily participate in kidney disease. Tumor necrosis factor (TNF and Fas ligand regulate renal cell survival and inflammation, and therapeutic targeting improves the outcome of experimental renal injury. TNF-related apoptosis-inducing ligand (TRAIL and its potential decoy receptor osteoprotegerin are the two most upregulated death-related genes in human diabetic nephropathy. TRAIL activates NF-kappaB in tubular cells and promotes apoptosis in tubular cells and podocytes, especially in a high-glucose environment. By contrast, osteoprotegerin plays a protective role against TRAIL-induced apoptosis. Another family member, TNF-like weak inducer of apoptosis (TWEAK induces inflammation and tubular cell death or proliferation, depending on the microenvironment. While TNF only activates canonical NF-kappaB signaling, TWEAK promotes both canonical and noncanonical NF-kappaB activation in tubular cells, regulating different inflammatory responses. TWEAK promotes the secretion of MCP-1 and RANTES through NF-kappaB RelA-containing complexes and upregulates CCl21 and CCL19 expression through NF-kappaB inducing kinase (NIK- dependent RelB/NF-kappaB2 complexes. In vivo TWEAK promotes postnephrectomy compensatory renal cell proliferation in a noninflammatory milieu. However, in the inflammatory milieu of acute kidney injury, TWEAK promotes tubular cell death and inflammation. Therapeutic targeting of TNF superfamily cytokines, including multipronged approaches targeting several cytokines should be further explored.

  20. Transient receptor potential (TRP gene superfamily encoding cation channels

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    Pan Zan

    2011-01-01

    Full Text Available Abstract Transient receptor potential (TRP non-selective cation channels constitute a superfamily, which contains 28 different genes. In mammals, this superfamily is divided into six subfamilies based on differences in amino acid sequence homology between the different gene products. Proteins within a subfamily aggregate to form heteromeric or homomeric tetrameric configurations. These different groupings have very variable permeability ratios for calcium versus sodium ions. TRP expression is widely distributed in neuronal tissues, as well as a host of other tissues, including epithelial and endothelial cells. They are activated by environmental stresses that include tissue injury, changes in temperature, pH and osmolarity, as well as volatile chemicals, cytokines and plant compounds. Their activation induces, via intracellular calcium signalling, a host of responses, including stimulation of cell proliferation, migration, regulatory volume behaviour and the release of a host of cytokines. Their activation is greatly potentiated by phospholipase C (PLC activation mediated by coupled GTP-binding proteins and tyrosine receptors. In addition to their importance in maintaining tissue homeostasis, some of these responses may involve various underlying diseases. Given the wealth of literature describing the multiple roles of TRP in physiology in a very wide range of different mammalian tissues, this review limits itself to the literature describing the multiple roles of TRP channels in different ocular tissues. Accordingly, their importance to the corneal, trabecular meshwork, lens, ciliary muscle, retinal, microglial and retinal pigment epithelial physiology and pathology is reviewed.

  1. Ancient origin of the new developmental superfamily DANGER.

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    Nikolas Nikolaidis

    Full Text Available Developmental proteins play a pivotal role in the origin of animal complexity and diversity. We report here the identification of a highly divergent developmental protein superfamily (DANGER, which originated before the emergence of animals (approximately 850 million years ago and experienced major expansion-contraction events during metazoan evolution. Sequence analysis demonstrates that DANGER proteins diverged via multiple mechanisms, including amino acid substitution, intron gain and/or loss, and recombination. Divergence for DANGER proteins is substantially greater than for the prototypic member of the superfamily (Mab-21 family and other developmental protein families (e.g., WNT proteins. DANGER proteins are widely expressed and display species-dependent tissue expression patterns, with many members having roles in development. DANGER1A, which regulates the inositol trisphosphate receptor, promotes the differentiation and outgrowth of neuronal processes. Regulation of development may be a universal function of DANGER family members. This family provides a model system to investigate how rapid protein divergence contributes to morphological complexity.

  2. Membrane and Protein Interactions of the Pleckstrin Homology Domain Superfamily.

    Science.gov (United States)

    Lenoir, Marc; Kufareva, Irina; Abagyan, Ruben; Overduin, Michael

    2015-10-23

    The human genome encodes about 285 proteins that contain at least one annotated pleckstrin homology (PH) domain. As the first phosphoinositide binding module domain to be discovered, the PH domain recruits diverse protein architectures to cellular membranes. PH domains constitute one of the largest protein superfamilies, and have diverged to regulate many different signaling proteins and modules such as Dbl homology (DH) and Tec homology (TH) domains. The ligands of approximately 70 PH domains have been validated by binding assays and complexed structures, allowing meaningful extrapolation across the entire superfamily. Here the Membrane Optimal Docking Area (MODA) program is used at a genome-wide level to identify all membrane docking PH structures and map their lipid-binding determinants. In addition to the linear sequence motifs which are employed for phosphoinositide recognition, the three dimensional structural features that allow peripheral membrane domains to approach and insert into the bilayer are pinpointed and can be predicted ab initio. The analysis shows that conserved structural surfaces distinguish which PH domains associate with membrane from those that do not. Moreover, the results indicate that lipid-binding PH domains can be classified into different functional subgroups based on the type of membrane insertion elements they project towards the bilayer.

  3. Membrane and Protein Interactions of the Pleckstrin Homology Domain Superfamily

    Directory of Open Access Journals (Sweden)

    Marc Lenoir

    2015-10-01

    Full Text Available The human genome encodes about 285 proteins that contain at least one annotated pleckstrin homology (PH domain. As the first phosphoinositide binding module domain to be discovered, the PH domain recruits diverse protein architectures to cellular membranes. PH domains constitute one of the largest protein superfamilies, and have diverged to regulate many different signaling proteins and modules such as Dbl homology (DH and Tec homology (TH domains. The ligands of approximately 70 PH domains have been validated by binding assays and complexed structures, allowing meaningful extrapolation across the entire superfamily. Here the Membrane Optimal Docking Area (MODA program is used at a genome-wide level to identify all membrane docking PH structures and map their lipid-binding determinants. In addition to the linear sequence motifs which are employed for phosphoinositide recognition, the three dimensional structural features that allow peripheral membrane domains to approach and insert into the bilayer are pinpointed and can be predicted ab initio. The analysis shows that conserved structural surfaces distinguish which PH domains associate with membrane from those that do not. Moreover, the results indicate that lipid-binding PH domains can be classified into different functional subgroups based on the type of membrane insertion elements they project towards the bilayer.

  4. MetaSINEs: Broad Distribution of a Novel SINE Superfamily in Animals

    OpenAIRE

    Nishihara, Hidenori; Plazzi, Federico; Passamonti, Marco; Okada, Norihiro

    2016-01-01

    SINEs (short interspersed elements) are transposable elements that typically originate independently in each taxonomic clade (order/family). However, some SINE families share a highly similar central sequence and are thus categorized as a SINE superfamily. Although only four SINE superfamilies (CORE-SINEs, V-SINEs, DeuSINEs, and Ceph-SINEs) have been reported so far, it is expected that new SINE superfamilies would be discovered by deep exploration of new SINEs in metazoan genomes. Here we de...

  5. Homo religiosus : philosophical anthropology Viktor Emil Frankl 's .

    Directory of Open Access Journals (Sweden)

    Marcos Vinícius da Costa Meireles

    2015-10-01

    Full Text Available This work, entitled The Homo religiosus: the philosophical anthropology of Viktor Emil Frankl, is rooted in the anthropology of Frankl and aims to understand Frankl’s anthropology and its spiritual dynamic in religious experience. Using theoretical-bibliographical research with these main works—The Ignored Presence of God (1948, The Unconditioned Man (1949, Patient Man (1950, and The Search for God and Questions about the Meaning of Life (1984—this work traverses through Frankl’s anthropology, the spiritual dimension, the search for meaning, and one’s relationship with God. The work is divided into three parts. The first part consists of contextualization and critique. The second part puts forward a proposal, and the third part discusses the experience of the Homo religiosus.

  6. HOMO ECONOMICUS IN MODERNIZATION OF EDUCATION IN UKRAINE: PHILOSOPHICAL ASPECT

    OpenAIRE

    Petinova O.B.

    2013-01-01

    In the article the author gives consideration to innovations in education as the main factor of modernization of the education of Ukraine and formation of homo economicus in conditions of eurointegration and establishing of market society. The innovation machanizm is considered what gives an opportunity to grade the innovation knowledge in social practice of education. Article also considers ne-oliberalism as a philosophy of life in XXI century which forms new entrepreneur ethics and defines ...

  7. Culture Prefigures Cognition in Pan/Homo Bonobos

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    Sue SAVAGE-RUMBAUGH

    2010-01-01

    Full Text Available This article questions traditional approaches to the study of primate cognition. Because of a widespread assumption that cognition in non-human primates is genetically encoded, these approaches neglect how profoundly apes’ cultural rearing experiences affect test results. We describe how three advanced cognitive abilities – imitation, theory of mind and language – emerged in bonobos maturing in a Pan/Homo culture.

  8. El monstruo y el potro: el Homo sacer totalizado

    Directory of Open Access Journals (Sweden)

    Luis Enrique Peñuelas Carrillo

    2016-01-01

    Full Text Available El sujeto dominado – Homo sacer – en las instituciones totales, cárcel y ejército, se construye en relación con un sujeto dominante – soberano – , que a través del lenguaje ejerce una desarticulación entre violencia y dependencia, los cuales se cristalizan en palabras que los nombran dentro de ambas instituciones, monstruo en la cárcel y potro en el ejército.

  9. The place of Homo floresiensis in human evolution.

    Science.gov (United States)

    Baab, Karen

    2016-06-20

    Two main evolutionary scenarios have been proposed to explain the presence of the small-bodied and small-brained Homo floresiensis species on the remote Indonesian island of Flores in the Late Pleistocene. According to these two scenarios, H. floresiensis was a dwarfed descendent of H. erectus or a late-surviving remnant of a older lineage, perhaps descended from H. habilis. Each scenario has interesting and important implications for hominin biogeography, body size evolution, brain evolution and morphological convergences. Careful evaluation reveals that only a small number of characters support each of these scenarios uniquely. H. floresiensis exhibits a cranial shape and many cranial characters that appear to be shared derived traits with H. erectus, but postcranial traits are more primitive and resemble those of early Homo or even australopiths. Mandibular and dental traits show a mix of derived and primitive features. Unfortunately, many traits cannot be used to assess these two hypotheses because their distribution in H. erectus, early Homo (e.g., H. habilis), or both is unknown. H. erectus ancestry implies evolutionary convergence on a postcranial configuration similar to australopiths and early Homo, which could be explained by a return to more climbing behaviors. Body size reduction as well as brain size reduction on a scale only rarely documented in mammals would also accompany the origin of H. floresiensis from a H. erectus ancestor. H. habilis ancestry implies parallel evolution of numerous cranial characters, as well as a few dentognathic traits. A pre-H. erectus ancestry also suggests an early migration to Southeast Asia that is as yet undocumented in mainland Asia, but minimal body and brain size reduction.

  10. Bone strength and athletic ability in hominids: Ardipithecus ramidus to Homo sapiens

    Science.gov (United States)

    Lee, S. A.

    2013-03-01

    The ability of the femur to resist bending stresses is determined by its midlength cross-sectional geometry, its length and the elastic properties of the mineral part of the bone. The animal's athletic ability, determined by a ``bone strength index,'' is limited by this femoral bending strength in relation to the loads on the femur. This analysis is applied to the fossil record for Homo sapiens, Homo neanderthalensis, Homo erectus, Homo habilis, Australopithecus afarensis and Ardipithecus ramidus. Evidence that the femoral bone strength index of modern Homo sapiens has weakened over the last 50,000 years is found.

  11. Brain size of Homo floresiensis and its evolutionary implications.

    Science.gov (United States)

    Kubo, Daisuke; Kono, Reiko T; Kaifu, Yousuke

    2013-06-07

    The extremely small endocranial volume (ECV) of LB1, the type specimen of Homo floresiensis, poses a challenge in our understanding of human brain evolution. Some researchers hypothesize dramatic dwarfing of relative brain size from Homo erectus presumably without significant decrease in intellectual function, whereas others expect a lesser degree of brain diminution from a more primitive, small-brained form of hominin currently undocumented in eastern Asia. However, inconsistency in the published ECVs for LB1 (380-430 cc), unclear human intraspecific brain-body size scaling and other uncertainties have hampered elaborative modelling of its brain size reduction. In this study, we accurately determine the ECV of LB1 using high-resolution micro-CT scan. The ECV of LB1 thus measured, 426 cc, is larger than the commonly cited figure in previous studies (400 cc). Coupled with brain-body size correlation in Homo sapiens calculated based on a sample from 20 worldwide modern human populations, we construct new models of the brain size reduction in the evolution of H. floresiensis. The results show a more significant contribution of scaling effect than previously claimed.

  12. Short interspersed elements (SINEs) of the Geomyoidea superfamily rodents.

    Science.gov (United States)

    Gogolevsky, Konstantin P; Kramerov, Dmitri A

    2006-05-24

    A new short interspersed element (SINE) was isolated from the genome of desert kangaroo rat (Dipodomys deserti) using single-primer PCR. This SINE consists of two monomers: the left monomer (IDL) resembles rodent ID element and other tRNAAla(CGC)-derived SINEs, whereas the right one (Geo) shows no similarity with known SINE sequences. PCR and hybridization analyses demonstrated that IDL-Geo SINE is restricted to the rodent superfamily Geomyoidea (families Geomyidea and Heteromyidea). Isolation and analysis of IDL-Geo from California pocket mouse (Chaetodipus californicus) and Botta's pocket gopher (Thomomys bottae) revealed some species-specific features of this SINE family. The structure and evolution of known dimeric SINEs are discussed.

  13. Modeling catalytic promiscuity in the alkaline phosphatase superfamily.

    Science.gov (United States)

    Duarte, Fernanda; Amrein, Beat Anton; Kamerlin, Shina Caroline Lynn

    2013-07-21

    In recent years, it has become increasingly clear that promiscuity plays a key role in the evolution of new enzyme function. This finding has helped to elucidate fundamental aspects of molecular evolution. While there has been extensive experimental work on enzyme promiscuity, computational modeling of the chemical details of such promiscuity has traditionally fallen behind the advances in experimental studies, not least due to the nearly prohibitive computational cost involved in examining multiple substrates with multiple potential mechanisms and binding modes in atomic detail with a reasonable degree of accuracy. However, recent advances in both computational methodologies and power have allowed us to reach a stage in the field where we can start to overcome this problem, and molecular simulations can now provide accurate and efficient descriptions of complex biological systems with substantially less computational cost. This has led to significant advances in our understanding of enzyme function and evolution in a broader sense. Here, we will discuss currently available computational approaches that can allow us to probe the underlying molecular basis for enzyme specificity and selectivity, discussing the inherent strengths and weaknesses of each approach. As a case study, we will discuss recent computational work on different members of the alkaline phosphatase superfamily (AP) using a range of different approaches, showing the complementary insights they have provided. We have selected this particular superfamily, as it poses a number of significant challenges for theory, ranging from the complexity of the actual reaction mechanisms involved to the reliable modeling of the catalytic metal centers, as well as the very large system sizes. We will demonstrate that, through current advances in methodologies, computational tools can provide significant insight into the molecular basis for catalytic promiscuity, and, therefore, in turn, the mechanisms of protein

  14. The cellulose synthase superfamily in fully sequenced plants and algae

    Directory of Open Access Journals (Sweden)

    Xu Ying

    2009-07-01

    Full Text Available Abstract Background The cellulose synthase superfamily has been classified into nine cellulose synthase-like (Csl families and one cellulose synthase (CesA family. The Csl families have been proposed to be involved in the synthesis of the backbones of hemicelluloses of plant cell walls. With 17 plant and algal genomes fully sequenced, we sought to conduct a genome-wide and systematic investigation of this superfamily through in-depth phylogenetic analyses. Results A single-copy gene is found in the six chlorophyte green algae, which is most closely related to the CslA and CslC families that are present in the seven land plants investigated in our analyses. Six proteins from poplar, grape and sorghum form a distinct family (CslJ, providing further support for the conclusions from two recent studies. CslB/E/G/H/J families have evolved significantly more rapidly than their widely distributed relatives, and tend to have intragenomic duplications, in particular in the grape genome. Conclusion Our data suggest that the CslA and CslC families originated through an ancient gene duplication event in land plants. We speculate that the single-copy Csl gene in green algae may encode a mannan synthase. We confirm that the rest of the Csl families have a different evolutionary origin than CslA and CslC, and have proposed a model for the divergence order among them. Our study provides new insights about the evolution of this important gene family in plants.

  15. Homo sapiens, Homo neanderthalensis and the Denisova specimen: new insights on their evolutionary histories using whole-genome comparisons

    Directory of Open Access Journals (Sweden)

    Vanessa Rodrigues Paixão-Côrtes

    2012-01-01

    Full Text Available After a brief review of the most recent findings in the study of human evolution, an extensive comparison of the complete genomes of our nearest relative, the chimpanzee (Pan troglodytes, of extant Homo sapiens, archaic Homo neanderthalensis and the Denisova specimen were made. The focus was on non-synonymous mutations, which consequently had an impact on protein levels and these changes were classified according to degree of effect. A total of 10,447 non-synonymous substitutions were found in which the derived allele is fixed or nearly fixed in humans as compared to chimpanzee. Their most frequent location was on chromosome 21. Their presence was then searched in the two archaic genomes. Mutations in 381 genes would imply radical amino acid changes, with a fraction of these related to olfaction and other important physiological processes. Eight new alleles were identified in the Neanderthal and/or Denisova genetic pools. Four others, possibly affecting cognition, occured both in the sapiens and two other archaic genomes. The selective sweep that gave rise to Homo sapiens could, therefore, have initiated before the modern/archaic human divergence.

  16. Homo sapiens, Homo neanderthalensis and the Denisova specimen: New insights on their evolutionary histories using whole-genome comparisons.

    Science.gov (United States)

    Paixão-Côrtes, Vanessa Rodrigues; Viscardi, Lucas Henrique; Salzano, Francisco Mauro; Hünemeier, Tábita; Bortolini, Maria Cátira

    2012-12-01

    After a brief review of the most recent findings in the study of human evolution, an extensive comparison of the complete genomes of our nearest relative, the chimpanzee (Pan troglodytes), of extant Homo sapiens, archaic Homo neanderthalensis and the Denisova specimen were made. The focus was on non-synonymous mutations, which consequently had an impact on protein levels and these changes were classified according to degree of effect. A total of 10,447 non-synonymous substitutions were found in which the derived allele is fixed or nearly fixed in humans as compared to chimpanzee. Their most frequent location was on chromosome 21. Their presence was then searched in the two archaic genomes. Mutations in 381 genes would imply radical amino acid changes, with a fraction of these related to olfaction and other important physiological processes. Eight new alleles were identified in the Neanderthal and/or Denisova genetic pools. Four others, possibly affecting cognition, occured both in the sapiens and two other archaic genomes. The selective sweep that gave rise to Homo sapiens could, therefore, have initiated before the modern/archaic human divergence.

  17. Implications of Mycobacterium Major Facilitator Superfamily for Novel Measures against Tuberculosis.

    Science.gov (United States)

    Wang, Rui; Zhang, Zhen; Xie, Longxiang; Xie, Jianping

    2015-01-01

    Major facilitator superfamily (MFS) is an important secondary membrane transport protein superfamily conserved from prokaryotes to eukaryotes. The MFS proteins are widespread among bacteria and are responsible for the transfer of substrates. Pathogenic Mycobacterium MFS transporters, their distribution, function, phylogeny, and predicted crystal structures were studied to better understand the function of MFS and to discover specific inhibitors of MFS for better tuberculosis control.

  18. The ribonuclease A superfamily of mammals and birds : identifying new members and tracing evolutionary histories

    NARCIS (Netherlands)

    Cho, S; Beintema, JJ; Zhang, JZ

    2005-01-01

    The RNase A superfamily has been important in biochemical, structural, and evolutionary studies and is believed to be the sole vertebratespecific enzyme family. To understand the origin and diversification of the superfamily, we here determine its entire repertoire in the sequenced genomes of human,

  19. The conserved scavenger receptor cysteine-rich superfamily in therapy and diagnosis

    DEFF Research Database (Denmark)

    Martínez, Vanesa Gabriela; Moestrup, Søren Kragh; Holmskov, Uffe;

    2011-01-01

    The scavenger receptor cysteine-rich (SRCR) superfamily of soluble or membrane-bound protein receptors is characterized by the presence of one or several repeats of an ancient and highly conserved protein module, the SRCR domain. This superfamily (SRCR-SF) has been in constant and progressive...

  20. What constitutes Homo sapiens? Morphology versus received wisdom.

    Science.gov (United States)

    Schwartz, Jeffrey

    2016-06-20

    Although Linnaeus coined Homo sapiens in 1735, it was Blumenbach forty years later who provided the first morphological definition of the species. Since humans were not then allowed to be ante-Diluvian, his effort applied to the genus, as well. After the Feldhofer Grotto Neanderthal disproved this creationist notion, and human-fossil hunting became legitimate, new specimens were allocated either to sapiens or new species within Homo, or even to new species within new genera. Yet as these taxonomic acts reflected the morphological differences between specimens, they failed to address the question: What constitutes H. sapiens? When in 1950 Mayr collapsed all human fossils into Homo, he not only denied humans a diverse evolutionary past, he also shifted the key to identifying its species from morphology to geological age - a practice most paleoanthropologists still follow. Thus, for example, H. erectus is the species that preceded H. sapiens, and H. sapiens is the species into which H. erectus morphed. In order to deal with a growing morass of morphologically dissimilar specimens, the non-taxonomic terms "archaic" (AS) and "anatomically modern" (AMS) were introduced to distinguish between the earlier and later versions of H. sapiens, thereby making the species impossible to define. In attempting to disentangle fact from scenario, I begin from the beginning, trying to delineate features that may be distinctive of extant humans (ES), and then turning to the fossils that have been included in the species. With the exception of Upper Paleolithic humans - e.g. from Cro-Magnon, Dolni Vestonice, Mladeč - I argue that many specimens regarded as AMS, and all those deemed AS, are not H. sapiens. The features these AMS do share with ES suggest the existence of a sapiens clade. Further, restudy of near-recent fossils, especially from southwestern China (∼11-14.5 ka), reinforces what discoveries such as H. floresiensis indicate: "If it's recent, it's not necessarily H. sapiens".

  1. Homo naledi and Pleistocene hominin evolution in subequatorial Africa

    Science.gov (United States)

    Berger, Lee R; Hawks, John; Dirks, Paul HGM; Elliott, Marina; Roberts, Eric M

    2017-01-01

    New discoveries and dating of fossil remains from the Rising Star cave system, Cradle of Humankind, South Africa, have strong implications for our understanding of Pleistocene human evolution in Africa. Direct dating of Homo naledi fossils from the Dinaledi Chamber (Berger et al., 2015) shows that they were deposited between about 236 ka and 335 ka (Dirks et al., 2017), placing H. naledi in the later Middle Pleistocene. Hawks and colleagues (Hawks et al., 2017) report the discovery of a second chamber within the Rising Star system (Dirks et al., 2015) that contains H. naledi remains. Previously, only large-brained modern humans or their close relatives had been demonstrated to exist at this late time in Africa, but the fossil evidence for any hominins in subequatorial Africa was very sparse. It is now evident that a diversity of hominin lineages existed in this region, with some divergent lineages contributing DNA to living humans and at least H. naledi representing a survivor from the earliest stages of diversification within Homo. The existence of a diverse array of hominins in subequatorial comports with our present knowledge of diversity across other savanna-adapted species, as well as with palaeoclimate and paleoenvironmental data. H. naledi casts the fossil and archaeological records into a new light, as we cannot exclude that this lineage was responsible for the production of Acheulean or Middle Stone Age tool industries. DOI: http://dx.doi.org/10.7554/eLife.24234.001 PMID:28483041

  2. Unique Dental Morphology of Homo floresiensis and Its Evolutionary Implications.

    Science.gov (United States)

    Kaifu, Yousuke; Kono, Reiko T; Sutikna, Thomas; Saptomo, Emanuel Wahyu; Jatmiko; Due Awe, Rokus

    2015-01-01

    Homo floresiensis is an extinct, diminutive hominin species discovered in the Late Pleistocene deposits of Liang Bua cave, Flores, eastern Indonesia. The nature and evolutionary origins of H. floresiensis' unique physical characters have been intensively debated. Based on extensive comparisons using linear metric analyses, crown contour analyses, and other trait-by-trait morphological comparisons, we report here that the dental remains from multiple individuals indicate that H. floresiensis had primitive canine-premolar and advanced molar morphologies, a combination of dental traits unknown in any other hominin species. The primitive aspects are comparable to H. erectus from the Early Pleistocene, whereas some of the molar morphologies are more progressive even compared to those of modern humans. This evidence contradicts the earlier claim of an entirely modern human-like dental morphology of H. floresiensis, while at the same time does not support the hypothesis that H. floresiensis originated from a much older H. habilis or Australopithecus-like small-brained hominin species currently unknown in the Asian fossil record. These results are however consistent with the alternative hypothesis that H. floresiensis derived from an earlier Asian Homo erectus population and experienced substantial body and brain size dwarfism in an isolated insular setting. The dentition of H. floresiensis is not a simple, scaled-down version of earlier hominins.

  3. Unique Dental Morphology of Homo floresiensis and Its Evolutionary Implications.

    Directory of Open Access Journals (Sweden)

    Yousuke Kaifu

    Full Text Available Homo floresiensis is an extinct, diminutive hominin species discovered in the Late Pleistocene deposits of Liang Bua cave, Flores, eastern Indonesia. The nature and evolutionary origins of H. floresiensis' unique physical characters have been intensively debated. Based on extensive comparisons using linear metric analyses, crown contour analyses, and other trait-by-trait morphological comparisons, we report here that the dental remains from multiple individuals indicate that H. floresiensis had primitive canine-premolar and advanced molar morphologies, a combination of dental traits unknown in any other hominin species. The primitive aspects are comparable to H. erectus from the Early Pleistocene, whereas some of the molar morphologies are more progressive even compared to those of modern humans. This evidence contradicts the earlier claim of an entirely modern human-like dental morphology of H. floresiensis, while at the same time does not support the hypothesis that H. floresiensis originated from a much older H. habilis or Australopithecus-like small-brained hominin species currently unknown in the Asian fossil record. These results are however consistent with the alternative hypothesis that H. floresiensis derived from an earlier Asian Homo erectus population and experienced substantial body and brain size dwarfism in an isolated insular setting. The dentition of H. floresiensis is not a simple, scaled-down version of earlier hominins.

  4. Direct evidence for the Homo-Pan clade.

    Science.gov (United States)

    Wimmer, Rainer; Kirsch, Stefan; Rappold, Gudrun A; Schempp, Werner

    2002-01-01

    For a long time, the evolutionary relationship between human and African apes, the 'trichotomy problem', has been debated with strong differences in opinion and interpretation. Statistical analyses of different molecular DNA data sets have been carried out and have primarily supported a Homo-Pan clade. An alternative way to address this question is by the comparison of evolutionarily relevant chromosomal breakpoints. Here, we made use of a P1-derived artificial chromosome (PAC)/bacterial artificial chromosome (BAC) contig spanning approximately 2.8 Mb on the long arm of the human Y chromosome, to comparatively map individual PAC clones to chromosomes from great apes, gibbons, and two species of Old World monkeys by fluorescence in-situ hybridization. During our search for evolutionary breakpoints on the Y chromosome, it transpired that a transposition of an approximately 100-kb DNA fragment from chromosome 1 onto the Y chromosome must have occurred in a common ancestor of human, chimpanzee and bonobo. Only the Y chromosomes of these three species contain the chromosome-1-derived fragment; it could not be detected on the Y chromosomes of gorillas or the other primates examined. Thus, this shared derived (synapomorphic) trait provides clear evidence for a Homo-Pan clade independent of DNA sequence analysis.

  5. Role of TNF superfamily ligands in innate immunity.

    Science.gov (United States)

    Vujanovic, Nikola L

    2011-08-01

    Natural killer (NK) cells and dendritic cells (DCs) are essential effector cells of the innate immune system that rapidly recognize and eliminate microbial pathogens and abnormal cells, and induce and regulate adaptive immune functions. While NK cells express perforin and granzymes in the lysosomal granules and transmembrane tumor necrosis factor superfamily ligands (tmTNFSFL) on the plasma membrane, DCs express only tmTNFSFL on the plasma membrane. Perforin and granzymes are cytolytic molecules, which NK cells use to mediate a secretory/necrotic killing mechanism against rare leukemia cell targets. TNFSFL are pleiotropic transmembrane molecules, which can mediate a variety of important functions such as apoptosis, development of peripheral lymphoid tissues, inflammation and regulation of immune functions. Using tmTNFSFL, NK cells and DCs mediate a cell contact-dependent non-secretory apoptotic cytotoxic mechanism against virtually all types of cancer cells, and cross talk that leads to polarization and reciprocal stimulation and amplification of Th1 type cytokines secreted by NK cells and DCs. In this paper, we review and discuss the supporting evidence of the non-secretory, tmTNFSFL-mediated innate mechanisms of NK cells and DCs, their roles in anticancer immune defense and potential of their modulation and use in prevention and treatment of cancer.

  6. A superfamily of DNA transposons targeting multicopy small RNA genes.

    Directory of Open Access Journals (Sweden)

    Kenji K Kojima

    Full Text Available Target-specific integration of transposable elements for multicopy genes, such as ribosomal RNA and small nuclear RNA (snRNA genes, is of great interest because of the relatively harmless nature, stable inheritance and possible application for targeted gene delivery of target-specific transposable elements. To date, such strict target specificity has been observed only among non-LTR retrotransposons. We here report a new superfamily of sequence-specific DNA transposons, designated Dada. Dada encodes a DDE-type transposase that shows a distant similarity to transposases encoded by eukaryotic MuDR, hAT, P and Kolobok transposons, as well as the prokaryotic IS256 insertion element. Dada generates 6-7 bp target site duplications upon insertion. One family of Dada DNA transposons targets a specific site inside the U6 snRNA genes and are found in various fish species, water flea, oyster and polycheate worm. Other target sequences of the Dada transposons are U1 snRNA genes and different tRNA genes. The targets are well conserved in multicopy genes, indicating that copy number and sequence conservation are the primary constraints on the target choice of Dada transposons. Dada also opens a new frontier for target-specific gene delivery application.

  7. Functions of Kinesin Superfamily Proteins in Neuroreceptor Trafficking

    Directory of Open Access Journals (Sweden)

    Na Wang

    2015-01-01

    Full Text Available Synaptic plasticity is widely regarded as the cellular basis of learning and memory. Understanding the molecular mechanism of synaptic plasticity has been one of center pieces of neuroscience research for more than three decades. It has been well known that the trafficking of α-amino-3-hydroxy-5-methylisoxazoloe-4-propionic acid- (AMPA- type, N-methyl-D-aspartate- (NMDA- type glutamate receptors to and from synapses is a key molecular event underlying many forms of synaptic plasticity. Kainate receptors are another type of glutamate receptors playing important roles in synaptic transmission. In addition, GABA receptors also play important roles in modulating the synaptic plasticity. Kinesin superfamily proteins (also known as KIFs transport various cargos in both anterograde and retrograde directions through the interaction with different adaptor proteins. Recent studies indicate that KIFs regulate the trafficking of NMDA receptors, AMPA receptors, kainate receptors, and GABA receptors and thus play important roles in neuronal activity. Here we review the essential functions of KIFs in the trafficking of neuroreceptor and synaptic plasticity.

  8. Chemical synthesis of peptides within the insulin superfamily.

    Science.gov (United States)

    Liu, Fa; Zaykov, Alexander N; Levy, Jay J; DiMarchi, Richard D; Mayer, John P

    2016-05-01

    The synthesis of insulin has inspired fundamental advances in the art of peptide science while simultaneously revealing the structure-function relationship of this centrally important metabolic hormone. This review highlights milestones in the chemical synthesis of insulin that can be divided into two separate approaches: (i) disulfide bond formation driven by protein folding and (ii) chemical reactivity-directed sequential disulfide bond formation. Common to the two approaches are the persistent challenges presented by the hydrophobic nature of the individual A-chain and B-chain and the need for selective disulfide formation under mildly oxidative conditions. The extension and elaboration of these synthetic approaches have been ongoing within the broader insulin superfamily. These structurally similar peptides include the insulin-like growth factors and also the related peptides such as relaxin that signal through G-protein-coupled receptors. After a half-century of advances in insulin chemistry, we have reached a point where synthesis is no longer limiting structural and biological investigation within this family of peptide hormones. The future will increasingly focus on the refinement of structure to meet medicinal purposes that have long been pursued, such as the development of a glucose-sensitive insulin. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  9. Homo noosphericus как актуализация образа Homo Futurus

    Directory of Open Access Journals (Sweden)

    Цветков А. П.

    2013-04-01

    Full Text Available The realisation of gap between existing and proper, and therefore, of deficit of one’s substantiality and fullness, that is identity, have caused the phenomenon which Hegel signified as “unhappy consciousness”. In the context of opposition of existing and proper and with the help of key points of Noospherology, the idea about sharp necessity of culture-forming ideal image actualization of a person, Homo Responsabilis, is grounded through possible implementation of homo noosphericus project. The deep nostalgia of an individual for integrity and fullness of one’s own existence caused the evolution of idealized Homo Responsabilis images in European culture: “Homo Sanctus” of Middle Ages, “Homo Humanitatis” of Renaissance, “Homo Sapiens” of the Rational Era, “Homo Machina” of Enlightenment , “Homo Economicus” of Modern Times and so on. Essentially, up to the middle of the 20th century the ideal image of Homo Responsabilis had actual projection not only to present but mainly to future that generated and stimulated the responsibility of a human for one’s present and future. A contemporary person finds oneself in other situation. A separate individual drops behind “the speed” of humankind development in the sense of intellectuality and civilization. In the condition of accelerating multiple increase of information a person is obliged to glide on the surface of signs without having even time to correlate them with corresponding meanings and even more to deepen into their sense. Sad as it may seem to admit the horizons of intellectual and spiritual wild-growing for a human are becoming more distant. The project Homo Noosphericus, the actualization of Homo Responsabilis image, is justified by the analysis of such key points of noosphere studies as “cosmism”, “biosphere”, “noosphere”, “semiosphere”, “gaia conception” and “anthropic principle”. Such an analysis allows to uncover and to frame an

  10. Two-Stage Approach for Protein Superfamily Classification

    Directory of Open Access Journals (Sweden)

    Swati Vipsita

    2013-01-01

    Full Text Available We deal with the problem of protein superfamily classification in which the family membership of newly discovered amino acid sequence is predicted. Correct prediction is a matter of great concern for the researchers and drug analyst which helps them in discovery of new drugs. As this problem falls broadly under the category of pattern classification problem, we have made all efforts to optimize feature extraction in the first stage and classifier design in the second stage with an overall objective to maximize the performance accuracy of the classifier. In the feature extraction phase, Genetic Algorithm- (GA- based wrapper approach is used to select few eigenvectors from the principal component analysis (PCA space which are encoded as binary strings in the chromosome. On the basis of position of 1’s in the chromosome, the eigenvectors are selected to build the transformation matrix which then maps the original high-dimension feature space to lower dimension feature space. Using PCA-NSGA-II (non-dominated sorting GA, the nondominated solutions obtained from the Pareto front solve the trade-off problem by compromising between the number of eigenvectors selected and the accuracy obtained by the classifier. In the second stage, recursive orthogonal least square algorithm (ROLSA is used for training radial basis function network (RBFN to select optimal number of hidden centres as well as update the output layer weighting matrix. This approach can be applied to large data set with much lower requirements of computer memory. Thus, very small architectures having few number of hidden centres are obtained showing higher level of performance accuracy.

  11. Crystal structure of Homo sapiens protein LOC79017

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Euiyoung; Bingman, Craig A.; Aceti, David J.; Phillips, Jr., George N. (UW)

    2010-02-08

    LOC79017 (MW 21.0 kDa, residues 1-188) was annotated as a hypothetical protein encoded by Homo sapiens chromosome 7 open reading frame 24. It was selected as a target by the Center for Eukaryotic Structural Genomics (CESG) because it did not share more than 30% sequence identity with any protein for which the three-dimensional structure is known. The biological function of the protein has not been established yet. Parts of LOC79017 were identified as members of uncharacterized Pfam families (residues 1-95 as PB006073 and residues 104-180 as PB031696). BLAST searches revealed homologues of LOC79017 in many eukaryotes, but none of them have been functionally characterized. Here, we report the crystal structure of H. sapiens protein LOC79017 (UniGene code Hs.530024, UniProt code O75223, CESG target number go.35223).

  12. 1997-2001: el estatus de Homo antecessor

    Directory of Open Access Journals (Sweden)

    José María BERMÚDEZ DE CASTRO

    2009-12-01

    Full Text Available RESUMEN: En 1997 denominamos una nueva especie del género Homo, H. antecessor (Bermúdez de Castro et alii, 1997, para incluir la variabilidad observada en los restos humanos fósiles procedentes del nivel TD6 (Estrato Autota del yacimiento de la Gtan Dolina de la Sierra de Atapuerca (Burgos. Los nuevos hallazgos realizados desde entonces en otros yacimientos europeos (e. g. Dmanisi, República de Georgia, así como la reinterpretación de algunos ejemplares fósiles han reforzado la credibilidad de la especie. El hipodigma de H. antecessor se ha incrementado con la inclusión del espécimen descubierto en 1994 cerca de la localidad italiana de Ceprano. Por otra parte, la especie H. antecessor continúa siendo la mejot candidata para representar el último antecesor común de los neandertales y de las poblaciones modernas.ABSTRACT: In 1997 we named a new Homo species, H. antecessor (Bermúdez de Castro et alii, 1997, to accommodate the variability observed in the human fossil remains coming from the TD6 level (Aurora Stratum of the Gran Dolina site in the Sierra de Atapuerca (Burgos, Spain. The new findings made since then in other European sites (e. g. Dmanisi, Republic of Georgia, as well as the re-examination of some fossil specimens have strengthened the credit of the species. The H. antecessor hypodigm has increased with the inclusion of the adult calvaría discovered in 1994 near Ceprano (Italy. Moteover, H. antecessor is still the best candidate for representing the last common ancestor to Neanderthals and modem humans.

  13. The Emergence of Homo sapiens in South Asia: The Central Narmada Valley as Witness

    Directory of Open Access Journals (Sweden)

    Anek R. Sankhyan

    2013-04-01

    Full Text Available :The emergence of anatomically modern Homo sapiens in South Asia is hotly debated due to a great gap in fossil record. A solitary partial cranium from Hathnora dated around 250 Kya is debated and conveniently interpreted as "evolved" Homo erectus or "archaic" Homo sapiens or Homo heidelbergensis or even Homo indet. Cranial fossils of Pre-Toba or post- Toba anatomically modern Homo sapiens are unknown barring the very late 30 Kya modern human remains from Sri Lanka. The present paper reviews the scenario of human evolution in South Asia with special reference to the cranial and recent postcranial fossil findings by the author in association with the archaeological evidences from Central Narmada valley. It is concluded that the Narmada fossils and archaeological findings support the presence of three hominins- two 'archaic' and one 'early modern'. The Mode 2 Acheulian hominin represented by the calvarium and the femur was a 'large-bodied' species akin to Homo heidelbergensis. It appeared first in the Central Narmada valley and was followed by a 'small-bodied' Mode 3 archaic type represented by two clavicles and the 9th rib, provisionally named here as Homo narmadensis. It likely continued and attained anatomical and behavioural modernity in South Asia as attested by the humerus and bone artifacts, and diversified to various short-bodied indigenous populations of South Asia supported by the genomic evidences.

  14. A Critical Discourse Analysis of "No Promo Homo" Policies in US Schools

    Science.gov (United States)

    Barrett, Brian; Bound, Arron M.

    2015-01-01

    This article presents a critical discourse analysis of "no promo homo" policies and their effects in US schools. "No promo homo"--short for "no promotion of homosexuality" (Eskridge, 2000, p. 1329)--polices have been adopted across nine states and several local school districts in the United States. They direct…

  15. Design of homo-organic acid producing strains using multi-objective optimization

    DEFF Research Database (Denmark)

    Kim, Tae Yong; Park, Jong Myoung; Kim, Hyun Uk

    2015-01-01

    acids, while maintaining sufficiently high growth rate and minimizing the secretion of undesired byproducts. Homo-productions of acetic, lactic and succinic acids were targeted as examples. Engineered E. coli strains capable of producing homo-acetic and homo-lactic acids could be developed by taking...... this systems approach for the minimal identification of gene knockout targets. Also, failure to predict effective gene knockout targets for the homo-succinic acid production suggests that the multi-objective optimization is useful in assessing the suitability of a microorganism as a host strain......Production of homo-organic acids without byproducts is an important challenge in bioprocess engineering to minimize operation cost for separation processes. In this study, we used multi-objective optimization to design Escherichia coli strains with the goals of maximally producing target organic...

  16. Effects of a chemically derived homo zwitterionic polysaccharide on immune activation in mice

    Institute of Scientific and Technical Information of China (English)

    Chun Meng; Xu Peng; Xian'ai Shi; Hang Wang; Yanghao Guo

    2009-01-01

    In this study, a chemically modified homo zwitterionic polysaccharide (ZPS), sulfated chitosan, was used to examine its effects on murine immune response. The results showed that homoZPS could markedly promote the proliferation of both splenic T/B cells and adhesive cells. In particular, flow cytometry assay demonstrated that the sulfated chitosan could non-specifically activate CD3+ and CD8+ T cells proliferation in vitro. The effectiveness of sulfated chitosan as adjuvant was tested using bovine serum albumin (BSA) and diphtheria toxin (DT) as antigens and compared with that of aluminum hydroxide. The levels of specific antibodies to BSA and DT significantly increased after homoZPS vaccination. Both homoZPS and aluminum hydroxide adjuvants could protect mice against the attack of DT from edemas of spleen and tail. The present findings demonstrated the chemically derived homoZPS could be a potential candidate in the development of T-lym-phocyte dependent vaccine adjuvants.

  17. Utility of the Amborella trichopoda expansin superfamily in elucidating the history of angiosperm expansins.

    Science.gov (United States)

    Seader, Victoria H; Thornsberry, Jennifer M; Carey, Robert E

    2016-03-01

    Expansins form a superfamily of plant proteins that assist in cell wall loosening during growth and development. The superfamily is divided into four families: EXPA, EXPB, EXLA, and EXLB (Sampedro and Cosgrove in Genome Biol 6:242, 2005. doi: 10.1186/gb-2005-6-12-242 ). Previous studies on Arabidopsis, rice, and Populus trichocarpa have clarified the evolutionary history of expansins in angiosperms (Sampedro et al. in Plant J 44:409-419, 2005. doi: 10.1111/j.1365-313X.2005.02540.x ). Amborella trichopoda is a flowering plant that diverged very early. Thus, it is a sister lineage to all other extant angiosperms (Amborella Genome Project in 342:1241089, 2013. doi: 10.1126/science.1241089 ). Because of this relationship, comparing the A. trichopoda expansin superfamily with those of other flowering plants may indicate which expansin genes were present in the last common ancestor of all angiosperms. The A. trichopoda expansin superfamily was assembled using BLAST searches with angiosperm expansin queries. The search results were analyzed and annotated to isolate the complete A. trichopoda expansin superfamily. This superfamily is similar to other angiosperm expansin superfamilies, but is somewhat smaller. This is likely because of a lack of genome duplication events (Amborella Genome Project 2013). Phylogenetic and syntenic analyses of A. trichopoda expansins have improved our understanding of the evolutionary history of expansins in angiosperms. Nearly all of the A. trichopoda expansins were placed into an existing Arabidopsis-rice expansin clade. Based on the results of phylogenetic and syntenic analyses, we estimate there were 12-13 EXPA genes, 2 EXPB genes, 1 EXLA gene, and 2 EXLB genes in the last common ancestor of all angiosperms.

  18. HOMO (PREFABER / Homo (prefaber

    Directory of Open Access Journals (Sweden)

    Miguel Ángel de la Cova Morillo-Velarde

    2012-05-01

    Full Text Available RESUMEN En el presente número de la Revista PpA, dedicado a la vivienda prefabricada, se entrelazan dos de los campos de investigación de la arquitectura más efervescentes del último siglo: técnica y habitar. Industrialización, estandarización, modulación y seriación se confunden con el concepto de prefabricación como finas capas de un hojaldre difíciles de separar, horneadas bajo un mismo fuego que no es otro que el de responder a través de la producción reglada al alojamiento. En todos estos términos, el valor de la técnica, donde la figura del artesano aún permite pensar en una respuesta específica para cada producto, virará hacia el de la tecnología, dificultando incluir el hecho particular dentro del proceso creativo. Esta confrontación entre objetividad y contingencia adquiere mayor relevancia en el caso de la vivienda prefabricada, por la distancia especulativa que implica la ultimación del diseño previo a su construcción. La actual proliferación de soluciones predefinidas a la hora de enfrentarse al proyecto arquitectónico –principalmente en aspectos constructivos– y el aumento de la producción prefabricada de viviendas a nivel mundial requieren una reflexión disciplinar en la materia, que hilvane relaciones intencionadas entre hombre y producto.SUMMARY This issue of PPA is dedicated to the prefabricated home, and intertwines two of the most lively research areas in architecture over the last century: craftsmanship and living. Industrialization, standardization, modularization and serial production become blended with the concept of prefabrication as thin layers of puff pastry, difficult to separate, baked under the same fire which is nothing more than responding to accommodation needs through regulated production. In all these terms, the value of craftsmanship, where the artisan is still allowed to think of a specific response for each product, will veer towards that of technology, making the inclusion of that response in the creative process more difficult. This confrontation between objectivity and contingency becomes more important in the case of the prefabricated home, due to the speculative distance involved in the finalization of the design, prior to its construction. The current proliferation of predefined solutions that are available for tackling the architectural project, mainly in construction aspects, and the increased prefabricated production of homes worldwide require a disciplinary reflection on the subject, which tacks together the intended relationships between man and product.

  19. DEFINIENDO HOMO SAPIENS-SAPIENS: APROXIMACIÓN ANTROPOLÓGICA DEFININDO HOMO SAPIENS-SAPIENS: APROXIMAÇÃO ANTROPOLÓGICA DEFINING HOMO SAPIENS-SAPIENS: ANTHROPOLOGICAL APPROACH

    Directory of Open Access Journals (Sweden)

    Carolina Valdebenito

    2007-06-01

    Full Text Available Este artículo reflexiona sobre los encuentros y desencuentros entre el ser humano y el resto de los animales, en tanto miembros de sistemas en permanente interacción(1. Abordar la definición de Homo, repasar su evolución biológica y cultural y reflexionar sobre los resabios de animalidad que quedan en el comportamiento social del Homo sapiens-sapiens es su objetivo principal. Se busca reflexionar sobre los dilemas morales que acompañan al hombre en tanto ser cultural; para ello se analizan dos dilemas éticos: la violencia y el incestoEste artigo reflete sobre os encontros e desencontros entre o ser humano e os demais animais, enquanto membros de sistemas em permanente interação(1. Seu principal objetivo é abordar a definição de Homo, traçar um panorama de sua evolução biológica e cultural e refletir sobre os resquícios da animalidade que permanecem no comportamento social do Homo sapiens-sapiens. Busca-se refletir sobre os dilemas morais que acompanham o homem enquanto ser cultural, o que para isso são considerados como dilemas éticos: a violência e o incestoThis paper reflects on the similarities and differences between human beings and animals as members of systems in permanent interaction. The main goal is to define Homo, reviewing his/her biological and cultural evolution and reflecting on the animal social behaviors that still remain in Homo sapiens-sapiens. The paper reflect on the moral dilemmas present in humans as cultural beings, taking as example the ethical dilemmas of violence and incest

  20. Genome digging: insight into the mitochondrial genome of Homo.

    Directory of Open Access Journals (Sweden)

    Igor V Ovchinnikov

    Full Text Available BACKGROUND: A fraction of the Neanderthal mitochondrial genome sequence has a similarity with a 5,839-bp nuclear DNA sequence of mitochondrial origin (numt on the human chromosome 1. This fact has never been interpreted. Although this phenomenon may be attributed to contamination and mosaic assembly of Neanderthal mtDNA from short sequencing reads, we explain the mysterious similarity by integration of this numt (mtAncestor-1 into the nuclear genome of the common ancestor of Neanderthals and modern humans not long before their reproductive split. PRINCIPAL FINDINGS: Exploiting bioinformatics, we uncovered an additional numt (mtAncestor-2 with a high similarity to the Neanderthal mtDNA and indicated that both numts represent almost identical replicas of the mtDNA sequences ancestral to the mitochondrial genomes of Neanderthals and modern humans. In the proteins, encoded by mtDNA, the majority of amino acids distinguishing chimpanzees from humans and Neanderthals were acquired by the ancestral hominins. The overall rate of nonsynonymous evolution in Neanderthal mitochondrial protein-coding genes is not higher than in other lineages. The model incorporating the ancestral hominin mtDNA sequences estimates the average divergence age of the mtDNAs of Neanderthals and modern humans to be 450,000-485,000 years. The mtAncestor-1 and mtAncestor-2 sequences were incorporated into the nuclear genome approximately 620,000 years and 2,885,000 years ago, respectively. CONCLUSIONS: This study provides the first insight into the evolution of the mitochondrial DNA in hominins ancestral to Neanderthals and humans. We hypothesize that mtAncestor-1 and mtAncestor-2 are likely to be molecular fossils of the mtDNAs of Homo heidelbergensis and a stem Homo lineage. The d(N/d(S dynamics suggests that the effective population size of extinct hominins was low. However, the hominin lineage ancestral to humans, Neanderthals and H. heidelbergensis, had a larger effective

  1. Alexis de Tocqueville y su daguerrotipo del homo democraticus

    Directory of Open Access Journals (Sweden)

    Aramayo, Roberto R.

    2011-08-01

    Full Text Available This article is on Tocqueville and his thoughts about the vicissitudes of the democracy which have been given a fresh impetus because of the massive demonstrations driven or generated by the 15th-May spirit. Such as the texts written by the rest of the classical authors, his writings were right when both approaching the problems and arousing diagnostics and are still capable to drive us to think anew about the rules of the democratic game. Following the paradoxical destiny of his great-grandfather Malesherbes, who defended the rights of the people before Louis 16th and next the rights of the King before the revolutionary court, the aristocratic Tocqueville became a champion of the unstoppable democratic revolution but without forgetting the potential dangers caused by this revolution. His comparison between both French and American revolutions helped him to define the qualities of the homo democraticus. The text intends to work as a sort of lay-out of the material collected in this issue.Tocqueville y sus reflexiones en torno a los avatares de la democracia cobran una inusitada vigencia con las movilizaciones generada por el espíritu del 15M. Como cualquier otro clásico que se precie de merecer tal nombre, sus escritos aciertan a la hora de plantear los problemas y suscitar diagnósticos que no han perdido su capacidad para hacernos repensar las reglas del juego democrático. Siguiendo el paradójico destino de su bisabuelo Malesherbes, quien defendió los derechos del pueblo ante Luis XVI y luego a éste frente al tribunal revolucionario, el aristocrático Tocqueville se convertiría en un paladín de la imparable revolución democrática, sin dejar de analizar los potenciales peligros entrañados por ésta. Su comparación entre las revoluciones americana y francesa le serviría para definir a los atributos del homo democraticus. El texto pretende servir de presentación a los materiales recogidos en este número.

  2. The evolutionary relationships and age of Homo naledi: An assessment using dated Bayesian phylogenetic methods.

    Science.gov (United States)

    Dembo, Mana; Radovčić, Davorka; Garvin, Heather M; Laird, Myra F; Schroeder, Lauren; Scott, Jill E; Brophy, Juliet; Ackermann, Rebecca R; Musiba, Chares M; de Ruiter, Darryl J; Mooers, Arne Ø; Collard, Mark

    2016-08-01

    Homo naledi is a recently discovered species of fossil hominin from South Africa. A considerable amount is already known about H. naledi but some important questions remain unanswered. Here we report a study that addressed two of them: "Where does H. naledi fit in the hominin evolutionary tree?" and "How old is it?" We used a large supermatrix of craniodental characters for both early and late hominin species and Bayesian phylogenetic techniques to carry out three analyses. First, we performed a dated Bayesian analysis to generate estimates of the evolutionary relationships of fossil hominins including H. naledi. Then we employed Bayes factor tests to compare the strength of support for hypotheses about the relationships of H. naledi suggested by the best-estimate trees. Lastly, we carried out a resampling analysis to assess the accuracy of the age estimate for H. naledi yielded by the dated Bayesian analysis. The analyses strongly supported the hypothesis that H. naledi forms a clade with the other Homo species and Australopithecus sediba. The analyses were more ambiguous regarding the position of H. naledi within the (Homo, Au. sediba) clade. A number of hypotheses were rejected, but several others were not. Based on the available craniodental data, Homo antecessor, Asian Homo erectus, Homo habilis, Homo floresiensis, Homo sapiens, and Au. sediba could all be the sister taxon of H. naledi. According to the dated Bayesian analysis, the most likely age for H. naledi is 912 ka. This age estimate was supported by the resampling analysis. Our findings have a number of implications. Most notably, they support the assignment of the new specimens to Homo, cast doubt on the claim that H. naledi is simply a variant of H. erectus, and suggest H. naledi is younger than has been previously proposed.

  3. "Homo reciprocusSeneka, Paulus en weldoenerskap1

    Directory of Open Access Journals (Sweden)

    Stephan Joubert

    1999-01-01

    Full Text Available "Homo reciprocus": Seneca, Paul and benefaction Reciprocity was basic to most forms of social interaction in the ancient Mediterranean world. Any exchange of services/gits was based on the principle that the obligations incurred between two parties required an adequate response. In his ethical treatise on beneit exchange, "De beneficiis,"Seneca presents an idealistic reinterpretation of the basic tenets of benefaction by providing a "lex vitae", a law of conduct, according to which the giving of beneits becomes an intrinsically rewarding experience in itself. On his part, the apostle Paul conceptualises his "ecumenical" collecion for the Jerusalem church in terms of the principles inherent to beneit exchange in the Graeco-Roman world. He involves his communities as beneiciaries in the reciprocal relationship between himself and Jerusalem. In Romans 15:25-31, when the acceptance of the collecion hangs in the balance, Paul reinterprets the reciprocal relationship with Jerusalem in terms of altruistic Christian principles. From this new angle of incidence his churches are presented as having successfully completed the collection since they unselishly fulilled their moral duies towards the latter.

  4. Spectroscopic properties, NLO, HOMO-LUMO and NBO of maltol

    Science.gov (United States)

    KrishnaKumar, V.; Barathi, D.; Mathammal, R.; Balamani, J.; Jayamani, N.

    2014-03-01

    Maltol (3-hydroxy-2-methyl-4pyrone) is widely known as metal ions chelator with many practical applications in catalysis, medicine and food chemistry. The FTIR and FT-Raman spectra of maltol have been recorded in the region 4000-400 and 4000-50 cm-1, respectively. The conformational analysis, optimized geometry, frequency and intensity of the vibrational bands of maltol were obtained by the density functional theory (DFT) with complete relaxation in the potential energy surface using 6-31G* basis set. The observed and the calculated frequencies are found to be in good agreement. The 1H and 13C NMR spectra have been recorded and 1H and 13C nuclear magnetic resonance chemical shifts of the molecule were also calculated using the gauge independent atomic orbital (GIAO) method and their respective linear correlations were obtained. The electronic properties HOMO and LUMO energies were measured. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound were calculated. The Mulliken charges, the values of electric dipole moment (μ) of the molecule were computed using DFT calculations. The first order hyperpolarizability (βo) and related properties (β, αo and Δα) of both are calculated using B3LYP/6-31G* method on the finite-field approach. The calculated first hyperpolarizability shows that the molecules are an attractive molecule for future applications in non-linear optics. The intramolecular contacts have been interpreted using Natural Bond Orbital (NBO).

  5. Molar crown inner structural organization in Javanese Homo erectus.

    Science.gov (United States)

    Zanolli, Clément

    2015-01-01

    This contribution investigates the inner organizational pattern (tooth tissue proportions and enamel-dentine junction morphology) of seven Homo erectus permanent molar crowns from the late Lower-early Middle Pleistocene Kabuh Formation of the Sangiran Dome (Central Java, Indonesia). The previous study of their external characteristics confirmed the degree of time-related structural reduction occurred in Javanese H. erectus, and also revealed a combination of nonmetric features which are rare in the Lower and early Middle Pleistocene dental record, but more frequently found in recent humans. In accordance with their outer occlusal morphology, the specimens exhibit a set of derived internal features, such as thick to hyperthick enamel, an incomplete expression of the crest patterns at the enamel-dentine junction (EDJ) level, a sharp EDJ topography. As a whole, these features differ from those expressed in some penecontemporaneous specimens/samples representing African H. erectus/ergaster and H. heidelbergensis, as well as in Neanderthals, but occur in recent human populations. Further research in virtual dental paleoanthropology to be developed at macroregional scale would clarify the polarity and intensity of the intermittent exchanges between continental and insular Southeast Asia around the Lower to Middle Pleistocene boundary, as well as should shed light on the still poorly understood longitudinal evolutionary dynamics across continental Asia.

  6. Homo Ludens Revisited: Huizinga y el deporte moderno

    Directory of Open Access Journals (Sweden)

    Gastaldo, Edison

    2012-06-01

    Full Text Available En este artículo me gustaría proponer una lectura del fenómeno del deporte contemporáneo, desde la perspectiva del magistral Homo Ludens, obra del filósofo holandés publicado originalmente en 1938. Para esto, después de una breve presentación del autor y su obra, se exploran algunas condiciones de posibilidad de la existencia del principio del juego en el deporte moderno. Para Huizinga, el "espíritu del juego" encabeza las principales manifestaciones de la cultura humana en todas las épocas y sociedades. Sin embargo, este principio se estaría pervirtiendo en el mundo moderno, donde el trabajo asume aspectos de un juego (el ganar de los concurrentes, vencer el récord de las ventas y el mundo del juego asume el carácter de trabajo (atletas profesionales, negocios, contratos, patrocinadores. ¿Como pensaría la perspectiva humanista y libertaria de Huizinga sobre el juego el mundo de los deportes contemporáneos? O, dicho de otro modo, ¿hay espacio para la práctica de ocio creativo y humanización en el mundo del deporte?

  7. Spectroscopic Signature of a Ubiquitous Metal Binding Site in the Metallo-beta-lactamase Superfamily

    Energy Technology Data Exchange (ETDEWEB)

    V Campos-Bermudez; J Gonzalez; D Tierney; A Vila

    2011-12-31

    The metallo-{beta}-lactamase (M{beta}L) superfamily is a functionally diverse group of metalloproteins sharing a distinctive {alpha}{beta}/{alpha}{beta} fold and a characteristic metal binding motif. A large number of open reading frames identified in genomic sequencing efforts have been annotated as members of this superfamily through sequence comparisons. However, structural and functional studies performed on purified proteins are normally needed to unequivocally include a newly discovered protein in the M{beta}L superfamily. Here we report the spectroscopic characterization of recombinant YcbL, a gene product annotated as a member of the M{beta}L superfamily whose function in vivo remains unknown. By taking advantage of the structural features characterizing the M{beta}L superfamily metal binding motif, we performed spectroscopic studies on Zn(II)- and Co(II)-substituted YcbL to structurally interrogate the metal binding site. The dinuclear center in Co(II)-YcbL was shown to display characteristic electronic absorption features in the visible region, which were also observed in an engineered M{beta}L aimed at mimicking this metal site. Thus, the spectroscopic features reported herein can be employed as a signature to readily identify and characterize the presence of these ubiquitous metal binding sites.

  8. A new method of research on molecular evolution of pro-teinase superfamily

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The molecular evolutionary tree, also known as a phylogenetic tree, of the serine proteinase superfamily was constructed by means of structural alignment. Three-dimensional structures of proteins were aligned by the SSAP program of Orengo and Taylor to obtain evolutionary dis-tances. The resulting evolutionary tree provides a topology graph that can reflect the evolution of structure and function of homology proteinase. Moreover, study on evolution of the serine proteinase superfamily can lead to better under-standing of the relationship and evolutionary difference among proteins of the superfamily, and is of significance to protein engineering, molecular design and protein structure prediction. Structure alignment is one of the useful methods of research on molecular evolution of protein.

  9. Preestrita pihtimus : Friedrich Nietzsche ja tema substantsiaalne mina (Ecce homo) / Jaan Undusk

    Index Scriptorium Estoniae

    Undusk, Jaan, 1958-

    1998-01-01

    Varem ilmunud raamatu järelsõnana: Nietzsche, Friedrich. Ecce homo : kuidas saadakse selleks, mis ollakse / tlk. Jaan Undusk. Tallinn : Vagabund, 1996. Sisu: Poeetiline, filosoofiline, dionüüsiline kaanon ; Künism contra hulluskahtlus ; Antikristlik pihtimus ; Egoretoorika

  10. The Role of the Imagination in Adam Smith’s Refutation of the Homo Economicus Thesis

    National Research Council Canada - National Science Library

    José de la Cruz Garrido

    2015-01-01

    .... In both cases, the role of the imagination in our moral psychology refutes the homo economicus thesis according to which human beings are motivated to enter into society due to personal interests...

  11. Continuous flow room temperature reductive aqueous homo-coupling of aryl halides using supported Pd catalysts

    National Research Council Canada - National Science Library

    Feiz, Afsaneh; Bazgir, Ayoob; Balu, Alina M; Luque, Rafael

    2016-01-01

    .... A simple reductive homo-coupling Ullmann-type reaction was performed in an H-Cube mini using commercially available supported Pd catalysts under mild reaction conditions, with quantitative conversion to target products...

  12. Sobre la identidad del fragmento craneal atribuido a Homo sp. en Venta Mlcena (Orce Granada

    Directory of Open Access Journals (Sweden)

    Moyá-Solá, S.

    1987-12-01

    Full Text Available The internal morphology of the cranial fragment attributed to Homo from Venta Micena (Granada is analysed. The presence of a coronal suture close to lambda does not permit its attribution to the genus Homo. The distace between the coronal suture and lambda (4 cm., the presence of tentorial procces and the digital impresions strongly suggesst its attribution to a juvenil specimen of Equus stenonis.Se analiza la morfología de la cara interna del fragmento craneal de Venta Micena atribuido inicialmente al género Homo. Se detecta la presencia de la sutura coronal a cuatro centímetros del punto lambda. Ello, conjuntamente a las fuertes impresiones digitales del endocraneo y la presencia de una cresta del proceso oseo tentoríal hacen imposible la adscripción de esta pieza al género Homo., atribuyendose a Equus stenonis.

  13. Preestrita pihtimus : Friedrich Nietzsche ja tema substantsiaalne mina (Ecce homo) / Jaan Undusk

    Index Scriptorium Estoniae

    Undusk, Jaan, 1958-

    1998-01-01

    Varem ilmunud raamatu järelsõnana: Nietzsche, Friedrich. Ecce homo : kuidas saadakse selleks, mis ollakse / tlk. Jaan Undusk. Tallinn : Vagabund, 1996. Sisu: Poeetiline, filosoofiline, dionüüsiline kaanon ; Künism contra hulluskahtlus ; Antikristlik pihtimus ; Egoretoorika

  14. New dates for the Fontéchevade (Charente, France) Homo remains.

    Science.gov (United States)

    Chase, Philip G; Debénath, André; Dibble, Harold L; McPherron, Shannon P; Schwarcz, Henry P; Stafford, Thomas W; Tournepiche, Jean-François

    2007-02-01

    Homo I from the site of Fontéchevade, France, has long been an anomaly in the European fossil record. The specimen is a fragment of human frontal bone that lacks a supraorbital torus and appears to belong to an anatomically modern Homo sapiens. However, the level from which it was recovered in 1947 was dated on the basis of associated faunal and lithic material to the last interglacial or earlier. As a result, Homo I has been interpreted, among other things, as a representative of a pre-sapiens lineage in Europe. This paper reports on recent ESR and radiocarbon dates that indicate that the specimen almost certainly dates to oxygen isotope stage 3, which brings it in line with other evidence for the entry of modern Homo sapiens into Europe.

  15. PASS2: an automated database of protein alignments organised as structural superfamilies

    Directory of Open Access Journals (Sweden)

    Sowdhamini Ramanathan

    2004-04-01

    Full Text Available Abstract Background The functional selection and three-dimensional structural constraints of proteins in nature often relates to the retention of significant sequence similarity between proteins of similar fold and function despite poor sequence identity. Organization of structure-based sequence alignments for distantly related proteins, provides a map of the conserved and critical regions of the protein universe that is useful for the analysis of folding principles, for the evolutionary unification of protein families and for maximizing the information return from experimental structure determination. The Protein Alignment organised as Structural Superfamily (PASS2 database represents continuously updated, structural alignments for evolutionary related, sequentially distant proteins. Description An automated and updated version of PASS2 is, in direct correspondence with SCOP 1.63, consisting of sequences having identity below 40% among themselves. Protein domains have been grouped into 628 multi-member superfamilies and 566 single member superfamilies. Structure-based sequence alignments for the superfamilies have been obtained using COMPARER, while initial equivalencies have been derived from a preliminary superposition using LSQMAN or STAMP 4.0. The final sequence alignments have been annotated for structural features using JOY4.0. The database is supplemented with sequence relatives belonging to different genomes, conserved spatially interacting and structural motifs, probabilistic hidden markov models of superfamilies based on the alignments and useful links to other databases. Probabilistic models and sensitive position specific profiles obtained from reliable superfamily alignments aid annotation of remote homologues and are useful tools in structural and functional genomics. PASS2 presents the phylogeny of its members both based on sequence and structural dissimilarities. Clustering of members allows us to understand diversification of

  16. Keanekaragaman Jenis Kupu-Kupu Superfamili Papilionoidae di Banyuwindu, Limbangan Kendal

    Directory of Open Access Journals (Sweden)

    Ratna Oqtafiana

    2013-03-01

    Full Text Available Kupu-kupu turut memberi andil dalam mempertahankan keseimbangan ekosistem dan memperkaya keanekaragaman hayati. Tujuan dari penelitian ini adalah untuk mengetahui keanekaragaman jenis kupu-kupu superfamili Papilionoidae di Dukuh Banyuwindu Desa Limbangan Kecamatan Limbangan Kabupaten Kendal khususnya di habitat hutan sekunder, permukiman, Daerah Aliran Sungai (DAS dan persawahan.Populasi dalam penelitian ini adalah semua jenis kupu-kupu superfamili Papilionoidae yang ada di Banyuwindu, Limbangan Kendal. Sampel penelitian ini adalah jenis kupu-kupu superfamili Papilionoidae yang teramati di Banyuwindu Limbangan Kendal khususnya di habitat hutan sekunder, permukiman, DAS dan persawahan. Penelitian dilakukan dengan metode Indeks Point Abudance (IPA atau metode titik hitung.Hasil penelitian ditemukan sebanyak 62 jenis kupu-kupu superfamili Papilionoidae yang terdiri dari 737 individu yang tergolong kedalam empat famili yaitu Papilionidae, Pieridae, Lycaenidae dan Nymphalidae. Hasil analisis indeks keanekaragaman jenis berkisar antara 2,74-3,09, indeks kemerataan jenis berkisar antara 0,86-0,87 dan memiliki dominansi berkisar antara 0,07-0,09. Indeks keanekaragaman jenis dan indeks kemerataan jenis tertinggi tercatat pada habitat permukiman yaitu 3,09 dan 0,87 dan memiliki dominansi 0,07 sedangkan terendah tercatat pada habitat persawahan yaitu 2,74 dan 0,86 dan memiliki dominansi 0,07.Butterfly also contribute in maintaining the ecological balance and enrich biodiversity. The aim of this research was to determine the diversity of butterflies’ superfamily Papilionoidae in Banyuwindu Hamlet Limbangan Sub district Kendal Regency, especially in the secondary forest habitat, settlements, river flow area (RFA and rice field. The population in this research were all kinds of butterflies’ Papilionoidae superfamily in Banyuwindu, Limbangan Kendal. The sample was kind of butterfly superfamily Papilionoidae that observed in Banyuwindu Limbangan Kendal

  17. Keanekaragaman Jenis Kupu-Kupu Superfamili Papilionoidae di Banyuwindu, Limbangan Kendal

    Directory of Open Access Journals (Sweden)

    Ratna Oqtafiana

    2013-03-01

    Full Text Available Kupu-kupu turut memberi andil dalam mempertahankan keseimbangan ekosistem dan memperkaya keanekaragaman hayati. Tujuan dari penelitian ini adalah untuk mengetahui keanekaragaman jenis kupu-kupu superfamili Papilionoidae di Dukuh Banyuwindu Desa Limbangan Kecamatan Limbangan Kabupaten Kendal khususnya di habitat hutan sekunder, permukiman, Daerah Aliran Sungai (DAS dan persawahan.Populasi dalam penelitian ini adalah semua jenis kupu-kupu superfamili Papilionoidae yang ada di Banyuwindu, Limbangan Kendal. Sampel penelitian ini adalah jenis kupu-kupu superfamili Papilionoidae yang teramati di Banyuwindu Limbangan Kendal khususnya di habitat hutan sekunder, permukiman, DAS dan persawahan. Penelitian dilakukan dengan metode Indeks Point Abudance (IPA atau metode titik hitung.Hasil penelitian ditemukan sebanyak 62 jenis kupu-kupu superfamili Papilionoidae yang terdiri dari 737 individu yang tergolong kedalam empat famili yaitu Papilionidae, Pieridae, Lycaenidae dan Nymphalidae. Hasil analisis indeks keanekaragaman jenis berkisar antara 2,74-3,09, indeks kemerataan jenis berkisar antara 0,86-0,87 dan memiliki dominansi berkisar antara 0,07-0,09. Indeks keanekaragaman jenis dan indeks kemerataan jenis tertinggi tercatat pada habitat permukiman yaitu 3,09 dan 0,87 dan memiliki dominansi 0,07 sedangkan terendah tercatat pada habitat persawahan yaitu 2,74 dan 0,86 dan memiliki dominansi 0,07.Butterfly also contribute in maintaining the ecological balance and enrich biodiversity. The aim of this research was to determine the diversity of butterflies’ superfamily Papilionoidae in Banyuwindu Hamlet Limbangan Sub district Kendal Regency, especially in the secondary forest habitat, settlements, river flow area (RFA and rice field. The population in this research were all kinds of butterflies’ Papilionoidae superfamily in Banyuwindu, Limbangan Kendal. The sample was kind of butterfly superfamily Papilionoidae that observed in Banyuwindu Limbangan Kendal

  18. Homo-psychologicus: Reactionary behavioural aspects of epidemics

    Directory of Open Access Journals (Sweden)

    Alhaji Cherif

    2016-03-01

    Full Text Available We formulate an in silico model of pathogen avoidance mechanism and investigate its impact on defensive behavioural measures (e.g., spontaneous social exclusions and distancing, crowd avoidance and voluntary vaccination adaptation. In particular, we use SIR(BS (e.g., susceptible-infected-recovered with additional behavioural component model to investigate the impact of homo-psychologicus aspects of epidemics. We focus on reactionary behavioural changes, which apply to both social distancing and voluntary vaccination participations. Our analyses reveal complex relationships between spontaneous and uncoordinated behavioural changes, the emergence of its contagion properties, and mitigation of infectious diseases. We find that the presence of effective behavioural changes can impede the persistence of disease. Furthermore, it was found that under perfect effective behavioural change, there are three regions in the response factor (e.g., imitation and/or reactionary and behavioural scale factor (e.g., global/local factors ρ–α behavioural space. Mainly, (1 disease is always endemic even in the presence of behavioural change, (2 behavioural-prevalence plasticity is observed and disease can sometimes be eradication, and (3 elimination of endemic disease under permanence of permanent behavioural change is achieved. These results suggest that preventive behavioural changes (e.g., non-pharmaceutical prophylactic measures, social distancing and exclusion, crowd avoidance are influenced by individual differences in perception of risks and are a salient feature of epidemics. Additionally, these findings indicates that care needs to be taken when considering the effect of adaptive behavioural change in predicting the course of epidemics, and as well as the interpretation and development of the public health measures that account for spontaneous behavioural changes.

  19. Is Homo sapiens polytypic? Human taxonomic diversity and its implications.

    Science.gov (United States)

    Woodley, Michael A

    2010-01-01

    The term race is a traditional synonym for subspecies, however it is frequently asserted that Homo sapiens is monotypic and that what are termed races are nothing more than biological illusions. In this manuscript a case is made for the hypothesis that H. sapiens is polytypic, and in this way is no different from other species exhibiting similar levels of genetic and morphological diversity. First it is demonstrated that the four major definitions of race/subspecies can be shown to be synonymous within the context of the framework of race as a correlation structure of traits. Next the issue of taxonomic classification is considered where it is demonstrated that H. sapiens possesses high levels morphological diversity, genetic heterozygosity and differentiation (F(ST)) compared to many species that are acknowledged to be polytypic with respect to subspecies. Racial variation is then evaluated in light of the phylogenetic species concept, where it is suggested that the least inclusive monophyletic units exist below the level of species within H. sapiens indicating the existence of a number of potential human phylogenetic species; and the biological species concept, where it is determined that racial variation is too small to represent differentiation at the level of biological species. Finally the implications of this are discussed in the context of anthropology where an accurate picture of the sequence and timing of events during the evolution of human taxa are required for a complete picture of human evolution, and medicine, where a greater appreciation of the role played by human taxonomic differences in disease susceptibility and treatment responsiveness will save lives in the future.

  20. Fossil evidence for the origin of Homo sapiens.

    Science.gov (United States)

    Schwartz, Jeffrey H; Tattersall, Ian

    2010-01-01

    Our species Homo sapiens has never received a satisfactory morphological definition. Deriving partly from Linnaeus's exhortation simply to "know thyself," and partly from the insistence by advocates of the Evolutionary Synthesis in the mid-20th Century that species are constantly transforming ephemera that by definition cannot be pinned down by morphology, this unfortunate situation has led to huge uncertainty over which hominid fossils ought to be included in H. sapiens, and even over which of them should be qualified as "archaic" or as "anatomically modern," a debate that is an oddity in the broader context of paleontology. Here, we propose a suite of features that seems to characterize all H. sapiens alive today, and we review the fossil evidence in light of those features, paying particular attention to the bipartite brow and the "chin" as examples of how, given the continuum from developmentally regulated genes to adult morphology, we might consider features preserved in fossil specimens in a comparative analysis that includes extant taxa. We also suggest that this perspective on the origination of novelty, which has gained a substantial foothold in the general field of evolutionary developmental biology, has an intellectual place in paleoanthropology and hominid systematics, including in defining our species, H. sapiens. Beginning solely with the distinctive living species reveals a startling variety in morphologies among late middle and late Pleistocene hominids, none of which can be plausibly attributed to H. sapiens/H. neanderthalensis admixture. Allowing for a slightly greater envelope of variation than exists today, basic "modern" morphology seems to have appeared significantly earlier in time than the first stirrings of the modern symbolic cognitive system.

  1. A New Kind of Economy is Born - Social Decision-Makers Beat the "Homo Economicus"

    CERN Document Server

    Helbing, Dirk

    2013-01-01

    The Internet and Social Media change our way of decision-making. We are no longer the independent decision makers we used to be. Instead, we have become networked minds, social decision-makers, more than ever before. This has several fundamental implications. First of all, our economic theories must change, and second, our economic institutions must be adapted to support the social decision-maker, the "homo socialis", rather than tailored to the perfect egoist, known as "homo economicus".

  2. Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents

    Directory of Open Access Journals (Sweden)

    Qiang Yu

    2008-12-01

    Full Text Available Enantioselective syntheses from dimethyl tartrate of 1,3,5-triazine homo-N-nucleoside analogs, containing a 1,4-dioxane moiety replacing the sugar unit in natural nucleosides, were accomplished. The triazine heterocycle in the nucleoside analogs was further substituted with combinations of NH2, OH and Cl in the 2,4-triazine positions.

  3. Selaginella moellendorffii has a reduced and highly conserved expansin superfamily with genes more closely related to angiosperms than to bryophytes.

    Science.gov (United States)

    Carey, Robert E; Hepler, Nathan K; Cosgrove, Daniel J

    2013-01-03

    Expansins are plant cell wall loosening proteins encoded by a large superfamily of genes, consisting of four families named EXPA, EXPB, EXLA, and EXLB. The evolution of the expansin superfamily is well understood in angiosperms, thanks to synteny-based evolutionary studies of the gene superfamily in Arabidopsis, rice, and Populus. Analysis of the expansin superfamily in the moss Physcomitrella patens revealed a superfamily without EXLA or EXLB genes that has evolved considerably and independently of angiosperm expansins. The sequencing of the Selaginella moellendorffii genome has allowed us to extend these analyses into an early diverging vascular plant. The expansin superfamily in Selaginella moellendorffii has now been assembled from genomic scaffolds. A smaller (and less diverse) superfamily is revealed, consistent with studies of other gene families in Selaginella. Selaginella has an expansin superfamily, which, like Physcomitrella, lacks EXLA or EXLB genes, but does contain two EXPA genes that are related to a particular Arabidopsis-rice clade involved in root hair development. From sequence-based phylogenetic analysis, most Selaginella expansins lie outside the Arabidopsis-rice clades, leading us to estimate the minimum number of expansins present in the last common ancestor of Selaginella and angiosperms at 2 EXPA genes and 1 EXPB gene. These results confirm Selaginella as an important intermediary between bryophytes and angiosperms.

  4. A robust and extracellular heme-containing peroxidase from Thermobifida fusca as prototype of a bacterial peroxidase superfamily

    NARCIS (Netherlands)

    van Bloois, Edwin; Torres Pazmino, Daniel; Winter, Remko T.; Fraaije, Marco W.

    2010-01-01

    DyP-type peroxidases comprise a novel superfamily of heme-containing peroxidases which is unrelated to the superfamilies of known peroxidases and of which only a few members have been characterized in some detail. Here, we report the identification and characterization of a DyP-type peroxidase (TfuD

  5. Novel insights into the function of the conserved domain of the CAP superfamily of proteins

    NARCIS (Netherlands)

    Olrichs, N.K.|info:eu-repo/dai/nl/304837571; Helms, J.B.|info:eu-repo/dai/nl/080626742

    2016-01-01

    Members of the Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins (CAP) superfamily are found in a remarkable variety of biological species. The presence of a highly conserved CAP domain defines the CAP family members, which in many cases is linked to other functional

  6. Disease causing mutations in the TNF and TNFR superfamilies: Focus on molecular mechanisms driving disease

    NARCIS (Netherlands)

    A.A. Lobito; T.L. Gabriel; J.P. Medema; F.C. Kimberley

    2011-01-01

    The tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamilies comprise multidomain proteins with diverse roles in cell activation, proliferation and cell death. These proteins play pivotal roles in the initiation, maintenance and termination of immune responses and have vital roles outside t

  7. Precursor De13.1 from Conus delessertii defines the novel G gene superfamily.

    Science.gov (United States)

    Aguilar, Manuel B; Ortiz, Ernesto; Kaas, Quentin; López-Vera, Estuardo; Becerril, Baltazar; Possani, Lourival D; de la Cotera, Edgar P Heimer

    2013-03-01

    Peptide de13a was previously purified from the venom of the worm-hunting cone snail Conus delessertii from the Yucatán Channel, México. This peptide has eight cysteine (Cys) residues in the unique arrangement C-C-C-CC-C-C-C, which defines the cysteine framework XIII ("-" represents one or more non-Cys residues). Remarkably, δ-hydroxy-lysine residues have been found only in conotoxin de13a, which also contains an unusually high proportion of hydroxylated amino acid residues. Here, we report the cDNA cloning of the complete precursor De13.1 of a related peptide, de13b, which has the same Cys framework and inter-Cys spacings as peptide de13a, and shares high protein/nucleic acid sequence identity (87%/90%) with de13a, suggesting that both peptides belong to the same conotoxin gene superfamily. Analysis of the signal peptide of precursor De13.1 reveals that this precursor belongs to a novel conotoxin gene superfamily that we chose to name gene superfamily G. Thus far superfamily G only includes two peptides, each of which contains the same, distinctive Cys framework and a high proportion of amino acid residues with hydroxylated side chains.

  8. Phylogeny, Function and evolution of the cupins, a structurally conserved, functionally diverse superfamily of proteins

    NARCIS (Netherlands)

    Khuri, S.; Bakker, F.T.; Dunwell, J.M.

    2001-01-01

    The cupin superfamily is a group of functionally diverse proteins that are found in all three kingdoms of life, Archaea, Eubacteria, and Eukaryota. These proteins have a characteristic signature domain comprising two histidine- containing motifs separated by an intermotif region of variable length.

  9. Transforming growth factor-β superfamily, implications in development and differentiation of stem cells.

    Science.gov (United States)

    Santibanez, Juan F; Kocic, Jelena

    2012-10-01

    Abstract Transforming growth factor-β (TGF-β) family members, including TGF-βs and bone morphogenetic proteins (BMPs), play important roles in directing the fate of stem cells. In embryonic stem cells, the TGF-β superfamily participates in almost all stages of cell development, such as cell maintenance, lineage selection, and progression of differentiation. In adult mesenchymal stem cells (MSCs), TGF-βs can provide competence for early stages of chondroblastic and osteoblastic differentiation, but they inhibit myogenesis, adipogenesis, and late-stage osteoblast differentiation. BMPs also inhibit adipogenesis and myogenesis, but they strongly promote osteoblast differentiation. The TGF-β superfamily members signal via specific serine/threonine kinase receptors and their nuclear effectors termed Smad proteins as well as through non-Smad pathways, which explain their pleiotropic effects in self-renewal and differentiation of stem cells. This review summarizes the current knowledge on the pleiotropic effects of the TGF-β superfamily of growth factors on the fate of stem cells and also discusses the mechanisms by which the TGF-β superfamily members control embryonic and MSCs differentiation.

  10. Expression of 6-Cys gene superfamily defines babesia bovis sexual stage development within rhipicephalus microplus

    Science.gov (United States)

    Babesia bovis, an intra-erythrocytic tick-borne apicomplexan protozoan, is one of the agents of bovine babesiosis. Its life cycle includes sexual reproduction within cattle fever ticks, Rhipicephalus spp. Six B. bovis 6-Cys gene superfamily members were previously identified (A, B, C, D, E, F) and t...

  11. Targeting of the tumor necrosis factor receptor superfamily for cancer immunotherapy

    NARCIS (Netherlands)

    Bremer, Edwin

    2013-01-01

    The tumor necrosis factor (TNF) ligand and cognate TNF receptor superfamilies constitute an important regulatory axis that is pivotal for immune homeostasis and correct execution of immune responses. TNF ligands and receptors are involved in diverse biological processes ranging from the selective in

  12. Brain size and encephalization in early to Mid-Pleistocene Homo.

    Science.gov (United States)

    Rightmire, G Philip

    2004-06-01

    Important changes in the brain have occurred during the course of human evolution. Both absolute and relative size increases can be documented for species of Homo, culminating in the appearance of modern humans. One species that is particularly well-represented by fossil crania is Homo erectus. The mean capacity for 30 individuals is 973 cm(3). Within this group there is substantial variation, but brain size increases slightly in specimens from later time periods. Other Middle Pleistocene crania differ from those of Homo erectus. Characters of the facial skeleton, vault, and cranial base suggest that fossils from sites such as Arago Cave in France, the Sima de los Huesos in Spain, Bodo in Ethiopia, Broken Hill in Zambia, and perhaps Dali in China belong to the taxon Homo heidelbergensis. Ten of these mid-Quaternary hominins have brains averaging 1,206 cm(3) in volume, and many fall beyond the limits of size predicted for Homo erectus of equivalent age. When orbit height is used to construct an index of relative brain size, it is apparent that the (significant) increase in volume documented for the Middle Pleistocene individuals is not simply a consequence of larger body mass. Encephalization quotient values confirm this finding. These changes in absolute and relative brain size can be taken as further corroborative evidence for a speciation event, in which Homo erectus produced a daughter lineage. It is probable that Homo heidelbergensis originated in Africa or western Eurasia and then ranged widely across the Old World. Archaeological traces indicate that these populations differed in their technology and behavior from earlier hominins. Copyright 2003 Wiley-Liss, Inc.

  13. Cell Adhesion Molecules of the Immunoglobulin Superfamily in the Nervous System

    DEFF Research Database (Denmark)

    Walmod, Peter Schledermann; Pedersen, Martin Volmer; Berezin, Vladimir

    2007-01-01

    ), and members of the CTX, IgLON, Robo, contactin, and L1 families. The individual descriptions include sections describing the expression, isoforms, structure, posttranslational modifications, homo- and heterophilic binding partners, signaling and functions of the individual CAMs. The chapter demonstrates CAMs...

  14. Are Homo sapiens nonsupranuchal fossa and Neanderthal suprainiac fossa convergent traits?

    Science.gov (United States)

    Nowaczewska, Wioletta

    2011-04-01

    The autapomorphic status of the Neanderthal suprainiac fossa was recently confirmed. This was a result of a detailed analysis of the internal bone composition in the area of the suprainiac depression on Neanderthal and Homo sapiens specimens. However, while anatomical differences between Neanderthal suprainiac fossa and the depression in the inion region of the occipital bone of fossil and recent Homo sapiens have been discussed in detail, the etiology of these structures has not been resolved. In this article, the hypothesis that the Homo sapiens non-supranuchal fossa and the Neanderthal suprainiac fossa both formed to maintain the optimal shape of the occipital plane (to minimize strain on the posterior cranial vault) is tested. First, the variation in the expression of the fossa above inion in the crania of recent Homo sapiens from European, African, and Australian samples was examined, and the degree of structural similarity between these depressions and the Neanderthal suprainiac fossa was assessed. Next, the relationship between the shape of the occipital squama in the midsagittal plane and two particular features (the degree of the occipital torus development and the occurrence of a depression in the inion region that is not the supranuchal fossa) were analyzed. Based on the results, it is suggested that the Homo sapiens non-supranuchal fossa and Neanderthal suprainiac fossa are convergent traits.

  15. Gamma-ray spectrometric dating of late Homo erectus skulls from Ngandong and Sambungmacan, Central Java, Indonesia.

    Science.gov (United States)

    Yokoyama, Yuji; Falguères, Christophe; Sémah, François; Jacob, Teuku; Grün, Rainer

    2008-08-01

    Hominid fossils from Ngandong and Sambungmacan, Central Java, Indonesia, are considered to be the most anatomically derived and youngest representatives of Homo erectus. Nondestructive gamma-ray spectrometric dating of three of these Homo erectus skulls showed that all samples underwent uranium leaching. Nevertheless, we could establish minimum age estimates of around 40ka, with an upper age limit of around 60 to 70ka. This means that the Homo erectus of Java very likely survived the Toba eruption and may have been contemporaneous with the earliest Homo sapiens in Southeast Asia and Australasia.

  16. Comparative skeletal features between Homo floresiensis and patients with primary growth hormone insensitivity (Laron Syndrome).

    Science.gov (United States)

    Hershkovitz, Israel; Kornreich, Liora; Laron, Zvi

    2007-10-01

    Comparison between the skeletal remains of Homo floresiensis and the auxological and roentgenological findings in a large Israeli cohort of patients with Laron Syndrome (LS, primary or classical GH insensitivity or resistance) revealed striking morphological similarities, including extremely small stature and reduced cranial volume. LS is an autosomal recessive disease caused by a molecular defect of the Growth Hormone (GH) receptor or in the post-receptor cascades. Epidemiological studies have shown that LS occurs more often in consanguineous families and isolates, and it has been described in several countries in South East Asia. It is our conclusion that the findings from the island of Flores, which were attributed to a new species of the genus Homo, may in fact represent a local, highly inbred, Homo sapiens population in whom a mutation for the GH receptor had occurred.

  17. Linking the HOMO-LUMO gap to torsional disorder in P3HT/PCBM blends

    Science.gov (United States)

    McLeod, John A.; Pitman, Amy L.; Kurmaev, Ernst Z.; Finkelstein, Larisa D.; Zhidkov, Ivan S.; Savva, Achilleas; Moewes, Alexander

    2015-12-01

    The electronic structure of [6,6]-phenyl C61 butyric acid methyl ester (PCBM), poly(3-hexylthiophene) (P3HT), and P3HT/PCBM blends is studied using soft X-ray emission and absorption spectroscopy and density functional theory calculations. We find that annealing reduces the HOMO-LUMO gap of P3HT and P3HT/PCBM blends, whereas annealing has little effect on the HOMO-LUMO gap of PCBM. We propose a model connecting torsional disorder in a P3HT polymer to the HOMO-LUMO gap, which suggests that annealing helps to decrease the torsional disorder in the P3HT polymers. Our model is used to predict the characteristic length scales of the flat P3TH polymer segments in P3HT and P3HT/PCBM blends before and after annealing. Our approach may prove useful in characterizing organic photovoltaic devices in situ or even in operando.

  18. Direction for Artificial Intelligence to Achieve Sapiency Inspired by Homo Sapiens

    Directory of Open Access Journals (Sweden)

    Mahmud Arif Pavel

    2016-10-01

    Full Text Available Artificial intelligence technology has developed significantly in the past decades. Although many computational programs are able to approximate many cognitive abilities of Homo sapiens, the intelligence and sapience level of these programs are not even close to Homo sapiens. Rather than developing a computational system with the intelligent or sapient attribute, I propose to develop a system capable of performing functions that could deem as intelligent or sapient by Homo sapiens or others. I advocate converting current computational systems to educable systems that have built-in capabilities to learn and be taught with a universal programming language. The idea is that this attempt would help to attain computational actions in artificial means, which could be viewed as similar to human intelligent and sapient acts. Although this paper is seemingly speculative, some feasible elements are proposed to advance the field of Artificial Intelligence.

  19. Variability in first Homo: Analysis of the ratio between the skulls KNM-ER 1470 and KNM-ER 1813 based on sexual dimorphism of Homo sapiens.

    Science.gov (United States)

    Guimarães, S W Ferreira; Lorenzo, C

    2015-10-01

    The study of the skulls KNM-ER 1470 and KNM-ER 1813, considered the first members of the genus Homo, has raised some debates. While some of researchers maintain that there is only one species, another group argues that there are two species. On one hand these two fossils are still taxonomically undetermined, on the other hand they bring up another problem related to the existence of a genus with multiple species since its beginning, according to the last discoveries. In this paper, we have compared the size ratio between these fossils with ratios established in populations of Homo sapiens, in order to know if they fit into the human standard, considering intra-sexual and inter-sexual variation. Results help to establish whether these fossils correspond to different species or their differences could be related to sexual dimorphism within a single species.

  20. Regulation of TGF-β Superfamily Signaling by SMAD Mono-Ubiquitination

    Directory of Open Access Journals (Sweden)

    Feng Xie

    2014-10-01

    Full Text Available TGF-β(transforming growth factor-β superfamily signaling mediators are important regulators of diverse physiological and pathological events. TGF-β signals are transduced by transmembrane type I and type II serine/threonine kinase receptors and their downstream effectors, the SMAD(drosophila mothers against decapentaplegic protein proteins. Numerous studies have already demonstrated crucial regulatory roles for modification of TGF-β pathway components by poly-ubiquitination. Recently, several studies also uncovered mono-ubiquitination of SMADs as a mechanism for SMAD activation or inactivation. Mono-ubiquitination and subsequent deubiquitination of SMAD proteins accordingly play important roles in the control of TGF-β superfamily signaling. This review highlights the major pathways regulated by SMAD mono-ubiquitination.

  1. A Comprehensive Bioinformatics Analysis of the Nudix Superfamily in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    D. Gunawardana

    2009-01-01

    Full Text Available Nudix enzymes are a superfamily with a conserved common reaction mechanism that provides the capacity for the hydrolysis of a broad spectrum of metabolites. We used hidden Markov models based on Nudix sequences from the PFAM and PROSITE databases to identify Nudix hydrolases encoded by the Arabidopsis genome. 25 Nudix hydrolases were identified and classified into 11 individual families by pairwise sequence alignments. Intron phases were strikingly conserved in each family. Phylogenetic analysis showed that all multimember families formed monophyletic clusters. Conserved familial sequence motifs were identified with the MEME motif analysis algorithm. One motif (motif 4 was found in three diverse families. All proteins containing motif 4 demonstrated a degree of preference for substrates containing an ADP moiety. We conclude that HMM model-based genome scanning and MEME motif analysis, respectively, can significantly improve the identification and assignment of function of new members of this mechanistically-diverse protein superfamily.

  2. Identification of maverick, a novel member of the TGF-beta superfamily in Drosophila.

    Science.gov (United States)

    Nguyen, M; Parker, L; Arora, K

    2000-07-01

    The transforming growth factor-beta (TGF-beta) superfamily of structurally related ligands regulates essential signaling pathways that control many aspects of cell behavior in organisms across the phylogenetic spectrum. Here we report the identification of maverick (mav), a gene that encodes a new member of the TGF-beta superfamily in Drosophila. Phylogenetic analysis and sequence comparison suggest that Mav cannot be easily assigned to any one sub-family, since it is equally related to BMP, activin and TGF-beta ligands. mav maps to the fourth chromosome and is expressed throughout development. In situ hybridization experiments reveal the presence of maternally derived mav transcript in precellular blastoderm embryos. Later in development, mav is expressed in a dynamic pattern in the developing gut, both in endodermal and visceral mesodermal cells. In adult females, high levels of mav mRNA are present in late stage egg chambers.

  3. The cytochrome P450 superfamily:Key players in plant development and defense

    Institute of Scientific and Technical Information of China (English)

    XU Jun; WANG Xin-yu; GUO Wang-zhen

    2015-01-01

    The cytochrome P450 (CYP) superfamily is the largest enzymatic protein family in plants, and it also widely exists in mammals, fungi, bacteria, insects and so on. Members of this superfamily are involved in multiple metabolic pathways with distinct and complex functions, playing important roles in a vast array of reactions. As a result, numerous secondary metabolites are synthesized that function as growth and developmental signals or protect plants from various biotic and abiotic stresses. Here, we summarize the characterization of CYPs, as wel as their phylogenetic classiifcation. We also focus on recent advances in elucidating the roles of CYPs in mediating plant growth and development as wel as biotic and abiotic stresses responses, providing insights into their potential utilization in plant breeding.

  4. Fetal antigen 1 (FA1), a circulating member of the epidermal growth factor (EGF) superfamily

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, T N; Støving, René Klinkby;

    1997-01-01

    We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3.2% and an aver......We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3...

  5. The Ribonuclease A Superfamily in Humans: Canonical RNases as the Buttress of Innate Immunity

    Directory of Open Access Journals (Sweden)

    Patrick Koczera

    2016-08-01

    Full Text Available In humans, the ribonuclease A (RNase A superfamily contains eight different members that have RNase activities, and all of these members are encoded on chromosome 14. The proteins are secreted by a large variety of different tissues and cells; however, a comprehensive understanding of these proteins’ physiological roles is lacking. Different biological effects can be attributed to each protein, including antiviral, antibacterial and antifungal activities as well as cytotoxic effects against host cells and parasites. Different immunomodulatory effects have also been demonstrated. This review summarizes the available data on the human RNase A superfamily and illustrates the significant role of the eight canonical RNases in inflammation and the host defence system against infections.

  6. The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

    Science.gov (United States)

    De Trez, Carl; Ware, Carl F.

    2008-01-01

    Dendritic cells (DC) constitute the most potent antigen presenting cells of the immune system, playing a key role bridging innate and adaptive immune responses. Specialized DC subsets differ depending on their origin, tissue location and the influence of trophic factors, the latter remain to be fully understood. Stromal cell and myeloid-associated Lymphotoxin-β receptor (LTβR) signaling is required for the local proliferation of lymphoid tissue DC. This review focuses the LTβR signaling cascade as a crucial positive trophic signal in the homeostasis of DC subsets. The noncanonical coreceptor pathway comprised of the Immunoglobulin (Ig) superfamily member, B and T lymphocyte attenuator (BTLA) and TNFR superfamily member, Herpesvirus entry mediator (HVEM) counter regulates the trophic signaling by LTβR. Together both pathways form an integrated signaling circuit achieving homeostasis of DC subsets. PMID:18511331

  7. Superfamily assignments for the yeast proteome through integration of structure prediction with the gene ontology.

    Directory of Open Access Journals (Sweden)

    Lars Malmström

    2007-04-01

    Full Text Available Saccharomyces cerevisiae is one of the best-studied model organisms, yet the three-dimensional structure and molecular function of many yeast proteins remain unknown. Yeast proteins were parsed into 14,934 domains, and those lacking sequence similarity to proteins of known structure were folded using the Rosetta de novo structure prediction method on the World Community Grid. This structural data was integrated with process, component, and function annotations from the Saccharomyces Genome Database to assign yeast protein domains to SCOP superfamilies using a simple Bayesian approach. We have predicted the structure of 3,338 putative domains and assigned SCOP superfamily annotations to 581 of them. We have also assigned structural annotations to 7,094 predicted domains based on fold recognition and homology modeling methods. The domain predictions and structural information are available in an online database at http://rd.plos.org/10.1371_journal.pbio.0050076_01.

  8. The insulin-like growth factor-binding protein (IGFBP) superfamily.

    Science.gov (United States)

    Hwa, V; Oh, Y; Rosenfeld, R G

    1999-12-01

    Over the last decade, the concept of an IGFBP family has been well accepted, based on structural similarities and on functional abilities to bind IGFs with high affinities. The existence of other potential IGFBPs was left open. The discovery of proteins with N-terminal domains bearing striking structural similarities to the N terminus of the IGFBPs, and with reduced, but demonstrable, affinity for IGFs, raised the question of whether these proteins were "new" IGFBPs (22, 23, 217). The N-terminal domain had been uniquely associated with the IGFBPs and has long been considered to be critical for IGF binding. No other function has been confirmed for this domain to date. Thus, the presence of this important IGFBP domain in the N terminus of other proteins must be considered significant. Although these other proteins appear capable of binding IGF, their relatively low affinity and the fact that their major biological actions are likely to not directly involve the IGF peptides suggest that they probably should not be classified within the IGFBP family as provisionally proposed (22, 23). The conservation of this single domain, so critical to high-affinity binding of IGF by the six IGFBPs, in all of the IGFBP-rPs, as well, speaks to its biological importance. Historically, and perhaps, functionally, this has led to the designation of an "IGFBP superfamily". The classification and nomenclature for the IGFBP superfamily, are, of course, arbitrary; what is ultimately relevant is the underlying biology, much of which still remains to be deciphered. The nomenclature for the IGFBP related proteins was derived from a consensus of researchers working in the IGFBP field (52). Obviously, a more general consensus on nomenclature, involving all groups working on each IGFBP-rP, has yet to be reached. Further understanding of the biological functions of each protein should help resolve the nomenclature dilemma. For the present, redesignating these proteins IGFBP-rPs simplifies the

  9. Induction and consolidation of calcium-based homo- and heterosynaptic potentiation and depression

    DEFF Research Database (Denmark)

    Li, Y; Kulvicius, T.; Tetzlaff, Christian

    2016-01-01

    The adaptive mechanisms of homo- and heterosynaptic plasticity play an important role in learning and memory. In order to maintain plasticity-induced changes for longer time scales (up to several days), they have to be consolidated by transferring them from a short-lasting early-phase to a long...... into the complex interactions between homo- and heterosynaptic plasticity over a broad variety of time (minutes to days) and spatial scales (several micrometers). © 2016 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use...

  10. New blue emissive conjugated small molecules with low lying HOMO energy levels for optoelectronic applications

    Science.gov (United States)

    Trupthi Devaiah, C.; Hemavathi, B.; Ahipa, T. N.

    2017-03-01

    Versatile conjugated small molecules bearing cyanopyridone core (CP1-5), composed of various donor/acceptor moieties at position - 4 and - 6 have been designed, developed and characterized. Their solvatochromic studies were conducted and analyzed using Lippert-Mataga, Kamlet-Taft and Catalan solvent scales and interesting results were obtained. The polarizability/dipolarity of the solvent greatly influenced the spectra. The electrochemical studies were carried out using cyclic voltammetry to calculate the HOMO-LUMO energy levels. The study revealed that the synthesized conjugated small molecules possess low lying HOMO energy levels which can be exploited for application in various fields of optoelectronics.

  11. Taxonomic distribution and origins of the extended LHC (light-harvesting complex antenna protein superfamily

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    Brinkmann Henner

    2010-07-01

    Full Text Available Abstract Background The extended light-harvesting complex (LHC protein superfamily is a centerpiece of eukaryotic photosynthesis, comprising the LHC family and several families involved in photoprotection, like the LHC-like and the photosystem II subunit S (PSBS. The evolution of this complex superfamily has long remained elusive, partially due to previously missing families. Results In this study we present a meticulous search for LHC-like sequences in public genome and expressed sequence tag databases covering twelve representative photosynthetic eukaryotes from the three primary lineages of plants (Plantae: glaucophytes, red algae and green plants (Viridiplantae. By introducing a coherent classification of the different protein families based on both, hidden Markov model analyses and structural predictions, numerous new LHC-like sequences were identified and several new families were described, including the red lineage chlorophyll a/b-binding-like protein (RedCAP family from red algae and diatoms. The test of alternative topologies of sequences of the highly conserved chlorophyll-binding core structure of LHC and PSBS proteins significantly supports the independent origins of LHC and PSBS families via two unrelated internal gene duplication events. This result was confirmed by the application of cluster likelihood mapping. Conclusions The independent evolution of LHC and PSBS families is supported by strong phylogenetic evidence. In addition, a possible origin of LHC and PSBS families from different homologous members of the stress-enhanced protein subfamily, a diverse and anciently paralogous group of two-helix proteins, seems likely. The new hypothesis for the evolution of the extended LHC protein superfamily proposed here is in agreement with the character evolution analysis that incorporates the distribution of families and subfamilies across taxonomic lineages. Intriguingly, stress-enhanced proteins, which are universally found in the

  12. Mechanistic and Evolutionary Insights from Comparative Enzymology of Phosphomonoesterases and Phosphodiesterases across the Alkaline Phosphatase Superfamily.

    Science.gov (United States)

    Sunden, Fanny; AlSadhan, Ishraq; Lyubimov, Artem Y; Ressl, Susanne; Wiersma-Koch, Helen; Borland, Jamar; Brown, Clayton L; Johnson, Tory A; Singh, Zorawar; Herschlag, Daniel

    2016-11-02

    Naively one might have expected an early division between phosphate monoesterases and diesterases of the alkaline phosphatase (AP) superfamily. On the contrary, prior results and our structural and biochemical analyses of phosphate monoesterase PafA, from Chryseobacterium meningosepticum, indicate similarities to a superfamily phosphate diesterase [Xanthomonas citri nucleotide pyrophosphatase/phosphodiesterase (NPP)] and distinct differences from the three metal ion AP superfamily monoesterase, from Escherichia coli AP (EcAP). We carried out a series of experiments to map out and learn from the differences and similarities between these enzymes. First, we asked why there would be independent instances of monoesterases in the AP superfamily? PafA has a much weaker product inhibition and slightly higher activity relative to EcAP, suggesting that different metabolic evolutionary pressures favored distinct active-site architectures. Next, we addressed the preferential phosphate monoester and diester catalysis of PafA and NPP, respectively. We asked whether the >80% sequence differences throughout these scaffolds provide functional specialization for each enzyme's cognate reaction. In contrast to expectations from this model, PafA and NPP mutants with the common subset of active-site groups embedded in each native scaffold had the same monoesterase:diesterase specificities; thus, the >10(7)-fold difference in native specificities appears to arise from distinct interactions at a single phosphoryl substituent. We also uncovered striking mechanistic similarities between the PafA and EcAP monoesterases, including evidence for ground-state destabilization and functional active-site networks that involve different active-site groups but may play analogous catalytic roles. Discovering common network functions may reveal active-site architectural connections that are critical for function, and identifying regions of functional modularity may facilitate the design of new enzymes

  13. Structural relationships in the lysozyme superfamily: significant evidence for glycoside hydrolase signature motifs.

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    Alexandre Wohlkönig

    Full Text Available BACKGROUND: Chitin is a polysaccharide that forms the hard, outer shell of arthropods and the cell walls of fungi and some algae. Peptidoglycan is a polymer of sugars and amino acids constituting the cell walls of most bacteria. Enzymes that are able to hydrolyze these cell membrane polymers generally play important roles for protecting plants and animals against infection with insects and pathogens. A particular group of such glycoside hydrolase enzymes share some common features in their three-dimensional structure and in their molecular mechanism, forming the lysozyme superfamily. RESULTS: Besides having a similar fold, all known catalytic domains of glycoside hydrolase proteins of lysozyme superfamily (families and subfamilies GH19, GH22, GH23, GH24 and GH46 share in common two structural elements: the central helix of the all-α domain, which invariably contains the catalytic glutamate residue acting as general-acid catalyst, and a β-hairpin pointed towards the substrate binding cleft. The invariant β-hairpin structure is interestingly found to display the highest amino acid conservation in aligned sequences of a given family, thereby allowing to define signature motifs for each GH family. Most of such signature motifs are found to have promising performances for searching sequence databases. Our structural analysis further indicates that the GH motifs participate in enzymatic catalysis essentially by containing the catalytic water positioning residue of inverting mechanism. CONCLUSIONS: The seven families and subfamilies of the lysozyme superfamily all have in common a β-hairpin structure which displays a family-specific sequence motif. These GH β-hairpin motifs contain potentially important residues for the catalytic activity, thereby suggesting the participation of the GH motif to catalysis and also revealing a common catalytic scheme utilized by enzymes of the lysozyme superfamily.

  14. A Comparative Analysis of Synonymous Codon Usage Bias Pattern in Human Albumin Superfamily

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    Hoda Mirsafian

    2014-01-01

    Full Text Available Synonymous codon usage bias is an inevitable phenomenon in organismic taxa across the three domains of life. Though the frequency of codon usage is not equal across species and within genome in the same species, the phenomenon is non random and is tissue-specific. Several factors such as GC content, nucleotide distribution, protein hydropathy, protein secondary structure, and translational selection are reported to contribute to codon usage preference. The synonymous codon usage patterns can be helpful in revealing the expression pattern of genes as well as the evolutionary relationship between the sequences. In this study, synonymous codon usage bias patterns were determined for the evolutionarily close proteins of albumin superfamily, namely, albumin, α-fetoprotein, afamin, and vitamin D-binding protein. Our study demonstrated that the genes of the four albumin superfamily members have low GC content and high values of effective number of codons (ENC suggesting high expressivity of these genes and less bias in codon usage preferences. This study also provided evidence that the albumin superfamily members are not subjected to mutational selection pressure.

  15. Evolutionary trace analysis of eukaryotic DNA topoisomerase I superfamily: Identification of novel antitumor drug binding site

    Institute of Scientific and Technical Information of China (English)

    SONG; Yunlong; QI; Yunpeng; ZHANG; Wannian; SHENG; Chunqu

    2005-01-01

    The studies of novel inhibitors of DNA topoisomerase I (Topo I) have already become very promising in cancer chemotherapy. Identifying the new drug-binding residues is playing an important role in the design and optimization of Topo I inhibitors. The designed compounds may have novel scaffolds, thus will be helpful to overcome the toxicities of current camptothecin (CPT) drugs and may provide a solution to cross resistance with these drugs. Multiple sequence alignments were performed on eukaryotic DNA topoisomerase I superfamily and thus the evolutionary tree was constructed. The Evolutionary Trace method was applied to identify functionally important residues of human Topo I. It has been demonstrated that class-specific hydrophobic residues Ala351, Met428, Pro431 are located around the 7,9-position of CPT, indicating suitable substitution of hydrophobic group on CPT will increase antitumor activity. The conservative residue Lys436 in the superfamily is of particular interest and new CPT derivatives designed based on this residue may greatly increase water solubility of such drugs. It has also been demonstrated that the residues Asn352 and Arg364 were conservative in the superfamily, whose mutation will render CPT resistance. As our molecular docking studies demonstrated they did not make any direct interaction with CPT, they are important drug-binding site residues for future design of novel non-camptothecin lead compounds. This work provided a strong basis for the design and synthesis of novel highly potent CPT derivatives and virtual screening for novel lead compounds.

  16. Cloning of Octopus cephalotocin receptor, a member of the oxytocin/vasopressin superfamily.

    Science.gov (United States)

    Kanda, Atsuhiro; Takuwa-Kuroda, Kyoko; Iwakoshi-Ukena, Eiko; Furukawa, Yasuo; Matsushima, Osamu; Minakata, Hiroyuki

    2003-11-01

    We reported that the common octopus, Octopus vulgaris, in common with vertebrates, possesses two members of the oxytocin/vasopressin superfamily: octopressin (OP) and cephalotocin (CT). This was the first observation of its kind in invertebrates. As OP and CT have different biological activities, the presence of specific receptors has been proposed. We cloned the cDNA of an orphan receptor from Octopus brain and found it to encode a polypeptide of 397 amino acids that displays sequences characteristic of G-protein coupled receptors. The orphan receptor showed high homology to receptors of the oxytocin/vasopressin superfamily and seemed to conserve the agonist-binding pocket common to the oxytocin and vasopressin receptors. Xenopus oocytes that express the orphan receptor responded to the application of CT by an induction of membrane Cl(-) currents coupled to the inositol phosphate/Ca(2+) pathway. OP and the other members of the oxytocin/vasopressin superfamily did not activate this receptor. HPLC fractionation of the Octopus brain extract combined with an oocyte assay yielded a single substance that was identical to CT. On the basis of these results, we conclude that the cloned receptor is the CT receptor (CTR). Expression of CTR mRNA in Octopus was detected in the central and the peripheral nervous systems, the pancreas, the oviduct and the ovary. This receptor may mediate physiological functions of CT in Octopus such as neurotransmission, reproduction and metabolism.

  17. Origination, expansion, evolutionary trajectory, and expression bias of AP2/ERF superfamily in Brassica napus

    Directory of Open Access Journals (Sweden)

    Xiaoming Song

    2016-08-01

    Full Text Available The AP2/ERF superfamily, one of the most important transcription factor families, plays crucial roles in response to biotic and abiotic stresses. So far, a comprehensive evolutionary inference of its origination and expansion has not been available. Here, we identified 515 AP2/ERF genes in B. napus, a neo-tetraploid forming ~7500 years ago, and found that 82.14% of them were duplicated in the tetraploidization. A prominent subgenome bias was revealed in gene expression, tissue-specific, and gene conversion. Moreover, a large-scale analysis across plants and alga suggested that this superfamily could have been originated from AP2 family, expanding to form other families (ERF, and RAV. This process was accompanied by duplicating and/or alternative deleting AP2 domain, intragenic domain sequence conversion, and/or by acquiring other domains, resulting in copy number variations, alternatively contributing to functional innovation. We found that significant positive selection occurred at certain critical nodes during the evolution of land plants, possibly responding to changing environment. In conclusion, the present research revealed origination, functional innovation, and evolutionary trajectory of the AP2/ERF superfamily, contributing to understanding their roles in plant stress tolerance.

  18. Analysis and update of the human solute carrier (SLC gene superfamily

    Directory of Open Access Journals (Sweden)

    He Lei

    2009-01-01

    Full Text Available Abstract The solute-carrier gene (SLC superfamily encodes membrane-bound transporters. The SLC superfamily comprises 55 gene families having at least 362 putatively functional protein-coding genes. The gene products include passive transporters, symporters and antiporters, located in all cellular and organelle membranes, except, perhaps, the nuclear membrane. Transport substrates include amino acids and oligopeptides, glucose and other sugars, inorganic cations and anions (H+, HCO3-, Cl-, Na+, K+, Ca2+, Mg2+, PO43-, HPO42-, H2PO4-, SO42-, C2O42-, OH-,CO32-, bile salts, carboxylate and other organic anions, acetyl coenzyme A, essential metals, biogenic amines, neurotransmitters, vitamins, fatty acids and lipids, nucleosides, ammonium, choline, thyroid hormone and urea. Contrary to gene nomenclature commonly assigned on the basis of evolutionary divergence http://www.genenames.org/, the SLC gene superfamily has been named based largely on transporter function by proteins having multiple transmembrane domains. Whereas all the transporters exist for endogenous substrates, it is likely that drugs, non-essential metals and many other environmental toxicants are able to 'hitch-hike' on one or another of these transporters, thereby enabling these moieties to enter (or leave the cell. Understanding and characterising the functions of these transporters is relevant to medicine, genetics, developmental biology, pharmacology and cancer chemotherapy.

  19. Genome-Wide Identification and Functional Classification of Tomato (Solanum lycopersicum) Aldehyde Dehydrogenase (ALDH) Gene Superfamily.

    Science.gov (United States)

    Jimenez-Lopez, Jose C; Lopez-Valverde, Francisco J; Robles-Bolivar, Paula; Lima-Cabello, Elena; Gachomo, Emma W; Kotchoni, Simeon O

    2016-01-01

    Aldehyde dehydrogenases (ALDHs) is a protein superfamily that catalyzes the oxidation of aldehyde molecules into their corresponding non-toxic carboxylic acids, and responding to different environmental stresses, offering promising genetic approaches for improving plant adaptation. The aim of the current study is the functional analysis for systematic identification of S. lycopersicum ALDH gene superfamily. We performed genome-based ALDH genes identification and functional classification, phylogenetic relationship, structure and catalytic domains analysis, and microarray based gene expression. Twenty nine unique tomato ALDH sequences encoding 11 ALDH families were identified, including a unique member of the family 19 ALDH. Phylogenetic analysis revealed 13 groups, with a conserved relationship among ALDH families. Functional structure analysis of ALDH2 showed a catalytic mechanism involving Cys-Glu couple. However, the analysis of ALDH3 showed no functional gene duplication or potential neo-functionalities. Gene expression analysis reveals that particular ALDH genes might respond to wounding stress increasing the expression as ALDH2B7. Overall, this study reveals the complexity of S. lycopersicum ALDH gene superfamily and offers new insights into the structure-functional features and evolution of ALDH gene families in vascular plants. The functional characterization of ALDHs is valuable and promoting molecular breeding in tomato for the improvement of stress tolerance and signaling.

  20. Exploring fold space preferences of new-born and ancient protein superfamilies.

    Directory of Open Access Journals (Sweden)

    Hannah Edwards

    Full Text Available The evolution of proteins is one of the fundamental processes that has delivered the diversity and complexity of life we see around ourselves today. While we tend to define protein evolution in terms of sequence level mutations, insertions and deletions, it is hard to translate these processes to a more complete picture incorporating a polypeptide's structure and function. By considering how protein structures change over time we can gain an entirely new appreciation of their long-term evolutionary dynamics. In this work we seek to identify how populations of proteins at different stages of evolution explore their possible structure space. We use an annotation of superfamily age to this space and explore the relationship between these ages and a diverse set of properties pertaining to a superfamily's sequence, structure and function. We note several marked differences between the populations of newly evolved and ancient structures, such as in their length distributions, secondary structure content and tertiary packing arrangements. In particular, many of these differences suggest a less elaborate structure for newly evolved superfamilies when compared with their ancient counterparts. We show that the structural preferences we report are not a residual effect of a more fundamental relationship with function. Furthermore, we demonstrate the robustness of our results, using significant variation in the algorithm used to estimate the ages. We present these age estimates as a useful tool to analyse protein populations. In particularly, we apply this in a comparison of domains containing greek key or jelly roll motifs.

  1. Turning points in the evolution of peroxidase-catalase superfamily: molecular phylogeny of hybrid heme peroxidases.

    Science.gov (United States)

    Zámocký, Marcel; Gasselhuber, Bernhard; Furtmüller, Paul G; Obinger, Christian

    2014-12-01

    Heme peroxidases and catalases are key enzymes of hydrogen peroxide metabolism and signaling. Here, the reconstruction of the molecular evolution of the peroxidase-catalase superfamily (annotated in pfam as PF00141) based on experimentally verified as well as numerous newly available genomic sequences is presented. The robust phylogenetic tree of this large enzyme superfamily was obtained from 490 full-length protein sequences. Besides already well-known families of heme b peroxidases arranged in three main structural classes, completely new (hybrid type) peroxidase families are described being located at the border of these classes as well as forming (so far missing) links between them. Hybrid-type A peroxidases represent a minor eukaryotic subfamily from Excavates, Stramenopiles and Rhizaria sharing enzymatic and structural features of ascorbate and cytochrome c peroxidases. Hybrid-type B peroxidases are shown to be spread exclusively among various fungi and evolved in parallel with peroxidases in land plants. In some ascomycetous hybrid-type B peroxidases, the peroxidase domain is fused to a carbohydrate binding (WSC) domain. Both here described hybrid-type peroxidase families represent important turning points in the complex evolution of the whole peroxidase-catalase superfamily. We present and discuss their phylogeny, sequence signatures and putative biological function.

  2. Origination, Expansion, Evolutionary Trajectory, and Expression Bias of AP2/ERF Superfamily in Brassica napus

    Science.gov (United States)

    Song, Xiaoming; Wang, Jinpeng; Ma, Xiao; Li, Yuxian; Lei, Tianyu; Wang, Li; Ge, Weina; Guo, Di; Wang, Zhenyi; Li, Chunjin; Zhao, Jianjun; Wang, Xiyin

    2016-01-01

    The AP2/ERF superfamily, one of the most important transcription factor families, plays crucial roles in response to biotic and abiotic stresses. So far, a comprehensive evolutionary inference of its origination and expansion has not been available. Here, we identified 515 AP2/ERF genes in B. napus, a neo-tetraploid forming ~7500 years ago, and found that 82.14% of them were duplicated in the tetraploidization. A prominent subgenome bias was revealed in gene expression, tissue-specific, and gene conversion. Moreover, a large-scale analysis across plants and alga suggested that this superfamily could have been originated from AP2 family, expanding to form other families (ERF, and RAV). This process was accompanied by duplicating and/or alternative deleting AP2 domain, intragenic domain sequence conversion, and/or by acquiring other domains, resulting in copy number variations, alternatively contributing to functional innovation. We found that significant positive selection occurred at certain critical nodes during the evolution of land plants, possibly responding to changing environment. In conclusion, the present research revealed origination, functional innovation, and evolutionary trajectory of the AP2/ERF superfamily, contributing to understanding their roles in plant stress tolerance. PMID:27570529

  3. cDNA Cloning of Two Novel T-superfamily Conotoxins from Conus leopardus

    Institute of Scientific and Technical Information of China (English)

    Wei-Hua CHEN; Yu-Hong HAN; Qi WANG; Xiao-Wei MIAO; Ling OU; Xiao-Xia SHAO

    2006-01-01

    The full-length cDNAs of two novel T-superfamily conotoxins, Lp5.1 and Lp5.2, were cloned from a vermivorous cone snail Conus leopardus using 3′/5′-rapid amplification of cDNA ends. The cDNA of Lp5.1 encodes a precursor of 65 residues, including a 22-residue signal peptide, a 28-residue propeptide and a 15-residue mature peptide. Lp5.1 is processed at the common signal site -X-Arg- immediately before the mature peptide sequences. In the case of Lp5.2, the precursor includes a 25-residue signal peptide and a 43-residue sequence comprising the propeptide and mature peptide, which is probably cleaved to yield a 29-residue propeptide and a 14-residue mature toxin. Although these two conotoxins share a similar signal sequence and a conserved disulfide pattern with the known T-superfamily, the pro-region and mature peptides are of low identity, especially Lp5.2 with an identity as low as 10.7% compared with the reference Mr5. 1a.The elucidated cDNAs of these two toxins will facilitate a better understanding of the species distribution,the sequence diversity of T-superfamily conotoxins, the special gene structure and the evolution of these peptides.

  4. Genome-level and biochemical diversity of the acyl-activating enzyme superfamily in plants.

    Science.gov (United States)

    Shockey, Jay; Browse, John

    2011-04-01

    In higher plants, the superfamily of carboxyl-CoA ligases and related proteins, collectively called acyl activating enzymes (AAEs), has evolved to provide enzymes for many pathways of primary and secondary metabolism and for the conjugation of hormones to amino acids. Across the superfamily there is only limited sequence similarity, but a series of highly conserved motifs, including the AMP-binding domain, make it easy to identify members. These conserved motifs are best understood in terms of the unique domain-rotation architecture that allows AAE enzymes to catalyze the two distinct steps of the CoA ligase reaction. Arabidopsis AAE sequences were used to identify the AAE gene families in the sequenced genomes of green algae, mosses, and trees; the size of the respective families increased with increasing degree of organismal cellular complexity, size, and generation time. Large-scale genome duplications and small-scale tandem gene duplications have contributed to AAE gene family complexity to differing extents in each of the multicellular species analyzed. Gene duplication and evolution of novel functions in Arabidopsis appears to have occurred rapidly, because acquisition of new substrate specificity is relatively easy in this class of proteins. Convergent evolution has also occurred between members of distantly related clades. These features of the AAE superfamily make it difficult to use homology searches and other genomics tools to predict enzyme function. The Plant Journal © 2011 Blackwell Publishing Ltd. No claim to original US government works.

  5. Duplication and divergent evolution of the CHS and CHS-like genes in the chalcone synthase (CHS) superfamily

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The enzymes of the CHS-superfamily are responsible for biosynthesis of a wide range of natural products in plants. They are important for flower pigmentation, protection against UV light and defense against phytopathogens. Many plants were found to contain multiple copies of CHS genes. This review summarizes the recent progress in the studies of the CHS-superfamily, focusing on the duplication and divergent evolution of the CHS and CHS-like genes. Comparative analyses of gene structure, expression patterns and catalytic properties revealed extensive differentiation in both regulation and function among duplicate CHS genes. It is also proposed that the CHS-like enzymes in the CHS-superfamily evolved from CHS at different times in various organisms. The CHS-superfamily thus offers a valuable model to study the rates and patterns of sequence divergence between duplicate genes.

  6. KEANEKARAGAMAN JENIS KUPU-KUPU SUPERFAMILI PAPILIONOIDAE DI DUKUH BANYUWINDU DESA LIMBANGAN KECAMATAN LIMBANGAN KABUPATEN KENDAL

    Directory of Open Access Journals (Sweden)

    M. Rahayuningsih

    2012-09-01

    Full Text Available Kupu-kupu merupakan bagian dari biodiversitas yang harus dijaga kelestariannya. Kupu-kupu memberikan keuntungan bagi kehidupan manusia. Secara ekologis kupu-kupu memberikan sumbangan dalam menjaga keseimbangan ekosistem dan memperkaya biodiversitas. Dukuh Banyuwindu merupakan salah satu pedukuhan di Desa Limbangan terletak di lembah dan berperan sebagai daerah ekoturisme. Tujuan kajian ini adalah untuk menentukan keanekaragaman spesies kupu-kupu superfamili Papilionoidae di Dukuh Banyuwindu Desa Limbangan Kabupaten Kendal, khususnya pada habitat hutan sekunder, pemukiman, daerah aliran sungai, dan persawahan. Penelitian dilakukan dengan metode Abundance Point Index. Penelitian menunjukkan terdapat 62 spesies kupu-kupu superfamili Papilionoidae yang terdiri dari 737 individu dan diklasifikasikan menjadi empat famili dinamai Papilionoidae, Pieridae, Lycaenidae, dan Nymphalidae. Indeks keanekaragaman jenis kupu-kupu superfamili Papilionoidae di Dukuh Banyuwindu berkisar antara 2,74-3,09, indeks kemerataan jenis berkisar antara 0,86-0,87 dan memiliki dominansi berkisar antara 0,07-0,09. Indeks keanekaragaman jenis dan indeks kemerataan jenis tertinggi tercatat pada habitat pemukiman yaitu 3,09 dan 0,87 sedangkan terendah tercatat pada habitat persawahan masing-masing sebesar 2,74 dan 0,86. The butterflies are part of biodiversity which must be preserved. These insect provide benefits to human life. Ecologically, butterfly contributed in maintain the balance of ecosystem and enrich the biodiversity. Banyuwindu Hamlet is one of the hamlets in Limbangan Village, located in the hills and will serve as an ecotourism area. The purpose of this study was to determine the diversity of butterfly species in the superfamily Papilionoidae at Banyuwindu Hamlet, Limbangan Village, Limbangan District, Kendal Regency, especially in secondary forest habitats, settlements, watershed, and rice fields. Research performed with Abundance Point Index Method. The

  7. Evolution of Enzymatic Activities in the Enolase Superfamily: D-Mannonate Dhydratase from Novosphingobium aromaticivorans

    Energy Technology Data Exchange (ETDEWEB)

    Rakus,J.; Fedorov, A.; Fedorov, E.; Glasner, M.; Vick, J.; Babbitt, P.; Almo, S.; Gerlt, J.

    2007-01-01

    The d-mannonate dehydratase (ManD) function was assigned to a group of orthologous proteins in the mechanistically diverse enolase superfamily by screening a library of acid sugars. Structures of the wild type ManD from Novosphingobium aromaticivorans were determined at pH 7.5 in the presence of Mg2+ and also in the presence of Mg2+ and the 2-keto-3-keto-d-gluconate dehydration product; the structure of the catalytically active K271E mutant was determined at pH 5.5 in the presence of the d-mannonate substrate. As previously observed in the structures of other members of the enolase superfamily, ManD contains two domains, an N-terminal a+{beta} capping domain and a ({beta}/a)7{beta}-barrel domain. The barrel domain contains the ligands for the essential Mg2+, Asp 210, Glu 236, and Glu 262, at the ends of the third, fourth, and fifth {beta}-strands of the barrel domain, respectively. However, the barrel domain lacks both the Lys acid/base catalyst at the end of the second {beta}-strand and the His-Asp dyad acid/base catalyst at the ends of the seventh and sixth {beta}-strands, respectively, that are found in many members of the superfamily. Instead, a hydrogen-bonded dyad of Tyr 159 in a loop following the second {beta}-strand and Arg 147 at the end of the second {beta}-strand are positioned to initiate the reaction by abstraction of the 2-proton. Both Tyr 159 and His 212, at the end of the third {beta}-strand, are positioned to facilitate both syn-dehydration and ketonization of the resulting enol intermediate to yield the 2-keto-3-keto-d-gluconate product with the observed retention of configuration. The identities and locations of these acid/base catalysts as well as of cationic amino acid residues that stabilize the enolate anion intermediate define a new structural strategy for catalysis (subgroup) in the mechanistically diverse enolase superfamily. With these differences, we provide additional evidence that the ligands for the essential Mg2+ are the only

  8. Stimulus-dependent dynamic homo- and heteromultimerization of synaptobrevin/VAMP and synaptophysin.

    Science.gov (United States)

    Khvotchev, Mikhail V; Südhof, Thomas C

    2004-11-30

    Synaptophysin and synaptobrevin/VAMP are abundant synaptic vesicle proteins that form homo- and heterooligomers. We now use chemical cross-linking in synaptosomes, pinched-off nerve terminals that are capable of stimulus-dependent neurotransmitter release, to investigate whether these complexes are regulated. We show that in synaptosomes treated with three stimuli that induce exocytosis (a depolarizing K(+) solution, the excitatory neurotoxin alpha-latrotoxin, or the Ca(2+)-ionophore ionomycin), the homo- and heteromultimerization of synaptophysin and synaptobrevin is increased up to 6-fold. Whereas at rest less than 10% of the total synaptobrevin and synaptophysin could be chemically cross-linked into homo- and heteromeric complexes, after stimulation up to 25% of synaptobrevin and synaptophysin are present in homo- and heteromultimers, suggesting that a large fraction of these synaptic vesicle proteins physiologically participate in such complexes. The increase in multimerization of synaptophysin and synaptobrevin was only observed in intact but not in lysed synaptosomes and could not be inhibited by general kinase or phosphatase inhibitors. The stimulus dependence of synaptophysin and synaptobrevin multimers indicates that the complexes are not composed of a fixed multisubunit structure, for example, as an ion channel, but represent distinct functional states of synaptobrevin and synaptophysin that are modulated in parallel with synaptic vesicle exo- and endocytosis.

  9. Stravovacích návyky z hlediska fylogeneze Homo sapiens sapiens.

    OpenAIRE

    2010-01-01

    This Bachelor's thesis on the synthesis of literature, is attempting to create an overview of our human ancestor's dietary habits. The time frame is from the oldest representative of the hominoid family, genus Ardipithecus ramidus, to neolithic Homo sapiens.This will show the connection between the changing food spectrum and the phylogeny of our species.

  10. Cold Spring Harbor symposia on quantitative biology: Volume 51, Molecular biology of /ital Homo sapiens/

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    This volume is the second part of a collection of papers submitted by the participants to the 1986 Cold Spring Harbor Symposium on Quantitative Biology entitled Molecular Biology of /ital Homo sapiens/. The 49 papers included in this volume are grouped by subject into receptors, human cancer genes, and gene therapy. (DT)

  11. Similar Pathogen Targets in Arabidopsis thaliana and Homo sapiens Protein Networks

    Science.gov (United States)

    2012-09-21

    transduction components between organelle such as the nucleus and mitochondria as the cell strives to maintain homeostasis. Many of these communication... Similar Pathogen Targets in Arabidopsis thaliana and Homo sapiens Protein Networks Paulo Shakarian1*, J. Kenneth Wickiser2 1 Paulo Shakarian...pathogens on host protein networks for humans and Arabidopsis - noting striking similarities . Specifically, we preform k-shell decomposition analysis on

  12. Improved age control on early Homo fossils from the upper Burgi Member at Koobi Fora, Kenya

    NARCIS (Netherlands)

    Joordens, J.C.A.; Dupont-Nivet, G.; Feibel, C.S.; Spoor, F.; Sier, M.J.; Lubbe, J.H.J.L. van der; Kellberg Nielsen, T.; Knul, M.V.; Davies, G.R.; Vonhof, H.B.

    2013-01-01

    To address questions regarding the evolutionary origin, radiation and dispersal of the genus Homo, it is crucial to be able to place the occurrence of hominin fossils in a high-resolution chronological framework. The period around 2 Ma (millions of years ago) in eastern Africa is of particular inter

  13. The evolution of the anatomically modern or advanced Homo sapiens: time, place, process, affinities and variations.

    Science.gov (United States)

    Raghavan, P; Pathmanathan, G; Talwar, I

    2009-06-01

    This paper surveys the opinions expressed in the recent literature on the origins of the anatomically- modern Homo sapiens, and reviews the evidence from cranial and dental morphology argued by proponents of opposing views to support their case. It also critically analyses problems facing the interpretation of the evidence in arriving at a definitive conclusion to the debate.

  14. Spatial Construction Skills of Chimpanzees ("Pan Troglodytes") and Young Human Children ("Homo Sapiens Sapiens")

    Science.gov (United States)

    Poti, Patrizia; Hayashi, Misato; Matsuzawa, Tetsuro

    2009-01-01

    Spatial construction tasks are basic tests of visual-spatial processing. Two studies have assessed spatial construction skills in chimpanzees (Pan troglodytes) and young children (Homo sapiens sapiens) with a block modelling task. Study 1a subjects were three young chimpanzees and five adult chimpanzees. Study 1b subjects were 30 human children…

  15. Homo erectus at Trinil on Java used shells for tool production and engraving

    NARCIS (Netherlands)

    Joordens, J.C.A.; d’Errico, F.; Wesselingh, F.P.; Munro, S.; Vos, de J.; Wallinga, J.; Ankjaergaard, C.; Reimann, T.; Wijbrans, J.R.; Kuiper, K.F.; Mücher, H.J.; Coqueugniot, H.; Prié, V.; Joosten, I.; Os, van B.; Schulp, A.S.; Panuel, M.; Haas, van der V.; Lustenhouwer, W.; Reijmer, J.J.G.; Roebroeks, W.

    2015-01-01

    The manufacture of geometric engravings is generally interpreted as indicative of modern cognition and behaviour1. Key questions in the debate on the origin of such behaviour are whether this innovation is restricted to Homo sapiens, and whether it has a uniquely African origin1. Here we report on a

  16. Disproportionate Cochlear Length in Genus Homo Shows a High Phylogenetic Signal during Apes' Hearing Evolution.

    Science.gov (United States)

    Braga, J; Loubes, J-M; Descouens, D; Dumoncel, J; Thackeray, J F; Kahn, J-L; de Beer, F; Riberon, A; Hoffman, K; Balaresque, P; Gilissen, E

    2015-01-01

    Changes in lifestyles and body weight affected mammal life-history evolution but little is known about how they shaped species' sensory systems. Since auditory sensitivity impacts communication tasks and environmental acoustic awareness, it may have represented a deciding factor during mammal evolution, including apes. Here, we statistically measure the influence of phylogeny and allometry on the variation of five cochlear morphological features associated with hearing capacities across 22 living and 5 fossil catarrhine species. We find high phylogenetic signals for absolute and relative cochlear length only. Comparisons between fossil cochleae and reconstructed ape ancestral morphotypes show that Australopithecus absolute and relative cochlear lengths are explicable by phylogeny and concordant with the hypothetized ((Pan,Homo),Gorilla) and (Pan,Homo) most recent common ancestors. Conversely, deviations of the Paranthropus oval window area from these most recent common ancestors are not explicable by phylogeny and body weight alone, but suggest instead rapid evolutionary changes (directional selection) of its hearing organ. Premodern (Homo erectus) and modern human cochleae set apart from living non-human catarrhines and australopiths. They show cochlear relative lengths and oval window areas larger than expected for their body mass, two features corresponding to increased low-frequency sensitivity more recent than 2 million years ago. The uniqueness of the "hypertrophied" cochlea in the genus Homo (as opposed to the australopiths) and the significantly high phylogenetic signal of this organ among apes indicate its usefulness to identify homologies and monophyletic groups in the hominid fossil record.

  17. Disproportionate Cochlear Length in Genus Homo Shows a High Phylogenetic Signal during Apes' Hearing Evolution.

    Directory of Open Access Journals (Sweden)

    J Braga

    Full Text Available Changes in lifestyles and body weight affected mammal life-history evolution but little is known about how they shaped species' sensory systems. Since auditory sensitivity impacts communication tasks and environmental acoustic awareness, it may have represented a deciding factor during mammal evolution, including apes. Here, we statistically measure the influence of phylogeny and allometry on the variation of five cochlear morphological features associated with hearing capacities across 22 living and 5 fossil catarrhine species. We find high phylogenetic signals for absolute and relative cochlear length only. Comparisons between fossil cochleae and reconstructed ape ancestral morphotypes show that Australopithecus absolute and relative cochlear lengths are explicable by phylogeny and concordant with the hypothetized ((Pan,Homo,Gorilla and (Pan,Homo most recent common ancestors. Conversely, deviations of the Paranthropus oval window area from these most recent common ancestors are not explicable by phylogeny and body weight alone, but suggest instead rapid evolutionary changes (directional selection of its hearing organ. Premodern (Homo erectus and modern human cochleae set apart from living non-human catarrhines and australopiths. They show cochlear relative lengths and oval window areas larger than expected for their body mass, two features corresponding to increased low-frequency sensitivity more recent than 2 million years ago. The uniqueness of the "hypertrophied" cochlea in the genus Homo (as opposed to the australopiths and the significantly high phylogenetic signal of this organ among apes indicate its usefulness to identify homologies and monophyletic groups in the hominid fossil record.

  18. Palladium-catalyzed homo-coupling of boronic acids with supported reagents in supercritical carbon dioxide

    Institute of Scientific and Technical Information of China (English)

    Lei Zhou; Qiu Xiang Xu; Huan Feng Jiang

    2007-01-01

    Palladium-catalyzed homo-coupling of arylboronic acids could proceed smoothly with a commercially available resin functionlised by phosphino or amino group as the ligand in supercritical carbon dioxide thereby offering a simple and efficient protocol for the synthesis of symmetrical bi-aryl molecules and their higher homologues.

  19. Homo-FRET Imaging Enables Quantification of Protein Cluster Sizes with Subcellular Resolution

    NARCIS (Netherlands)

    Bader, A.N.; Hofman, E.G.; Voortman, J.; Henegouwen, P.; Gerritsen, H.C.

    2009-01-01

    Fluorescence-anisotropy-based homo-FRET detection methods can be employed to study clustering of identical proteins in cells. Here, the potential of fluorescence anisotropy microscopy for the quantitative imaging of protein clusters with subcellular resolution is investigated. Steady-state and

  20. Homo- and heterofermentative lactobacilli differently affect sugarcane-based fuel ethanol fermentation

    Science.gov (United States)

    The antagonism between by yeast and lactobacilli is largely dependent on the initial population of each organism. While homo-fermentative lactobacillus present higher inhibitory effect upon yeast when in equal cell number, in industrial fuel ethanol conditions where high yeast cell densities prevail...

  1. Disproportionate Cochlear Length in Genus Homo Shows a High Phylogenetic Signal during Apes’ Hearing Evolution

    Science.gov (United States)

    Braga, J.; Loubes, J-M.; Descouens, D.; Dumoncel, J.; Thackeray, J. F.; Kahn, J-L.; de Beer, F.; Riberon, A.; Hoffman, K.; Balaresque, P.; Gilissen, E.

    2015-01-01

    Changes in lifestyles and body weight affected mammal life-history evolution but little is known about how they shaped species’ sensory systems. Since auditory sensitivity impacts communication tasks and environmental acoustic awareness, it may have represented a deciding factor during mammal evolution, including apes. Here, we statistically measure the influence of phylogeny and allometry on the variation of five cochlear morphological features associated with hearing capacities across 22 living and 5 fossil catarrhine species. We find high phylogenetic signals for absolute and relative cochlear length only. Comparisons between fossil cochleae and reconstructed ape ancestral morphotypes show that Australopithecus absolute and relative cochlear lengths are explicable by phylogeny and concordant with the hypothetized ((Pan,Homo),Gorilla) and (Pan,Homo) most recent common ancestors. Conversely, deviations of the Paranthropus oval window area from these most recent common ancestors are not explicable by phylogeny and body weight alone, but suggest instead rapid evolutionary changes (directional selection) of its hearing organ. Premodern (Homo erectus) and modern human cochleae set apart from living non-human catarrhines and australopiths. They show cochlear relative lengths and oval window areas larger than expected for their body mass, two features corresponding to increased low-frequency sensitivity more recent than 2 million years ago. The uniqueness of the “hypertrophied” cochlea in the genus Homo (as opposed to the australopiths) and the significantly high phylogenetic signal of this organ among apes indicate its usefulness to identify homologies and monophyletic groups in the hominid fossil record. PMID:26083484

  2. Homo floresiensis contextualized: a geometric morphometric comparative analysis of fossil and pathological human samples.

    Directory of Open Access Journals (Sweden)

    Karen L Baab

    Full Text Available The origin of hominins found on the remote Indonesian island of Flores remains highly contentious. These specimens may represent a new hominin species, Homo floresiensis, descended from a local population of Homo erectus or from an earlier (pre-H. erectus migration of a small-bodied and small-brained hominin out of Africa. Alternatively, some workers suggest that some or all of the specimens recovered from Liang Bua are pathological members of a small-bodied modern human population. Pathological conditions proposed to explain their documented anatomical features include microcephaly, myxoedematous endemic hypothyroidism ("cretinism" and Laron syndrome (primary growth hormone insensitivity. This study evaluates evolutionary and pathological hypotheses through comparative analysis of cranial morphology. Geometric morphometric analyses of landmark data show that the sole Flores cranium (LB1 is clearly distinct from healthy modern humans and from those exhibiting hypothyroidism and Laron syndrome. Modern human microcephalic specimens converge, to some extent, on crania of extinct species of Homo. However in the features that distinguish these two groups, LB1 consistently groups with fossil hominins and is most similar to H. erectus. Our study provides further support for recognizing the Flores hominins as a distinct species, H. floresiensis, whose affinities lie with archaic Homo.

  3. Homo floresiensis contextualized: a geometric morphometric comparative analysis of fossil and pathological human samples.

    Science.gov (United States)

    Baab, Karen L; McNulty, Kieran P; Harvati, Katerina

    2013-01-01

    The origin of hominins found on the remote Indonesian island of Flores remains highly contentious. These specimens may represent a new hominin species, Homo floresiensis, descended from a local population of Homo erectus or from an earlier (pre-H. erectus) migration of a small-bodied and small-brained hominin out of Africa. Alternatively, some workers suggest that some or all of the specimens recovered from Liang Bua are pathological members of a small-bodied modern human population. Pathological conditions proposed to explain their documented anatomical features include microcephaly, myxoedematous endemic hypothyroidism ("cretinism") and Laron syndrome (primary growth hormone insensitivity). This study evaluates evolutionary and pathological hypotheses through comparative analysis of cranial morphology. Geometric morphometric analyses of landmark data show that the sole Flores cranium (LB1) is clearly distinct from healthy modern humans and from those exhibiting hypothyroidism and Laron syndrome. Modern human microcephalic specimens converge, to some extent, on crania of extinct species of Homo. However in the features that distinguish these two groups, LB1 consistently groups with fossil hominins and is most similar to H. erectus. Our study provides further support for recognizing the Flores hominins as a distinct species, H. floresiensis, whose affinities lie with archaic Homo.

  4. New fossils from Koobi Fora in northern Kenya confirm taxonomic diversity in early Homo.

    Science.gov (United States)

    Leakey, Meave G; Spoor, Fred; Dean, M Christopher; Feibel, Craig S; Antón, Susan C; Kiarie, Christopher; Leakey, Louise N

    2012-08-09

    Since its discovery in 1972 (ref. 1), the cranium KNM-ER 1470 has been at the centre of the debate over the number of species of early Homo present in the early Pleistocene epoch of eastern Africa. KNM-ER 1470 stands out among other specimens attributed to early Homo because of its larger size, and its flat and subnasally orthognathic face with anteriorly placed maxillary zygomatic roots. This singular morphology and the incomplete preservation of the fossil have led to different views as to whether KNM-ER 1470 can be accommodated within a single species of early Homo that is highly variable because of sexual, geographical and temporal factors, or whether it provides evidence of species diversity marked by differences in cranial size and facial or masticatory adaptation. Here we report on three newly discovered fossils, aged between 1.78 and 1.95 million years (Myr) old, that clarify the anatomy and taxonomic status of KNM-ER 1470. KNM-ER 62000, a well-preserved face of a late juvenile hominin, closely resembles KNM-ER 1470 but is notably smaller. It preserves previously unknown morphology, including moderately sized, mesiodistally long postcanine teeth. The nearly complete mandible KNM-ER 60000 and mandibular fragment KNM-ER 62003 have a dental arcade that is short anteroposteriorly and flat across the front, with small incisors; these features are consistent with the arcade morphology of KNM-ER 1470 and KNM-ER 62000. The new fossils confirm the presence of two contemporary species of early Homo, in addition to Homo erectus, in the early Pleistocene of eastern Africa.

  5. Aldehyde Dehydrogenase Gene Superfamily in Populus: Organization and Expression Divergence between Paralogous Gene Pairs.

    Directory of Open Access Journals (Sweden)

    Feng-Xia Tian

    Full Text Available Aldehyde dehydrogenases (ALDHs constitute a superfamily of NAD(P+-dependent enzymes that catalyze the irreversible oxidation of a wide range of reactive aldehydes to their corresponding nontoxic carboxylic acids. ALDHs have been studied in many organisms from bacteria to mammals; however, no systematic analyses incorporating genome organization, gene structure, expression profiles, and cis-acting elements have been conducted in the model tree species Populus trichocarpa thus far. In this study, a comprehensive analysis of the Populus ALDH gene superfamily was performed. A total of 26 Populus ALDH genes were found to be distributed across 12 chromosomes. Genomic organization analysis indicated that purifying selection may have played a pivotal role in the retention and maintenance of PtALDH gene families. The exon-intron organizations of PtALDHs were highly conserved within the same family, suggesting that the members of the same family also may have conserved functionalities. Microarray data and qRT-PCR analysis indicated that most PtALDHs had distinct tissue-specific expression patterns. The specificity of cis-acting elements in the promoter regions of the PtALDHs and the divergence of expression patterns between nine paralogous PtALDH gene pairs suggested that gene duplications may have freed the duplicate genes from the functional constraints. The expression levels of some ALDHs were up- or down-regulated by various abiotic stresses, implying that the products of these genes may be involved in the adaptation of Populus to abiotic stresses. Overall, the data obtained from our investigation contribute to a better understanding of the complexity of the Populus ALDH gene superfamily and provide insights into the function and evolution of ALDH gene families in vascular plants.

  6. Evolution and diversity of the Ras superfamily of small GTPases in prokaryotes.

    Science.gov (United States)

    Wuichet, Kristin; Søgaard-Andersen, Lotte

    2014-12-04

    The Ras superfamily of small GTPases are single domain nucleotide-dependent molecular switches that act as highly tuned regulators of complex signal transduction pathways. Originally identified in eukaryotes for their roles in fundamental cellular processes including proliferation, motility, polarity, nuclear transport, and vesicle transport, recent studies have revealed that single domain GTPases also control complex functions such as cell polarity, motility, predation, development and antibiotic resistance in bacteria. Here, we used a computational genomics approach to understand the abundance, diversity, and evolution of small GTPases in prokaryotes. We collected 520 small GTPase sequences present in 17% of 1,611 prokaryotic genomes analyzed that cover diverse lineages. We identified two discrete families of small GTPases in prokaryotes that show evidence of three distinct catalytic mechanisms. The MglA family includes MglA homologs, which are typically associated with the MglB GTPase activating protein, whereas members of the Rup (Ras superfamily GTPase of unknown function in prokaryotes) family are not predicted to interact with MglB homologs. System classification and genome context analyses support the involvement of small GTPases in diverse prokaryotic signal transduction pathways including two component systems, laying the foundation for future experimental characterization of these proteins. Phylogenetic analysis of prokaryotic and eukaryotic GTPases supports that the last universal common ancestor contained ancestral MglA and Rup family members. We propose that the MglA family was lost from the ancestral eukaryote and that the Ras superfamily members in extant eukaryotes are the result of vertical and horizontal gene transfer events of ancestral Rup GTPases. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Using sequence similarity networks for visualization of relationships across diverse protein superfamilies.

    Directory of Open Access Journals (Sweden)

    Holly J Atkinson

    Full Text Available The dramatic increase in heterogeneous types of biological data--in particular, the abundance of new protein sequences--requires fast and user-friendly methods for organizing this information in a way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity--GPCRs and kinases from humans, and the crotonase superfamily of enzymes--we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships.

  8. [Scarabaeoidea superfamily (Insecta: Coleoptera) as a bioindicator element of anthropogenic disturbance in an amazon national park].

    Science.gov (United States)

    Otavo, Samuel Eduardo; Parrado-Rosselli, Angela; Noriega, Jorge Ari

    2013-06-01

    Abstract: Scarabaeoidea superfamily (Insecta: Coleoptera) as a bioindicator element of anthropogenic disturbance in an amazon national park. Insects have been recognized to be important indicators of the quality elements of ecosystems, among others, because of their rapid response to environmental variability and ease cost-effective capture. In this work we evaluated whether beetles of the Scarabaeoidea superfamily may be used as bioindicators of anthropogenic disturbance of Amazonian terra firme rain forests, in order to provide guidelines for monitoring strategies of the Amacayacu National Park. We considered three different levels of anthropogenic disturbance (i.e. low, medium, high) in 12 transects (four in each intervention level), and caught all beetle species of this superfamily. Three interception traps, two light traps, three pitfalls and four bottle fruit traps were used per transect, as well as manual catch. In total, 593 individuals belonging to 92 species, 44 genera and seven families were collected. Scarabaeidae (n = 232, 27 spp.) and Dynastidae (n = 161, 26 spp.) were the families with the highest number of individuals and species, while Aphodiidae, Cetoniidae and Geotrupidae exhibited the lowest. The most abundant species per family were Ateuchus sp. (33.2%) from Scarabaeidae, Cyclocephala verticalis (55.9%) from Dynastidae, Astaena sp. (75.8%) from Melolonthidae, Ceratocanthus amazonicus (66.7%) from Ceratocanthidae y Chaetodus asuai (96.8%) from Hybosoridae. Results showed that the number of species and individuals increased with the anthropogenic disturbance. The Margalef and Shannon indexes also revealed that the highest richness and equity occurred in the high-disturbed site, respectively. Dynastidae exhibited the highest number of exclusive species per gradient, while Scarabaeidae shared most of its species. Ten species were recorded in the three disturbance levels, 26 species in two and 56 species were exclusive to one level. The most

  9. Modulation of Bacterial Multidrug Resistance Efflux Pumps of the Major Facilitator Superfamily

    Directory of Open Access Journals (Sweden)

    Sanath Kumar

    2013-01-01

    Full Text Available Bacterial infections pose a serious public health concern, especially when an infectious disease has a multidrug resistant causative agent. Such multidrug resistant bacteria can compromise the clinical utility of major chemotherapeutic antimicrobial agents. Drug and multidrug resistant bacteria harbor several distinct molecular mechanisms for resistance. Bacterial antimicrobial agent efflux pumps represent a major mechanism of clinical resistance. The major facilitator superfamily (MFS is one of the largest groups of solute transporters to date and includes a significant number of bacterial drug and multidrug efflux pumps. We review recent work on the modulation of multidrug efflux pumps, paying special attention to those transporters belonging primarily to the MFS.

  10. General survey of hAT transposon superfamily with highlight on hobo element in Drosophila.

    Science.gov (United States)

    Ladevèze, Véronique; Chaminade, Nicole; Lemeunier, Françoise; Periquet, Georges; Aulard, Sylvie

    2012-09-01

    The hAT transposons, very abundant in all kingdoms, have a common evolutionary origin probably predating the plant-fungi-animal divergence. In this paper we present their general characteristics. Members of this superfamily belong to Class II transposable elements. hAT elements share transposase, short terminal inverted repeats and eight base-pairs duplication of genomic target. We focus on hAT elements in Drosophila, especially hobo. Its distribution, dynamics and impact on genome restructuring in laboratory strains as well as in natural populations are reported. Finally, the evolutionary history of hAT elements, their domestication and use as transgenic tools are discussed.

  11. Understanding transport by the major facilitator superfamily (MFS): structures pave the way.

    Science.gov (United States)

    Quistgaard, Esben M; Löw, Christian; Guettou, Fatma; Nordlund, Pär

    2016-02-01

    Members of the major facilitator superfamily (MFS) of transport proteins are essential for the movement of a wide range of substrates across biomembranes. As this transport requires a series of conformational changes, structures of MFS transporters captured in different conformational states are needed to decipher the transport mechanism. Recently, a large number of MFS transporter structures have been determined, which has provided us with an unprecedented opportunity to understand general aspects of the transport mechanism. We propose an updated model for the conformational cycle of MFS transporters, the 'clamp-and-switch model', and discuss the role of so-called 'gating residues' and the substrate in modulating these conformational changes.

  12. Stability for Function Trade-Offs in the Enolase Superfamily 'Catalytic Module'

    Energy Technology Data Exchange (ETDEWEB)

    Nagatani, R.A.; Gonzalez, A.; Shoichet, B.K.; Brinen, L.S.; Babbitt, P.C.; /UC, San Francisco /SLAC, SSRL

    2007-07-12

    Enzyme catalysis reflects a dynamic interplay between charged and polar active site residues that facilitate function, stabilize transition states, and maintain overall protein stability. Previous studies show that substituting neutral for charged residues in the active site often significantly stabilizes a protein, suggesting a stability trade-off for functionality. In the enolase superfamily, a set of conserved active site residues (the ''catalytic module'') has repeatedly been used in nature in the evolution of many different enzymes for the performance of unique overall reactions involving a chemically diverse set of substrates. This catalytic module provides a robust solution for catalysis that delivers the common underlying partial reaction that supports all of the different overall chemical reactions of the superfamily. As this module has been so broadly conserved in the evolution of new functions, we sought to investigate the extent to which it follows the stability-function trade-off. Alanine substitutions were made for individual residues, groups of residues, and the entire catalytic module of o-succinylbenzoate synthase (OSBS), a member of the enolase superfamily from Escherichia coli. Of six individual residue substitutions, four (K131A, D161A, E190A, and D213A) substantially increased protein stability (by 0.46-4.23 kcal/mol), broadly consistent with prediction of a stability-activity trade-off. The residue most conserved across the superfamily, E190, is by far the most destabilizing. When the individual substitutions were combined into groups (as they are structurally and functionally organized), nonadditive stability effects emerged, supporting previous observations that residues within the module interact as two functional groups within a larger catalytic system. Thus, whereas the multiple-mutant enzymes D161A/E190A/D213A and K131A/K133A/D161A/E190A/D213A/K235A (termed 3KDED) are stabilized relative to the wild-type enzyme (by 1

  13. Combining metabolic engineering and biocompatible chemistry for high-yield production of homo-diacetyl and homo-(S,S)-2,3-butanediol.

    Science.gov (United States)

    Liu, Jianming; Chan, Siu Hung Joshua; Brock-Nannestad, Theis; Chen, Jun; Lee, Sang Yup; Solem, Christian; Jensen, Peter Ruhdal

    2016-07-01

    Biocompatible chemistry is gaining increasing attention because of its potential within biotechnology for expanding the repertoire of biological transformations carried out by enzymes. Here we demonstrate how biocompatible chemistry can be used for synthesizing valuable compounds as well as for linking metabolic pathways to achieve redox balance and rescued growth. By comprehensive rerouting of metabolism, activation of respiration, and finally metal ion catalysis, we successfully managed to convert the homolactic bacterium Lactococcus lactis into a homo-diacetyl producer with high titer (95mM or 8.2g/L) and high yield (87% of the theoretical maximum). Subsequently, the pathway was extended to (S,S)-2,3-butanediol (S-BDO) through efficiently linking two metabolic pathways via chemical catalysis. This resulted in efficient homo-S-BDO production with a titer of 74mM (6.7g/L) S-BDO and a yield of 82%. The diacetyl and S-BDO production rates and yields obtained are the highest ever reported, demonstrating the promising combination of metabolic engineering and biocompatible chemistry as well as the great potential of L. lactis as a new production platform.

  14. From the human capital defined as "homo oeconomicus rationalis" to that of the rationally bounded and oportunistic "homo contractualis". An institutionalist approach

    Directory of Open Access Journals (Sweden)

    Ion POHOATA

    2008-05-01

    Full Text Available The rationality (its presence or its absence of the business, be it producer or consumer, has been a constant preoccupation of all those who dedicated their energy and talent on the sinuous road of the history of economic thinking. Without rational behaviour it was inconceivable to determine a development path. From this point of view the position of the great schools of thought is based, essentially, on two main approaches. The classics and the neoclassics had in mind the perfectly rational and well-informed individual. In reply, the institutional economy, in its old or new form (NIE, opposes to homo oeconomicus rationalis a narrow-minded and insufficiently informed homo contractualis. The consequences of this re-evaluation of the basics of the business’s potencies on the physiognomy of the theoretical approach and also on the results of practical actions are significant. Those linked to the bounded rationality hypothesis, an important operating concept in the analytical structures of NIE, may trigger debates on the theoretical basis of standard economics.

  15. Dental size reduction in Indonesian Homo erectus: Implications for the PU-198 premolar and the appearance of Homo sapiens on Java.

    Science.gov (United States)

    Polanski, Joshua M; Marsh, Hannah E; Maddux, Scott D

    2016-01-01

    The recent recovery of a hominin maxillary third premolar, PU-198, within the faunal collections from Punung Cave (East Java) has led to assertions that Homo sapiens appeared on Java between 143,000 and 115,000 years ago. The taxonomic assignment of PU-198 to H. sapiens was based predominantly on the small size of the specimen, following an analysis which found little to no overlap in premolar size between Homo erectus and terminal Pleistocene/Holocene H. sapiens. Here, we re-evaluate the use of size in the taxonomic assignment of PU-198 in light of 1) new buccolingual and mesiodistal measurements taken on the fossil, 2) comparisons to a larger sample of H. erectus and H. sapiens maxillary third premolars, and 3) evidence of a diachronic trend in post-canine dental size reduction among Javan H. erectus. Our results demonstrate PU-198 to be slightly larger than previously suggested, reveal substantial overlap in premolar size between H. erectus and H. sapiens, and indicate a statistically significant reduction in premolar size between early and late Javan H. erectus. Our findings cast doubt on the assignment of PU-198 to H. sapiens, and accordingly, question the appearance of H. sapiens on Java between 143,000 and 115,000 years ago.

  16. Biased versus unbiased randomness in homo-polymers and copolymers of amino acids in the prebiotic world.

    Science.gov (United States)

    Mosqueira, Fernando G; Negron, Alicia; Ramos, Sergio; Polanco, Carlos

    2012-01-01

    The polymerization of amino acids under anhydrous prebiotic conditions was first studied several decades ago. Here we use a stochastic model stressing the relevant role of the polarity of amino acids in the formation of oligopeptides in a prebiotic milieu. Our goal is to outline the predominance of co-polypeptides over homo-polypeptides, resulting not only from the randomness, but also from polarity properties of amino acids. Our results conclude that there was a higher probability of the formation of co-polypeptides than of homo-polymers. Besides, we may hypothesize that the former would have a more ample spectrum of possible chemical functions than homo-polypeptides.

  17. Homo Clima: Climate Man and Productive Power - Government through Climate Change as Bioaesthetic Frame; Homo Clima: Klimatmaenniskan och den produktiva makten - styrning genom klimatfoeraendring som bioestetisk inramning

    Energy Technology Data Exchange (ETDEWEB)

    Skoglund, Annika

    2011-07-01

    Former creative resistance to environmentally hazardous activities has during the last decades, through discussions on climate change, been increasingly reoriented by meteorology, expert knowledge and policy discourse. The ecological system's perspective on climate change, proclaiming the human not simply as a disturbance in a natural balancing system, but as changing it, has become a causal model for the possibility to change that human. This PhD thesis interrogates how statements in IPCC reports and a Swedish newspaper (DN) constitute truth claims on climate change. What subjectivities does parlance on climate change produce and what type of citizen is called upon to optimize vitality in relation to atmospheric molecules? How is self-management of every-day activities established by help to interactivity and self-techniques framed by technical artefacts? These questions are addressed by a 'governmentality' perspective on how discourse, conceived as partaking in a process of productive power, strives to make climate change an ethico-politic question that fosters 'Homo Clima', climate man. What strategies and techniques this form of 'government' deploys are described by six interconnecting themes; 'Atmospheric biopolitics fosters contingency', 'Mortality/Vitality', 'The moral population in the atmosphere moral economy', 'Homo Clima' and 'Bioaesthetics through technical artefacts', ending in a discussion upon these themes as an act which 'Re-thematizes climate change'. The chapters illustrate how statements on the prevention and mitigation of climate risks mold scientific rationalities, mathematically modelled futures and calculations of molecular compounds with how these same futures and molecules correlate to individual culpability, responsibility and morality. From Foucauldian biopolitics to Foucauldian ethics, this can be conceived as an optimization of the vitality of

  18. Polymerization or Cyclic Dimerization: Solvent Dependent Homo-Coupling of Terminal Alkynes at HOPG Surface

    Science.gov (United States)

    Zhang, Xuemei; Liao, Lingyan; Wang, Shuai; Hu, Fangyun; Wang, Chen; Zeng, Qingdao

    2014-01-01

    Surface reactivity has become one of the most important issues in surface chemistry over the past few years. In this work, we, for the first time, have investigated the homo-coupling of a special terminal alkyne derivative on the highly oriented pyrolitic graphite (HOPG) surface. Using scanning tunneling microscopy (STM) technique, we have found that such coupling reaction seriously depends on the supramolecular assembly of the monomer on the studied substrate, whereas the latter appears an obvious solvent effect. As a result, the reaction in our system undergoes polymerization and cyclic dimerization process in 1-phenyloctane and 1,2,4-trichlorobenzene, respectively. That is to say, the solvent effect can be extended from the two-dimensional (2D) supramolecular self-assembly to surface chemical reactions, and the selective homo-coupling has been successfully achieved at the solid/liquid interface.

  19. Improved age control on early Homo fossils from the upper Burgi Member at Koobi Fora, Kenya

    DEFF Research Database (Denmark)

    Nielsen, Trine Kellberg

    2013-01-01

    To address questions regarding the evolutionary origin, radiation and dispersal of the genus Homo, it is crucial to be able to place the occurrence of hominin fossils in a high-resolution chronological framework. The period around 2 Ma (millions of years ago) in eastern Africa is of particular...... interest as it is at this time that a more substantial fossil record of the genus Homo is first found. Here we combine magnetostratigraphy and strontium (Sr) isotope stratigraphy to improve age control on hominin-bearing upper Burgi (UBU) deposits in Areas 105 and 131 on the Karari Ridge in the eastern......, the magnetostratigraphic data allow us to construct an age model for the UBU deposits. We provide detailed age constraints for 15 hominin fossils from Area 131, showing that key specimens such as cranium KNM-ER 1470, partial face KNM-ER 62000 and mandibles KNM-ER 1482, KNM-ER 1801, and KNM-ER 1802 can be constrained...

  20. Electrostatic considerations affecting the calculated HOMO-LUMO gap in protein molecules

    CERN Document Server

    Lever, Greg; Hine, Nicholas D M; Haynes, Peter D; Payne, Mike C

    2013-01-01

    A detailed study of energy differences between the highest occupied and lowest unoccupied molecular orbitals (HOMO-LUMO gaps) in protein systems and water clusters is presented. Recent work questioning the applicability of Kohn-Sham density-functional theory to proteins and large water clusters (E. Rudberg, J. Phys.: Condens. Mat. 2012, 24, 072202) has demonstrated vanishing HOMO-LUMO gaps for these systems, which is generally attributed to the treatment of exchange in the functional used. The present work shows that the vanishing gap is, in fact, an electrostatic artefact of the method used to prepare the system. Practical solutions for ensuring the gap is maintained when the system size is increased are demonstrated. This work has important implications for the use of large-scale density-functional theory in biomolecular systems, particularly in the simulation of photoemission, optical absorption and electronic transport, all of which depend critically on differences between energies of molecular orbitals.

  1. A one-million-year-old Homo cranium from the Danakil (Afar) Depression of Eritrea.

    Science.gov (United States)

    Abbate, E; Albianelli, A; Azzaroli, A; Benvenuti, M; Tesfamariam, B; Bruni, P; Cipriani, N; Clarke, R J; Ficcarelli, G; Macchiarelli, R; Napoleone, G; Papini, M; Rook, L; Sagri, M; Tecle, T M; Torre, D; Villa, I

    1998-06-04

    One of the most contentious topics in the study of human evolution is that of the time, place and mode of origin of Homo sapiens. The discovery in the Northern Danakil (Afar) Depression, Eritrea, of a well-preserved Homo cranium with a mixture of characters typical of H. erectus and H. sapiens contributes significantly to this debate. The cranium was found in a succession of fluvio-deltaic and lacustrine deposits and is associated with a rich mammalian fauna of early to early-middle Pleistocene age. A magnetostratigraphic survey indicates two reversed and two normal magnetozones. The layer in which the cranium was found is near the top of the lower normal magnetozone, which is identified as the Jaramillo subchron. Consequently, the human remains can be dated at approximately 1 million years before present.

  2. Life as a Cosmic Phenomenon: 2. the Panspermic Trajectory of Homo Sapiens

    Science.gov (United States)

    Tokoro, Gensuke; Wickramasinghe, N. Chandra

    We discuss the origin and evolution of Homo sapiens in a cosmic context, and in relation to the Hoyle-Wickramasinghe theory of panspermia for which there is now overwhelming evidence. It is argued that the first bacteria (archea) incident on the Earth via the agency of comets 3.8-4 billion years ago continued at later times to be augmented by viral genes (DNA, RNA) from space that eventually led to the evolutionary patterns we see in present-day biology. We argue that the current evolutionary status of Homo sapiens as well as its future trajectory is circumscribed by evolutionary processes that were pre-determined on a cosmic scale -- over vast distances and enormous spans of cosmic time. Based on this teleological hypothesis we postulate that two distinct classes of cosmic viruses (cosmic viral genes) are involved in accounting for the facts relating to the evolution of life.

  3. Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution.

    Science.gov (United States)

    Zihlman, Adrienne L; Bolter, Debra R

    2015-06-16

    The human body has been shaped by natural selection during the past 4-5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition.

  4. Révision de l’espèce Homo erectus (Dubois, 1893)

    OpenAIRE

    Zeitoun, V.

    2009-01-01

    L’hypodigme de Homo erectus est un problème qui restait non résolu. Les désaccords étaient davantage fondés sur la chronologie que sur la morphologie, une méthodologie ne reposant ni sur la similitude globale ni sur la position chronologique a été nécessaire pour clarifier les questions taxinomiques. Ainsi a-t-il été entrepris d’identifier des caractères apomorphiques pour Homo erectus. La première étape consiste à rechercher des critères permettant de définir l’espèce comme un clade ou un gr...

  5. The Hotdog fold: wrapping up a superfamily of thioesterases and dehydratases

    Directory of Open Access Journals (Sweden)

    Bateman Alex

    2004-08-01

    Full Text Available Abstract Background The Hotdog fold was initially identified in the structure of Escherichia coli FabA and subsequently in 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. strain CBS. Since that time structural determinations have shown a number of other apparently unrelated proteins also share the Hotdog fold. Results Using sequence analysis we unify a large superfamily of HotDog domains. Membership includes numerous prokaryotic, archaeal and eukaryotic proteins involved in several related, but distinct, catalytic activities, from metabolic roles such as thioester hydrolysis in fatty acid metabolism, to degradation of phenylacetic acid and the environmental pollutant 4-chlorobenzoate. The superfamily also includes FapR, a non-catalytic bacterial homologue that is involved in transcriptional regulation of fatty acid biosynthesis. We have defined 17 subfamilies, with some characterisation. Operon analysis has revealed numerous HotDog domain-containing proteins to be fusion proteins, where two genes, once separate but adjacent open-reading frames, have been fused into one open-reading frame to give a protein with two functional domains. Finally we have generated a Hidden Markov Model library from our analysis, which can be used as a tool for predicting the occurrence of HotDog domains in any protein sequence. Conclusions The HotDog domain is both an ancient and ubiquitous motif, with members found in the three branches of life.

  6. Evolution of the ferric reductase domain (FRD) superfamily: modularity, functional diversification, and signature motifs.

    Science.gov (United States)

    Zhang, Xuezhi; Krause, Karl-Heinz; Xenarios, Ioannis; Soldati, Thierry; Boeckmann, Brigitte

    2013-01-01

    A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria.

  7. Structural basis for amino acid export by DMT superfamily transporter YddG.

    Science.gov (United States)

    Tsuchiya, Hirotoshi; Doki, Shintaro; Takemoto, Mizuki; Ikuta, Tatsuya; Higuchi, Takashi; Fukui, Keita; Usuda, Yoshihiro; Tabuchi, Eri; Nagatoishi, Satoru; Tsumoto, Kouhei; Nishizawa, Tomohiro; Ito, Koichi; Dohmae, Naoshi; Ishitani, Ryuichiro; Nureki, Osamu

    2016-05-30

    The drug/metabolite transporter (DMT) superfamily is a large group of membrane transporters ubiquitously found in eukaryotes, bacteria and archaea, and includes exporters for a remarkably wide range of substrates, such as toxic compounds and metabolites. YddG is a bacterial DMT protein that expels aromatic amino acids and exogenous toxic compounds, thereby contributing to cellular homeostasis. Here we present structural and functional analyses of YddG. Using liposome-based analyses, we show that Escherichia coli and Starkeya novella YddG export various amino acids. The crystal structure of S. novella YddG at 2.4 Å resolution reveals a new membrane transporter topology, with ten transmembrane segments in an outward-facing state. The overall structure is basket-shaped, with a large substrate-binding cavity at the centre of the molecule, and is composed of inverted structural repeats related by two-fold pseudo-symmetry. On the basis of this intramolecular symmetry, we propose a structural model for the inward-facing state and a mechanism of the conformational change for substrate transport, which we confirmed by biochemical analyses. These findings provide a structural basis for the mechanism of transport of DMT superfamily proteins.

  8. The cellulose synthase (CESA) gene superfamily of the moss Physcomitrella patens.

    Science.gov (United States)

    Roberts, Alison W; Bushoven, John T

    2007-01-01

    The CESA gene superfamily of Arabidopsis and other seed plants comprises the CESA family, which encodes the catalytic subunits of cellulose synthase, and eight families of CESA-like (CSL) genes whose functions are largely unknown. The CSL genes have been proposed to encode processive beta-glycosyl transferases that synthesize noncellulosic cell wall polysaccharides. BLAST searches of EST and shotgun genomic sequences from the moss Physcomitrella patens (Hedw.) B.S.G. were used to identify genes with high similarity to vascular plant CESAs, CSLAs, CSLCs, and CSLDs. However, searches using Arabidopsis CSLBs, CSLEs, and CSLGs or rice CSLFs or CSLHs as queries identified no additional CESA superfamily members in P. patens, indicating that this moss lacks representatives of these families. Intron insertion sites are highly conserved between Arabidopsis and P. patens in all four shared gene families. However, phylogenetic analysis strongly supports independent diversification of the shared families in mosses and vascular plants. The lack of orthologs of vascular plant CESAs in the P. patens genome indicates that the divergence of mosses and vascular plants predated divergence and specialization of CESAs for primary and secondary cell wall syntheses and for distinct roles within the rosette terminal complexes. In contrast to Arabidopsis, the CSLD family is highly represented among P. patens ESTs. This is consistent with the proposed function of CSLDs in tip growth and the central role of tip growth in the development of the moss protonema.

  9. The maize ALDH protein superfamily: linking structural features to functional specificities

    Directory of Open Access Journals (Sweden)

    Seufferheld Manfredo J

    2010-12-01

    Full Text Available Abstract Background The completion of maize genome sequencing has resulted in the identification of a large number of uncharacterized genes. Gene annotation and functional characterization of gene products are important to uncover novel protein functionality. Results In this paper, we identify, and annotate members of all the maize aldehyde dehydrogenase (ALDH gene superfamily according to the revised nomenclature criteria developed by ALDH Gene Nomenclature Committee (AGNC. The maize genome contains 24 unique ALDH sequences encoding members of ten ALDH protein families including the previously identified male fertility restoration RF2A gene, which encodes a member of mitochondrial class 2 ALDHs. Using computational modeling analysis we report here the identification, the physico-chemical properties, and the amino acid residue analysis of a novel tunnel like cavity exclusively found in the maize sterility restorer protein, RF2A/ALDH2B2 by which this protein is suggested to bind variably long chain molecular ligands and/or potentially harmful molecules. Conclusions Our finding indicates that maize ALDH superfamily is the most expanded of plant ALDHs ever characterized, and the mitochondrial maize RF2A/ALDH2B2 is the only plant ALDH that harbors a newly defined pocket/cavity with suggested functional specificity.

  10. Homology models guide discovery of diverse enzyme specificities among dipeptide epimerases in the enolase superfamily

    Science.gov (United States)

    Lukk, Tiit; Sakai, Ayano; Kalyanaraman, Chakrapani; Brown, Shoshana D.; Imker, Heidi J.; Song, Ling; Fedorov, Alexander A.; Fedorov, Elena V.; Toro, Rafael; Hillerich, Brandan; Seidel, Ronald; Patskovsky, Yury; Vetting, Matthew W.; Nair, Satish K.; Babbitt, Patricia C.; Almo, Steven C.; Gerlt, John A.; Jacobson, Matthew P.

    2012-01-01

    The rapid advance in genome sequencing presents substantial challenges for protein functional assignment, with half or more of new protein sequences inferred from these genomes having uncertain assignments. The assignment of enzyme function in functionally diverse superfamilies represents a particular challenge, which we address through a combination of computational predictions, enzymology, and structural biology. Here we describe the results of a focused investigation of a group of enzymes in the enolase superfamily that are involved in epimerizing dipeptides. The first members of this group to be functionally characterized were Ala-Glu epimerases in Eschericiha coli and Bacillus subtilis, based on the operon context and enzymological studies; these enzymes are presumed to be involved in peptidoglycan recycling. We have subsequently studied more than 65 related enzymes by computational methods, including homology modeling and metabolite docking, which suggested that many would have divergent specificities;, i.e., they are likely to have different (unknown) biological roles. In addition to the Ala-Phe epimerase specificity reported previously, we describe the prediction and experimental verification of: (i) a new group of presumed Ala-Glu epimerases; (ii) several enzymes with specificity for hydrophobic dipeptides, including one from Cytophaga hutchinsonii that epimerizes D-Ala-D-Ala; and (iii) a small group of enzymes that epimerize cationic dipeptides. Crystal structures for certain of these enzymes further elucidate the structural basis of the specificities. The results highlight the potential of computational methods to guide experimental characterization of enzymes in an automated, large-scale fashion. PMID:22392983

  11. The Anabaena sensory rhodopsin transducer defines a novel superfamily of prokaryotic small-molecule binding domains

    Directory of Open Access Journals (Sweden)

    De Souza Robson F

    2009-08-01

    Full Text Available Abstract The Anabaena sensory rhodopsin transducer (ASRT is a small protein that has been claimed to function as a signaling molecule downstream of the cyanobacterial sensory rhodopsin. However, orthologs of ASRT have been detected in several bacteria that lack rhodopsin, raising questions about the generality of this function. Using sequence profile searches we show that ASRT defines a novel superfamily of β-sandwich fold domains. Through contextual inference based on domain architectures and predicted operons and structural analysis we present strong evidence that these domains bind small molecules, most probably sugars. We propose that the intracellular versions like ASRT probably participate as sensors that regulate a diverse range of sugar metabolism operons or even the light sensory behavior in Anabaena by binding sugars or related metabolites. We also show that one of the extracellular versions define a predicted sugar-binding structure in a novel cell-surface lipoprotein found across actinobacteria, including several pathogens such as Tropheryma, Actinomyces and Thermobifida. The analysis of this superfamily also provides new data to investigate the evolution of carbohydrate binding modes in β-sandwich domains with very different topologies. Reviewers: This article was reviewed by M. Madan Babu and Mark A. Ragan.

  12. Primate brains, the 'island rule' and the evolution of Homo floresiensis

    OpenAIRE

    Montgomery, S. H.

    2013-01-01

    The taxonomic status of the small bodied hominin, Homo floresiensis, remains controversial. One contentious aspect of the debate concerns the small brain size estimated for specimen LB1 (Liang Bua 1). Based on intraspecific mammalian allometric relationships between brain and body size, it has been argued that the brain of LB1 is too small for its body mass and is therefore likely to be pathological. The relevance and general applicability of these scaling rules has, however, been challenged,...

  13. Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens.

    Science.gov (United States)

    Mekel-Bobrov, Nitzan; Gilbert, Sandra L; Evans, Patrick D; Vallender, Eric J; Anderson, Jeffrey R; Hudson, Richard R; Tishkoff, Sarah A; Lahn, Bruce T

    2005-09-09

    The gene ASPM (abnormal spindle-like microcephaly associated) is a specific regulator of brain size, and its evolution in the lineage leading to Homo sapiens was driven by strong positive selection. Here, we show that one genetic variant of ASPM in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing rapid adaptive evolution.

  14. Post-cranial skeletons of hypothyroid cretins show a similar anatomical mosaic as Homo floresiensis.

    Directory of Open Access Journals (Sweden)

    Charles Oxnard

    Full Text Available Human remains, some as recent as 15 thousand years, from Liang Bua (LB on the Indonesian island of Flores have been attributed to a new species, Homo floresiensis. The definition includes a mosaic of features, some like modern humans (hence derived: genus Homo, some like modern apes and australopithecines (hence primitive: not species sapiens, and some unique (hence new species: floresiensis. Conversely, because only modern humans (H. sapiens are known in this region in the last 40 thousand years, these individuals have also been suggested to be genetic human dwarfs. Such dwarfs resemble small humans and do not show the mosaic combination of the most complete individuals, LB1 and LB6, so this idea has been largely dismissed. We have previously shown that some features of the cranium of hypothyroid cretins are like those of LB1. Here we examine cretin postcrania to see if they show anatomical mosaics like H. floresiensis. We find that hypothyroid cretins share at least 10 postcranial features with Homo floresiensis and unaffected humans not found in apes (or australopithecines when materials permit. They share with H. floresiensis, modern apes and australopithecines at least 11 postcranial features not found in unaffected humans. They share with H. floresiensis, at least 8 features not found in apes, australopithecines or unaffected humans. Sixteen features can be rendered metrically and multivariate analyses demonstrate that H. floresiensis co-locates with cretins, both being markedly separate from humans and chimpanzees (P0.999. We therefore conclude that LB1 and LB6, at least, are, most likely, endemic cretins from a population of unaffected Homo sapiens. This is consistent with recent hypothyroid endemic cretinism throughout Indonesia, including the nearby island of Bali.

  15. Post-cranial skeletons of hypothyroid cretins show a similar anatomical mosaic as Homo floresiensis.

    Science.gov (United States)

    Oxnard, Charles; Obendorf, Peter J; Kefford, Ben J

    2010-09-27

    Human remains, some as recent as 15 thousand years, from Liang Bua (LB) on the Indonesian island of Flores have been attributed to a new species, Homo floresiensis. The definition includes a mosaic of features, some like modern humans (hence derived: genus Homo), some like modern apes and australopithecines (hence primitive: not species sapiens), and some unique (hence new species: floresiensis). Conversely, because only modern humans (H. sapiens) are known in this region in the last 40 thousand years, these individuals have also been suggested to be genetic human dwarfs. Such dwarfs resemble small humans and do not show the mosaic combination of the most complete individuals, LB1 and LB6, so this idea has been largely dismissed. We have previously shown that some features of the cranium of hypothyroid cretins are like those of LB1. Here we examine cretin postcrania to see if they show anatomical mosaics like H. floresiensis. We find that hypothyroid cretins share at least 10 postcranial features with Homo floresiensis and unaffected humans not found in apes (or australopithecines when materials permit). They share with H. floresiensis, modern apes and australopithecines at least 11 postcranial features not found in unaffected humans. They share with H. floresiensis, at least 8 features not found in apes, australopithecines or unaffected humans. Sixteen features can be rendered metrically and multivariate analyses demonstrate that H. floresiensis co-locates with cretins, both being markedly separate from humans and chimpanzees (P0.999). We therefore conclude that LB1 and LB6, at least, are, most likely, endemic cretins from a population of unaffected Homo sapiens. This is consistent with recent hypothyroid endemic cretinism throughout Indonesia, including the nearby island of Bali.

  16. Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo.

    Science.gov (United States)

    Nishimura, Takeshi; Mori, Futoshi; Hanida, Sho; Kumahata, Kiyoshi; Ishikawa, Shigeru; Samarat, Kaouthar; Miyabe-Nishiwaki, Takako; Hayashi, Misato; Tomonaga, Masaki; Suzuki, Juri; Matsuzawa, Tetsuro; Matsuzawa, Teruo

    2016-03-01

    We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD) with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved "Out of Africa" to explore the more severe climates of

  17. Australopithecus sediba at 1.977 Ma and implications for the origins of the genus Homo.

    Science.gov (United States)

    Pickering, Robyn; Dirks, Paul H G M; Jinnah, Zubair; de Ruiter, Darryl J; Churchil, Steven E; Herries, Andy I R; Woodhead, Jon D; Hellstrom, John C; Berger, Lee R

    2011-09-01

    Newly exposed cave sediments at the Malapa site include a flowstone layer capping the sedimentary unit containing the Australopithecus sediba fossils. Uranium-lead dating of the flowstone, combined with paleomagnetic and stratigraphic analysis of the flowstone and underlying sediments, provides a tightly constrained date of 1.977 ± 0.002 million years ago (Ma) for these fossils. This refined dating suggests that Au. sediba from Malapa predates the earliest uncontested evidence for Homo in Africa.

  18. Multiplex detection of homo- and heterodimerization of g protein-coupled receptors by proximity biotinylation.

    Directory of Open Access Journals (Sweden)

    Elisabeth Steel

    Full Text Available Dimerization of G protein-coupled receptors (GPCRs represents a potential mechanism by which GPCR functions are regulated. Several resonance energy transfer (RET-based methods have revealed GPCR homo- and heterodimerization. However, interpretation of an increase in FRET efficiency could be attributed to either dimerization/oligomerization events or conformational changes within an already dimerized/oligomerized receptor complex. Furthermore, RET-based methods can only measure pairwise dimerization, and cannot easily achieve multiplex detection. In this study, we applied proximity-based biotinylation for detecting receptor dimerization by utilizing a specific enzyme-substrate pair that are fused to GPCRs. The biotin ligase BirA is fused to CXCR4 and site-specifically biotinylates an acceptor peptide (AP in the presence of biotin. As a test case for our newly developed assay, we have characterized the homo-dimerization of chemokine receptor CXCR4 and heterodimerization of CXCR4 with CCR2 or CCR5. The degree of biotinylation varies with the amount of GPCR-AP as well as biotinylation time. Using enzyme/substrate receptor pairs and measuring receptor biotinylation, we demonstrate that CXCR4 can homo-dimerize and hetero-dimerize with CCR2 and CCR5. The effect of CXCL12, agonist for CXCR4, was found to decrease surface biotinylation of CXCR4-AP. This effect is due to a combination of CXCR4 endocytosis and stabilization of CXCR4 homodimers. Finally, when CXCR4-AP, CCR2-AP, and CCR5-AP were expressed together, we observed CXCR4-CXCR4 homodimers and CXCR4-CCR2 and CXCR4-CCR5 heterodimers. The newly developed assay opens new opportunity for multiplex detection for GPCR homo- and heterodimerization within the same cellular context.

  19. Enantioselective Intramolecular Aldehyde α-Alkylation with Simple Olefins: Direct Access to Homo-Ene Products

    OpenAIRE

    Comito, Robert J.; Finelli, Fernanda G.; MacMillan, David W. C.

    2013-01-01

    A highly selective method for the synthesis of asymmetrically substituted carbocycles and heterocycles from unactivated aldehyde–olefin precursors has been achieved via enantioselective SOMO-catalysis. Addition of a catalytically generated enamine radical cation across a pendent olefin serves to establish a general asymmetric strategy towards the production of a wide range of formyl-substituted rings with alkene transposition. Conceptually, this novel mechanism allows direct access to “homo-e...

  20. Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo.

    Directory of Open Access Journals (Sweden)

    Takeshi Nishimura

    2016-03-01

    Full Text Available We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved "Out of Africa" to explore the more

  1. Synthesis and Catalytic Application of Homo-bimetallic Metallocene Complexes as Ethylene Polymerization Catalysts

    Institute of Scientific and Technical Information of China (English)

    FENG,Zuo-Feng(冯作锋); HUANG,Ji-Ling(黄吉玲); QIAN,Yan-Long(钱延龙); SUN,Jun-Quan(孙俊全); CHEN,Wei(陈伟)

    2002-01-01

    Three new homo-birnetallic metallocene complexes were prepared by RCpMCl3(M = Ti, Zr) and Si-bridged cornpounds,and were all well characterized structurally. These complexes with the methylaluminoxane (MAO) are highly active catats for the polymerization of ethylene. Compared to the polyethylene obtained by Cp2ZrCl2, the molecular weight (Mw =78784-238021) of the polyethylene was higher and the molecular weight distribution (MwD= 2.10-2.44) was broader.

  2. What do cranial bones of LB1 tell us about Homo floresiensis?

    Science.gov (United States)

    Balzeau, Antoine; Charlier, Philippe

    2016-04-01

    Cranial vault thickness (CVT) of Liang Bua 1, the specimen that is proposed to be the holotype of Homo floresiensis, has not yet been described in detail and compared with samples of fossil hominins, anatomically modern humans or microcephalic skulls. In addition, a complete description from a forensic and pathological point of view has not yet been carried out. It is important to evaluate scientifically if features related to CVT bring new information concerning the possible pathological status of LB1, and if it helps to recognize affinities with any hominin species and particularly if the specimen could belong to the species Homo sapiens. Medical examination of the skull based on a micro-CT examination clearly brings to light the presence of a sincipital T (a non-metrical variant of normal anatomy), a scar from an old frontal trauma without any evident functional consequence, and a severe bilateral hyperostosis frontalis interna that may have modified the anterior morphology of the endocranium of LB1. We also show that LB1 displays characteristics, related to the distribution of bone thickness and arrangements of cranial structures, that are plesiomorphic traits for hominins, at least for Homo erectus s.l. relative to Homo neanderthalensis and H. sapiens. All the microcephalic skulls analyzed here share the derived condition of anatomically modern H. sapiens. Cranial vault thickness does not help to clarify the definition of the species H. floresiensis but it also does not support an attribution of LB1 to H. sapiens. We conclude that there is no support for the attribution of LB1 to H. sapiens as there is no evidence of systemic pathology and because it does not have any of the apomorphic traits of our species.

  3. ‘Welc(homo Naledi’! What does our newest relative have to say to us?

    Directory of Open Access Journals (Sweden)

    Daniël P. Veldsman

    2016-05-01

    Full Text Available The new hominin fossil called Homo naledi that was discovered 2 years ago in the Dinaledi Chamber (South Africa was welcomed into the species of human relatives on 10 September 2015. Welcomed? Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa. Do, however, these bones represent a new Homo species? It is this question that I have tried to capture in my playful grammatically incorrect title ‘Welc(homo Naledi’! However, it is not this question that I will endeavour to answer, but a very different theological implication. My aim in this article is definitely not to argue an opinion on the diverse question regarding the discovery of the fossil skeletons from the Dinaledi Chamber. My aim is related but different, much more modest, restricted and focused. It is to ask ‘on the other historic side’ (that is, beyond the fossil record! of Naledi about human distinctiveness and symbolic behaviour, specifically on soteriology. Within the broader contemporary philosophical-theological discourses on anthropology and specifically the fundamental question, ‘Are we special?’, I would like ultimately to take on the intriguing theological implications for soteriology from the Naledi (and earlier findings.

  4. Application of Orthodromic Island Flap Prosthetics of Homo-Digital Artery in Finger-Tip Defect

    Institute of Scientific and Technical Information of China (English)

    Lu Daming; Lu Xiangrong; Lu Zehnliang; Zhu Jinhong

    2014-01-01

    Objective:To investigate the clinical efficacy of orthodromic island flap prosthetics of homo-digital artery on ifnger-tip defect. Methods: A total of 21 patients with ifnger-tip defect from December, 2010 to April, 2013 were given orthodromic island lfap prosthetics of homo-digital artery, with the maximum and minimum sizes of lfaps being 20 mm×22 mm and 10 mm×15 mm, respectively. Results: All patients with ifnger-tip defect survived from the lfap surgery and the wounds were favorably healed. 3~12 months follow-up after operation, the lfaps were observed with approving appearance, soft texture and favorable elasticity, with two-point discrimination being 6~8 mm. According to TAM detection of hand functions, lfaps were excellent healed in 19 cases, good and fairish in 1 case respectively, with effective rate being 95.2%. Conclusion:Orthodromic island flap prosthetics of homo-digital artery is simple and safe in operation with satisfactory effcacy, being the most ideal method for the repair of ifnger-tip defect.

  5. Linking the HOMO-LUMO gap to torsional disorder in P3HT/PCBM blends

    Energy Technology Data Exchange (ETDEWEB)

    McLeod, John A., E-mail: jmcleod@suda.edu.cn [College of Nano Science and Technology, Soochow University, 199 Ren-Ai Rd., Suzhou, Jiangsu 215123 (China); Pitman, Amy L.; Moewes, Alexander [Department of Physics and Engineering Physics, University of Saskatchewan, 116 Science Place, Saskatoon, Saskatchewan S7N 5E2 (Canada); Kurmaev, Ernst Z.; Finkelstein, Larisa D. [Institute of Metal Physics, Russian Academy of Sciences–Ural Division, 620990 Yekaterinburg (Russian Federation); Zhidkov, Ivan S. [Ural Federal University, 620002 Yekaterinburg (Russian Federation); Savva, Achilleas [Molecular Electronics and Photonics Research Unit, Department of Mechanical Engineering and Materials Science and Engineering, Cyprus University of Technology, Kitiou Kiprianou St. 45, 3603 Limassol (Cyprus)

    2015-12-14

    The electronic structure of [6,6]-phenyl C{sub 61} butyric acid methyl ester (PCBM), poly(3-hexylthiophene) (P3HT), and P3HT/PCBM blends is studied using soft X-ray emission and absorption spectroscopy and density functional theory calculations. We find that annealing reduces the HOMO-LUMO gap of P3HT and P3HT/PCBM blends, whereas annealing has little effect on the HOMO-LUMO gap of PCBM. We propose a model connecting torsional disorder in a P3HT polymer to the HOMO-LUMO gap, which suggests that annealing helps to decrease the torsional disorder in the P3HT polymers. Our model is used to predict the characteristic length scales of the flat P3TH polymer segments in P3HT and P3HT/PCBM blends before and after annealing. Our approach may prove useful in characterizing organic photovoltaic devices in situ or even in operando.

  6. Development of the palatal size in Pan troglodytes, Hominids and Homo sapiens.

    Science.gov (United States)

    Arnold, W H; Zoellner, A; Sebastian, T

    2004-12-01

    As the hard palate plays an important role in speech production it was the aim of this study whether similarities or dissimilarities in palatal size may allow conclusions about the ability to produce speech in the extant investigated species. The palatal size of Pan troglodytes, Homo sapiens, Australopithecus afarensis, Australopithecus africanus, Australopithecus robustus, Australopithecus boisei, Homo erectus, Homo neanderthalensis and Cro-Magnon has been investigated using euclidian distance matrix analysis (EDMA) and thin-plate-spline analysis. The results show that the palatal size of all australopithecine specimens and H. erectus is very similar to that of P toglodytes, whereas the palatal size of H. neanderthalensis more closely resembles that of H. sapiens. Postnatal development of palatal size in P troglodytes is different from that of H. sapiens. In P troglodytes not only the size of the palate changes but also the form. In H. sapiens there is little change in form, but a continuos uniform growth from infantile to adult specimens. From the results we conclude that in all australopithecine samples which have been investigated, the palatal size is similar to that of P troglodytes. Therefore, it is unlikely that austraopithecine individuals were capable of producing vowels and consonants. The palatal size of H. neandethalensis and Cro-Magnon is similar to that of H. sapiens which may indicate the possibility that they were capable of speech production.

  7. Radiometric dating of the type-site for Homo heidelbergensis at Mauer, Germany.

    Science.gov (United States)

    Wagner, Günther A; Krbetschek, Matthias; Degering, Detlev; Bahain, Jean-Jacques; Shao, Qingfeng; Falguères, Christophe; Voinchet, Pierre; Dolo, Jean-Michel; Garcia, Tristan; Rightmire, G Philip

    2010-11-16

    The Mauer mandible, holotype of Homo heidelbergensis, was found in 1907 in fluvial sands deposited by the Neckar River 10 km southeast of Heidelberg, Germany. The fossil is an important key to understanding early human occupation of Europe north of the Alps. Given the associated mammal fauna and the geological context, the find layer has been placed in the early Middle Pleistocene, but confirmatory chronometric evidence has hitherto been missing. Here we show that two independent techniques, the combined electron spin resonance/U-series method used with mammal teeth and infrared radiofluorescence applied to sand grains, date the type-site of Homo heidelbergensis at Mauer to 609 ± 40 ka. This result demonstrates that the mandible is the oldest hominin fossil reported to date from central and northern Europe and raises questions concerning the phyletic relationship of Homo heidelbergensis to more ancient populations documented from southern Europe and in Africa. We address the paleoanthropological significance of the Mauer jaw in light of this dating evidence.

  8. Homo-Tandem Polymer Solar Cells withVOC>1.8 V for Efficient PV-Driven Water Splitting

    KAUST Repository

    Gao, Yangqin

    2016-03-06

    Efficient homo-tandem and triple-junction polymer solar cells are constructed by stacking identical subcells composed of the wide-bandgap polymer PBDTTPD, achieving power conversion efficiencies >8% paralleled by open-circuit voltages >1.8 V. The high-voltage homo-tandem is used to demonstrate PV-driven electrochemical water splitting with an estimated solar-to-hydrogen conversion efficiency of ≈6%. © 2016 WILEY-VCH Verlag GmbH & Co.

  9. Convento del Santo Ecce-Homo síntesis histórica y esbozo analítico

    Directory of Open Access Journals (Sweden)

    Alberto Corradine

    2012-08-01

    Full Text Available Convento del Santo ECCE-HOMO, Síntesis histórica y esbozo-analítico/ Alberto Corradine. No. 6-7, 1971-1972; p. 57-68. El autor describe y analiza el estilo arquitectónico del ECCE-HOMO señalando especialmente la influencia del estilo mudejar venido de España en el siglo XVII. 

  10. Convento del santo ecce-homo síntesis histórica y esbozo analítico

    OpenAIRE

    Alberto Corradine

    2012-01-01

    Convento del Santo ECCE-HOMO, Síntesis histórica y esbozo-analítico/ Alberto Corradine. No. 6-7, 1971-1972; p. 57-68. El autor describe y analiza el estilo arquitectónico del ECCE-HOMO señalando especialmente la influencia del estilo mudejar venido de España en el siglo XVII. 

  11. Combining metabolic engineering and biocompatible chemistry for high-yield production of homo-diacetyl and homo-(S,S)-2,3-butanediol

    DEFF Research Database (Denmark)

    Liu, Jianming; Chan, Siu Hung Joshua; Brock-Nannestad, Theis;

    2016-01-01

    Biocompatible chemistry is gaining increasing attention because of its potential within biotechnology for expanding the repertoire of biological transformations carried out by enzymes. Here we demonstrate how biocompatible chemistry can be used for synthesizing valuable compounds as well as for l...... of 82%. The diacetyl and S-BDO production rates and yields obtained are the highest ever reported, demonstrating the promising combination of metabolic engineering and biocompatible chemistry as well as the great potential of L. lactis as a new production platform.......M or 8.2g/L) and high yield (87% of the theoretical maximum). Subsequently, the pathway was extended to (S,S)-2,3-butanediol (S-BDO) through efficiently linking two metabolic pathways via chemical catalysis. This resulted in efficient homo-S-BDO production with a titer of 74mM (6.7g/L) S-BDO and a yield...

  12. RASOnD - A comprehensive resource and search tool for RAS superfamily oncogenes from various species

    Directory of Open Access Journals (Sweden)

    Singh Tej P

    2011-07-01

    Full Text Available Abstract Background The Ras superfamily plays an important role in the control of cell signalling and division. Mutations in the Ras genes convert them into active oncogenes. The Ras oncogenes form a major thrust of global cancer research as they are involved in the development and progression of tumors. This has resulted in the exponential growth of data on Ras superfamily across different public databases and in literature. However, no dedicated public resource is currently available for data mining and analysis on this family. The present database was developed to facilitate straightforward accession, retrieval and analysis of information available on Ras oncogenes from one particular site. Description We have developed the RAS Oncogene Database (RASOnD as a comprehensive knowledgebase that provides integrated and curated information on a single platform for oncogenes of Ras superfamily. RASOnD encompasses exhaustive genomics and proteomics data existing across diverse publicly accessible databases. This resource presently includes overall 199,046 entries from 101 different species. It provides a search tool to generate information about their nucleotide and amino acid sequences, single nucleotide polymorphisms, chromosome positions, orthologies, motifs, structures, related pathways and associated diseases. We have implemented a number of user-friendly search interfaces and sequence analysis tools. At present the user can (i browse the data (ii search any field through a simple or advance search interface and (iii perform a BLAST search and subsequently CLUSTALW multiple sequence alignment by selecting sequences of Ras oncogenes. The Generic gene browser, GBrowse, JMOL for structural visualization and TREEVIEW for phylograms have been integrated for clear perception of retrieved data. External links to related databases have been included in RASOnD. Conclusions This database is a resource and search tool dedicated to Ras oncogenes. It has

  13. Expression profiling and integrative analysis of the CESA/CSL superfamily in rice

    Directory of Open Access Journals (Sweden)

    Tu Yuanyuan

    2010-12-01

    Full Text Available Abstract Background The cellulose synthase and cellulose synthase-like gene superfamily (CESA/CSL is proposed to encode enzymes for cellulose and non-cellulosic matrix polysaccharide synthesis in plants. Although the rice (Oryza sativa L. genome has been sequenced for a few years, the global expression profiling patterns and functions of the OsCESA/CSL superfamily remain largely unknown. Results A total of 45 identified members of OsCESA/CSL were classified into two clusters based on phylogeny and motif constitution. Duplication events contributed largely to the expansion of this superfamily, with Cluster I and II mainly attributed to tandem and segmental duplication, respectively. With microarray data of 33 tissue samples covering the entire life cycle of rice, fairly high OsCESA gene expression and rather variable OsCSL expression were observed. While some members from each CSL family (A1, C9, D2, E1, F6 and H1 were expressed in all tissues examined, many of OsCSL genes were expressed in specific tissues (stamen and radicles. The expression pattern of OsCESA/CSL and OsBC1L which extensively co-expressed with OsCESA/CSL can be divided into three major groups with ten subgroups, each showing a distinct co-expression in tissues representing typically distinct cell wall constitutions. In particular, OsCESA1, -3 & -8 and OsCESA4, -7 & -9 were strongly co-expressed in tissues typical of primary and secondary cell walls, suggesting that they form as a cellulose synthase complex; these results are similar to the findings in Arabidopsis. OsCESA5/OsCESA6 is likely partially redundant with OsCESA3 for OsCESA complex organization in the specific tissues (plumule and radicle. Moreover, the phylogenetic comparison in rice, Arabidopsis and other species can provide clues for the prediction of orthologous gene expression patterns. Conclusions The study characterized the CESA/CSL of rice using an integrated approach comprised of phylogeny, transcriptional

  14. Ensembler: Enabling High-Throughput Molecular Simulations at the Superfamily Scale.

    Science.gov (United States)

    Parton, Daniel L; Grinaway, Patrick B; Hanson, Sonya M; Beauchamp, Kyle A; Chodera, John D

    2016-06-01

    The rapidly expanding body of available genomic and protein structural data provides a rich resource for understanding protein dynamics with biomolecular simulation. While computational infrastructure has grown rapidly, simulations on an omics scale are not yet widespread, primarily because software infrastructure to enable simulations at this scale has not kept pace. It should now be possible to study protein dynamics across entire (super)families, exploiting both available structural biology data and conformational similarities across homologous proteins. Here, we present a new tool for enabling high-throughput simulation in the genomics era. Ensembler takes any set of sequences-from a single sequence to an entire superfamily-and shepherds them through various stages of modeling and refinement to produce simulation-ready structures. This includes comparative modeling to all relevant PDB structures (which may span multiple conformational states of interest), reconstruction of missing loops, addition of missing atoms, culling of nearly identical structures, assignment of appropriate protonation states, solvation in explicit solvent, and refinement and filtering with molecular simulation to ensure stable simulation. The output of this pipeline is an ensemble of structures ready for subsequent molecular simulations using computer clusters, supercomputers, or distributed computing projects like Folding@home. Ensembler thus automates much of the time-consuming process of preparing protein models suitable for simulation, while allowing scalability up to entire superfamilies. A particular advantage of this approach can be found in the construction of kinetic models of conformational dynamics-such as Markov state models (MSMs)-which benefit from a diverse array of initial configurations that span the accessible conformational states to aid sampling. We demonstrate the power of this approach by constructing models for all catalytic domains in the human tyrosine kinase

  15. Ensembler: Enabling High-Throughput Molecular Simulations at the Superfamily Scale.

    Directory of Open Access Journals (Sweden)

    Daniel L Parton

    2016-06-01

    Full Text Available The rapidly expanding body of available genomic and protein structural data provides a rich resource for understanding protein dynamics with biomolecular simulation. While computational infrastructure has grown rapidly, simulations on an omics scale are not yet widespread, primarily because software infrastructure to enable simulations at this scale has not kept pace. It should now be possible to study protein dynamics across entire (superfamilies, exploiting both available structural biology data and conformational similarities across homologous proteins. Here, we present a new tool for enabling high-throughput simulation in the genomics era. Ensembler takes any set of sequences-from a single sequence to an entire superfamily-and shepherds them through various stages of modeling and refinement to produce simulation-ready structures. This includes comparative modeling to all relevant PDB structures (which may span multiple conformational states of interest, reconstruction of missing loops, addition of missing atoms, culling of nearly identical structures, assignment of appropriate protonation states, solvation in explicit solvent, and refinement and filtering with molecular simulation to ensure stable simulation. The output of this pipeline is an ensemble of structures ready for subsequent molecular simulations using computer clusters, supercomputers, or distributed computing projects like Folding@home. Ensembler thus automates much of the time-consuming process of preparing protein models suitable for simulation, while allowing scalability up to entire superfamilies. A particular advantage of this approach can be found in the construction of kinetic models of conformational dynamics-such as Markov state models (MSMs-which benefit from a diverse array of initial configurations that span the accessible conformational states to aid sampling. We demonstrate the power of this approach by constructing models for all catalytic domains in the human

  16. Evolution of Enzymatic Activities in the Enolase Superfamily: L-Rhamnonate Dehydratase

    Energy Technology Data Exchange (ETDEWEB)

    Rakus,J.; Fedorov, A.; Fedorov, E.; Glaner, M.; Hubbard, B.; Delli, J.; Babbitt, P.; Almo, S.; Gerlt, J.

    2008-01-01

    The l-rhamnonate dehydratase (RhamD) function was assigned to a previously uncharacterized family in the mechanistically diverse enolase superfamily that is encoded by the genome of Escherichia coli K-12. We screened a library of acid sugars to discover that the enzyme displays a promiscuous substrate specificity: l-rhamnonate (6-deoxy-l-mannonate) has the 'best' kinetic constants, with l-mannonate, l-lyxonate, and d-gulonate dehydrated less efficiently. Crystal structures of the RhamDs from both E. coli K-12 and Salmonella typhimurium LT2 (95% sequence identity) were obtained in the presence of Mg2+; the structure of the RhamD from S. typhimurium was also obtained in the presence of 3-deoxy-l-rhamnonate (obtained by reduction of the product with NaBH4). Like other members of the enolase superfamily, RhamD contains an N-terminal a + {beta} capping domain and a C-terminal ({beta}/a)7{beta}-barrel (modified TIM-barrel) catalytic domain with the active site located at the interface between the two domains. In contrast to other members, the specificity-determining '20s loop' in the capping domain is extended in length and the '50s loop' is truncated. The ligands for the Mg2+ are Asp 226, Glu 252 and Glu 280 located at the ends of the third, fourth and fifth {beta}-strands, respectively. The active site of RhamD contains a His 329-Asp 302 dyad at the ends of the seventh and sixth {beta}-strands, respectively, with His 329 positioned to function as the general base responsible for abstraction of the C2 proton of l-rhamnonate to form a Mg2+-stabilized enediolate intermediate. However, the active site does not contain other acid/base catalysts that have been implicated in the reactions catalyzed by other members of the MR subgroup of the enolase superfamily. Based on the structure of the liganded complex, His 329 also is expected to function as the general acid that both facilitates departure of the 3-OH group in a syn-dehydration reaction and

  17. "Homo High"

    Science.gov (United States)

    Kilman, Carrie

    2010-01-01

    In Chicago's public school system, LGBT students were three times more likely than straight peers to miss school because of threats to their safety, according to 2003 districtwide survey; and students who face regular harassment were more like to drop out. In this article, the author shares her thoughts on the move of Chicago school officials to…

  18. Homo Participatus

    DEFF Research Database (Denmark)

    The paper notes two different approaches to 'engagement' in the STS litterature: critical public engagement of science and co-construction studies respectively. It argues that the construction of publics and users may be thoroughly intertwined. Finally, it explores these connections through...... an empirical analysis of how public/user engagement is framed in a particular case of design work....

  19. Structure of Bacterial LigD -phosphoesterase Unveils a DNA Repair Superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Nair, P.; Smith, P; Shuman, S

    2010-01-01

    The DNA ligase D (LigD) 3{prime}-phosphoesterase (PE) module is a conserved component of the bacterial nonhomologous end-joining (NHEJ) apparatus that performs 3{prime} end-healing reactions at DNA double-strand breaks. Here we report the 1.9 {angstrom} crystal structure of Pseudomonas aeruginosa PE, which reveals that PE exemplifies a unique class of DNA repair enzyme. PE has a distinctive fold in which an eight stranded {beta} barrel with a hydrophobic interior supports a crescent-shaped hydrophilic active site on its outer surface. Six essential side chains coordinate manganese and a sulfate mimetic of the scissile phosphate. The PE active site and mechanism are unique vis a vis other end-healing enzymes. We find PE homologs in archaeal and eukaryal proteomes, signifying that PEs comprise a DNA repair superfamily.

  20. Tools and techniques to study ligand-receptor interactions and receptor activation by TNF superfamily members.

    Science.gov (United States)

    Schneider, Pascal; Willen, Laure; Smulski, Cristian R

    2014-01-01

    Ligands and receptors of the TNF superfamily are therapeutically relevant targets in a wide range of human diseases. This chapter describes assays based on ELISA, immunoprecipitation, FACS, and reporter cell lines to monitor interactions of tagged receptors and ligands in both soluble and membrane-bound forms using unified detection techniques. A reporter cell assay that is sensitive to ligand oligomerization can identify ligands with high probability of being active on endogenous receptors. Several assays are also suitable to measure the activity of agonist or antagonist antibodies, or to detect interactions with proteoglycans. Finally, self-interaction of membrane-bound receptors can be evidenced using a FRET-based assay. This panel of methods provides a large degree of flexibility to address questions related to the specificity, activation, or inhibition of TNF-TNF receptor interactions in independent assay systems, but does not substitute for further tests in physiologically relevant conditions.

  1. Myosin superfamily: The multi-functional and irreplaceable factors in spermatogenesis and testicular tumors.

    Science.gov (United States)

    Li, Yan-Ruide; Yang, Wan-Xi

    2016-01-15

    Spermatogenesis is a fundamental process in sexual development and reproduction, in which the diploid spermatogonia transform into haploid mature spermatozoa. This process is under the regulation of multiple factors and pathway. Myosin has been implicated in various aspects during spermatogenesis. Myosins constitute a diverse superfamily of actin-based molecular motors that translocate along microfilament in an ATP-dependent manner, and six kinds of myosins have been proved that function during spermatogenesis. In mitosis and meiosis, myosins play an important role in spindle assembly and positioning, karyokinesis and cytokinesis. During spermiogenesis, myosins participate in acrosomal formation, nuclear morphogenesis, mitochondrial translocation and spermatid individualization. In this review, we summarize current understanding of the functions of myosin in spermatogenesis and some reproductive system diseases such as testicular tumors and prostate cancer, and discuss the roles of possible upstream molecules which regulate myosin in these processes.

  2. Proton-coupled sugar transport in the prototypical major facilitator superfamily protein XylE.

    Science.gov (United States)

    Wisedchaisri, Goragot; Park, Min-Sun; Iadanza, Matthew G; Zheng, Hongjin; Gonen, Tamir

    2014-08-04

    The major facilitator superfamily (MFS) is the largest collection of structurally related membrane proteins that transport a wide array of substrates. The proton-coupled sugar transporter XylE is the first member of the MFS that has been structurally characterized in multiple transporting conformations, including both the outward and inward-facing states. Here we report the crystal structure of XylE in a new inward-facing open conformation, allowing us to visualize the rocker-switch movement of the N-domain against the C-domain during the transport cycle. Using molecular dynamics simulation, and functional transport assays, we describe the movement of XylE that facilitates sugar translocation across a lipid membrane and identify the likely candidate proton-coupling residues as the conserved Asp27 and Arg133. This study addresses the structural basis for proton-coupled substrate transport and release mechanism for the sugar porter family of proteins.

  3. The Tumor Necrosis Factor Superfamily of Cytokines in the Inflammatory Myopathies: Potential Targets for Therapy

    Directory of Open Access Journals (Sweden)

    Boel De Paepe

    2012-01-01

    Full Text Available The idiopathic inflammatory myopathies (IM represent a heterogeneous group of autoimmune diseases, of which dermatomyositis (DM, polymyositis (PM, and sporadic inclusion body myositis (IBM are the most common. The crucial role played by tumor necrosis factor alpha (TNFα in the IM has long been recognized. However, so far, 18 other members of the TNF superfamily have been characterized, and many of these have not yet received the attention they deserve. In this paper, we summarize current findings for all TNF cytokines in IM, pinpointing what we know already and where current knowledge fails. For each TNF family member, possibilities for treating inflammatory diseases in general and the IM in particular are explored.

  4. Two differentially regulated Arabidopsis genes define a new branch of the DFR superfamily

    DEFF Research Database (Denmark)

    Østergaard, L; Lauvergeat, V; Naested, H

    2001-01-01

    Two tandem genes were identified on Arabidopsis chromosome II (AtCRL1 and AtCRL2) encoding proteins with homology to members of the dihydroflavonol-4-reductase (DFR) superfamily. The encoded CRL1 and CRL2 proteins share 87% mutual amino acid sequence identity whereas their promoter regions...... resembling the expression pattern of late embryogenic abundant ABA-responsive genes. Differential expression of the two genes during plant development was confirmed in plants expressing transcriptional fusions between the two promoters and the Escherichia coli beta-glucuronidase reporter gene. This showed...... that, whereas high expression of AtCRL1 in mature seeds declines during subsequent vegetative growth, transcriptional activity from the AtCRL2 promoter increases during vegetative growth. Expression of both genes is restricted to vascular tissue. Based upon their homology to proteins involved in lignin...

  5. The barber's pole worm CAP protein superfamily--A basis for fundamental discovery and biotechnology advances.

    Science.gov (United States)

    Mohandas, Namitha; Young, Neil D; Jabbar, Abdul; Korhonen, Pasi K; Koehler, Anson V; Amani, Parisa; Hall, Ross S; Sternberg, Paul W; Jex, Aaron R; Hofmann, Andreas; Gasser, Robin B

    2015-12-01

    Parasitic worm proteins that belong to the cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 (CAP) superfamily are proposed to play key roles in the infection process and the modulation of immune responses in host animals. However, there is limited information on these proteins for most socio-economically important worms. Here, we review the CAP protein superfamily of Haemonchus contortus (barber's pole worm), a highly significant parasitic roundworm (order Strongylida) of small ruminants. To do this, we mined genome and transcriptomic datasets, predicted and curated full-length amino acid sequences (n=45), undertook systematic phylogenetic analyses of these data and investigated transcription throughout the life cycle of H. contortus. We inferred functions for selected Caenorhabditis elegans orthologs (including vap-1, vap-2, scl-5 and lon-1) based on genetic networking and by integrating data and published information, and were able to infer that a subset of orthologs and their interaction partners play pivotal roles in growth and development via the insulin-like and/or the TGF-beta signalling pathways. The identification of the important and conserved growth regulator LON-1 led us to appraise the three-dimensional structure of this CAP protein by comparative modelling. This model revealed the presence of different topological moieties on the canonical fold of the CAP domain, which coincide with an overall charge separation as indicated by the electrostatic surface potential map. These observations suggest the existence of separate sites for effector binding and receptor interactions, and thus support the proposal that these worm molecules act in similar ways as venoms act as ligands for chemokine receptors or G protein-coupled receptor effectors. In conclusion, this review should guide future molecular studies of these molecules, and could support the development of novel interventions against haemonchosis.

  6. Functional interaction of Parkinson's disease-associated LRRK2 with members of the dynamin GTPase superfamily

    Science.gov (United States)

    Stafa, Klodjan; Tsika, Elpida; Moser, Roger; Musso, Alessandra; Glauser, Liliane; Jones, Amy; Biskup, Saskia; Xiong, Yulan; Bandopadhyay, Rina; Dawson, Valina L.; Dawson, Ted M.; Moore, Darren J.

    2014-01-01

    Mutations in LRRK2 cause autosomal dominant Parkinson's disease (PD). LRRK2 encodes a multi-domain protein containing GTPase and kinase domains, and putative protein–protein interaction domains. Familial PD mutations alter the GTPase and kinase activity of LRRK2 in vitro. LRRK2 is suggested to regulate a number of cellular pathways although the underlying mechanisms are poorly understood. To explore such mechanisms, it has proved informative to identify LRRK2-interacting proteins, some of which serve as LRRK2 kinase substrates. Here, we identify common interactions of LRRK2 with members of the dynamin GTPase superfamily. LRRK2 interacts with dynamin 1–3 that mediate membrane scission in clathrin-mediated endocytosis and with dynamin-related proteins that mediate mitochondrial fission (Drp1) and fusion (mitofusins and OPA1). LRRK2 partially co-localizes with endosomal dynamin-1 or with mitofusins and OPA1 at mitochondrial membranes. The subcellular distribution and oligomeric complexes of dynamin GTPases are not altered by modulating LRRK2 in mouse brain, whereas mature OPA1 levels are reduced in G2019S PD brains. LRRK2 enhances mitofusin-1 GTP binding, whereas dynamin-1 and OPA1 serve as modest substrates of LRRK2-mediated phosphorylation in vitro. While dynamin GTPase orthologs are not required for LRRK2-induced toxicity in yeast, LRRK2 functionally interacts with dynamin-1 and mitofusin-1 in cultured neurons. LRRK2 attenuates neurite shortening induced by dynamin-1 by reducing its levels, whereas LRRK2 rescues impaired neurite outgrowth induced by mitofusin-1 potentially by reversing excessive mitochondrial fusion. Our study elucidates novel functional interactions of LRRK2 with dynamin-superfamily GTPases that implicate LRRK2 in the regulation of membrane dynamics important for endocytosis and mitochondrial morphology. PMID:24282027

  7. The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans.

    Science.gov (United States)

    Danielson, P B

    2002-12-01

    Cytochrome p450s comprise a superfamily of heme-thiolate proteins named for the spectral absorbance peak of their carbon-monoxide-bound species at 450 nm. Having been found in every class of organism, including Archaea, the p450 superfamily is believed to have originated from an ancestral gene that existed over 3 billion years ago. Repeated gene duplications have subsequently given rise to one of the largest of multigene families. These enzymes are notable both for the diversity of reactions that they catalyze and the range of chemically dissimilar substrates upon which they act. Cytochrome p450s support the oxidative, peroxidative and reductive metabolism of such endogenous and xenobiotic substrates as environmental pollutants, agrochemicals, plant allelochemicals, steroids, prostaglandins and fatty acids. In humans, cytochrome p450s are best know for their central role in phase I drug metabolism where they are of critical importance to two of the most significant problems in clinical pharmacology: drug interactions and interindividual variability in drug metabolism. Recent advances in our understanding of cytochrome p450-mediated drug metabolism have been accelerated as a result of an increasing emphasis on functional genomic approaches to p450 research. While human cytochrome p450 databases have swelled with a flood of new human sequence variants, however, the functional characterization of the corresponding gene products has not kept pace. In response researchers have begun to apply the tools of proteomics as well as homology-based and ab initio modeling to salient questions of cytochrome p450 structure/function. This review examines the latest advances in our understanding of human cytochrome p450s.

  8. The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Batot, Gaëlle; Michalska, Karolina; Ekberg, Greg; Irimpan, Ervin M.; Joachimiak, Grazyna; Jedrzejczak, Robert; Babnigg, Gyorgy; Hayes, Christopher S.; Joachimiak, Andrzej; Goulding, Celia W.

    2017-04-10

    Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition found in many Gram-negative pathogens. CDI+ cells express cell-surface CdiA proteins that bind neighboring bacteria and deliver C-terminal toxin domains (CdiA-CT) to inhibit target-cell growth. CDI+ bacteria also produce CdiI immunity proteins, which specifically neutralize cognate CdiA-CT toxins to prevent self-inhibition. Here, we present the crystal structure of the CdiA-CT/CdiI(Ykris) complex from Yersinia kris-tensenii ATCC 33638. CdiA-CTYkris adopts the same fold as angiogenin and other RNase A paralogs, but the toxin does not share sequence similarity with these nucleases and lacks the characteristic disulfide bonds of the superfamily. Consistent with the structural homology, CdiA-CTYkris has potent RNase activity in vitro and in vivo. Structure-guided mutagenesis reveals that His175, Arg186, Thr276 and Tyr278 contribute to CdiA-CTYkris activity, suggesting that these residues participate in substrate binding and/or catalysis. CdiI(Ykris) binds directly over the putative active site and likely neutralizes toxicity by blocking access to RNA substrates. Significantly, CdiA-CTYkris is the first non-vertebrate protein found to possess the RNase A superfamily fold, and homologs of this toxin are associated with secretion systems in many Gram-negative and Gram-positive bacteria. These observations suggest that RNase Alike toxins are commonly deployed in inter-bacterial competition.

  9. Annotation error in public databases: misannotation of molecular function in enzyme superfamilies.

    Directory of Open Access Journals (Sweden)

    Alexandra M Schnoes

    2009-12-01

    Full Text Available Due to the rapid release of new data from genome sequencing projects, the majority of protein sequences in public databases have not been experimentally characterized; rather, sequences are annotated using computational analysis. The level of misannotation and the types of misannotation in large public databases are currently unknown and have not been analyzed in depth. We have investigated the misannotation levels for molecular function in four public protein sequence databases (UniProtKB/Swiss-Prot, GenBank NR, UniProtKB/TrEMBL, and KEGG for a model set of 37 enzyme families for which extensive experimental information is available. The manually curated database Swiss-Prot shows the lowest annotation error levels (close to 0% for most families; the two other protein sequence databases (GenBank NR and TrEMBL and the protein sequences in the KEGG pathways database exhibit similar and surprisingly high levels of misannotation that average 5%-63% across the six superfamilies studied. For 10 of the 37 families examined, the level of misannotation in one or more of these databases is >80%. Examination of the NR database over time shows that misannotation has increased from 1993 to 2005. The types of misannotation that were found fall into several categories, most associated with "overprediction" of molecular function. These results suggest that misannotation in enzyme superfamilies containing multiple families that catalyze different reactions is a larger problem than has been recognized. Strategies are suggested for addressing some of the systematic problems contributing to these high levels of misannotation.

  10. Heterochrony and the paleoanthropological record: the origins o the genus homo reconsidered

    Directory of Open Access Journals (Sweden)

    Bermúdez de Castro, Jose María

    1992-12-01

    Full Text Available In this paper a critical review is made of the main theories concerning the process of appearance and subsequent evolutionary success of the genus Homo. Furthennore, the current evidence coming from the paleoanthropological record is analyzed in order to establish the interrelation between the biological and cultural factors implicated in that process. It is suggested that the evidence of the paleoanthropological record presumably related to early Homo is basically explicable from the consideration of the strengthening of the social links in the bosom of the group, likely due to the abandonment of an hierarchyzed society in favour of a more cooperative one. This change does not necessarily imply, nor does it exclude the possibility of the formation of stable nuclear families, and probably appeared as a result of a biological change consisting of a decrease of the rate of development, that produced certain prolongation of all life history periods, and some delay in the offset signal for growth (but resulting in paedomorphic adults. As a consequence, there was an increase of the interactive and operative capacities that permitted the emergence of a novel and successful ecological niche under the new environmental conditions arised in the late Pliocene. Other additional heterochrony processes are suggested to explain the subsequent morphological evolution of the genus Homo.

    En este trabajo se realiza una revisión critica de las principales teorías relacionadas con el proceso de aparición y subsiguiente éxito evolutivo del género Homo. Se analiza asimismo la evidencia más reciente procedente del registro paleoantropológico, para establecer la interrelación entre los factores biológicos y culturales implicados en dicho proceso. Se sugiere que la evidencia del registro paleoantropológico presumiblemente relacionado con los primeros representantes del género Homo puede explicarse básicamente desde

  11. The chemical versatility of the beta-alpha-beta fold : Catalytic promiscuity and divergent evolution in the tautomerase superfamily

    NARCIS (Netherlands)

    Poelarends, G. J.; Veetil, V. Puthan; Whitman, C. P.

    2008-01-01

    Tautomerase superfamily members have an amino-terminal proline and a beta-alpha-beta fold, and include 4-oxalocrotonate tautomerase (4-OT), 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), trans- and cis-3-chloroacrylic acid dehalogenase (CaaD and cis-CaaD, respectively), malonate semialdehyde

  12. Systematics of some Lower and Middle Devonian spiriferid brachiopods from Gaspe with a revision of the superfamily Delthyridoidea

    DEFF Research Database (Denmark)

    Bizzarro, Martin; Lespérance, P.J.

    1999-01-01

    The component subfamilies of the Delthyridoidea are critically reviewed and subjected to phylogenetic analysis. This shows the presence of two clades, assigned to the Delthyrididae and Acrospiriferidae, within the superfamily. The subfamilial categories are redefined mainly on the basis of the ch...

  13. Cloning, crystallization and preliminary X-ray study of XC1258, a CN-hydrolase superfamily protein from Xanthomonas campestris

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Ying-Der; Chin, Ko-Hsin [Institute of Biochemistry, National Chung-Hsing University, Taichung 40227,Taiwan (China); Shr, Hui-Lin [Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei,Taiwan (China); Core Facility for Protein Crystallography, Academia Sinica, Nankang, Taipei,Taiwan (China); Gao, Fei Philip [National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310 (United States); Lyu, Ping-Chiang [Department of Life Science, National Tsing Hua University, Hsin-Chu,Taiwan (China); Wang, Andrew H.-J. [Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei,Taiwan (China); Core Facility for Protein Crystallography, Academia Sinica, Nankang, Taipei,Taiwan (China); Chou, Shan-Ho, E-mail: shchou@nchu.edu.tw [Institute of Biochemistry, National Chung-Hsing University, Taichung 40227,Taiwan (China)

    2006-10-01

    A CN-hydrolase superfamily protein from the plant pathogen X. campestris has been overexpressed in E. coli, purified and crystallized. CN-hydrolase superfamily proteins are involved in a wide variety of non-peptide carbon–nitrogen hydrolysis reactions, producing some important natural products such as auxin, biotin, precursors of antibiotics etc. These reactions all involve attack on a cyano or carbonyl carbon by a conserved novel catalytic triad Glu-Lys-Cys through a thiol acylenzyme intermediate. However, classification into the CN-hydrolase superfamily based on sequence similarity alone is not straightforward and further structural data are necessary to improve this categorization. Here, the cloning, expression, crystallization and preliminary X-ray analysis of XC1258, a CN-hydrolase superfamily protein from the plant pathogen Xanthomonas campestris (Xcc), are reported. The SeMet-substituted XC1258 crystals diffracted to a resolution of 1.73 Å. They are orthorhombic and belong to space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 143.8, b = 154.63, c = 51.3 Å, respectively.

  14. TGF-β superfamily members from the helminth Fasciola hepatica show intrinsic effects on viability and development.

    Science.gov (United States)

    Japa, Ornampai; Hodgkinson, Jane E; Emes, Richard D; Flynn, Robin J

    2015-03-11

    The helminth Fasciola hepatica causes fasciolosis throughout the world, a major disease of livestock and an emerging zoonotic disease in humans. Sustainable control mechanisms such as vaccination are urgently required. To discover potential vaccine targets we undertook a genome screen to identify members of the transforming growth factor (TGF) family of proteins. Herein we describe the discovery of three ligands belonging to this superfamily and the cloning and characterisation of an activin/TGF like molecule we term FhTLM. FhTLM has a limited expression pattern both temporally across the parasite stages but also spatially within the worm. Furthermore, a recombinant form of this protein is able to enhance the rate (or magnitude) of multiple developmental processes of the parasite indicating a conserved role for this protein superfamily in the developmental biology of a major trematode parasite. Our study demonstrates for the first time the existence of this protein superfamily within F. hepatica and assigns a function to one of the three identified ligands. Moreover further exploration of this superfamily may yield future targets for diagnostic or vaccination purposes due to its stage restricted expression and functional role.

  15. Modeling-dependent protein characterization of the rice aldehyde dehydrogenase (ALDH superfamily reveals distinct functional and structural features.

    Directory of Open Access Journals (Sweden)

    Simeon O Kotchoni

    Full Text Available The completion of the rice genome sequence has made it possible to identify and characterize new genes and to perform comparative genomics studies across taxa. The aldehyde dehydrogenase (ALDH gene superfamily encoding for NAD(P(+-dependent enzymes is found in all major plant and animal taxa. However, the characterization of plant ALDHs has lagged behind their animal- and prokaryotic-ALDH homologs. In plants, ALDHs are involved in abiotic stress tolerance, male sterility restoration, embryo development and seed viability and maturation. However, there is still no structural property-dependent functional characterization of ALDH protein superfamily in plants. In this paper, we identify members of the rice ALDH gene superfamily and use the evolutionary nesting events of retrotransposons and protein-modeling-based structural reconstitution to report the genetic and molecular and structural features of each member of the rice ALDH superfamily in abiotic/biotic stress responses and developmental processes. Our results indicate that rice-ALDHs are the most expanded plant ALDHs ever characterized. This work represents the first report of specific structural features mediating functionality of the whole families of ALDHs in an organism ever characterized.

  16. Homo floresiensis-like fossils from the early Middle Pleistocene of Flores.

    Science.gov (United States)

    van den Bergh, Gerrit D; Kaifu, Yousuke; Kurniawan, Iwan; Kono, Reiko T; Brumm, Adam; Setiyabudi, Erick; Aziz, Fachroel; Morwood, Michael J

    2016-06-09

    The evolutionary origin of Homo floresiensis, a diminutive hominin species previously known only by skeletal remains from Liang Bua in western Flores, Indonesia, has been intensively debated. It is a matter of controversy whether this primitive form, dated to the Late Pleistocene, evolved from early Asian Homo erectus and represents a unique and striking case of evolutionary reversal in hominin body and brain size within an insular environment. The alternative hypothesis is that H. floresiensis derived from an older, smaller-brained member of our genus, such as Homo habilis, or perhaps even late Australopithecus, signalling a hitherto undocumented dispersal of hominins from Africa into eastern Asia by two million years ago (2 Ma). Here we describe hominin fossils excavated in 2014 from an early Middle Pleistocene site (Mata Menge) in the So'a Basin of central Flores. These specimens comprise a mandible fragment and six isolated teeth belonging to at least three small-jawed and small-toothed individuals. Dating to ~0.7 Ma, these fossils now constitute the oldest hominin remains from Flores. The Mata Menge mandible and teeth are similar in dimensions and morphological characteristics to those of H. floresiensis from Liang Bua. The exception is the mandibular first molar, which retains a more primitive condition. Notably, the Mata Menge mandible and molar are even smaller in size than those of the two existing H. floresiensis individuals from Liang Bua. The Mata Menge fossils are derived compared with Australopithecus and H. habilis, and so tend to support the view that H. floresiensis is a dwarfed descendent of early Asian H. erectus. Our findings suggest that hominins on Flores had acquired extremely small body size and other morphological traits specific to H. floresiensis at an unexpectedly early time.

  17. A Critical Evaluation of the Down Syndrome Diagnosis for LB1, Type Specimen of Homo floresiensis.

    Science.gov (United States)

    Baab, Karen L; Brown, Peter; Falk, Dean; Richtsmeier, Joan T; Hildebolt, Charles F; Smith, Kirk; Jungers, William

    2016-01-01

    The Liang Bua hominins from Flores, Indonesia, have been the subject of intense scrutiny and debate since their initial description and classification in 2004. These remains have been assigned to a new species, Homo floresiensis, with the partial skeleton LB1 as the type specimen. The Liang Bua hominins are notable for their short stature, small endocranial volume, and many features that appear phylogenetically primitive relative to modern humans, despite their late Pleistocene age. Recently, some workers suggested that the remains represent members of a small-bodied island population of modern Austro-Melanesian humans, with LB1 exhibiting clinical signs of Down syndrome. Many classic Down syndrome signs are soft tissue features that could not be assessed in skeletal remains. Moreover, a definitive diagnosis of Down syndrome can only be made by genetic analysis as the phenotypes associated with Down syndrome are variable. Most features that contribute to the Down syndrome phenotype are not restricted to Down syndrome but are seen in other chromosomal disorders and in the general population. Nevertheless, we re-evaluated the presence of those phenotypic features used to support this classification by comparing LB1 to samples of modern humans diagnosed with Down syndrome and euploid modern humans using comparative morphometric analyses. We present new data regarding neurocranial, brain, and symphyseal shape in Down syndrome, additional estimates of stature for LB1, and analyses of inter- and intralimb proportions. The presence of cranial sinuses is addressed using CT images of LB1. We found minimal congruence between the LB1 phenotype and clinical descriptions of Down syndrome. We present important differences between the phenotypes of LB1 and individuals with Down syndrome, and quantitative data that characterize LB1 as an outlier compared with Down syndrome and non-Down syndrome groups. Homo floresiensis remains a phenotypically unique, valid species with its roots

  18. Viral and vector zoonotic exploitation of a homo-sociome memetic complex.

    Science.gov (United States)

    Rupprecht, C E; Burgess, G W

    2015-05-01

    As most newly characterized emerging infectious diseases are considered to be zoonotic, a modern pre-eminence ascribed within this classification lies clearly within the viral taxonomic realm. In particular, RNA viruses deserve special concern given their documented impact on conservation biology, veterinary medicine and public health, with an unprecedented ability to promote an evolutionary host-pathogen arms race from the ultimate infection and immunity perspective. However, besides the requisite molecular/gross anatomical and physiological bases for infectious diseases to transmit from one host to another, both viral pathogens and their reservoirs/vectors exploit a complex anthropological, cultural, historical, psychological and social suite that specifically defines the phylodynamics within Homo sapiens, unlike any other species. Some of these variables include the ecological benefits of living in groups, decisions on hunting and foraging behaviours and dietary preferences, myths and religious doctrines, health economics, travel destinations, population planning, political decisions on agricultural product bans and many others, in a homo-sociome memetic complex. Taken to an extreme, such complexities elucidate the underpinnings of explanations as to why certain viral zoonoses reside in neglected people, places and things, whereas others are chosen selectively and prioritized for active mitigation. Canine-transmitted rabies serves as one prime example of how a neglected viral zoonosis may transition to greater attention on the basis of renewed advocacy, social media, local champions and vested international community engagement. In contrast, certain bat-associated and arboviral diseases suffer from basic ignorance and perpetuated misunderstanding of fundamental reservoir and vector ecology tenets, translated into failed control policies that only exacerbate the underlying environmental conditions of concern. Beyond applied biomedical knowledge, epidemiological

  19. Mandibular molar root morphology in Neanderthals and Late Pleistocene and recent Homo sapiens.

    Science.gov (United States)

    Kupczik, Kornelius; Hublin, Jean-Jacques

    2010-11-01

    Neanderthals have a distinctive suite of dental features, including large anterior crown and root dimensions and molars with enlarged pulp cavities. Yet, there is little known about variation in molar root morphology in Neanderthals and other recent and fossil members of Homo. Here, we provide the first comprehensive metric analysis of permanent mandibular molar root morphology in Middle and Late Pleistocene Homo neanderthalensis, and Late Pleistocene (Aterian) and recent Homo sapiens. We specifically address the question of whether root form can be used to distinguish between these groups and assess whether any variation in root form can be related to differences in tooth function. We apply a microtomographic imaging approach to visualise and quantify the external and internal dental morphologies of both isolated molars and molars embedded in the mandible (n=127). Univariate and multivariate analyses reveal both similarities (root length and pulp volume) and differences (occurrence of pyramidal roots and dental tissue volume proportion) in molar root morphology among penecontemporaneous Neanderthals and Aterian H. sapiens. In contrast, the molars of recent H. sapiens are markedly smaller than both Pleistocene H. sapiens and Neanderthals, but share with the former the dentine volume reduction and a smaller root-to-crown volume compared with Neanderthals. Furthermore, we found the first molar to have the largest average root surface area in recent H. sapiens and Neanderthals, although in the latter the difference between M(1) and M(2) is small. In contrast, Aterian H. sapiens root surface areas peak at M(2). Since root surface area is linked to masticatory function, this suggests a distinct occlusal loading regime in Neanderthals compared with both recent and Pleistocene H. sapiens.

  20. Homo ludens : Proeve eener bepaling van het spel-element der cultuur

    OpenAIRE

    Huizinga, J.

    2008-01-01

    In addition to his historical works, and his biographies, as his life was drawing to a close, Huizinga spent his time studying general cultural theories. Huizinga saw the instinct for play as a central element in human culture: 'In myth and ritual the great instinctive forces of civilized life have their origin: law and order, commerce and profit, craft and art, poetry, wisdom and science. All are rooted in the primeval soil of play.' In Homo Ludens Huizinga attempts to show the impact of pla...

  1. Improved age control on early Homo fossils from the upper Burgi Member at Koobi Fora, Kenya.

    Science.gov (United States)

    Joordens, Josephine C A; Dupont-Nivet, Guillaume; Feibel, Craig S; Spoor, Fred; Sier, Mark J; van der Lubbe, Jeroen H J L; Nielsen, Trine Kellberg; Knul, Monika V; Davies, Gareth R; Vonhof, Hubert B

    2013-12-01

    To address questions regarding the evolutionary origin, radiation and dispersal of the genus Homo, it is crucial to be able to place the occurrence of hominin fossils in a high-resolution chronological framework. The period around 2 Ma (millions of years ago) in eastern Africa is of particular interest as it is at this time that a more substantial fossil record of the genus Homo is first found. Here we combine magnetostratigraphy and strontium (Sr) isotope stratigraphy to improve age control on hominin-bearing upper Burgi (UBU) deposits in Areas 105 and 131 on the Karari Ridge in the eastern Turkana Basin (Kenya). We identify the base of the Olduvai subchron (bC2n) plus a short isolated interval of consistently normal polarity that we interpret to be the Pre-Olduvai event. Combined with precession-forced (~20 kyr [thousands of years]) wet-dry climate cycles resolved by Sr isotope ratios, the magnetostratigraphic data allow us to construct an age model for the UBU deposits. We provide detailed age constraints for 15 hominin fossils from Area 131, showing that key specimens such as cranium KNM-ER 1470, partial face KNM-ER 62000 and mandibles KNM-ER 1482, KNM-ER 1801, and KNM-ER 1802 can be constrained between 1.945 ± 0.004 and 2.058 ± 0.034 Ma, and thus older than previously estimated. The new ages are consistent with a temporal overlap of two species of early Homo that can be distinguished by their facial morphology. Further, our results show that in this time interval, hominins occurred throughout the wet-dry climate cycles, supporting the hypothesis that the lacustrine Turkana Basin was a refugium during regionally dry periods. By establishing the observed first appearance datum of a marine-derived stingray in UBU deposits at 2.058 ± 0.034 Ma, we show that at this time the Turkana Basin was hydrographically connected to the Indian Ocean, facilitating dispersal of fauna between these areas. From a biogeographical perspective, we propose that the Indian Ocean

  2. Homo sportivus in Physical Education Teachers’ Training in Uruguay (1906–1956

    Directory of Open Access Journals (Sweden)

    Paola Dogliotti Moro

    2016-08-01

    Full Text Available This study inquires about the shaping of sports in Uruguay (1906–1956, especially about physical education teachers’ training. The central hypothesis states that the Homo sportivus was configured following the anglo–saxon influence, through the batllista discourse about sports and the arrival of the ymca American missionaries in the second decade of the twentieth century. By that time, there were differences and disagreements between the sport practice in educational institutions and the practice of soccer and its spreading in the Uruguayan society

  3. El ‘Homo videns’ de un intelectual combativo (Giovanni Sartori o de

    Directory of Open Access Journals (Sweden)

    Lic. Concha Mateos - cmateos@ull.es

    2002-01-01

    Full Text Available Si abres el libro de Giovanni Sartori "Homo videns. La sociedad teledirigida" (1, estate atento a los dos brazos que van a saltar de entre sus páginas para cogerte por los hombros y zarandearte un poco mientras en el aire titilen advertencias de este talante: ¡Vamos, chaval! ¿es que no te das cuenta? Espabila un poco, desamodorra tu sensibilidad intelectual, que se está desquebrajando la fibra que nos permite ahora mismo a ti y a mí conversar a través de este texto, aunque estemos lejos, aunque alguno de nosotros esté muerto.

  4. Is HOMO Energy Level a Good Parameter to Characterize Antioxidant Activity

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Semiempirical quantum chemical method AM1 was employed to calculate the highest occupied molecular orbital (HOMO) energy levels (EHOMO) for various types of antioxidants. It was verified that the correlation between logarithm of free radical scavenging rate constants (lgks) and EHOMO substantially arises from the correlation between EHOMO and O-H bond dissociation energies (BDE) of antioxidants. Furthermore, EHOMO were poorly correlated with the logarithm of relative free radical scavenging rate constants (lgk3/k1) for various types of antioxidants that possess complex structures (r = 0.5602). So in a broad sense, EHOMO was not an appropriate parameter to characterize the free radical scavenging activity of antioxidants.

  5. Improved age control on early Homo fossils from the upper Burgi Member at Koobi Fora, Kenya

    DEFF Research Database (Denmark)

    Nielsen, Trine Kellberg

    2013-01-01

    Turkana Basin (Kenya). We identify the base of the Olduvai subchron (bC2n) plus a short isolated interval of consistently normal polarity that we interpret to be the Pre-Olduvai event. Combined with precession-forced (∼20 kyr [thousands of years]) wet–dry climate cycles resolved by Sr isotope ratios...... interest as it is at this time that a more substantial fossil record of the genus Homo is first found. Here we combine magnetostratigraphy and strontium (Sr) isotope stratigraphy to improve age control on hominin-bearing upper Burgi (UBU) deposits in Areas 105 and 131 on the Karari Ridge in the eastern...

  6. Structural instability of N-acceptors in homo- and heteroepitaxially grown ZnO by MBE

    Energy Technology Data Exchange (ETDEWEB)

    Ando, K.; Abe, T.; Taya, T.; Ishihara, Y.; Enomoto, K.; Yamazaki, Y.; Yoshikawa, J.; Fujino, K.; Nakamura, H.; Ohno, T.; Kasada, H. [Department of Information and Electronic Engineering, Graduate School of Engineering, Tottori University, 4-1-1 Koyama-Minami, Tottori 680-8550 (Japan)

    2010-06-15

    Unique properties of the N-acceptor in homo- and heteroepitaxially grown ZnO by molecular beam epitaxy (MBE) are studied by means of microproving of surface sheet-resistance, Hall-effect measurement, persistent photoconduction (PPC) and thermally stimulated current (TSC). Rapid postanneal of N-doped ZnO is found to induce the change in the conduction type from n-type (as-grown) to p/n-type mixed conduction, forming island structure, and these properties are related to a structural instability of the N-acceptor. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  7. Homo- and Copolymerization of Ethylene and Norbornene with Anilido–Imine Chromium Catalysts

    Directory of Open Access Journals (Sweden)

    Lixia Pei

    2016-03-01

    Full Text Available A series of anilido–imine chromium complexes have been used as precursors to catalyze homo- and copolymerization of ethylene and norbornene. The chromium complexes activated with methylalumoxane (MAO exhibit good activities for homopolymerization of ethylene (E to produce linear polyethylene and moderate activities for norbornene (N polymerization to afford vinyl-type polynorbornene. Ethylene–norbornene copolymers with high incorporation of norbornene can be also produced by these catalysts. 13C NMR and differential scanning calorimetry (DSC analyses show that the copolymers are random products, and –NNN– and –EEE– units can be observed in the microstructure of the copolymers.

  8. Inventing Homo gardarensis: Prestige, Pressure and Human Evolution in Interwar Scandinavia

    DEFF Research Database (Denmark)

    2014-01-01

    In the 1920s there were still very few fossil human remains to support an evolutionary explanation of human origins. Nonetheless, evolution as an explanatory framework was widely accepted. This led to a search for ancestors in several continents with fierce international competition. With so little...... fossil evidence available and the idea of a Missing Link as a crucial piece of evidence in human evolution still intact, many actors participated in the scientific race to identify the human ancestor. The curious case of Homo gardarensis serves as an example of how personal ambitions and national pride...

  9. Inventing Homo gardarensis: Prestige, Pressure and Human Evolution in Interwar Scandinavia

    DEFF Research Database (Denmark)

    2014-01-01

    In the 1920s there were still very few fossil human remains to support an evolutionary explanation of human origins. Nonetheless, evolution as an explanatory framework was widely accepted. This led to a search for ancestors in several continents with fierce international competition. With so little...... fossil evidence available and the idea of a Missing Link as a crucial piece of evidence in human evolution still intact, many actors participated in the scientific race to identify the human ancestor. The curious case of Homo gardarensis serves as an example of how personal ambitions and national pride...

  10. p53 Superfamily proteins in marine bivalve cancer and stress biology.

    Science.gov (United States)

    Walker, Charles W; Van Beneden, Rebecca J; Muttray, Annette F; Böttger, S Anne; Kelley, Melissa L; Tucker, Abraham E; Thomas, W Kelley

    2011-01-01

    The human p53 tumour suppressor protein is inactivated in many cancers and is also a major player in apoptotic responses to cellular stress. The p53 protein and the two other members of this protein family (p63, p73) are encoded by distinct genes and their functions have been extensively documented for humans and some other vertebrates. The structure and relative expression levels for members of the p53 superfamily have also been reported for most major invertebrate taxa. The functions of homologous proteins have been investigated for only a few invertebrates (specifically, p53 in flies, nematodes and recently a sea anemone). These studies of classical model organisms all suggest that the gene family originally evolved to mediate apoptosis of damaged germ cells or to protect germ cells from genotoxic stress. Here, we have correlated data from a number of molluscan and other invertebrate sequencing projects to provide a framework for understanding p53 signalling pathways in marine bivalve cancer and stress biology. These data suggest that (a) the two identified p53 and p63/73-like proteins in soft shell clam (Mya arenaria), blue mussel (Mytilus edulis) and Northern European squid (Loligo forbesi) have identical core sequences and may be splice variants of a single gene, while some molluscs and most other invertebrates have two or more distinct genes expressing different p53 family members; (b) transcriptional activation domains (TADs) in bivalve p53 and p63/73-like protein sequences are 67-69% conserved with human p53, while those in ecdysozoan, cnidarian, placozoan and choanozoan eukaryotes are ≤33% conserved; (c) the Mdm2 binding site in the transcriptional activation domain is 100% conserved in all sequenced bivalve p53 proteins (e.g. Mya, Mytilus, Crassostrea and Spisula) but is not present in other non-deuterostome invertebrates; (d) an Mdm2 homologue has been cloned for Mytilus trossulus; (e) homologues for both human p53 upstream regulatory and

  11. New 1.5 million-year-old Homo erectus maxilla from Sangiran (Central Java, Indonesia).

    Science.gov (United States)

    Zaim, Yahdi; Ciochon, Russell L; Polanski, Joshua M; Grine, Frederick E; Bettis, E Arthur; Rizal, Yan; Franciscus, Robert G; Larick, Roy R; Heizler, Matthew; Aswan; Eaves, K Lindsay; Marsh, Hannah E

    2011-10-01

    Sangiran (Solo Basin, Central Java, Indonesia) is the singular Homo erectus fossil locale for Early Pleistocene Southeast Asia. Sangiran is the source for more than 80 specimens in deposits with (40)Ar/(39)Ar ages of 1.51-0.9 Ma. In April 2001, we recovered a H. erectus left maxilla fragment (preserving P(3)- M(2)) from the Sangiran site of Bapang. The find spot lies at the base of the Bapang Formation type section in cemented gravelly sands traditionally called the Grenzbank Zone. Two meters above the find spot, pumice hornblende has produced an (40)Ar/(39)Ar age of 1.51 ± 0.08 Ma. With the addition of Bpg 2001.04, Sangiran now has five H. erectus maxillae. We compare the new maxilla with homologs representing Sangiran H. erectus, Zhoukoudian H. erectus, Western H. erectus (pooled African and Georgian specimens), and Homo habilis. Greatest contrast is with the Zhoukoudian maxillae, which appear to exhibit a derived pattern of premolar-molar relationships compared to Western and Sangiran H. erectus. The dental patterns suggest distinct demic origins for the earlier H. erectus populations represented at Sangiran and the later population represented at Zhoukoudian. These two east Asian populations, separated by 5000 km and nearly 800 k.yr., may have had separate origins from different African/west Eurasian populations.

  12. The brain morphology of Homo Liujiang cranium fossil by three-dimensional computed tomography

    Institute of Scientific and Technical Information of China (English)

    WU XiuJie; LIU Wu; DONG Wei; QUE JieMin; WANG YanFang

    2008-01-01

    The Liujiang cranium is the most complete and well-preserved late Pleistocene human fossils ever unearthed in south China.Because the endocranial cavity is filled with hard stone matrix,earlier stud-ies focused only on the exterior morphology of the specimen using the traditional methods.In order to derive more information for the phyletic evaluation of the Liujiang cranium,high-resolution industrial computed tomography (CT) was used to scan the fossil,and the three-dimensional (3D) brain image was reconstructed.Compared with the endocasts of the hominin fossils (Hexian,Zhoukoudian,KNM-WT 15000,Sm 3,Kabwe,Brunn 3,Predmost) and modern Chinese,most morphological features of the Liujiang brain are in common with modern humans,including a round brain shape,bulged and wide frontal lobes,an enlarged brain height,a full orbital margin and long parietal lobes.A few differ-ences exist between Liujiang and the modern Chinese in our sample,including a strong posterior pro-jection of the occipital lobes,and a reduced cerebellar lobe.The measurement of the virtual endocast shows that the endocranial capacity of Liujiang is 1567 cc,which is in the range of Late Homo sapiens and much beyond the mean of modern humans.The brain morphology of Liujiang is assigned to Late Homo sapiens.

  13. Application of Orthodromic Island Flap Prosthetics of Homo-Digital Artery in Finger-Tip Defect

    Directory of Open Access Journals (Sweden)

    Daming Lu

    2014-03-01

    Full Text Available Objective: To investigate the clinical efficacy of orthodromic island flap prosthetics of homodigital artery on finger-tip defect. Methods: A total of 21 patients with finger-tip defect from December, 2010 to April, 2013 were given orthodromic island flap prosthetics of homo-digital artery, with the maximum and minimum sizes of flaps being 20 mm×22 mm and 10 mm×15 mm, respectively. Results: All patients with finger-tip defect survived from the flap surgery and the wounds were favorably healed. 3 - 12 months follow-up after operation, the flaps were observed with approving appearance, soft texture and favorable elasticity, with two-point discrimination being 6 - 8 mm. According to TAM detection of hand functions, flaps were excellent healed in 19 cases, good and fairish in 1 case respectively, with effective rate being 95.2%. Conclusion: Orthodromic island flap prosthetics of homo-digital artery is simple and safe in operation with satisfactory effcacy, being the most ideal method for the repair of finger-tip defect.

  14. Did the loss of endogenous ascorbate propel the evolution of Anthropoidea and Homo sapiens?

    Science.gov (United States)

    Challem, J J

    1997-05-01

    It has been previously theorized that free-radical reactions led to the first life on Earth, and their ability to randomly cause mutations may have subsequently led to the evolution of life. One of the most efficient free-radical quenchers is ascorbate, which most animals manufacture endogenously. It is generally believed that, approximately 25 million years ago, an ancestor of the Anthropoidea primate suborder, which includes Homo sapiens, lost the ability to produce its own ascorbate, and all descending species inherited this genetic defect. The first of three hypotheses presented here proposes that a genetic defect, caused by either free radicals or a virus, deleted the gene needed by Anthropoidea to manufacture endogenous ascorbate. The second hypothesis proposes that this evolutionary accident permitted large numbers of free radicals to remain metabolically unquenched. The third hypothesis proposes that the presence of these excessive free radicals increased the likelihood of free-radical-induced genetic mutations, and these mutations propelled the evolution of Anthropoidea, leading to Homo sapiens.

  15. Morphological variation in Homo erectus and the origins of developmental plasticity.

    Science.gov (United States)

    Antón, Susan C; Taboada, Hannah G; Middleton, Emily R; Rainwater, Christopher W; Taylor, Andrea B; Turner, Trudy R; Turnquist, Jean E; Weinstein, Karen J; Williams, Scott A

    2016-07-05

    Homo erectus was the first hominin to exhibit extensive range expansion. This extraordinary departure from Africa, especially into more temperate climates of Eurasia, has been variously related to technological, energetic and foraging shifts. The temporal and regional anatomical variation in H. erectus suggests that a high level of developmental plasticity, a key factor in the ability of H. sapiens to occupy a variety of habitats, may also have been present in H. erectus. Developmental plasticity, the ability to modify development in response to environmental conditions, results in differences in size, shape and dimorphism across populations that relate in part to levels of resource sufficiency and extrinsic mortality. These differences predict not only regional variations but also overall smaller adult sizes and lower levels of dimorphism in instances of resource scarcity and high predator load. We consider the metric variation in 35 human and non-human primate 'populations' from known environmental contexts and 14 time- and space-restricted paleodemes of H. erectus and other fossil Homo Human and non-human primates exhibit more similar patterns of variation than expected, with plasticity evident, but in differing patterns by sex across populations. The fossil samples show less evidence of variation than expected, although H. erectus varies more than Neandertals.This article is part of the themed issue 'Major transitions in human evolution'. © 2016 The Author(s).

  16. Relationship between cusp size and occlusal wear pattern in Neanderthal and Homo sapiens first maxillary molars.

    Science.gov (United States)

    Fiorenza, Luca; Benazzi, Stefano; Viola, Bence; Kullmer, Ottmar; Schrenk, Friedemann

    2011-03-01

    Tooth wear studies in mammals have highlighted the relationship between wear facets (attritional areas produced during occlusion by the contact between opposing teeth) and physical properties of the ingested food. However, little is known about the influence of tooth morphology on the formation of occlusal wear facets. We analyzed the occlusal wear patterns of first maxillary molars (M(1) s) in Neanderthals, early Homo sapiens, and contemporary modern humans. We applied a virtual method to analyze wear facets on the crown surface of three-dimensional digital models. Absolute and relative wear facet areas are compared with cusp area and cusp height. Although the development of wear facets partially follows the cusp pattern, the results obtained from the between-group comparisons do not reflect the cusp size differences characterizing these groups. In particular, the wear facets developed along the slopes of the most discriminate cusp between Neanderthals and Homo sapiens (hypocone) do not display any significant difference. Moreover, no correlations have been found between cusp size and wear facet areas (with the exception of the modern sample) and between cusp height and wear facet areas. Our results suggest that cusp size is only weakly related to the formation of the occlusal wear facets. Other factors, such as, diet, food processing, environmental abrasiveness, and nondietary habits are probably more important for the development and enlargement of wear facets, corroborating the hypotheses suggested from previous dental wear studies.

  17. The dispersal of Homo sapiens across southern Asia: how early, how often, how complex?

    Science.gov (United States)

    Dennell, Robin; Petraglia, Michael D.

    2012-07-01

    The timing and the paths of colonization of southern Asia by Homo sapiens are poorly known, though many population geneticists, paleoanthropologists, and archaeologists have contended that this process began with dispersal from East Africa, and occurred between 60,000 and 40,000 years ago. However, the evidence for this scenario is very weak, particularly the lack of human skeletal evidence between the Levant and Borneo before 40 ka, and other explanations are possible. Here we argue that environmental and archaeological information is increasingly indicating the likelihood that H. sapiens exited Africa much earlier than commonly thought, and may have colonized much of southern Asia well before 60,000 years ago. Additionally, we cannot exclude the possibility that several dispersal events occurred, from both North and East Africa, nor the likelihood that early populations of H. sapiens in southern Asia interbred with indigenous populations of Neanderthals, Denisovans and Homo erectus. The population history of southern Asia during the Upper Pleistocene is likely far more complex than currently envisaged.

  18. ESR dating of tooth enamel from yunxian homo erectus site, China

    Science.gov (United States)

    Chen, Tie-Mei; Yang, Quan; Hu, Yan-Qiu; Bao, Wen-Bo; Li, Tian-Yuan

    Two almost complete fossil hominid crania (EV9001 and EV9002) were found in 1989 and 1990 in Middle Pleistocene terrace deposit of Han River, Yunxian county, Hubei province, China. They are classified as Homo erectus. Nine fossil animal teeth stratigraphically associated with the skulls were selected for electron spin resonance (ESR) dating. The simple exponential function was used for determination of the accumulated dose De and its appropriateness was discussed on the base of the experimental study. The closed system assumption was checked and the early uranium uptake model was applied to age determination. A mean age value was yielded to be 581±93 ka. It deviates from the palaeomagnetic dating result of 830-870 ka. Micro-regional complete saturation of ESR signal in enamel of very high U-content may account for the underestimation of ESR ages. Nevertheless both ESR and palaeomagnetic dating results place Yunxian crania in between the Homo erectus of Lantian and Zhoukoudian, which means that Yunxian crania constitute an important link in the human evolutionary lineage of China.

  19. Ensembler: Enabling High-Throughput Molecular Simulations at the Superfamily Scale

    Science.gov (United States)

    Parton, Daniel L.; Grinaway, Patrick B.; Hanson, Sonya M.; Beauchamp, Kyle A.; Chodera, John D.

    2016-01-01

    The rapidly expanding body of available genomic and protein structural data provides a rich resource for understanding protein dynamics with biomolecular simulation. While computational infrastructure has grown rapidly, simulations on an omics scale are not yet widespread, primarily because software infrastructure to enable simulations at this scale has not kept pace. It should now be possible to study protein dynamics across entire (super)families, exploiting both available structural biology data and conformational similarities across homologous proteins. Here, we present a new tool for enabling high-throughput simulation in the genomics era. Ensembler takes any set of sequences—from a single sequence to an entire superfamily—and shepherds them through various stages of modeling and refinement to produce simulation-ready structures. This includes comparative modeling to all relevant PDB structures (which may span multiple conformational states of interest), reconstruction of missing loops, addition of missing atoms, culling of nearly identical structures, assignment of appropriate protonation states, solvation in explicit solvent, and refinement and filtering with molecular simulation to ensure stable simulation. The output of this pipeline is an ensemble of structures ready for subsequent molecular simulations using computer clusters, supercomputers, or distributed computing projects like Folding@home. Ensembler thus automates much of the time-consuming process of preparing protein models suitable for simulation, while allowing scalability up to entire superfamilies. A particular advantage of this approach can be found in the construction of kinetic models of conformational dynamics—such as Markov state models (MSMs)—which benefit from a diverse array of initial configurations that span the accessible conformational states to aid sampling. We demonstrate the power of this approach by constructing models for all catalytic domains in the human tyrosine

  20. Functional Annotation of Two New Carboxypeptidases from the Amidohydrolase Superfamily of Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, D.; Xu, C; Kumaran, D; Brown, A; Sauder, M; Burley, S; Swaminathan, S; Raushel, F

    2009-01-01

    Two proteins from the amidohydrolase superfamily of enzymes were cloned, expressed, and purified to homogeneity. The first protein, Cc0300, was from Caulobacter crescentus CB-15 (Cc0300), while the second one (Sgx9355e) was derived from an environmental DNA sequence originally isolated from the Sargasso Sea (gi|44371129). The catalytic functions and the substrate profiles for the two enzymes were determined with the aid of combinatorial dipeptide libraries. Both enzymes were shown to catalyze the hydrolysis of l-Xaa-l-Xaa dipeptides in which the amino acid at the N-terminus was relatively unimportant. These enzymes were specific for hydrophobic amino acids at the C-terminus. With Cc0300, substrates terminating in isoleucine, leucine, phenylalanine, tyrosine, valine, methionine, and tryptophan were hydrolyzed. The same specificity was observed with Sgx9355e, but this protein was also able to hydrolyze peptides terminating in threonine. Both enzymes were able to hydrolyze N-acetyl and N-formyl derivatives of the hydrophobic amino acids and tripeptides. The best substrates identified for Cc0300 were l-Ala-l-Leu with kcat and kcat/Km values of 37 s-1 and 1.1 x 105 M-1 s-1, respectively, and N-formyl-l-Tyr with kcat and kcat/Km values of 33 s-1 and 3.9 x 105 M-1 s-1, respectively. The best substrate identified for Sgx9355e was l-Ala-l-Phe with kcat and kcat/Km values of 0.41 s-1 and 5.8 x 103 M-1 s-1. The three-dimensional structure of Sgx9355e was determined to a resolution of 2.33 Angstroms with l-methionine bound in the active site. The a-carboxylate of the methionine is ion-paired to His-237 and also hydrogen bonded to the backbone amide groups of Val-201 and Leu-202. The a-amino group of the bound methionine interacts with Asp-328. The structural determinants for substrate recognition were identified and compared with other enzymes in this superfamily that hydrolyze dipeptides with different specificities.

  1. Genome-wide analysis of the MYB transcription factor superfamily in soybean

    Directory of Open Access Journals (Sweden)

    Du Hai

    2012-07-01

    Full Text Available Abstract Background The MYB superfamily constitutes one of the most abundant groups of transcription factors described in plants. Nevertheless, their functions appear to be highly diverse and remain rather unclear. To date, no genome-wide characterization of this gene family has been conducted in a legume species. Here we report the first genome-wide analysis of the whole MYB superfamily in a legume species, soybean (Glycine max, including the gene structures, phylogeny, chromosome locations, conserved motifs, and expression patterns, as well as a comparative genomic analysis with Arabidopsis. Results A total of 244 R2R3-MYB genes were identified and further classified into 48 subfamilies based on a phylogenetic comparative analysis with their putative orthologs, showed both gene loss and duplication events. The phylogenetic analysis showed that most characterized MYB genes with similar functions are clustered in the same subfamily, together with the identification of orthologs by synteny analysis, functional conservation among subgroups of MYB genes was strongly indicated. The phylogenetic relationships of each subgroup of MYB genes were well supported by the highly conserved intron/exon structures and motifs outside the MYB domain. Synonymous nucleotide substitution (dN/dS analysis showed that the soybean MYB DNA-binding domain is under strong negative selection. The chromosome distribution pattern strongly indicated that genome-wide segmental and tandem duplication contribute to the expansion of soybean MYB genes. In addition, we found that ~ 4% of soybean R2R3-MYB genes had undergone alternative splicing events, producing a variety of transcripts from a single gene, which illustrated the extremely high complexity of transcriptome regulation. Comparative expression profile analysis of R2R3-MYB genes in soybean and Arabidopsis revealed that MYB genes play conserved and various roles in plants, which is indicative of a divergence in

  2. Analytical morphies on mid-sagittal craniograms glabella-opisthocranion of Homo erectus and Homo sapiens neanderthalensis: Fourier parameters and synthesis of mean craniograms.

    Science.gov (United States)

    Vacca, E; Pesce Delfino, V

    1991-03-01

    Among mathematic procedures used in morphological description, Fourier analysis was indicated as extremely effective in obtaining numerical representations of shape. In order to fully exploit its potentiality in morphology the worked data have to be referred exclusively to the shape of the investigated object and the application of suitable procedures of dimensional normalization are necessary, moreover the significance of the parameters obtained from the analysis must be referable univocally to the morphological datum. In these conditions the numerical characterization of shapes and the relations detectable from different parameters obtained from the description assume the significance of real "analytical morphies". These statements were verified by performing morphological description and comparison, by means of the Fourier harmonic analysis on two groups of mid-sagittal glabella-opisthocranIon craniograms to point out their possible distinctive analytical characteristics: the first group relates to classical neanderthalian group, the second one is made up of asiatic samples of Homo erectus. Some typical patterns of the obtained parameters were discussed and explained in terms of analytical morphies characterizing the given specimens, the traditional morphological classifications were verified and, above all, a numerical description of these samples was obtained.

  3. Primase-polymerases are a functionally diverse superfamily of replication and repair enzymes.

    Science.gov (United States)

    Guilliam, Thomas A; Keen, Benjamin A; Brissett, Nigel C; Doherty, Aidan J

    2015-08-18

    Until relatively recently, DNA primases were viewed simply as a class of proteins that synthesize short RNA primers requisite for the initiation of DNA replication. However, recent studies have shown that this perception of the limited activities associated with these diverse enzymes can no longer be justified. Numerous examples can now be cited demonstrating how the term 'DNA primase' only describes a very narrow subset of these nucleotidyltransferases, with the vast majority fulfilling multifunctional roles from DNA replication to damage tolerance and repair. This article focuses on the archaeo-eukaryotic primase (AEP) superfamily, drawing on recently characterized examples from all domains of life to highlight the functionally diverse pathways in which these enzymes are employed. The broad origins, functionalities and enzymatic capabilities of AEPs emphasizes their previous functional misannotation and supports the necessity for a reclassification of these enzymes under a category called primase-polymerases within the wider functional grouping of polymerases. Importantly, the repositioning of AEPs in this way better recognizes their broader roles in DNA metabolism and encourages the discovery of additional functions for these enzymes, aside from those highlighted here.

  4. Patterning of cell assemblies regulated by adhesion receptors of the cadherin superfamily.

    Science.gov (United States)

    Takeichi, M; Nakagawa, S; Aono, S; Usui, T; Uemura, T

    2000-07-29

    During morphogenesis, cell-cell association patterns are dynamically altered. We are interested in how cell adhesion molecules can regulate the patterning of cellular assemblies. Cadherins, a group of cell-cell adhesion receptors, are crucial for the organized assembly of many cell types, but they also regulate dynamic aspects of cell association. For example, during neural crest emigration from the neural tube, the cadherin subtypes expressed by crest cells are switched from one subtype to another. Artificial perturbation of this switch results in blocking of their escape from the neural tube. Intracellular modulations of cadherin activity also seem to play a role in regulation of cell adhesion. We identified p120ctn as a regulator of cadherin function in carcinoma cells. With such regulators, cells may make a choice as to whether they should maintain stable cell contacts or disrupt their association. Finally, we found another type of cadherin-mediated cell patterning: Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity in Drosophila imaginal discs. Thus, the cadherin superfamily receptors control the patterning of cell assemblies through a variety of mechanisms.

  5. Stonefish toxin defines an ancient branch of the perforin-like superfamily.

    Science.gov (United States)

    Ellisdon, Andrew M; Reboul, Cyril F; Panjikar, Santosh; Huynh, Kitmun; Oellig, Christine A; Winter, Kelly L; Dunstone, Michelle A; Hodgson, Wayne C; Seymour, Jamie; Dearden, Peter K; Tweten, Rodney K; Whisstock, James C; McGowan, Sheena

    2015-12-15

    The lethal factor in stonefish venom is stonustoxin (SNTX), a heterodimeric cytolytic protein that induces cardiovascular collapse in humans and native predators. Here, using X-ray crystallography, we make the unexpected finding that SNTX is a pore-forming member of an ancient branch of the Membrane Attack Complex-Perforin/Cholesterol-Dependent Cytolysin (MACPF/CDC) superfamily. SNTX comprises two homologous subunits (α and β), each of which comprises an N-terminal pore-forming MACPF/CDC domain, a central focal adhesion-targeting domain, a thioredoxin domain, and a C-terminal tripartite motif family-like PRY SPla and the RYanodine Receptor immune recognition domain. Crucially, the structure reveals that the two MACPF domains are in complex with one another and arranged into a stable early prepore-like assembly. These data provide long sought after near-atomic resolution insights into how MACPF/CDC proteins assemble into prepores on the surface of membranes. Furthermore, our analyses reveal that SNTX-like MACPF/CDCs are distributed throughout eukaryotic life and play a broader, possibly immune-related function outside venom.

  6. Fauna Europaea: Coleoptera 2 (excl. series Elateriformia, Scarabaeiformia, Staphyliniformia and superfamily Curculionoidea

    Directory of Open Access Journals (Sweden)

    Paolo Audisio

    2015-04-01

    Coleoptera represent a huge assemblage of holometabolous insects, including as a whole more than 200 recognized families and some 400,000 described species worldwide. Basic information is summarized on their biology, ecology, economic relevance, and estimated number of undescribed species worldwide. Little less than 30,000 species are listed from Europe. The Coleoptera 2 section of the Fauna Europaea database (Archostemata, Myxophaga, Adephaga and Polyphaga excl. the series Elateriformia, Scarabaeiformia, Staphyliniformia and the superfamily Curculionoidea encompasses 80 families (according to the previously accepted family-level systematic framework and approximately 13,000 species. Tabulations included a complete list of the families dealt with, the number of species in each, the names of all involved specialists, and, when possible, an estimate of the gaps in terms of total number of species at an European level. A list of some recent useful references is appended. Most families included in the Coleoptera 2 Section have been updated in the most recent release of the Fauna Europaea index, or are ready to be updated as soon as the FaEu data management environment completes its migration from Zoological Museum Amsterdam to Berlin Museum für Naturkunde.

  7. Characterization of putative multidrug resistance transporters of the major facilitator-superfamily expressed in Salmonella Typhi.

    Science.gov (United States)

    Shaheen, Aqsa; Ismat, Fouzia; Iqbal, Mazhar; Haque, Abdul; De Zorzi, Rita; Mirza, Osman; Walz, Thomas; Rahman, Moazur

    2015-05-01

    Multidrug resistance mediated by efflux pumps is a well-known phenomenon in infectious bacteria. Although much work has been carried out to characterize multidrug efflux pumps in Gram-negative and Gram-positive bacteria, such information is still lacking for many deadly pathogens. The aim of this study was to gain insight into the substrate specificity of previously uncharacterized transporters of Salmonella Typhi to identify their role in the development of multidrug resistance. S. Typhi genes encoding putative members of the major facilitator superfamily were cloned and expressed in the drug-hypersensitive Escherichia coli strain KAM42, and tested for transport of 25 antibacterial compounds, including representative antibiotics of various classes, antiseptics, dyes and detergents. Of the 15 tested putative transporters, STY0901, STY2458 and STY4874 exhibited a drug-resistance phenotype. Among these, STY4874 conferred resistance to at least ten of the tested antimicrobials: ciprofloxacin, norfloxacin, levofloxacin, kanamycin, streptomycin, gentamycin, nalidixic acid, chloramphenicol, ethidium bromide, and acriflavine, including fluoroquinolone antibiotics, which were drugs of choice to treat S. Typhi infections. Cell-based functional studies using ethidium bromide and acriflavine showed that STY4874 functions as a H(+)-dependent exporter. These results suggest that STY4874 may be an important drug target, which can now be tested by studying the susceptibility of a STY4874-deficient S. Typhi strain to antimicrobials.

  8. Correlated Mutation in the Evolution of Catalysis in Uracil DNA Glycosylase Superfamily

    Science.gov (United States)

    Xia, Bo; Liu, Yinling; Guevara, Jose; Li, Jing; Jilich, Celeste; Yang, Ye; Wang, Liangjiang; Dominy, Brian N.; Cao, Weiguo

    2017-01-01

    Enzymes in Uracil DNA glycosylase (UDG) superfamily are essential for the removal of uracil. Family 4 UDGa is a robust uracil DNA glycosylase that only acts on double-stranded and single-stranded uracil-containing DNA. Based on mutational, kinetic and modeling analyses, a catalytic mechanism involving leaving group stabilization by H155 in motif 2 and water coordination by N89 in motif 3 is proposed. Mutual Information analysis identifies a complexed correlated mutation network including a strong correlation in the EG doublet in motif 1 of family 4 UDGa and in the QD doublet in motif 1 of family 1 UNG. Conversion of EG doublet in family 4 Thermus thermophilus UDGa to QD doublet increases the catalytic efficiency by over one hundred-fold and seventeen-fold over the E41Q and G42D single mutation, respectively, rectifying the strong correlation in the doublet. Molecular dynamics simulations suggest that the correlated mutations in the doublet in motif 1 position the catalytic H155 in motif 2 to stabilize the leaving uracilate anion. The integrated approach has important implications in studying enzyme evolution and protein structure and function. PMID:28397787

  9. The Role of Immunoglobulin Superfamily Cell Adhesion Molecules in Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Chee Wai Wong

    2012-01-01

    Full Text Available Metastasis is a major clinical problem and results in a poor prognosis for most cancers. The metastatic pathway describes the process by which cancer cells give rise to a metastatic lesion in a new tissue or organ. It consists of interconnecting steps all of which must be successfully completed to result in a metastasis. Cell-cell adhesion is a key aspect of many of these steps. Adhesion molecules belonging to the immunoglobulin superfamily (Ig-SF commonly play a central role in cell-cell adhesion, and a number of these molecules have been associated with cancer progression and a metastatic phenotype. Surprisingly, the contribution of Ig-SF members to metastasis has not received the attention afforded other cell adhesion molecules (CAMs such as the integrins. Here we examine the steps in the metastatic pathway focusing on how the Ig-SF members, melanoma cell adhesion molecule (MCAM, L1CAM, neural CAM (NCAM, leukocyte CAM (ALCAM, intercellular CAM-1 (ICAM-1 and platelet endothelial CAM-1 (PECAM-1 could play a role. Although much remains to be understood, this review aims to raise the profile of Ig-SF members in metastasis formation and prompt further research that could lead to useful clinical outcomes.

  10. Relative Stabilities of Conserved and Non-Conserved Structures in the OB-Fold Superfamily

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    Andrei T. Alexandrescu

    2009-05-01

    Full Text Available The OB-fold is a diverse structure superfamily based on a β-barrel motif that is often supplemented with additional non-conserved secondary structures. Previous deletion mutagenesis and NMR hydrogen exchange studies of three OB-fold proteins showed that the structural stabilities of sites within the conserved β-barrels were larger than sites in non-conserved segments. In this work we examined a database of 80 representative domain structures currently classified as OB-folds, to establish the basis of this effect. Residue-specific values were obtained for the number of Cα-Cα distance contacts, sequence hydrophobicities, crystallographic B-factors, and theoretical B-factors calculated from a Gaussian Network Model. All four parameters point to a larger average flexibility for the non-conserved structures compared to the conserved β-barrels. The theoretical B-factors and contact densities show the highest sensitivity.Our results suggest a model of protein structure evolution in which novel structural features develop at the periphery of conserved motifs. Core residues are more resistant to structural changes during evolution since their substitution would disrupt a larger number of interactions. Similar factors are likely to account for the differences in stability to unfolding between conserved and non-conserved structures.

  11. Tumor Necrosis Factor-Superfamily 15 Gene Expression in Patients with Sickle Cell Disease

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    Ahmet Ata Özçimen

    2014-09-01

    Full Text Available OBJECTIVE: The aim of this study was to investigate the relation between tumor necrosis factor-superfamily 15 (TNFSF15 gene expression and clinical findings in children with sickle cell disease (SCD. METHODS: Forty-nine patients with SCD and 38 healthy controls were included in this study. TNFSF15 gene expression and plasma levels were analyzed. TNFSF15 gene expression was compared in subgroups considering the frequency of painful crises and acute chest syndrome (ACS. RESULTS: It was found that TNFSF15 gene expression was significantly higher in patients with SCD than the controls (p=0.001, whereas there was no significant difference between the patients with SCD and the control groups considering plasma levels of TNFSF15. TNFSF15 gene expression was also significantly higher in SCD patients with ACS (p=0.008. CONCLUSION: These findings suggest that TNFSF15 may have a role in the pathogenesis of SCD presenting with ACS. Further studies on larger groups are needed to determine the function of TNFSF15 in SCD patients with ACS and pulmonary hypertension. Analysis of TNFSF15 expression may also serve as a promising approach in ACS therapy.

  12. Superfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening.

    Science.gov (United States)

    Bachovchin, Daniel A; Ji, Tianyang; Li, Weiwei; Simon, Gabriel M; Blankman, Jacqueline L; Adibekian, Alexander; Hoover, Heather; Niessen, Sherry; Cravatt, Benjamin F

    2010-12-07

    Serine hydrolases (SHs) are one of the largest and most diverse enzyme classes in mammals. They play fundamental roles in virtually all physiological processes and are targeted by drugs to treat diseases such as diabetes, obesity, and neurodegenerative disorders. Despite this, we lack biological understanding for most of the 110+ predicted mammalian metabolic SHs, in large part because of a dearth of assays to assess their biochemical activities and a lack of selective inhibitors to probe their function in living systems. We show here that the vast majority (> 80%) of mammalian metabolic SHs can be labeled in proteomes by a single, active site-directed fluorophosphonate probe. We exploit this universal activity-based assay in a library-versus-library format to screen 70+ SHs against 140+ structurally diverse carbamates. Lead inhibitors were discovered for ∼40% of the screened enzymes, including many poorly characterized SHs. Global profiles identified carbamate inhibitors that discriminate among highly sequence-related SHs and, conversely, enzymes that share inhibitor sensitivity profiles despite lacking sequence homology. These findings indicate that sequence relatedness is not a strong predictor of shared pharmacology within the SH superfamily. Finally, we show that lead carbamate inhibitors can be optimized into pharmacological probes that inactivate individual SHs with high specificity in vivo.

  13. Redox regulation by thioredoxin superfamily; protection against oxidative stress and aging.

    Science.gov (United States)

    Tanaka, T; Nakamura, H; Nishiyama, A; Hosoi, F; Masutani, H; Wada, H; Yodoi, J

    2000-12-01

    Thioredoxin (TRX) is a 12 kD protein with redox-active dithiol in the active site; -Cys-Gly-Pro-Cys-. We originally cloned human TRX as adult T cell leukemia derived factor (ADF) produced by HTLV-I transformed cells. TRX and related molecules maintain a cellular reducing enviroment, working in concert with the glutathione system. Physiologically, TRX has cytoprotective effects against oxidative stress. TRX promotes DNA binding of transcription factors such as NF-kB, AP-1, p53, and PEBP-2. The TRX superfamily, including thioredoxin-2 (mitochondrial thioredoxin) and glutaredoxin, are involved in biologically important phenomena via the redox-regulating system. Thioredoxin-binding protein-2, which we recently identified by a yeast two-hybrid system, is a type of endogenous modulator of TRX activity. TRX is secreted from the cells and exhibits cytokine-like and chemokine-like activities. Redox regulation by TRX plays a crucial role in biological responses against oxidative stress.

  14. Evolution of the B3 DNA binding superfamily: new insights into REM family gene diversification.

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    Elisson A C Romanel

    Full Text Available BACKGROUND: The B3 DNA binding domain includes five families: auxin response factor (ARF, abscisic acid-insensitive3 (ABI3, high level expression of sugar inducible (HSI, related to ABI3/VP1 (RAV and reproductive meristem (REM. The release of the complete genomes of the angiosperm eudicots Arabidopsis thaliana and Populus trichocarpa, the monocot Orysa sativa, the bryophyte Physcomitrella patens,the green algae Chlamydomonas reinhardtii and Volvox carteri and the red algae Cyanidioschyzon melorae provided an exceptional opportunity to study the evolution of this superfamily. METHODOLOGY: In order to better understand the origin and the diversification of B3 domains in plants, we combined comparative phylogenetic analysis with exon/intron structure and duplication events. In addition, we investigated the conservation and divergence of the B3 domain during the origin and evolution of each family. CONCLUSIONS: Our data indicate that showed that the B3 containing genes have undergone extensive duplication events, and that the REM family B3 domain has a highly diverged DNA binding. Our results also indicate that the founding member of the B3 gene family is likely to be similar to the ABI3/HSI genes found in C. reinhardtii and V. carteri. Among the B3 families, ABI3, HSI, RAV and ARF are most structurally conserved, whereas the REM family has experienced a rapid divergence. These results are discussed in light of their functional and evolutionary roles in plant development.

  15. The major facilitator superfamily transporter Knq1p modulates boron homeostasis in Kluyveromyces lactis.

    Science.gov (United States)

    Svrbicka, Alexandra; Toth Hervay, Nora; Gbelska, Yvetta

    2016-03-01

    Boron is an essential micronutrient for living cells, yet its excess causes toxicity. To date, the mechanisms of boron toxicity are poorly understood. Recently, the ScATR1 gene has been identified encoding the main boron efflux pump in Saccharomyces cerevisiae. In this study, we analyzed the ScATR1 ortholog in Kluyveromyces lactis--the KNQ1 gene, to understand whether it participates in boron stress tolerance. We found that the KNQ1 gene, encoding a permease belonging to the major facilitator superfamily, is required for K. lactis boron tolerance. Deletion of the KNQ1 gene led to boron sensitivity and its overexpression increased K. lactis boron tolerance. The KNQ1 expression was induced by boron and the intracellular boron concentration was controlled by Knq1p. The KNQ1 promoter contains two putative binding motifs for the AP-1-like transcription factor KlYap1p playing a central role in oxidative stress defense. Our results indicate that the induction of the KNQ1 expression requires the presence of KlYap1p and that Knq1p like its ortholog ScAtr1p in S. cerevisiae functions as a boron efflux pump providing boron resistance in K. lactis.

  16. A new gene superfamily of pathogen-response (repat) genes in Lepidoptera: classification and expression analysis.

    Science.gov (United States)

    Navarro-Cerrillo, G; Hernández-Martínez, P; Vogel, H; Ferré, J; Herrero, S

    2013-01-01

    Repat (REsponse to PAThogens) genes were first identified in the midgut of Spodoptera exigua (Lepidoptera: Noctuidae) in response to Bacillus thuringiensis and baculovirus exposure. Since then, additional repat gene homologs have been identified in different studies. In this study the comprehensive larval transcriptome from S. exigua was analyzed for the presence of novel repat-homolog sequences. These analyses revealed the presence of at least 46 repat genes in S. exigua, establishing a new gene superfamily in this species. Phylogenetic analysis and studies of conserved motifs in these hypothetical proteins have allowed their classification in two main classes, αREPAT and βREPAT. Studies on the transcriptional response of repat genes have shown that αREPAT and βREPAT differ in their sequence but also in the pattern of regulation. The αREPAT were mainly regulated in response to the Cry1Ca toxin from B. thuringiensis but not to the increase in the midgut microbiota load. In contrast, βREPAT were neither responding to Cry1Ca toxin nor to midgut microbiota. Differential expression between midgut stem cells and the whole midgut tissue was studied for the different repat genes revealing changes in the gene expression distribution between midgut stem cells and midgut tissue in response to midgut microbiota. This high diversity found in their sequence and in their expression profile suggests that REPAT proteins may be involved in multiple processes that could be of relevance for the understanding of the insect gut physiology.

  17. Manipulation of receptor oligomerization as a strategy to inhibit signaling by TNF superfamily members.

    Science.gov (United States)

    Warren, Julia T; Nelson, Christopher A; Decker, Corinne E; Zou, Wei; Fremont, Daved H; Teitelbaum, Steven L

    2014-08-19

    Signaling by receptor activator of nuclear factor κB (RANK) in response to its ligand RANKL, which is a member of the tumor necrosis factor (TNF) superfamily of cytokines, stimulates osteoclast formation and bone resorption. Thus, this ligand-receptor pair is a therapeutic target for various disorders, such as osteoporosis and metastasis of cancer to bone. RANKL exists as a physiological homotrimer, with each monomer recognizing a single molecule of RANK or the decoy receptor osteoprotegerin (OPG), which inhibits osteoclastogenesis. We engineered a RANKL protein in which all three monomers of RANKL were encoded as a single polypeptide chain, which enabled us to independently control receptor binding at each binding interface. To generate an effective RANK inhibitor, we used an unbiased forward genetic approach to identify mutations in RANKL that had a 500-fold increased affinity for RANK but had decreased affinity for the decoy receptor OPG. Incorporating mutations that blocked receptor binding into this high-affinity RANKL variant generated a mutant RANKL that completely inhibited wild-type RANKL-induced osteoclastogenesis in vitro and bone resorption in mice. Our approach may be generalized to enable the inhibition of other TNF receptor signaling systems, which are implicated in a wide range of pathological conditions.

  18. Glutathione Transferases Superfamily: Cold-Inducible Expression of Distinct GST Genes in Brassica oleracea.

    Science.gov (United States)

    Vijayakumar, Harshavardhanan; Thamilarasan, Senthil Kumar; Shanmugam, Ashokraj; Natarajan, Sathishkumar; Jung, Hee-Jeong; Park, Jong-In; Kim, HyeRan; Chung, Mi-Young; Nou, Ill-Sup

    2016-07-27

    Plants, as sessile organisms, can suffer serious growth and developmental consequences under cold stress conditions. Glutathione transferases (GSTs, EC 2.5.1.18) are ubiquitous and multifunctional conjugating proteins, which play a major role in stress responses by preventing oxidative damage by reactive oxygen species (ROS). Currently, understanding of their function(s) during different biochemical and signaling pathways under cold stress condition remain unclear. In this study, using combined computational strategy, we identified 65 Brassica oleracea glutathione transferases (BoGST) and characterized them based on evolutionary analysis into 11 classes. Inter-species and intra-species duplication was evident between BoGSTs and Arabidopsis GSTs. Based on localization analyses, we propose possible pathways in which GST genes are involved during cold stress. Further, expression analysis of the predicted putative functions for GST genes were investigated in two cold contrasting genotypes (cold tolerance and susceptible) under cold condition, most of these genes were highly expressed at 6 h and 1 h in the cold tolerant (CT) and cold susceptible (CS) lines, respectively. Overall, BoGSTU19, BoGSTU24, BoGSTF10 are candidate genes highly expressed in B. oleracea. Further investigation of GST superfamily in B. oleracea will aid in understanding complex mechanism underlying cold tolerance in plants.

  19. Glutathione Transferases Superfamily: Cold-Inducible Expression of Distinct GST Genes in Brassica oleracea

    Directory of Open Access Journals (Sweden)

    Harshavardhanan Vijayakumar

    2016-07-01

    Full Text Available Plants, as sessile organisms, can suffer serious growth and developmental consequences under cold stress conditions. Glutathione transferases (GSTs, EC 2.5.1.18 are ubiquitous and multifunctional conjugating proteins, which play a major role in stress responses by preventing oxidative damage by reactive oxygen species (ROS. Currently, understanding of their function(s during different biochemical and signaling pathways under cold stress condition remain unclear. In this study, using combined computational strategy, we identified 65 Brassica oleracea glutathione transferases (BoGST and characterized them based on evolutionary analysis into 11 classes. Inter-species and intra-species duplication was evident between BoGSTs and Arabidopsis GSTs. Based on localization analyses, we propose possible pathways in which GST genes are involved during cold stress. Further, expression analysis of the predicted putative functions for GST genes were investigated in two cold contrasting genotypes (cold tolerance and susceptible under cold condition, most of these genes were highly expressed at 6 h and 1 h in the cold tolerant (CT and cold susceptible (CS lines, respectively. Overall, BoGSTU19, BoGSTU24, BoGSTF10 are candidate genes highly expressed in B. oleracea. Further investigation of GST superfamily in B. oleracea will aid in understanding complex mechanism underlying cold tolerance in plants.

  20. New superfamily members identified for Schiff-base enzymes based on verification of catalytically essential residues.

    Science.gov (United States)

    Choi, Kyung H; Lai, Vicky; Foster, Christine E; Morris, Aaron J; Tolan, Dean R; Allen, Karen N

    2006-07-18

    Enzymes that utilize a Schiff-base intermediate formed with their substrates and that share the same alpha/beta barrel fold comprise a mechanistically diverse superfamily defined in the SCOPS database as the class I aldolase family. The family includes the "classical" aldolases fructose-1,6-(bis)phosphate (FBP) aldolase, transaldolase, and 2-keto-3-deoxy-6-phosphogluconate aldolase. Moreover, the N-acetylneuraminate lyase family has been included in the class I aldolase family on the basis of similar Schiff-base chemistry and fold. Herein, we generate primary sequence identities based on structural alignment that support the homology and reveal additional mechanistic similarities beyond the common use of a lysine for Schiff-base formation. The structural and mechanistic correspondence comprises the use of a catalytic dyad, wherein a general acid/base residue (Glu, Tyr, or His) involved in Schiff-base chemistry is stationed on beta-strand 5 of the alpha/beta barrel. The role of the acid/base residue was probed by site-directed mutagenesis and steady-state and pre-steady-state kinetics on a representative member of this family, FBP aldolase. The kinetic results are consistent with the participation of this conserved residue or position in the protonation of the carbinolamine intermediate and dehydration of the Schiff base in FBP aldolase and, by analogy, the class I aldolase family.

  1. Evolutionary Pattern of N-Glycosylation Sequon Numbers in Eukaryotic ABC Protein Superfamilies

    DEFF Research Database (Denmark)

    Rao, R Shyama Prasad; Buus, Ole Thomsen; Wollenweber, Bernd

    2010-01-01

    Many proteins contain a large number of NXS/T sequences (where X is any amino acid except proline) which are the potential sites of asparagine (N) linked glycosylation. However, the patterns of occurrence of these N-glycosylation sequons in related proteins or groups of proteins and their underly......Many proteins contain a large number of NXS/T sequences (where X is any amino acid except proline) which are the potential sites of asparagine (N) linked glycosylation. However, the patterns of occurrence of these N-glycosylation sequons in related proteins or groups of proteins...... and their underlying causes have largely been unexplored. We computed the actual and probabilistic occurrence of NXS/T sequons in ABC protein superfamilies from eight diverse eukaryotic organisms. The ABC proteins contained significantly higher NXS/T sequon numbers compared to respective genome-wide average......-against the recent findings of only threonine specific Darwinian selection of sequons in proteins. The occurrence of sequons was positively correlated with the frequency of sequon specific amino acids and negatively correlated with proline and the NPS/T sequences. Further, the NPS/T sequences were significantly...

  2. Selective regulation of axonal growth from developing hippocampal neurons by tumor necrosis factor superfamily member APRIL☆

    Science.gov (United States)

    Osório, Catarina; Chacón, Pedro J.; White, Matthew; Kisiswa, Lilian; Wyatt, Sean; Rodríguez-Tébar, Alfredo; Davies, Alun M.

    2014-01-01

    APRIL (A Proliferation-Inducing Ligand, TNFSF13) is a member of the tumor necrosis factor superfamily that regulates lymphocyte survival and activation and has been implicated in tumorigenesis and autoimmune diseases. Here we report the expression and first known activity of APRIL in the nervous system. APRIL and one of its receptors, BCMA (B-Cell Maturation Antigen, TNFRSF17), are expressed by hippocampal pyramidal cells of fetal and postnatal mice. In culture, these neurons secreted APRIL, and function-blocking antibodies to either APRIL or BCMA reduced axonal elongation. Recombinant APRIL enhanced axonal elongation, but did not influence dendrite elongation. The effect of APRIL on axon elongation was inhibited by anti-BCMA and the expression of a signaling-defective BCMA mutant in these neurons, suggesting that the axon growth-promoting effect of APRIL is mediated by BCMA. APRIL promoted phosphorylation and activation of ERK1, ERK2 and Akt and serine phosphorylation and inactivation of GSK-3β in cultured hippocampal pyramidal cells. Inhibition of MEK1/MEK2 (activators of ERK1/ERK2), PI3-kinase (activator of Akt) or Akt inhibited the axon growth-promoting action of APRIL, as did pharmacological activation of GSK-3β and the expression of a constitutively active form of GSK-3β. These findings suggest that APRIL promotes axon elongation by a mechanism that depends both on ERK signaling and PI3-kinase/Akt/GSK-3β signaling. PMID:24444792

  3. Roles for transforming growth factor beta superfamily proteins in early folliculogenesis.

    Science.gov (United States)

    Trombly, Daniel J; Woodruff, Teresa K; Mayo, Kelly E

    2009-01-01

    Primordial follicle formation and the subsequent transition of follicles to the primary and secondary stages encompass the early events during folliculogenesis in mammals. These processes establish the ovarian follicle pool and prime follicles for entry into subsequent growth phases during the reproductive cycle. Perturbations during follicle formation can affect the size of the primordial follicle pool significantly, and alterations in follicle transition can cause follicles to arrest at immature stages or result in premature depletion of the follicle reserve. Determining the molecular events that regulate primordial follicle formation and early follicle growth may lead to the development of new fertility treatments. Over the last decade, many of the growth factors and signaling proteins that mediate the early stages of folliculogenesis have been identified using mouse genetic models, in vivo injection studies, and ex vivo organ culture approaches. These studies reveal important roles for the transforming growth factor beta (TGF-beta) superfamily of proteins in the ovary. This article reviews these roles for TGF-beta family proteins and focuses in particular on work from our laboratories on the functions of activin in early folliculogenesis.

  4. Identification of the GTPase superfamily in Mycoplasma synoviae and Mycoplasma hyopneumoniae

    Directory of Open Access Journals (Sweden)

    Clayton Luiz Borges

    2007-01-01

    Full Text Available Mycoplasmas are the smallest known prokaryotes with self-replication ability. They are obligate parasites, taking up many molecules of their hosts and acting as pathogens in men, animals, birds and plants. Mycoplasma hyopneumoniae is the infective agent of swine mycoplasmosis and Mycoplasma synoviae is responsible for subclinical upper respiratory infections that may result in airsacculitis and synovitis in chickens and turkeys. These highly infectious organisms present a worldwide distribution and are responsible for major economic problems. Proteins of the GTPase superfamily occur in all domains of life, regulating functions such as protein synthesis, cell cycle and differentiation. Despite their functional diversity, all GTPases are believed to have evolved from a single common ancestor. In this work we have identified mycoplasma GTPases by searching the complete genome databases of Mycoplasma synoviae and Mycoplasma hyopneumoniae, J (non-pathogenic and 7448 (pathogenic strains. Fifteen ORFs encoding predicted GTPases were found in M. synoviae and in the two strains of M. hyopneumoniae. Searches for conserved G domains in GTPases were performed and the sequences were classified into families. The GTPase phylogenetic analysis showed that the subfamilies were well resolved into clades. The presence of GTPases in the three strains suggests the importance of GTPases in 'minimalist' genomes.

  5. Expression Divergence of Duplicate Genes in the Protein Kinase Superfamily in Pacific Oyster.

    Science.gov (United States)

    Gao, Dahai; Ko, Dennis C; Tian, Xinmin; Yang, Guang; Wang, Liuyang

    2015-01-01

    Gene duplication has been proposed to serve as the engine of evolutionary innovation. It is well recognized that eukaryotic genomes contain a large number of duplicated genes that evolve new functions or expression patterns. However, in mollusks, the evolutionary mechanisms underlying the divergence and the functional maintenance of duplicate genes remain little understood. In the present study, we performed a comprehensive analysis of duplicate genes in the protein kinase superfamily using whole genome and transcriptome data for the Pacific oyster. A total of 64 duplicated gene pairs were identified based on a phylogenetic approach and the reciprocal best BLAST method. By analyzing gene expression from RNA-seq data from 69 different developmental and stimuli-induced conditions (nine tissues, 38 developmental stages, eight dry treatments, seven heat treatments, and seven salty treatments), we found that expression patterns were significantly correlated for a number of duplicate gene pairs, suggesting the conservation of regulatory mechanisms following divergence. Our analysis also identified a subset of duplicate gene pairs with very high expression divergence, indicating that these gene pairs may have been subjected to transcriptional subfunctionalization or neofunctionalization after the initial duplication events. Further analysis revealed a significant correlation between expression and sequence divergence (as revealed by synonymous or nonsynonymous substitution rates) under certain conditions. Taken together, these results provide evidence for duplicate gene sequence and expression divergence in the Pacific oyster, accompanying its adaptation to harsh environments. Our results provide new insights into the evolution of duplicate genes and their expression levels in the Pacific oyster.

  6. Roles of major facilitator superfamily transporters in phosphate response in Drosophila.

    Directory of Open Access Journals (Sweden)

    Clemens Bergwitz

    Full Text Available The major facilitator superfamily (MFS transporter Pho84 and the type III transporter Pho89 are responsible for metabolic effects of inorganic phosphate in yeast. While the Pho89 ortholog Pit1 was also shown to be involved in phosphate-activated MAPK in mammalian cells, it is currently unknown, whether orthologs of Pho84 have a role in phosphate-sensing in metazoan species. We show here that the activation of MAPK by phosphate observed in mammals is conserved in Drosophila cells, and used this assay to characterize the roles of putative phosphate transporters. Surprisingly, while we found that RNAi-mediated knockdown of the fly Pho89 ortholog dPit had little effect on the activation of MAPK in Drosophila S2R+ cells by phosphate, two Pho84/SLC17A1-9 MFS orthologs (MFS10 and MFS13 specifically inhibited this response. Further, using a Xenopus oocyte assay, we show that MSF13 mediates uptake of [(33P]-orthophosphate in a sodium-dependent fashion. Consistent with a role in phosphate physiology, MSF13 is expressed highest in the Drosophila crop, midgut, Malpighian tubule, and hindgut. Altogether, our findings provide the first evidence that Pho84 orthologs mediate cellular effects of phosphate in metazoan cells. Finally, while phosphate is essential for Drosophila larval development, loss of MFS13 activity is compatible with viability indicating redundancy at the levels of the transporters.

  7. Roles of major facilitator superfamily transporters in phosphate response in Drosophila.

    Science.gov (United States)

    Bergwitz, Clemens; Rasmussen, Matthew D; DeRobertis, Charles; Wee, Mark J; Sinha, Sumi; Chen, Hway H; Huang, Joanne; Perrimon, Norbert

    2012-01-01

    The major facilitator superfamily (MFS) transporter Pho84 and the type III transporter Pho89 are responsible for metabolic effects of inorganic phosphate in yeast. While the Pho89 ortholog Pit1 was also shown to be involved in phosphate-activated MAPK in mammalian cells, it is currently unknown, whether orthologs of Pho84 have a role in phosphate-sensing in metazoan species. We show here that the activation of MAPK by phosphate observed in mammals is conserved in Drosophila cells, and used this assay to characterize the roles of putative phosphate transporters. Surprisingly, while we found that RNAi-mediated knockdown of the fly Pho89 ortholog dPit had little effect on the activation of MAPK in Drosophila S2R+ cells by phosphate, two Pho84/SLC17A1-9 MFS orthologs (MFS10 and MFS13) specifically inhibited this response. Further, using a Xenopus oocyte assay, we show that MSF13 mediates uptake of [(33)P]-orthophosphate in a sodium-dependent fashion. Consistent with a role in phosphate physiology, MSF13 is expressed highest in the Drosophila crop, midgut, Malpighian tubule, and hindgut. Altogether, our findings provide the first evidence that Pho84 orthologs mediate cellular effects of phosphate in metazoan cells. Finally, while phosphate is essential for Drosophila larval development, loss of MFS13 activity is compatible with viability indicating redundancy at the levels of the transporters.

  8. Mycobacterium smegmatis MSMEG_3705 encodes a selective major facilitator superfamily efflux pump with multiple roles.

    Science.gov (United States)

    Zhang, Zhen; Wang, Rui; Xie, Jianping

    2015-06-01

    Mycobacterium smegmatis mc(2)155 MSMEG_3705 gene was annotated to encode a transporter protein that contains 12 alpha-helical transmembrane domains. We predicted MSMEG_3705 encoding a major facilitator superfamily (MFS) member. To confirm the prediction, the M. smegmatis mc(2)155 MSMEG_3705 gene was deleted. The MSMEG_3705 deletion mutant strain M. smegmatis mc(2)155 ∆MSMEG_3705 was more sensitive to capreomycin. Moreover, M. smegmatis mc(2)155 ∆MSMEG_3705 strain accumulated more ethidium bromide intracellular than wild-type M. smegmatis mc(2)155. Quite unexpectedly, M. smegmatis mc(2)155 ∆MSMEG_3705 grew faster than the wild-type M. smegmatis mc(2)155. The upregulation of the expression of MSMEG_3706, a gene encoding isocitrate lyase downstream MSMEG_3705, in the deletion mutant, might underlie such faster growth in the mutant. The study showed that MSMEG_3705 encodes a genuine MFS member and plays significant role in bacterial growth and antibiotics resistance.

  9. New species and records of mites of the superfamily Sarcoptoidea (Acariformes: Psoroptidia) from mammals in Brazil.

    Science.gov (United States)

    Bochkov, Andre V; Valim, Michel P

    2016-01-01

    Sixteen species of the superfamily Sarcoptoidea (Acariformes: Psoroptidia) belonging to 10 genera of the families Atopomelidae, Listrophoridae, Chirodiscidae, and Listropsoralgidae are recorded in Brazil. Among them, three species, Prolistrophorus hylaeamys sp. nov. from Hylaeamys laticeps (Lund, 1840) (Cricetidae: Sigmodontinae) from Minas Gerais, Lynxacarus serrafreirei sp. nov. from Galictis cuja (Molina, 1782) (Carnivora: Mustelidae) from Rio de Janeiro (Listrophoridae), and Didelphoecius micoureus sp. nov. (Atopomelidae) from Micoureus paraguayanus (Tate, 1931) (Didelphimorphia: Didelphidae) from Minas Gerais are described as new for science. Three species of the family Listrophoridae, Prolistrophorus bidentatus Fain et Lukoschus, 1984 from Akodon cursor (Winge, 1887) (Rodentia: Cricetidae) (new host), Prolistrophorus ctenomys Fain, 1970 from Ctenomys torquatus Lichtenstein, 1830 (Rodentia: Ctenomyidae) (new host), and Leporacarus sylvilagi Fain, Whitaker et Lukoschus, 1981 from Sylvilagus brasiliensis (Linnaeus, 1758) (Lagomorpha: Leporidae) (new host) -from Minas Gerais and Rio Grande do Sul, and one species of the family Chirodiscidae, Parakosa tadarida McDaniel and Lawrence, 1962 from Molossus molossus (Pallas, 1766) (Chiroptera: Molossidae) are recorded for the first time in Brazil. The previously unknown female of Didelphoecius validus Fain, Zanatta-Coutinho et Fonseca, 1996 (Atopomelidae) from Metachirus nudicaudatus (Geoffroy, 1803) (Didelphimorphia: Didelphidae) from Minas Gerais is described. All data on host-parasite associations of sarcoptoids in Brazil are summarized. Totally, 61 sarcoptoid species of 8 families are recorded in Brazil.

  10. Function, Structure, and Evolution of the Major Facilitator Superfamily: The LacY Manifesto

    Directory of Open Access Journals (Sweden)

    M. Gregor Madej

    2014-01-01

    Full Text Available The major facilitator superfamily (MFS is a diverse group of secondary transporters with members found in all kingdoms of life. A paradigm for MFS is the lactose permease (LacY of Escherichia coli, which couples the stoichiometric translocation of a galactopyranoside and an H+ across the cytoplasmic membrane. LacY has been the test bed for the development of many methods applied for the analysis of transport proteins. X-ray structures of an inward-facing conformation and the most recent structure of an almost occluded conformation confirm many conclusions from previous studies. Although structure models are critical, they are insufficient to explain the catalysis of transport. The clues to understanding transport are based on the principles of enzyme kinetics. Secondary transport is a dynamic process—static snapshots of X-ray crystallography describe it only partially. However, without structural information, the underlying chemistry is virtually impossible to conclude. A large body of biochemical/biophysical data derived from systematic studies of site-directed mutants in LacY suggests residues critically involved in the catalysis, and a working model for the symport mechanism that involves alternating access of the binding site is presented. The general concepts derived from the bacterial LacY are examined for their relevance to other MFS transporters.

  11. The first mitochondrial genome for the wasp superfamily Platygastroidea: the egg parasitoid Trissolcus basalis.

    Science.gov (United States)

    Mao, Meng; Valerio, Alejandro; Austin, Andrew D; Dowton, Mark; Johnson, Norman F

    2012-03-01

    The nearly complete mitochondrial (mt) genome of an egg parasitoid, Trissolcus basalis (Wollaston), was sequenced using both 454 and Illumina next-generation sequencing technologies. A portion of the noncoding region remained unsequenced, possibly owing to the presence of repeats. The sequenced portion of the genome is 15,768 bp and has a high A+T content (84.2%), as is typical for hymenopteran mt genomes. A total of 36 of the 37 genes normally present in animal mt genomes were located. The one exception was trnR; a truncated version of this gene is present between trnS(1) and nd5, but it is unclear whether this gene fragment could code for the entire trnR gene. The mt gene arrangement of T. basalis is different from other Proctotrupomorpha mt genomes, with a number of trn genes in different positions. However, no shared derived gene rearrangements were identified in the present study. Bayesian analyses of mt genomes from 29 hymenopteran taxa and seven other orders of holometabolous insects support some uncontroversial evolutionary relationships, but indicate that much higher levels of taxonomic sampling are necessary for the resolution of family and superfamily relationships.

  12. Plum, an immunoglobulin superfamily protein, regulates axon pruning by facilitating TGF-β signaling.

    Science.gov (United States)

    Yu, Xiaomeng M; Gutman, Itai; Mosca, Timothy J; Iram, Tal; Ozkan, Engin; Garcia, K Christopher; Luo, Liqun; Schuldiner, Oren

    2013-05-08

    Axon pruning during development is essential for proper wiring of the mature nervous system, but its regulation remains poorly understood. We have identified an immunoglobulin superfamily (IgSF) transmembrane protein, Plum, that is cell autonomously required for axon pruning of mushroom body (MB) γ neurons and for ectopic synapse refinement at the developing neuromuscular junction in Drosophila. Plum promotes MB γ neuron axon pruning by regulating the expression of Ecdysone Receptor-B1, a key initiator of axon pruning. Genetic analyses indicate that Plum acts to facilitate signaling of Myoglianin, a glial-derived TGF-β, on MB γ neurons upstream of the type-I TGF-β receptor Baboon. Myoglianin, Baboon, and Ecdysone Receptor-B1 are also required for neuromuscular junction ectopic synapse refinement. Our study highlights both IgSF proteins and TGF-β facilitation as key promoters of developmental axon elimination and demonstrates a mechanistic conservation between MB axon pruning during metamorphosis and the refinement of ectopic larval neuromuscular connections.

  13. The Role of TNF Superfamily Member 13 in the Progression of IgA Nephropathy.

    Science.gov (United States)

    Han, Seung Seok; Yang, Seung Hee; Choi, Murim; Kim, Hang-Rae; Kim, Kwangsoo; Lee, Sangmoon; Moon, Kyung Chul; Kim, Joo Young; Lee, Hajeong; Lee, Jung Pyo; Jung, Ji Yong; Kim, Sejoong; Joo, Kwon Wook; Lim, Chun Soo; Kang, Shin-Wook; Kim, Yon Su; Kim, Dong Ki

    2016-11-01

    TNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.

  14. La cultura del consumismo: de la oikos aristotélica al homo oeconomicus de la posmodernidad.

    OpenAIRE

    Vázquez Larrea, Iñaki

    2010-01-01

    El presente ensayo se presenta como un breve recorrido por la Historia del pensamiento Económico. Desde el clásico“homo oeconómicus” aristotélico hasta la génesis del ethos capitalista, que según Max Weber definiría a la Modernidad. Ello nos serviría como punto de partida para reflexionar sobre la naturaleza de la sociedad postindustrial de consumo, y, a su vez, sobre lo que la supuesta crisis del espirítu capitalista weberiano implica en la definición sociológica del “homo oeconómicus” ...

  15. Geological and taphonomic context for the new hominin species Homo naledi from the Dinaledi Chamber, South Africa

    OpenAIRE

    Dirks, Paul, H.G.M; Berger, Lee; Roberts, Eric; Kramers, Jan; Hawks, John; Randolph-Quinney, Patrick; Elliott, Marina; Musiba, Charles; Churchill, Steven, E.; de Ruiter, Darryl, J.; Schmid, Peter; Backwell, Lucinda, R.; Belyanin, Georgy, A.; Boshoff, Pedro; Hunter, Lyndsay, K.

    2015-01-01

    eLife digest Modern humans, or Homo sapiens, are now the only living species in their genus. But as recently as 20,000 years ago there were other species that belonged to the genus Homo. Together with modern humans, these extinct human species, our immediate ancestors and their close relatives are collectively referred to as ‘hominins’. Now, Dirks et al. describe an unusual collection of hominin fossils that were found within the Dinaledi Chamber in the Rising Star cave system in South Africa...

  16. Reconstructing the ups and downs of primate brain evolution: implications for adaptive hypotheses and Homo floresiensis.

    Science.gov (United States)

    Montgomery, Stephen H; Capellini, Isabella; Barton, Robert A; Mundy, Nicholas I

    2010-01-27

    Brain size is a key adaptive trait. It is often assumed that increasing brain size was a general evolutionary trend in primates, yet recent fossil discoveries have documented brain size decreases in some lineages, raising the question of how general a trend there was for brains to increase in mass over evolutionary time. We present the first systematic phylogenetic analysis designed to answer this question. We performed ancestral state reconstructions of three traits (absolute brain mass, absolute body mass, relative brain mass) using 37 extant and 23 extinct primate species and three approaches to ancestral state reconstruction: parsimony, maximum likelihood and Bayesian Markov-chain Monte Carlo. Both absolute and relative brain mass generally increased over evolutionary time, but body mass did not. Nevertheless both absolute and relative brain mass decreased along several branches. Applying these results to the contentious case of Homo floresiensis, we find a number of scenarios under which the proposed evolution of Homo floresiensis' small brain appears to be consistent with patterns observed along other lineages, dependent on body mass and phylogenetic position. Our results confirm that brain expansion began early in primate evolution and show that increases occurred in all major clades. Only in terms of an increase in absolute mass does the human lineage appear particularly striking, with both the rate of proportional change in mass and relative brain size having episodes of greater expansion elsewhere on the primate phylogeny. However, decreases in brain mass also occurred along branches in all major clades, and we conclude that, while selection has acted to enlarge primate brains, in some lineages this trend has been reversed. Further analyses of the phylogenetic position of Homo floresiensis and better body mass estimates are required to confirm the plausibility of the evolution of its small brain mass. We find that for our dataset the Bayesian analysis for

  17. Reconstructing the ups and downs of primate brain evolution: implications for adaptive hypotheses and Homo floresiensis

    Directory of Open Access Journals (Sweden)

    Barton Robert A

    2010-01-01

    Full Text Available Abstract Background Brain size is a key adaptive trait. It is often assumed that increasing brain size was a general evolutionary trend in primates, yet recent fossil discoveries have documented brain size decreases in some lineages, raising the question of how general a trend there was for brains to increase in mass over evolutionary time. We present the first systematic phylogenetic analysis designed to answer this question. Results We performed ancestral state reconstructions of three traits (absolute brain mass, absolute body mass, relative brain mass using 37 extant and 23 extinct primate species and three approaches to ancestral state reconstruction: parsimony, maximum likelihood and Bayesian Markov-chain Monte Carlo. Both absolute and relative brain mass generally increased over evolutionary time, but body mass did not. Nevertheless both absolute and relative brain mass decreased along several branches. Applying these results to the contentious case of Homo floresiensis, we find a number of scenarios under which the proposed evolution of Homo floresiensis' small brain appears to be consistent with patterns observed along other lineages, dependent on body mass and phylogenetic position. Conclusions Our results confirm that brain expansion began early in primate evolution and show that increases occurred in all major clades. Only in terms of an increase in absolute mass does the human lineage appear particularly striking, with both the rate of proportional change in mass and relative brain size having episodes of greater expansion elsewhere on the primate phylogeny. However, decreases in brain mass also occurred along branches in all major clades, and we conclude that, while selection has acted to enlarge primate brains, in some lineages this trend has been reversed. Further analyses of the phylogenetic position of Homo floresiensis and better body mass estimates are required to confirm the plausibility of the evolution of its small brain

  18. Reconstructing the ups and downs of primate brain evolution: implications for adaptive hypotheses and Homo floresiensis

    Science.gov (United States)

    2010-01-01

    Background Brain size is a key adaptive trait. It is often assumed that increasing brain size was a general evolutionary trend in primates, yet recent fossil discoveries have documented brain size decreases in some lineages, raising the question of how general a trend there was for brains to increase in mass over evolutionary time. We present the first systematic phylogenetic analysis designed to answer this question. Results We performed ancestral state reconstructions of three traits (absolute brain mass, absolute body mass, relative brain mass) using 37 extant and 23 extinct primate species and three approaches to ancestral state reconstruction: parsimony, maximum likelihood and Bayesian Markov-chain Monte Carlo. Both absolute and relative brain mass generally increased over evolutionary time, but body mass did not. Nevertheless both absolute and relative brain mass decreased along several branches. Applying these results to the contentious case of Homo floresiensis, we find a number of scenarios under which the proposed evolution of Homo floresiensis' small brain appears to be consistent with patterns observed along other lineages, dependent on body mass and phylogenetic position. Conclusions Our results confirm that brain expansion began early in primate evolution and show that increases occurred in all major clades. Only in terms of an increase in absolute mass does the human lineage appear particularly striking, with both the rate of proportional change in mass and relative brain size having episodes of greater expansion elsewhere on the primate phylogeny. However, decreases in brain mass also occurred along branches in all major clades, and we conclude that, while selection has acted to enlarge primate brains, in some lineages this trend has been reversed. Further analyses of the phylogenetic position of Homo floresiensis and better body mass estimates are required to confirm the plausibility of the evolution of its small brain mass. We find that for our

  19. HOMO VIATOR – O DIMENSIUNE FUNDAMENTALĂ A SPIRITUALITĂŢII OCCIDENTALE

    Directory of Open Access Journals (Sweden)

    Tatiana CIOCOI

    2015-12-01

    Full Text Available Articolul de faţă reflectă modificările fundamentale care s-au produs în mentalitatea occidentală contemporană prin intermediul conceptului de călător (homo viator. Noţiunea de călător este tratată în sens culturologic larg drept  desco­peritor de lumi necunoscute, explorator, navigator sau aventurier al oricărui tip de cunoaştere, care reprezintă trăsătura fundamentală a omului occidental. Prototipul absolut al acestui model cultural îl reprezintă Ulise, eroul din Odiseea lui Homer. Conceptul de „călătorie” oferă, astfel, o viziune transversală asupra evoluţiei literaturii occidentale, al cărei centru iradiant – tensiunea cunoaşterii – a problematizat cele mai variate forme de călătorie şi de călător. Istoria romanului occidental este urmărit dea lungul secolelor şi a epocilor literare pentru a observa cum s-a modificat percepţia călătoriei, iar odată cu ea, şi spiritualitatea occidentală. Viziunea contemporană asupra călătoriei este analizată în baza romanului lui Michel Houellebecq „Harta şi teritoriul” (2010. HOMO VIATOR – A FUNDAMENTAL DIMENSION  OF WESTERN SPIRITUALITYThe article reflects the changes produced in the western contemporary mentality through the concept of the traveler (homo viator. The notion of traveler is approached in wide cultural meaning as a discoverer of unknown worlds, explorer, navigator or adventurer of every type of knowing, that represents the fundamental feature of the occidental man. The absolute prototype of this cultural model is represented by Ulysses, the hero of Homer’s Odyssey. The concept of “travel” offers thus a transverse vision upon the evolution of the occidental literature whose irradiant centre – the tension of knowing – discussed the problems of the most varied forms of travel and traveler. The history of the western novel is followed over centuries and literary epochs in order to observe which way the perception of travel

  20. The Flores speleothem carbon isotope record: vegetation, volcanism and the demise of Homo floresiensis

    Science.gov (United States)

    Scroxton, N.; Gagan, M. K.; Ayliffe, L. K.; Hantoro, W. S.; Hellstrom, J. C.; Cheng, H.; Edwards, R. L.; Zhao, J. X.; Suwargadi, B. W.; Scott-Gagan, H.; Cowley, J. A.; Rifai, H.

    2015-12-01

    The last surviving non-human member of the Homo genus: Homo floresiensis, disappeared from the stratigraphic record in Liang Bua cave, Flores, Indonesia, between 17 and 10 kyr BP (Roberts et al. 2009, J. Hum. Evol.). The cause of the disappearance (e.g. climate change, volcanic catastrophe or human competition) has not been established. Here, we present a new 92,000-year long speleothem δ13C record for Liang Luar cave, 800m South of Liang Bua. Our record acts as a proxy for local environmental and vegetation health throughout H. floresiensis' occupation of the area. The Liang Luar speleothem δ13C record is primarily a record of vegetation productivity and soil respiration rates, highlighting local ecological responses to changing regional and global climate forcings such as temperature, atmospheric pCO2 and precipitation amount. Changes in speleothem δ13C can largely be considered an environmental response to climate change. Events that caused significant harm to the local environment and H. floresiensis are likely to be outside the natural range of variability: being quick enough or extreme enough that adaptation to new conditions is not possible. We identify disturbances to the vegetation system using two indicators in the speleothem record. 1) Abrupt positive δ13C excursions which indicate periods of reduced vegetative activity. 2) A loss of correlation between the δ13C and δ18O records, indicating that precipitation is no longer a dominant control on vegetation productivity. The largest (8‰) and longest (7 kyr) abrupt positive excursion, the 68 kyr event, sees positive speleothem δ13C values, due to increased bedrock contribution and/or C4 vegetation at this time. Crucially a H. floresiensis occupation interval dates to this period. The largest abrupt deterioration in vegetation (positive δ13C excursion) between 17 and 10 kyr BP is a 1 in 5kyr occurrence - An event of a magnitude that was likely encountered and survived by H. floresiensis multiple

  1. Phylogenetic position of the family Orientocreadiidae within the superfamily Plagiorchioidea (Trematoda) based on partial 28S rDNA sequence.

    Science.gov (United States)

    Sokolov, S G; Shchenkov, S V

    2017-08-22

    Trematodes of the family Orientocreadiidae are mostly parasites of freshwater fishes. Here, the phylogenetic position of this family is inferred based on the partial 28S rDNA sequence from a representative of the genus Orientocreadium s. str.-О. pseudobagri Yamaguti, 1934. Sequences were analysed by maximum likelihood and Bayesian inference algorithms. Both approaches placed the Orientocreadiidae within a clade corresponding to the superfamily Plagiorchioidea and supported the family Leptophallidae as a sister taxon.

  2. Decontestualizzazione del sintomo e biografia: il malessere dell'Homo narrativus - Narrarsi nella precarietà

    Directory of Open Access Journals (Sweden)

    Gloria Bardi

    2011-07-01

    Full Text Available Partendo da alcune considerazioni antropologiche, che si riferiscono all'uomo come "narrativus" o "narrans" che dir si voglia, identificherei come condizione di benessere psicofisico il bisogno di vivere narrativamente, il bisogno cioè di biografia. Procederei poi a identificare come la medicina sia oggi spesso messa sotto accusa perché ha smarrito questa dimensione nell'eccesso di tecnologia e specializzazione. così si è creata un'estraneità tra medicina e salute in senso ampio. Procederei poi a rilevare come la posizione dell'uomo oggi venga resa frammentaria anche a livello lavorativo, impedendo il consolidarsi di biografie lineari- la precarietà sul lavoro costituirebbe come ulteriore attacco all'homo narrativus. In conclusione evidenzierei come recupero di salute "antropologica" implichi un modificarsi e della medicina e del lavoro.

  3. The mystery of the seven spheres how homo sapiens will conquer space

    CERN Document Server

    Bignami, Giovanni F

    2015-01-01

    In this book, Giovanni Bignami, the outstanding Italian scientist and astronomer, takes the reader on a journey through the “seven spheres”, from our own planet to neighboring stars. The author offers a gripping account of the evolution of Homo Sapiens to the stage where our species is developing capabilities, in the form of new energy propulsion systems, that will enable us to conquer space. The reader will learn how we first expanded our activities to reach beyond our planet, to the Moon, and how nuclear energy, nuclear fusion, and matter–antimatter annihilation will enable us to extend our exploration. After Mars and Jupiter we shall finally reach the nearest stars, which we now know are surrounded by numerous planets, some of which are bound to be habitable. The book includes enticing descriptions of such newly discovered planets and also brings alive key historical characters in our story, such as Jules Verne and Werner von Braun.

  4. Solution-based growth and structural characterization of homo- and heterobranched semiconductor nanowires.

    Science.gov (United States)

    Dong, Angang; Tang, Rui; Buhro, William E

    2007-10-10

    Colloidal homobranched ZnSe nanowires (NWs) and heterobranched CdSe-ZnSe NWs are successfully synthesized by combining a sequential seeding strategy with the solution-liquid-solid (SLS) growth process. We have developed an efficient approach to deposit secondary bismuth nanoparticles onto the NW backbone to induce the subsequent SLS branch growth. The density, length, and diameter of branches are rationally controlled by varying reaction conditions. Structural characterization reveals that crystalline branches grow epitaxially from the backbone in both homo- and heterobranched NWs. Two different branching structures are observed in the CdSe-ZnSe heterobranched NWs, owing to the phase admixture, i.e., cubic and hexagonal crystal structures, coexisting in the CdSe NW backbones. These branched NWs with well-designed architectures are expected to have potential as three-dimensional building blocks in the fabrication of nanoscale electronics and photonics.

  5. Arqueología del lenguaje en el proceso evolutivo del Género Homo

    Directory of Open Access Journals (Sweden)

    Ángel Rivera Arrizabalaga

    1998-01-01

    Full Text Available Las siguientes páginas prestan atención al papel desempeñado por el lenguaje en el proceso evolutivo del Género Homo. Las diferentes relaciones neurológicas que se establecen en el cerebro según los diferentes niveles de lenguaje y las posibilidades anatómicas de su empleo en cada tipo tiumano. Todo ello contrastado con los datos que aporta el registro arqueológico, cruzando informaciones procedentes de la neurología, la psicología y la arqueología.Thíe following pages deal witfi the role played by ttie lenguage in ttie evolutionary fiuman emerging process. Ttie different neurologic relationships developed among the mind and the human anathomic changes. Everything is compared to Ítems of archaeological record, adding some neurological, psicological and archaeological information.

  6. BIOGRAPHY OR A DECLARATION OF PHILOSOPHICAL AMBITION: HOW TO READ ECCE HOMO BY NIETZSCHE

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    Lúcia Schneider Hardt

    2015-06-01

    Full Text Available This article discusses the book Ecce homo, by Nietzsche, defending that the text is an interpretation of the philosopher himself on her own thought, not to give the book a sacred tone, nor to stress his biography, but affirming a dissonant thought that indicates his philosophical ambition. With no constraints, Nietzsche presents his conflicts, passions, deceptions, announcing a tragic dimension of life that is not guided by pessimism, but by happiness of living intensely, understanding suffering as one of the facets of life. His philosophy derives from a life demand, transfigured by an experience that promotes self cultivation and the possibility of “becoming what one really is” through the “applying” of one’s own genealogic method.

  7. De novo design of protein homo-oligomers with modular hydrogen bond network-mediated specificity

    Science.gov (United States)

    Boyken, Scott E.; Chen, Zibo; Groves, Benjamin; Langan, Robert A.; Oberdorfer, Gustav; Ford, Alex; Gilmore, Jason; Xu, Chunfu; DiMaio, Frank; Pereira, Jose Henrique; Sankaran, Banumathi; Seelig, Georg; Zwart, Peter H.; Baker, David

    2017-01-01

    In nature, structural specificity in DNA and proteins is encoded quite differently: in DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen bond networks. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen bond networks with atomic accuracy is a milestone for protein design and enables the programming of protein interaction specificity for a broad range of synthetic biology applications. PMID:27151862

  8. FOSSIL REPTILES FROM THE PLEISTOCENE HOMO-BEARING LOCALITY OF BUIA (ERITREA, NORTHERN DANAKIL DEPRESSION

    Directory of Open Access Journals (Sweden)

    MASSIMO DELFINO

    2004-12-01

    Full Text Available The early to early-Middle Pleistocene fossil assemblage form the Buia area (Northern Danakil Depression, Eritrea hosts, along with Homo and several other large mammal taxa, the following reptiles: Nile Crocodile, Crocodylus niloticus, Serrated Hinged Terrapin, Pelusios cf. P. sinuatus, Nile Monitor, Varanus niloticus and African Rock Python, Python gr. sebae. All the identified taxa belong to living species. At present, these taxa do not occur in the Northern Danakil depression since it is an arid area. P. sinuatus is not a member of the Eritrean herpetofauna. Although the marked preponderance of the crocodile remains is probably connected to the taphonomy of the sites and the collecting methods used, the ecological value of the reptile fauna corroborates that of the mammals, in indicating a lacustrine or fluvio-deltaic palaeoenvironment and a tropical/subtropical or even sub-Sahelic climate. The Buia remains represent the first reported Eritrean palaeoherpetofauna. 

  9. HOMO ACADEMICUS: CRISE IDENTITÁRIA E PRÁTICA CIENTÍFICA

    Directory of Open Access Journals (Sweden)

    Dina Maria Martins Ferreira

    2012-12-01

    Full Text Available Este estudo visa a argumentar sobre o construto identitário do homo academicus, ou seja, o intelectual que se estabelece no campo universitário, compartilha habitus e atitude dóxica (Bourdieu, 2007; 2009; 2011. No que tange às etiquetas identificadoras,  Bauman  (2007 categoriza o intelectual pela prática científica, situada por relações históricas. Na convergência entre espaço, valores e performativos, constrói-se uma estrada da qual emergem a  prática logocêntrica que se transforma em dogma a partir da permanência de práticas dóxicas do século das Luzes. 

  10. Protamines and spermatogenesis in Drosophila and Homo sapiens : A comparative analysis.

    Science.gov (United States)

    Kanippayoor, Rachelle L; Alpern, Joshua H M; Moehring, Amanda J

    2013-04-01

    The production of mature and motile sperm is a detailed process that utilizes many molecular players to ensure the faithful execution of spermatogenesis. In most species that have been examined, spermatogenesis begins with a single cell that undergoes dramatic transformation, culminating with the hypercompaction of DNA into the sperm head by replacing histones with protamines. Precise execution of the stages of spermatogenesis results in the production of motile sperm. While comparative analyses have been used to identify similarities and differences in spermatogenesis between species, the focus has primarily been on vertebrate spermatogenesis, particularly mammals. To understand the evolutionary basis of spermatogenetic variation, however, a more comprehensive comparison is needed. In this review, we examine spermatogenesis and the final packaging of DNA into the sperm head in the insect Drosophila melanogaster and compare it to spermatogenesis in Homo sapiens.

  11. Earliest evidence for the structure of Homo sapiens populations in Africa

    Science.gov (United States)

    Scerri, Eleanor M. L.; Drake, Nick A.; Jennings, Richard; Groucutt, Huw S.

    2014-10-01

    Understanding the structure and variation of Homo sapiens populations in Africa is critical for interpreting multiproxy evidence of their subsequent dispersals into Eurasia. However, there is no consensus on early H. sapiens demographic structure, or its effects on intra-African dispersals. Here, we show how a patchwork of ecological corridors and bottlenecks triggered a successive budding of populations across the Sahara. Using a temporally and spatially explicit palaeoenvironmental model, we found that the Sahara was not uniformly ameliorated between ∼130 and 75 thousand years ago (ka), as has been stated. Model integration with multivariate analyses of corresponding stone tools then revealed several spatially defined technological clusters which correlated with distinct palaeobiomes. Similarities between technological clusters were such that they decreased with distance except where connected by palaeohydrological networks. These results indicate that populations at the Eurasian gateway were strongly structured, which has implications for refining the demographic parameters of dispersals out of Africa.

  12. Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

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    Matthias C. Letzel

    2017-01-01

    Full Text Available Diastereoselective radical coupling was achieved with chiral auxiliaries. The radicals were generated by anodic decarboxylation of five malonic acid derivatives. These were prepared from benzyl malonates and four menthol auxiliaries. Coelectrolyses with 3,3-dimethylbutanoic acid in methanol at platinum electrodes in an undivided cell afforded hetero-coupling products in 22–69% yield with a diastereoselectivity ranging from 5 to 65% de. Electrolyses without a coacid led to diastereomeric homo-coupling products in 21–50% yield with ratios of diastereomers being 1.17:2.00:0.81 to 7.03:2.00. The stereochemistry of the new stereogenic centers was confirmed by X-ray structure analysis and 13C NMR data.

  13. Climate indexes of phytoliths from Homo erectus' cave deposits in Nanjing

    Institute of Scientific and Technical Information of China (English)

    WANG Weiming; LIU Jinling; ZHOU Xiaodan

    2003-01-01

    A study on phytoliths and their climate indexes is carried out from Homo erectus' cave deposits in Hulu Cave, Nanjing. Evidence shows that phytolith assemblages of the cave deposits are dominated by the cold resistant types with a lower warm index, reflecting an overall cold inclined climate. This possibly connects the cave deposits with glacial climate to a great extent, which is in accordance with the northern fauna revealed by fossil mammals and temperate climate indicated by pollen assemblages. According to the distributional state of the phytoliths and their climate indexes on 4 profiles in the cave, it is revealed that profiles Ⅰ and Ⅱ display certain cold/warm, and dry/wet fluctuations; profile Ⅲ shows a humid and cold condition with the highest humility in the cave deposits; while profile Ⅳ indicates a possible quick accumulating process because of its stable climate indexes except for its bottom and top.

  14. Homo-epitaxial diamond film growth on ion implanted diamond substrates

    Energy Technology Data Exchange (ETDEWEB)

    Weiser, P.S.; Prawer, S.; Nugent, K.W.; Bettiol, A.A.; Kostidis, L.I.; Jamieson, D.N. [Melbourne Univ., Parkville, VIC (Australia). School of Physics

    1996-12-31

    The nucleation of CVD diamond is a complicated process, governed by many interrelated parameters. In the present work we attempt to elucidate the effect of strain on the growth of a homo-epitaxial CVD diamond. We have employed laterally confined high dose (MeV) Helium ion implantation to produce surface swelling of the substrate. The strain is enhanced by the lateral confinement of the implanted region to squares of 100 x 100 {mu}m{sup 2}. After ion implantation, micro-Raman spectroscopy was employed to map the surface strain. The substrates were then inserted into a CVD reactor and a CVD diamond film was grown upon them. Since the strained regions were laterally confined, it was then possible to monitor the effect of strain on diamond nucleation. The substrates were also analysed using Rutherford Backscattering Spectroscopy (RBS), Proton induced X-ray Emission (PIXE) and Ion Beam induced Luminescence (IBIL). 7 refs., 5 figs.

  15. Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia

    DEFF Research Database (Denmark)

    Sutikna, Thomas; Tocheri, Matthew W.; Morwood, Michael J.

    2016-01-01

    Homo floresiensis, a primitive hominin species discovered in Late Pleistocene sediments at Liang Bua (Flores, Indonesia), has generated wide interest and scientific debate. A major reason this taxon is controversial is because the H. floresiensis-bearing deposits, which include associated stone...... and the deposits containing them are dated to between about 100 and 60 kyr ago, whereas stone artefacts attributable to this species range from about 190 to 50 kyr in age. Whether H. floresiensis survived after 50 kyr ago--potentially encountering modern humans on Flores or other hominins dispersing through...... artefacts and remains of other extinct endemic fauna, were dated to between about 95 and 12 thousand calendar years (kyr) ago. These ages suggested that H. floresiensis survived until long after modern humans reached Australia by ~50 kyr ago. Here we report new stratigraphic and chronological evidence from...

  16. Molecular cloning, bioinformatics analysis and functional characterization of HWTX-XI toxin superfamily from the spider Ornithoctonus huwena.

    Science.gov (United States)

    Jiang, Liping; Deng, Meichun; Duan, Zhigui; Tang, Xing; Liang, Songping

    2014-04-01

    Spider venom contains a very valuable repertoire of natural resources to discover novel components for molecular diversity analyses and therapeutic applications. In this study, HWTX-XI toxins from the spider venom glands of Ornithoctonus huwena which are Kunitz-type toxins (KTTs) and were directly cloned, analyzed and functionally characterized. To date, the HWTX-XI superfamily consists of 38 members deduced from 121 high-quality expressed sequence tags, which is the largest spider KTT superfamily with significant molecular diversity mainly resulted from cDNA tandem repeats as well as focal hypermutation. Among them, HW11c40 and HW11c50 may be intermediate variants between native Kunitz toxins and sub-Kunitz toxins based on evolutionary analyses. In order to elucidate their biological activities, recombinant HW11c4, HW11c24, HW11c27 and HW11c39 were successfully expressed, further purified and functionally characterized. Both HW11c4 and HW11c27 display inhibitory activities against trypsin, chymotrypsin and kallikrein. Moreover, HW11c4 is also an inhibitor relatively specific for Kv1.1 channels. HW11c24 and HW11c39 are found to be inactive on chymotrysin, trypsin, kallikrein, thrombin and ion channels. These findings provide molecular evidence for toxin diversification of the HWTX-XI superfamily and useful molecular templates of serine protease inhibitors and ion channel blockers for the development of potentially clinical applications.

  17. The Association between Gene-Environment Interactions and Diseases Involving the Human GST Superfamily with SNP Variants

    Directory of Open Access Journals (Sweden)

    Antoinesha L. Hollman

    2016-03-01

    Full Text Available Exposure to environmental hazards has been associated with diseases in humans. The identification of single nucleotide polymorphisms (SNPs in human populations exposed to different environmental hazards, is vital for detecting the genetic risks of some important human diseases. Several studies in this field have been conducted on glutathione S-transferases (GSTs, a phase II detoxification superfamily, to investigate its role in the occurrence of diseases. Human GSTs consist of cytosolic and microsomal superfamilies that are further divided into subfamilies. Based on scientific search engines and a review of the literature, we have found a large amount of published articles on human GST super- and subfamilies that have greatly assisted in our efforts to examine their role in health and disease. Because of its polymorphic variations in relation to environmental hazards such as air pollutants, cigarette smoke, pesticides, heavy metals, carcinogens, pharmaceutical drugs, and xenobiotics, GST is considered as a significant biomarker. This review examines the studies on gene-environment interactions related to various diseases with respect to single nucleotide polymorphisms (SNPs found in the GST superfamily. Overall, it can be concluded that interactions between GST genes and environmental factors play an important role in human diseases.

  18. The Structure of a Sugar Transporter of the Glucose EIIC Superfamily Provides Insight into the Elevator Mechanism of Membrane Transport.

    Science.gov (United States)

    McCoy, Jason G; Ren, Zhenning; Stanevich, Vitali; Lee, Jumin; Mitra, Sharmistha; Levin, Elena J; Poget, Sebastien; Quick, Matthias; Im, Wonpil; Zhou, Ming

    2016-06-07

    The phosphoenolpyruvate:carbohydrate phosphotransferase systems are found in bacteria, where they play central roles in sugar uptake and regulation of cellular uptake processes. Little is known about how the membrane-embedded components (EIICs) selectively mediate the passage of carbohydrates across the membrane. Here we report the functional characterization and 2.55-Å resolution structure of a maltose transporter, bcMalT, belonging to the glucose superfamily of EIIC transporters. bcMalT crystallized in an outward-facing occluded conformation, in contrast to the structure of another glucose superfamily EIIC, bcChbC, which crystallized in an inward-facing occluded conformation. The structures differ in the position of a structurally conserved substrate-binding domain that is suggested to play a central role in sugar transport. In addition, molecular dynamics simulations suggest a potential pathway for substrate entry from the periplasm into the bcMalT substrate-binding site. These results provide a mechanistic framework for understanding substrate recognition and translocation for the glucose superfamily EIIC transporters.

  19. Evolutionary analysis of the ENTH/ANTH/VHS protein superfamily reveals a coevolution between membrane trafficking and metabolism.

    Science.gov (United States)

    De Craene, Johan-Owen; Ripp, Raymond; Lecompte, Odile; Thompson, Julie D; Poch, Olivier; Friant, Sylvie

    2012-07-02

    Membrane trafficking involves the complex regulation of proteins and lipids intracellular localization and is required for metabolic uptake, cell growth and development. Different trafficking pathways passing through the endosomes are coordinated by the ENTH/ANTH/VHS adaptor protein superfamily. The endosomes are crucial for eukaryotes since the acquisition of the endomembrane system was a central process in eukaryogenesis. Our in silico analysis of this ENTH/ANTH/VHS superfamily, consisting of proteins gathered from 84 complete genomes representative of the different eukaryotic taxa, revealed that genomic distribution of this superfamily allows to discriminate Fungi and Metazoa from Plantae and Protists. Next, in a four way genome wide comparison, we showed that this discriminative feature is observed not only for other membrane trafficking effectors, but also for proteins involved in metabolism and in cytokinesis, suggesting that metabolism, cytokinesis and intracellular trafficking pathways co-evolved. Moreover, some of the proteins identified were implicated in multiple functions, in either trafficking and metabolism or trafficking and cytokinesis, suggesting that membrane trafficking is central to this co-evolution process. Our study suggests that membrane trafficking and compartmentalization were not only key features for the emergence of eukaryotic cells but also drove the separation of the eukaryotes in the different taxa.

  20. Evolutionary analysis of the ENTH/ANTH/VHS protein superfamily reveals a coevolution between membrane trafficking and metabolism

    Directory of Open Access Journals (Sweden)

    De Craene Johan-Owen

    2012-07-01

    Full Text Available Abstract Background Membrane trafficking involves the complex regulation of proteins and lipids intracellular localization and is required for metabolic uptake, cell growth and development. Different trafficking pathways passing through the endosomes are coordinated by the ENTH/ANTH/VHS adaptor protein superfamily. The endosomes are crucial for eukaryotes since the acquisition of the endomembrane system was a central process in eukaryogenesis. Results Our in silico analysis of this ENTH/ANTH/VHS superfamily, consisting of proteins gathered from 84 complete genomes representative of the different eukaryotic taxa, revealed that genomic distribution of this superfamily allows to discriminate Fungi and Metazoa from Plantae and Protists. Next, in a four way genome wide comparison, we showed that this discriminative feature is observed not only for other membrane trafficking effectors, but also for proteins involved in metabolism and in cytokinesis, suggesting that metabolism, cytokinesis and intracellular trafficking pathways co-evolved. Moreover, some of the proteins identified were implicated in multiple functions, in either trafficking and metabolism or trafficking and cytokinesis, suggesting that membrane trafficking is central to this co-evolution process. Conclusions Our study suggests that membrane trafficking and compartmentalization were not only key features for the emergence of eukaryotic cells but also drove the separation of the eukaryotes in the different taxa.

  1. Microbial synthesis of functional homo-, random, and block polyhydroxyalkanoates by β-oxidation deleted Pseudomonas entomophila.

    Science.gov (United States)

    Li, Shijun; Cai, Longwei; Wu, Linping; Zeng, Guodong; Chen, Jinchun; Wu, Qiong; Chen, Guo-Qiang

    2014-06-01

    Functional polyhydroxyalkanoates (PHAs) allow chemical modifications to widen PHA diversity, promising to increase values of these biodegradable and biocompatible polyesters. Among functional PHAs, unsaturated PHA site chains can be easily grafted to add chemical groups, and to cross-link with other PHA polymer chains. However, it has been very difficult to obtain structurally controllable functional homo-, random, or block PHA. For the first time, a β-oxidation deleted Pseudomonas entomophila was used to successfully synthesize random copolymers of 3-hydroxydodecanoate (3HDD) and 3-hydroxy-9-decenoate (3H9D). Compositions of the random copolymers P(3HDD-co-3H9D) can be adjusted by ratios of dodecanoic acid (DDA) to 9-decenol (9DEO) fed to the culture of P. entomophila. Homopolymer P3H9D was formed when only 9DEO was added to the culture. Diblock copolymers of P3HDD-b-P3H9D were produced by feeding DDA as the first precursor to form a P3HDD block followed by adding 9DEO as the second precursor to form a second P3H9D block. It was demonstrated that random copolymers P(3HDD-co-3H9D) could be crossed-linked under UV-radiation due to the presence of the unsaturated bonds. Thermal and mechanical characterizations of the above homo-, random, and diblock PHA polymers were conducted. It was found that the diblock polymer P3HDD-b-P3H9D increased at least 2-fold on Young's modulus compared with its random copolymers consisting of similar 3HDD/3H9D ratios. This study demonstrates that PHA functionality could be controlled to meet various requirements.

  2. The Sambungmacan 3 Homo erectus calvaria: a comparative morphometric and morphological analysis.

    Science.gov (United States)

    Delson, E; Harvati, K; Reddy, D; Marcus, L F; Mowbray, K; Sawyer, G J; Jacob, T; Márquez, S

    2001-04-01

    The Sambungmacan (Sm) 3 calvaria, discovered on Java in 1977, was illegally removed from Indonesia in 1998 and appeared in New York City in early 1999 at the Maxilla & Mandible, Ltd. natural history shop. Here we undertake an analysis of its phylogenetic and systematic position using geometric morphometrics and comparative morphology. The coordinates of points in the sagittal plane from glabella to opisthion were resampled to yield "lines" of 50 semi-landmarks. Coordinates of glabella, bregma, lambda, inion, and opisthion were also collected and analyzed separately. Casts of Homo erectus fossils from Indonesia, China, and Kenya and of "archaic H. sapiens" from Kabwe and Petralona, as well as 10 modern human crania, were used as the primary comparative sample. The modern humans were well separated from the fossils in a graphical superimposition of Procrustes-aligned semi-landmarks as well as in principal component and canonical discriminant analyses. In all of these, Sm 3 falls intermediate between the fossil and modern groups. Morphological comparisons of Sm 3 with a selection of Homo erectus fossils revealed its greatest similarity to specimens from Ngandong and the Sm 1 calvaria. Compared to all other H. erectus, Sm 3 was distinctive in its more vertical supratoral plane, less anteriorly projecting glabella and less sharply angled occiput. In these features it was somewhat similar to modern humans. It is not yet possible to determine if this similarity implies an evolutionary relationship or (more likely) individual or local populational variation. Several features of Sm 3 (small size, gracile supraorbital torus and lack of angular torus, and position in principal component analysis) suggest that it was a female. The use of geometric morphometrics provides a means to statistically test the shapes of such fossils in a manner not easily duplicated by other methods. The intermediate position of Sm 3 between fossil and modern samples in several different subanalyses

  3. Photodetachment of a Homo-Nuclear Linear Tetra-Atomic Negative Molecular Ion

    Institute of Scientific and Technical Information of China (English)

    A. Rahman; Iftikhar Ahmad; A. Afaq; H. J. Zhao

    2012-01-01

    The photodetachment of a homo-nuclear linear tetra-atomic negative molecular ion is studied theoretically for an arbitrary laser polarization.An expression for the total cross section is obtained by using an extended version of the two center model,where each center acts as a source of coherent photodetached-electron waves.Strong oscillations on observation plane,placed at a large distance from the ion,are observed.The amplitude of these oscillations is maximum when the laser polarization is parallel to the molecular axis.Furthermore,the amplitude decreases as the angle between the laser polarization and molecular axis increases and consequently vanishes when they are perpendicular to each other.It is also found that if the distance between the adjacent centers is very small or very large,then the ampplitude of oscillations is negligibly small.%The photodetachment of a homo-nuclear linear tetra-atomic negative molecular ion is studied theoretically for an arbitrary laser polarization. An expression for the total cross section is obtained by using an extended version of the two center model, where each center acts as a source of coherent photodetached-electron waves. Strong oscillations on observation plane, placed at a large distance from the ion, are observed. The amplitude of these oscillations is maximum when the laser polarization is parallel to the molecular axis. Furthermore, the amplitude decreases as the angle between the laser polarization and molecular axis increases and consequently vanishes when they are perpendicular to each other. It is also found that if the distance between the adjacent centers is very small or very large, then the amplitude of oscillations is negligibly small.

  4. Nonlinear Socio-Ecological Dynamics and First Principles ofCollective Choice Behavior of ``Homo Socialis"

    Science.gov (United States)

    Sonis, M.

    Socio-ecological dynamics emerged from the field of Mathematical SocialSciences and opened up avenues for re-examination of classical problems of collective behavior in Social and Spatial sciences. The ``engine" of this collective behavior is the subjective mental evaluation of level of utilities in the future, presenting sets of composite socio-economic-temporal-locational advantages. These dynamics present new laws of collective multi-population behavior which are the meso-level counterparts of the utility optimization individual behavior. The central core of the socio-ecological choice dynamics includes the following first principle of the collective choice behavior of ``Homo Socialis" based on the existence of ``collective consciousness": the choice behavior of ``Homo Socialis" is a collective meso-level choice behavior such that the relative changes in choice frequencies depend on the distribution of innovation alternatives between adopters of innovations. The mathematical basis of the Socio-Ecological Dynamics includes two complementary analytical approaches both based on the use of computer modeling as a theoretical and simulation tool. First approach is the ``continuous approach" --- the systems of ordinary and partial differential equations reflecting the continuous time Volterra ecological formalism in a form of antagonistic and/or cooperative collective hyper-games between different sub-sets of choice alternatives. Second approach is the ``discrete approach" --- systems of difference equations presenting a new branch of the non-linear discrete dynamics --- the Discrete Relative m-population/n-innovations Socio-Spatial Dynamics (Dendrinos and Sonis, 1990). The generalization of the Volterra formalism leads further to the meso-level variational principle of collective choice behavior determining the balance between the resulting cumulative social spatio-temporal interactions among the population of adopters susceptible to the choice alternatives and the

  5. Targeting Bax interaction sites reveals that only homo-oligomerization sites are essential for its activation

    Science.gov (United States)

    Peng, R; Tong, J-S; Li, H; Yue, B; Zou, F; Yu, J; Zhang, L

    2013-01-01

    Bax is a proapoptotic Bcl-2 family member that has a central role in the initiation of mitochondria-dependent apoptosis. However, the mechanism of Bax activation during apoptosis remains unsettled. It is believed that the activation of Bax is mediated by either dissociation from prosurvival Bcl-2 family members, or direct association with BH3-only members. Several interaction sites on Bax that mediate its interactions with other Bcl-2 family members, as well as its proapoptotic activity, have been identified in previous studies by other groups. To rigorously investigate the functional role of these interaction sites, we knocked in their respective mutants using HCT116 colon cancer cells, in which apoptosis induced by several stimuli is strictly Bax-dependent. Bax-mediated apoptosis was intact upon knock-in (KI) of K21E and D33A, which were shown to block the interaction of Bax with BH3-only activators. Apoptosis was partially reduced by KI of D68R, which impairs the interaction of Bax with prosurvival members, and S184V, a constitutively mitochondria-targeting mutant. In contrast, apoptosis was largely suppressed by KI of L70A/D71A, which blocks homo-oligomerization of Bax and its binding to prosurvival Bcl-2 family proteins. Collectively, our results suggest that the activation of endogenous Bax in HCT116 cells is dependent on its homo-oligomerization sites, but not those previously shown to interact with BH3-only activators or prosurvival proteins only. We therefore postulate that critical interaction sites yet to be identified, or mechanisms other than protein-protein interactions, need to be pursued to delineate the mechanism of Bax activation during apoptosis. PMID:23392123

  6. Cranial vault thickness in primates: Homo erectus does not have uniquely thick vault bones.

    Science.gov (United States)

    Copes, Lynn E; Kimbel, William H

    2016-01-01

    Extremely thick cranial vaults have been noted as a diagnostic characteristic of Homo erectus since the first fossil of the species was identified, but relatively little work has been done on elucidating its etiology or variation across fossils, living humans, or extant non-human primates. Cranial vault thickness (CVT) is not a monolithic trait, and the responsiveness of its layers to environmental stimuli is unknown. We obtained measurements of cranial vault thickness in fossil hominins from the literature and supplemented those data with additional measurements taken on African fossil specimens. Total CVT and the thickness of the cortical and diploë layers individually were compared to measures of CVT in extant species measured from more than 500 CT scans of human and non-human primates. Frontal and parietal CVT in fossil primates was compared to a regression of CVT on cranial capacity calculated for extant species. Even after controlling for cranial capacity, African and Asian H. erectus do not have uniquely high frontal or parietal thickness residuals, either among hominins or extant primates. Extant primates with residual CVT thickness similar to or exceeding H. erectus (depending on the sex and bone analyzed) include Nycticebus coucang, Perodicticus potto, Alouatta caraya, Lophocebus albigena, Galago alleni, Mandrillus sphinx, and Propithecus diadema. However, the especially thick vaults of extant non-human primates that overlap with H. erectus values are composed primarily of cortical bone, while H. erectus and other hominins have diploë-dominated vault bones. Thus, the combination of thick vaults comprised of a thickened diploë layer may be a reliable autapomorphy for members of the genus Homo.

  7. GEOLOGY OF THE HOMO-BEARING PLEISTOCENE DANDIERO BASIN (BUIA REGION, ERITREAN DANAKIL DEPRESSION

    Directory of Open Access Journals (Sweden)

    ERNESTO ABBATE

    2004-12-01

    Full Text Available This paper deals with the geological context of the northernmost site in the East Africa Rift system which has yielded Homo erectus-like remains. They are dated ca. 1 Ma and have been found in the deltaic deposits of the Alat Formation belonging to the Dandiero group. This newly defined group crops out extensively in an elongated belt from the Gulf of Zula to the North to the Garsat area to the south. In the Buia-Dandiero area it ranges in age from the Early to the Middle Pleistocene, and incorporates six formations, from bottom up: the fluvial Bukra Sand and Gravel, the deltaic and lacustrine Alat Formation, fluvial Wara Sand and Gravel, the lacustrine Goreya Formation, the fluvio-deltaic Aro Sand and alluvial Addai Fanglomerate. This succession is bounded by two major unconformities, which separate it from the Neoproterozoic basement and from the overlaying Boulder Beds fanglomerate, and has been designated the Maebele Synthem. The latter is the result of two lacustrine transgression and regressions evidenced by two depositional sequences. The unconformities bounding the Maebele Synthem are related to the tectonic history of the basin fill and its substrate. The development of the two sequences was, instead, mainly controlled by lake level fluctuations and, hence, by climatic variations connected with the weakening and strengthening of the monsoons in the northwestern Indian ocean. The environment where the Buia Homo lived was a savannah with some scattered water pools. This environment probably extended farther north along the western coastal plain of the Red Sea, and was a preferential pathway for the dispersal of the hominids from East Africa toward Eurasia. 

  8. MAGNETOSTRATIGRAPHY OF THE HOMO-BEARING PLEISTOCENE DANDIERO BASIN (DANAKIL DEPRESSION, ERITREA

    Directory of Open Access Journals (Sweden)

    ANDREA ALBIANELLI

    2004-12-01

    Full Text Available Four magnetozones have been found in the 530 m thick profile of the Dandiero Group. The lower unit, the Bukra Sand and Gravel, extends in the R1 reversed magnetozone from 150 m below the tephra level which was used as the reference marker between the sampled sections. The normal magnetozone N1 is almost completely covered by the lacustrine and deltaic sediments of the Alat Formation, while the following reversed magnetozone contains both the Wara Sand and Gravel and the lacustrine Goreya Fm. The N2 polarity zone is completely occupied by the Aro Sand. This polarity sequence has been calibrated to the geomagnetic time scale using the Early to Middle Pleistocene age of the associated vertebrate fauna and fission-track dating. The four magnetozones were thus regarded as representing the chrons by which the Pleistocene is correlated with magnetochronology. Their three reversal boundaries provided the dates of 1.07, 0.99 and 0.78 Ma, allowing to determine average sedimentation rates close to 1 m/ky. Cyclostratigraphy of the magnetic signal, analysed by the spectral analysis of the time series across the Jaramillo and late Matuyama chrons, confirmed that value. The evidenced cyclicities were directly related to the alternating lithofacies, and both to the astronomical parameters driving the climate changes during the deposition of the Dandiero group (some five hundred thousand years. The section with the Homo site covers the Jaramillo/Matuyama boundary, and the Homo bed located 2 m below this limit is dated 0.992 Ma. 

  9. Non-Growth-Associated Demethylation of Dimethylsulfoniopropionate by (Homo)acetogenic Bacteria

    Science.gov (United States)

    Jansen, Michael; Hansen, Theo A.

    2001-01-01

    The demethylation of the algal osmolyte dimethylsulfoniopropionate (DMSP) to methylthiopropionate (MTPA) by (homo)acetogenic bacteria was studied. Five Eubacterium limosum strains (including the type strain), Sporomusa ovata DSM 2662T, Sporomusa sphaeroides DSM 2875T, and Acetobacterium woodii DSM 1030T were shown to demethylate DMSP stoichiometrically to MTPA. The (homo)acetogenic fermentation based on this demethylation did not result in any significant increase in biomass. The analogous demethylation of glycine betaine to dimethylglycine does support growth of acetogens. In batch cultures of E. limosum PM31 DMSP and glycine betaine were demethylated simultaneously. In mixed substrates experiments with fructose-DMSP or methanol-DMSP, DMSP was used rapidly but only after exhaustion of the fructose or the methanol. In steady-state fructose-limited chemostat cultures (at a dilution rate of 0.03 h−1) with DMSP as a second reservoir substrate, DMSP was biotransformed to MTPA but this did not result in higher biomass values than in cultures without DMSP; cells from such cultures demethylated DMSP at rates of approximately 50 nmol min−1 mg of protein−1, both after growth in the presence of DMSP and after growth in its absence. In cell extracts of glycine betaine-grown strain PM31, DMSP demethylation activities of 21 to 24 nmol min−1 mg of protein−1 were detected with tetrahydrofolate as a methyl acceptor; the activities seen with glycine betaine were approximately 10-fold lower. A speculative explanation for the demethylation of DMSP without an obvious benefit for the organism is that the DMSP-demethylating activity is catalyzed by the glycine betaine-demethylating enzyme and that a transport-related factor, in particular a higher energy demand for DMSP transport across the cytoplasmic membrane than for glycine betaine transport, may reduce the overall ATP yield of the fermentation to virtually zero. PMID:11133459

  10. Mechanistic Diversity in the RuBisCO Superfamily: The Enolase in the Methionine

    Energy Technology Data Exchange (ETDEWEB)

    Imker,H.; Fedorov, A.; Fedorov, E.; Almo, S.; Gerlt, J.

    2007-01-01

    D-Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), the most abundant enzyme, is the paradigm member of the recently recognized mechanistically diverse RuBisCO superfamily. The RuBisCO reaction is initiated by abstraction of the proton from C3 of the D-ribulose 1,5-bisphosphate substrate by a carbamate oxygen of carboxylated Lys 201 (spinach enzyme). Heterofunctional homologues of RuBisCO found in species of Bacilli catalyze the tautomerization ('enolization') of 2,3-diketo-5-methylthiopentane 1-phosphate (DK-MTP 1-P) in the methionine salvage pathway in which 5-methylthio-D-ribose (MTR) derived from 5'-methylthioadenosine is converted to methionine [Ashida, H., Saito, Y., Kojima, C., Kobayashi, K., Ogasawara, N., and Yokota, A. (2003) A functional link between RuBisCO-like protein of Bacillus and photosynthetic RuBisCO, Science 302, 286-290]. The reaction catalyzed by this 'enolase' is accomplished by abstraction of a proton from C1 of the DK-MTP 1-P substrate to form the tautomerized product, a conjugated enol. Because the RuBisCO- and 'enolase'-catalyzed reactions differ in the regiochemistry of proton abstraction but are expected to share stabilization of an enolate anion intermediate by coordination to an active site Mg{sup 2+}, we sought to establish structure-function relationships for the 'enolase' reaction so that the structural basis for the functional diversity could be established. We determined the stereochemical course of the reaction catalyzed by the 'enolases' from Bacillus subtilis and Geobacillus kaustophilus. Using stereospecifically deuterated samples of an alternate substrate derived from D-ribose (5-OH group instead of the 5-methylthio group in MTR) as well as of the natural DK-MTP 1-P substrate, we determined that the 'enolase'-catalyzed reaction involves abstraction of the 1-proS proton. We also determined the structure of the activated 'enolase' from G

  11. Functional Identification of Incorrectly Annotated Prolidases from the Amidohydrolase Superfamily of Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, D.; Patskovsky, Y; Xu, C; Meyer, A; Sauder, J; Burley, S; Almo, S; Raushel, F

    2009-01-01

    The substrate profiles for two proteins from Caulobacter crescentus CB15 (Cc2672 and Cc3125) and one protein (Sgx9359b) derived from a DNA sequence (gi|44368820) isolated from the Sargasso Sea were determined using combinatorial libraries of dipeptides and N-acyl derivatives of amino acids. These proteins are members of the amidohydrolase superfamily and are currently misannotated in NCBI as catalyzing the hydrolysis of l-Xaa-l-Pro dipeptides. Cc2672 was shown to catalyze the hydrolysis of l-Xaa-l-Arg/Lys dipeptides and the N-acetyl and N-formyl derivatives of lysine and arginine. This enzyme will also hydrolyze longer peptides that terminate in either lysine or arginine. The N-methyl phosphonate derivative of l-lysine was a potent competitive inhibitor of Cc2672 with a Ki value of 120 nM. Cc3125 was shown to catalyze the hydrolysis of l-Xaa-l-Arg/Lys dipeptides but will not hydrolyze tripeptides or the N-formyl and N-acetyl derivatives of lysine or arginine. The substrate profile for Sgx9359b is similar to that of Cc2672 except that compounds with a C-terminal lysine are not recognized as substrates. The X-ray structure of Sgx9359b was determined to a resolution of 2.3 Angstroms. The protein folds as a (e/a)8-barrel and self-associates to form a homooctamer. The active site is composed of a binuclear metal center similar to that found in phosphotriesterase and dihydroorotase. In one crystal form, arginine was bound adventitiously to the eight active sites within the octamer. The orientation of the arginine in the active site identified the structural determinants for recognition of the a-carboxylate and the positively charged side chains of arginine-containing substrates. This information was used to identify 18 other bacterial sequences that possess identical or similar substrate profiles.

  12. Evolutionary Dynamics of the Cellulose Synthase Gene Superfamily in Grasses1[OPEN

    Science.gov (United States)

    Schwerdt, Julian G.; Wright, Frank; Oehme, Daniel; Wagner, John M.; Shirley, Neil J.; Burton, Rachel A.; Schreiber, Miriam; Zimmer, Jochen; Marshall, David F.; Waugh, Robbie; Fincher, Geoffrey B.

    2015-01-01

    Phylogenetic analyses of cellulose synthase (CesA) and cellulose synthase-like (Csl) families from the cellulose synthase gene superfamily were used to reconstruct their evolutionary origins and selection histories. Counterintuitively, genes encoding primary cell wall CesAs have undergone extensive expansion and diversification following an ancestral duplication from a secondary cell wall-associated CesA. Selection pressure across entire CesA and Csl clades appears to be low, but this conceals considerable variation within individual clades. Genes in the CslF clade are of particular interest because some mediate the synthesis of (1,3;1,4)-β-glucan, a polysaccharide characteristic of the evolutionarily successful grasses that is not widely distributed elsewhere in the plant kingdom. The phylogeny suggests that duplication of either CslF6 and/or CslF7 produced the ancestor of a highly conserved cluster of CslF genes that remain located in syntenic regions of all the grass genomes examined. A CslF6-specific insert encoding approximately 55 amino acid residues has subsequently been incorporated into the gene, or possibly lost from other CslFs, and the CslF7 clade has undergone a significant long-term shift in selection pressure. Homology modeling and molecular dynamics of the CslF6 protein were used to define the three-dimensional dispositions of individual amino acids that are subject to strong ongoing selection, together with the position of the conserved 55-amino acid insert that is known to influence the amounts and fine structures of (1,3;1,4)-β-glucans synthesized. These wall polysaccharides are attracting renewed interest because of their central roles as sources of dietary fiber in human health and for the generation of renewable liquid biofuels. PMID:25999407

  13. Novel members of the adipokinetic hormone family in beetles of the superfamily Scarabaeoidea.

    Science.gov (United States)

    Gäde, Gerd; Šimek, Petr; Marco, Heather G

    2016-12-01

    Eight beetle species of the superfamily Scarabaeoidea were investigated with respect to peptides belonging to the adipokinetic hormone (AKH) family in their neurohemal organs, the corpora cardiaca (CC). The following beetle families are represented: Scarabaeidae, Lucanidae, and Geotrupidae. AKH peptides were identified through a heterospecific trehalose-mobilizing bioassay and by sequence analyses, using liquid chromatography coupled to positive electrospray mass spectrometry (LC-ESI-MS) and analysis of the tandem MS(2) spectra obtained by collision-induced dissociation. All the beetle species have octapeptide AKHs; some have two AKHs, while others have only one. Novel AKH members were found in Euoniticellus intermedius and Circellium bacchus (family Scarabaeidae), as well as in Dorcus parallelipipedus (family Lucanidae). Two species of the family Geotrupidae and two species of the Scarabaeidae subfamily Cetoniinae contain one known AKH peptide, Melme-CC, while E. intermedius produces a novel peptide code named Euoin-AKH: pEINFTTGWamide. Two AKH peptides were each identified in CC of C. bacchus and D. parallelipipedus: the novel Cirba-AKH: pEFNFSAGWamide and the known peptide, Scade-CC-I in the former, and the novel Dorpa-AKH: pEVNYSPVW amide and the known peptide, Melme-CC in the latter. Kheper bonelli (subfamily Scarabaeinae) also has two AKHs, the known Scade-CC-I and Scade-CC-II. All the novel peptides were synthesized and the amino acid sequence assignments were unequivocally confirmed by co-elution of the synthetic peptides with their natural equivalent, and identical MS parameters of the two forms. The novel synthetic peptides are all active in inducing hypertrehalosemia in cockroaches.

  14. Up-regulation of tumor necrosis factor superfamily genes in early phases of photoreceptor degeneration.

    Directory of Open Access Journals (Sweden)

    Sem Genini

    Full Text Available We used quantitative real-time PCR to examine the expression of 112 genes related to retinal function and/or belonging to known pro-apoptotic, cell survival, and autophagy pathways during photoreceptor degeneration in three early-onset canine models of human photoreceptor degeneration, rod cone dysplasia 1 (rcd1, X-linked progressive retinal atrophy 2 (xlpra2, and early retinal degeneration (erd, caused respectively, by mutations in PDE6B, RPGRORF15, and STK38L. Notably, we found that expression and timing of differentially expressed (DE genes correlated with the cell death kinetics. Gene expression profiles of rcd1 and xlpra2 were similar; however rcd1 was more severe as demonstrated by the results of the TUNEL and ONL thickness analyses, a greater number of genes that were DE, and the identification of altered expression that occurred at earlier time points. Both diseases differed from erd, where a smaller number of genes were DE. Our studies did not highlight the potential involvement of mitochondrial or autophagy pathways, but all three diseases were accompanied by the down-regulation of photoreceptor genes, and up-regulation of several genes that belong to the TNF superfamily, the extrinsic apoptotic pathway, and pro-survival pathways. These proteins were expressed by different retinal cells, including horizontal, amacrine, ON bipolar, and Müller cells, and suggest an interplay between the dying photoreceptors and inner retinal cells. Western blot and immunohistochemistry results supported the transcriptional regulation for selected proteins. This study highlights a potential role for signaling through the extrinsic apoptotic pathway in early cell death events and suggests that retinal cells other than photoreceptors might play a primary or bystander role in the degenerative process.

  15. New insights into family relationships within the avian superfamily Sylvioidea (Passeriformes based on seven molecular markers

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    Fregin Silke

    2012-08-01

    Full Text Available Abstract Background The circumscription of the avian superfamily Sylvioidea is a matter of long ongoing debate. While the overall inclusiveness has now been mostly agreed on and 20 families recognised, the phylogenetic relationships among the families are largely unknown. We here present a phylogenetic hypothesis for Sylvioidea based on one mitochondrial and six nuclear markers, in total ~6.3 kbp, for 79 ingroup species representing all currently recognised families and some species with uncertain affinities, making this the most comprehensive analysis of this taxon. Results The resolution, especially of the deeper nodes, is much improved compared to previous studies. However, many relationships among families remain uncertain and are in need of verification. Most families themselves are very well supported based on the total data set and also by indels. Our data do not support the inclusion of Hylia in Cettiidae, but do not strongly reject a close relationship with Cettiidae either. The genera Scotocerca and Erythrocercus are closely related to Cettiidae, but separated by relatively long internodes. The families Paridae, Remizidae and Stenostiridae clustered among the outgroup taxa and not within Sylvioidea. Conclusions Although the phylogenetic position of Hylia is uncertain, we tentatively support the recognition of the family Hyliidae Bannerman, 1923 for this genus and Pholidornis. We propose new family names for the genera Scotocerca and Erythrocercus, Scotocercidae and Erythrocercidae, respectively, rather than including these in Cettiidae, and we formally propose the name Macrosphenidae, which has been in informal use for some time. We recommend that Paridae, Remizidae and Stenostiridae are not included in Sylvioidea. We also briefly discuss the problems of providing a morphological diagnosis when proposing a new family-group name (or genus-group name based on a clade.

  16. Structural basis for the roles of starch and sucrose in homo-exopolysaccharide formation by Lactobacillus reuteri 35-5

    NARCIS (Netherlands)

    Bai, Yuxiang; Dobruchowska, Justyna M; van der Kaaij, Rachel M; Gerwig, Gerrit J; Dijkhuizen, Lubbert

    2016-01-01

    Lactic acid bacteria (LAB) produce exopolysaccharides (EPS) that are important for biofilm formation in the mammalian oral cavity and gastrointestinal tract. Sucrose is a well-known substrate for homo-EPS formation by Lactobacillus reuteri glucansucrases (GS). Starch is the main fermentable carbohyd

  17. The Homo sapiens Cave hominin site of Mulan Mountain,Jiangzhou District,Chongzuo,Guangxi with emphasis on its age

    Institute of Scientific and Technical Information of China (English)

    JIN ChangZhu; PAN WenShi; ZHANG YingQi; CAI YanJun; XU QinQi; TANG ZhiLu; WANG Wei; WANG Yuan; LIU JinYi; QIN DaGong; R.Lawrence Edwards; CHENG Hai

    2009-01-01

    One of the most hotly debated and frontal issues in paleoanthropology focuses on the origins of modern humans.Recently,an incomplete hominin mandible with a distinctly weaker mental protuberance than modern human and a great variety of coexisting fossil mammals were unearthed from the Homo sapiens Cave of Mulan Mountain,Chongzuo,Guangxi.The mammalian fauna from the Homo sapiens Cave characterized by the combination of Elephas kiangnanensis,first occurring Elephas maixmus,and Megatapirus augustus,and strikingly different from the Early Pleistocene Gigantopithecus fauna and the Middle Pleistocene Ailuropoda-Stogodon fauna of South China could be regarded as an early representive of the typical Asian elephant fauna.Faunal analysis,biostratigraphic correlation,and,most importantly,U-series dating all consistently support an estimate of ca.110 ka for the age of the fossil Homo sapiens and coexisting mammalian fauna,that is,the early Late Pleistocene.The fauna is mainly made up of tropical-subtropical elements,but grassland elements have a much greater variety than forest elements,which probably indicates a drier climate at that time.This discovery of early Homo sapiens at the Mulan Mountain will play a significant role in the study of the origin and its environmental background of modern humans.

  18. Yeast fermentation affected by homo- and hetero-fermentative Lactobacilli isolated from fuel ethanol distilleries with sugarcane products as substrates

    Science.gov (United States)

    The antagonism between by yeast and lactobacilli is largely dependent on the initial population of each organism. While homo-fermentative lactobacillus present higher inhibitory effect upon yeast when in equal cell number, in industrial fuel ethanol conditions where high yeast cell densities prevail...

  19. Gold(I) NHC-based homo- and heterobimetallic complexes : synthesis, characterization and evaluation as potential anticancer agents

    NARCIS (Netherlands)

    Bertrand, Benoit; Citta, Anna; Franken, Inge L.; Picquet, Michel; Folda, Alessandra; Scalcon, Valeria; Rigobello, Maria Pia; Le Gendre, Pierre; Casini, Angela; Bodio, Ewen

    2015-01-01

    While N-heterocyclic carbenes (NHC) are ubiquitous ligands in catalysis for organic or industrial syntheses, their potential to form transition metal complexes for medicinal applications has still to be exploited. Within this frame, we synthesized new homo- and heterobimetallic complexes based on th

  20. Molecular biology of Homo sapiens: Abstracts of papers presented at the 51st Cold Spring Harbor symposium on quantitative biology

    Energy Technology Data Exchange (ETDEWEB)

    Watson, J.D.; Siniscalco, M.

    1986-01-01

    This volume contains abstracts of papers presented at the 51st Cold Springs Harbor Symposium on Quantitative Biology. The topic for this meeting was the ''Molecular Biology of Homo sapiens.'' Sessions were entitled Human Gene Map, Human Cancer Genes, Genetic Diagnosis, Human Evolution, Drugs Made Off Human Genes, Receptors, and Gene Therapy. (DT)

  1. Mis juhtus Andres Lapeteusega? : error'ist kõrgklassi homo soveticus'e näitel / Liisa Kaljula

    Index Scriptorium Estoniae

    Kaljula, Liisa, 1982-

    2014-01-01

    Autor analüüsib 2014. a. Tallinna Semiosalongi loengute sarja põhiteema - error'i mõiste avamiseks ühe inimliigi kujunemislugu - Eesti filmiklassikast tuntud tegelaskuju Andres Lapeteuse tõusu ning langust homo soveticus'ena

  2. Implications of natural selection in shaping 99.4% nonsynonymous DNA identity between humans and chimpanzees: Enlarging genus Homo

    Science.gov (United States)

    Wildman, Derek E.; Uddin, Monica; Liu, Guozhen; Grossman, Lawrence I.; Goodman, Morris

    2003-01-01

    What do functionally important DNA sites, those scrutinized and shaped by natural selection, tell us about the place of humans in evolution? Here we compare ≈90 kb of coding DNA nucleotide sequence from 97 human genes to their sequenced chimpanzee counterparts and to available sequenced gorilla, orangutan, and Old World monkey counterparts, and, on a more limited basis, to mouse. The nonsynonymous changes (functionally important), like synonymous changes (functionally much less important), show chimpanzees and humans to be most closely related, sharing 99.4% identity at nonsynonymous sites and 98.4% at synonymous sites. On a time scale, the coding DNA divergencies separate the human–chimpanzee clade from the gorilla clade at between 6 and 7 million years ago and place the most recent common ancestor of humans and chimpanzees at between 5 and 6 million years ago. The evolutionary rate of coding DNA in the catarrhine clade (Old World monkey and ape, including human) is much slower than in the lineage to mouse. Among the genes examined, 30 show evidence of positive selection during descent of catarrhines. Nonsynonymous substitutions by themselves, in this subset of positively selected genes, group humans and chimpanzees closest to each other and have chimpanzees diverge about as much from the common human–chimpanzee ancestor as humans do. This functional DNA evidence supports two previously offered taxonomic proposals: family Hominidae should include all extant apes; and genus Homo should include three extant species and two subgenera, Homo (Homo) sapiens (humankind), Homo (Pan) troglodytes (common chimpanzee), and Homo (Pan) paniscus (bonobo chimpanzee). PMID:12766228

  3. Discovery of a distinct superfamily of Kunitz-type toxin (KTT from tarantulas.

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    Chun-Hua Yuan

    Full Text Available BACKGROUND: Kuntiz-type toxins (KTTs have been found in the venom of animals such as snake, cone snail and sea anemone. The main ancestral function of Kunitz-type proteins was the inhibition of a diverse array of serine proteases, while toxic activities (such as ion-channel blocking were developed under a variety of Darwinian selection pressures. How new functions were grafted onto an old protein scaffold and what effect Darwinian selection pressures had on KTT evolution remains a puzzle. PRINCIPAL FINDINGS: Here we report the presence of a new superfamily of ktts in spiders (TARANTULAS: Ornithoctonus huwena and Ornithoctonus hainana, which share low sequence similarity to known KTTs and is clustered in a distinct clade in the phylogenetic tree of KTT evolution. The representative molecule of spider KTTs, HWTX-XI, purified from the venom of O. huwena, is a bi-functional protein which is a very potent trypsin inhibitor (about 30-fold more strong than BPTI as well as a weak Kv1.1 potassium channel blocker. Structural analysis of HWTX-XI in 3-D by NMR together with comparative function analysis of 18 expressed mutants of this toxin revealed two separate sites, corresponding to these two activities, located on the two ends of the cone-shape molecule of HWTX-XI. Comparison of non-synonymous/synonymous mutation ratios (omega for each site in spider and snake KTTs, as well as PBTI like body Kunitz proteins revealed high Darwinian selection pressure on the binding sites for Kv channels and serine proteases in snake, while only on the proteases in spider and none detected in body proteins, suggesting different rates and patterns of evolution among them. The results also revealed a series of key events in the history of spider KTT evolution, including the formation of a novel KTT family (named sub-Kuntiz-type toxins derived from the ancestral native KTTs with the loss of the second disulfide bridge accompanied by several dramatic sequence modifications

  4. Biochemistry and Crystal Structure of Ectoine Synthase: A Metal-Containing Member of the Cupin Superfamily.

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    Nils Widderich

    Full Text Available Ectoine is a compatible solute and chemical chaperone widely used by members of the Bacteria and a few Archaea to fend-off the detrimental effects of high external osmolarity on cellular physiology and growth. Ectoine synthase (EctC catalyzes the last step in ectoine production and mediates the ring closure of the substrate N-gamma-acetyl-L-2,4-diaminobutyric acid through a water elimination reaction. However, the crystal structure of ectoine synthase is not known and a clear understanding of how its fold contributes to enzyme activity is thus lacking. Using the ectoine synthase from the cold-adapted marine bacterium Sphingopyxis alaskensis (Sa, we report here both a detailed biochemical characterization of the EctC enzyme and the high-resolution crystal structure of its apo-form. Structural analysis classified the (SaEctC protein as a member of the cupin superfamily. EctC forms a dimer with a head-to-tail arrangement, both in solution and in the crystal structure. The interface of the dimer assembly is shaped through backbone-contacts and weak hydrophobic interactions mediated by two beta-sheets within each monomer. We show for the first time that ectoine synthase harbors a catalytically important metal co-factor; metal depletion and reconstitution experiments suggest that EctC is probably an iron-dependent enzyme. We found that EctC not only effectively converts its natural substrate N-gamma-acetyl-L-2,4-diaminobutyric acid into ectoine through a cyclocondensation reaction, but that it can also use the isomer N-alpha-acetyl-L-2,4-diaminobutyric acid as its substrate, albeit with substantially reduced catalytic efficiency. Structure-guided site-directed mutagenesis experiments targeting amino acid residues that are evolutionarily highly conserved among the extended EctC protein family, including those forming the presumptive iron-binding site, were conducted to functionally analyze the properties of the resulting EctC variants. An assessment of

  5. Biochemistry and Crystal Structure of Ectoine Synthase: A Metal-Containing Member of the Cupin Superfamily.

    Science.gov (United States)

    Widderich, Nils; Kobus, Stefanie; Höppner, Astrid; Riclea, Ramona; Seubert, Andreas; Dickschat, Jeroen S; Heider, Johann; Smits, Sander H J; Bremer, Erhard

    2016-01-01

    Ectoine is a compatible solute and chemical chaperone widely used by members of the Bacteria and a few Archaea to fend-off the detrimental effects of high external osmolarity on cellular physiology and growth. Ectoine synthase (EctC) catalyzes the last step in ectoine production and mediates the ring closure of the substrate N-gamma-acetyl-L-2,4-diaminobutyric acid through a water elimination reaction. However, the crystal structure of ectoine synthase is not known and a clear understanding of how its fold contributes to enzyme activity is thus lacking. Using the ectoine synthase from the cold-adapted marine bacterium Sphingopyxis alaskensis (Sa), we report here both a detailed biochemical characterization of the EctC enzyme and the high-resolution crystal structure of its apo-form. Structural analysis classified the (Sa)EctC protein as a member of the cupin superfamily. EctC forms a dimer with a head-to-tail arrangement, both in solution and in the crystal structure. The interface of the dimer assembly is shaped through backbone-contacts and weak hydrophobic interactions mediated by two beta-sheets within each monomer. We show for the first time that ectoine synthase harbors a catalytically important metal co-factor; metal depletion and reconstitution experiments suggest that EctC is probably an iron-dependent enzyme. We found that EctC not only effectively converts its natural substrate N-gamma-acetyl-L-2,4-diaminobutyric acid into ectoine through a cyclocondensation reaction, but that it can also use the isomer N-alpha-acetyl-L-2,4-diaminobutyric acid as its substrate, albeit with substantially reduced catalytic efficiency. Structure-guided site-directed mutagenesis experiments targeting amino acid residues that are evolutionarily highly conserved among the extended EctC protein family, including those forming the presumptive iron-binding site, were conducted to functionally analyze the properties of the resulting EctC variants. An assessment of enzyme activity

  6. The Plant Short-Chain Dehydrogenase (SDR superfamily: genome-wide inventory and diversification patterns

    Directory of Open Access Journals (Sweden)

    Moummou Hanane

    2012-11-01

    Full Text Available Abstract Background Short-chain dehydrogenases/reductases (SDRs form one of the largest and oldest NAD(P(H dependent oxidoreductase families. Despite a conserved ‘Rossmann-fold’ structure, members of the SDR superfamily exhibit low sequence similarities, which constituted a bottleneck in terms of identification. Recent classification methods, relying on hidden-Markov models (HMMs, improved identification and enabled the construction of a nomenclature. However, functional annotations of plant SDRs remain scarce. Results Wide-scale analyses were performed on ten plant genomes. The combination of hidden Markov model (HMM based analyses and similarity searches led to the construction of an exhaustive inventory of plant SDR. With 68 to 315 members found in each analysed genome, the inventory confirmed the over-representation of SDRs in plants compared to animals, fungi and prokaryotes. The plant SDRs were first classified into three major types — ‘classical’, ‘extended’ and ‘divergent’ — but a minority (10% of the predicted SDRs could not be classified into these general types (‘unknown’ or ‘atypical’ types. In a second step, we could categorize the vast majority of land plant SDRs into a set of 49 families. Out of these 49 families, 35 appeared early during evolution since they are commonly found through all the Green Lineage. Yet, some SDR families — tropinone reductase-like proteins (SDR65C, ‘ABA2-like’-NAD dehydrogenase (SDR110C, ‘salutaridine/menthone-reductase-like’ proteins (SDR114C, ‘dihydroflavonol 4-reductase’-like proteins (SDR108E and ‘isoflavone-reductase-like’ (SDR460A proteins — have undergone significant functional diversification within vascular plants since they diverged from Bryophytes. Interestingly, these diversified families are either involved in the secondary metabolism routes (terpenoids, alkaloids, phenolics or participate in developmental processes (hormone biosynthesis or

  7. The plant short-chain dehydrogenase (SDR) superfamily: genome-wide inventory and diversification patterns.

    Science.gov (United States)

    Moummou, Hanane; Kallberg, Yvonne; Tonfack, Libert Brice; Persson, Bengt; van der Rest, Benoît

    2012-11-20

    Short-chain dehydrogenases/reductases (SDRs) form one of the largest and oldest NAD(P)(H) dependent oxidoreductase families. Despite a conserved 'Rossmann-fold' structure, members of the SDR superfamily exhibit low sequence similarities, which constituted a bottleneck in terms of identification. Recent classification methods, relying on hidden-Markov models (HMMs), improved identification and enabled the construction of a nomenclature. However, functional annotations of plant SDRs remain scarce. Wide-scale analyses were performed on ten plant genomes. The combination of hidden Markov model (HMM) based analyses and similarity searches led to the construction of an exhaustive inventory of plant SDR. With 68 to 315 members found in each analysed genome, the inventory confirmed the over-representation of SDRs in plants compared to animals, fungi and prokaryotes. The plant SDRs were first classified into three major types - 'classical', 'extended' and 'divergent' - but a minority (10% of the predicted SDRs) could not be classified into these general types ('unknown' or 'atypical' types). In a second step, we could categorize the vast majority of land plant SDRs into a set of 49 families. Out of these 49 families, 35 appeared early during evolution since they are commonly found through all the Green Lineage. Yet, some SDR families - tropinone reductase-like proteins (SDR65C), 'ABA2-like'-NAD dehydrogenase (SDR110C), 'salutaridine/menthone-reductase-like' proteins (SDR114C), 'dihydroflavonol 4-reductase'-like proteins (SDR108E) and 'isoflavone-reductase-like' (SDR460A) proteins - have undergone significant functional diversification within vascular plants since they diverged from Bryophytes. Interestingly, these diversified families are either involved in the secondary metabolism routes (terpenoids, alkaloids, phenolics) or participate in developmental processes (hormone biosynthesis or catabolism, flower development), in opposition to SDR families involved in primary

  8. Isolation of a novel member of small G protein superfamily and its expression in colon cancer

    Institute of Scientific and Technical Information of China (English)

    Wei Yan; Wen-Liang Wang; Feng Zhu; Sheng-Quan Chen; Qing-Long Li; Li Wang

    2003-01-01

    AIM: APMCF1 is a novel human gene whose transcripts are up-regulated in apoptotic MCF-7 cells. In order to learn more about this gene′s function in other tumors, we cloned its full length cDNA and prepared its polyclonal antibody to investigate its expression in colon cancers with immunohistochemistry.METHODS: With the method of 5′ rapid amplification of cDNA end (RACE) and EST assembled in GenBank, we extended the length of APMCF1 at 5′ end. Then the sequence encoding the APMCF1 protein was amplified by RT-PCR from the total RNA of apoptotic MCF-7 cells and cloned into the prokaryotic expression vector pGEX-KG to construct recombinant expression vector pGEX-APMCF1. The GSTAPMCF1 fusion protein was expressed in E. coli and used to immunize rabbits to get the rabbit anti-APMCF1 serum. The specificity of polyclonal anti-APMCF1 antibody was determined by Western blot. Then we investigated the expression of Apmcf1 in colon cancers and normal colonic mucosa with immunohistochemistry.RESULTS: A cDNA fragment with a length of 1 745 bp was obtained. APMCF1 was mapped to chromosome 3q22.2and spanned at least 14.8 kb of genomic DNA with seven exons and six introns contained. Bioinformatic analysis showed the protein encoded by APMCF1 contained a small GTP-binding protein (G proteins) domain and was homologous to mouse signal recognition particle receptor β(SRβ). A coding region covering 816 bp was cloned and polyclonal anti-APMCF1 antibody was prepared successfully.The immunohistochemistry study showed that APMCF1 had a strong expression in colon cancer.CONCLUSION: APMCF1 may be the gene coding human signal recognition particle receptor β and belongs to the small-G protein superfamily. Its strong expression pattern in colon cancer suggests it may play a role in colon cancer development.

  9. Synthesis and antiproliferative activity of some A- and B modified D-homo lactone androstane derivatives

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    Savić Marina P.

    2013-01-01

    Full Text Available An efficient synthesis of several A- and B-modified D-homo lactone androstane derivatives from 3β-hydroxy-17-oxa-D-homoandrost-5-en-16-one (1 is reported. 17-Oxa-Dhomoandrost- 4-ene-3,16-dione (2, obtained by the Oppenauer oxidation of compound 1, was converted via the unstable intermediate 3,16-dioxo-4,17-dioxa-D-homoandrostane- 5α-carboxaldehyde (3 to 17-oxa-D-homo-3,5-seco-4-norandrostan-5-one-3-carboxylic acid (4, which was also obtained directly from compound 2. Compound 1 was acetylated to give 17-oxa-D-homoandrost-5-en-16-on-3β-yl acetate (5 which was then oxidized with chromium(VI-oxide in 50% acetic acid or with meta-chlorperbenzoic acid and chromium(VI-oxide to yield compounds 6-8 and 5α-hydroxy-17-oxa-D-homoandrostane- 6,16-dion-3β-yl acetate (9, respectively. The oximination of compound 9 gave a mixture of 6(E-hydroximino-5α-hydroxy-17-oxa-D-homoandrostan-16-on-3β-yl acetate (10 and 6(Z-hydroximino-5α-hydroxy-17-oxa-D-homoandrostan-16-on-3β-yl acetate (11, the hydrolysis of which gave 6(E-hydroximino-3β,5α-dihydroxy-17-oxa-D-homoandrostan- 16-one (12 and 6(Z-hydroximino-3β,5α-dihydroxy-17-oxa-D-homoandrostan-16-one (13. 6-Nitrile-17-oxa-5,6-seco-D-homoandrostane-5,16-dion-3β-yl acetate (14 was obtained under the Beckmann fragmentation of compounds 10 and 11. Only pure and stable compounds (1, 2, 4, 5, 9 and 14 were tested in vitro on six malignant cell lines (MCF-7, MDA-MB-231, PC-3, HeLa, HT-29, K562 and one non-tumor MRC-5 cell line. Significant antiproliferative activity against MDA-MB-231 cells showed compounds 1, 5 and 9, while compound 2 exhibited a strong antiproliferative activity. Only compound 14 showed weak antiproliferative activity against MCF-7 cells. All tested compounds were not toxic on MRC-5 cells, whereas Doxorubicin was highly toxic on these cells. [Projekat Ministarstva nauke Republike Srbije, br. 172021

  10. The Ferritin-like superfamily: Evolution of the biological iron storeman from a rubrerythrin-like ancestor.

    Science.gov (United States)

    Andrews, Simon C

    2010-08-01

    The Ferritins are part of the extensive 'Ferritin-like superfamily' which have diverse functions but are linked by the presence of a common four-helical bundle domain. The role performed by Ferritins as the cellular repository of excess iron is unique. In many ways Ferritins act as tiny organelles in their ability to secrete iron away from the delicate machinery of the cell, and then to release it again in a controlled fashion avoiding toxicity. The Ferritins are ancient proteins, being common in all three domains of life. This ubiquity reflects the key contribution that Ferritins provide in achieving iron homeostasis. This review compares the features of the different Ferritins and considers how they, and other members of the Ferritin-like superfamily, have evolved. It also considers relevant features of the eleven other known families within the Ferritin-like superfamily, particularly the highly diverse rubrerythrins. The Ferritins have travelled a considerable evolutionary journey, being derived from far more simplistic rubrerythrin-like molecules which play roles in defence against toxic oxygen species. The forces of evolution have moulded such molecules into three distinct types of iron storing (or detoxifying) protein: the classical and universal 24-meric ferritins; the haem-containing 24-meric bacterioferritins of prokaryotes; and the prokaryotic 12-meric Dps proteins. These three Ferritin types are similar, but also possess unique properties that distinguish them and enable then to achieve their specific physiological purposes. A wide range of biological functions have evolved from a relatively simple structural unit. Copyright 2010. Published by Elsevier B.V.

  11. Intracellular mediators of transforming growth factor β superfamily signaling localize to endosomes in chicken embryo and mouse lenses in vivo

    Directory of Open Access Journals (Sweden)

    Ishii Shunsuke

    2007-06-01

    Full Text Available Abstract Background Endocytosis is a key regulator of growth factor signaling pathways. Recent studies showed that the localization to endosomes of intracellular mediators of growth factor signaling may be required for their function. Although there is substantial evidence linking endocytosis and growth factor signaling in cultured cells, there has been little study of the endosomal localization of signaling components in intact tissues or organs. Results Proteins that are downstream of the transforming growth factor-β superfamily signaling pathway were found on endosomes in chicken embryo and postnatal mouse lenses, which depend on signaling by members of the TGFβ superfamily for their normal development. Phosphorylated Smad1 (pSmad1, pSmad2, Smad4, Smad7, the transcriptional repressors c-Ski and TGIF and the adapter molecules Smad anchor for receptor activation (SARA and C184M, localized to EEA-1- and Rab5-positive vesicles in chicken embryo and/or postnatal mouse lenses. pSmad1 and pSmad2 also localized to Rab7-positive late endosomes. Smad7 was found associated with endosomes, but not caveolae. Bmpr1a conditional knock-out lenses showed decreased nuclear and endosomal localization of pSmad1. Many of the effectors in this pathway were distributed differently in vivo from their reported distribution in cultured cells. Conclusion Based on the findings reported here and data from other signaling systems, we suggest that the localization of activated intracellular mediators of the transforming growth factor-β superfamily to endosomes is important for the regulation of growth factor signaling.

  12. Crystallization and preliminary X-ray diffraction analysis of Sfh3, a member of the Sec14 protein superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jihui; Schaaf, Gabriel; Bankaitis, Vytas A.; Ortlund, Eric A.; Pathak, Manish C. (Emory-MED); (UNC)

    2012-03-26

    Sec14 is the major phosphatidylinositol (PtdIns)/phosphatidylcholine (PtdCho) transfer protein in the yeast Saccharomyces cerevisiae and is the founding member of the Sec14 protein superfamily. Recent functional data suggest that Sec14 functions as a nanoreactor for PtdCho-regulated presentation of PtdIns to PtdIns kinase to affect membrane trafficking. Extrapolation of this concept to other members of the Sec14 superfamily suggests a mechanism by which a comprehensive cohort of Sec14-like nanoreactors sense correspondingly diverse pools of lipid metabolites. In turn, metabolic information is translated to signaling circuits driven by phosphoinositide metabolism. Sfh3, one of five Sec14 homologs in yeast, exhibits several interesting functional features, including its unique localization to lipid particles and microsomes. This localization forecasts novel regulatory interfaces between neutral lipid metabolism and phosphoinositide signaling. To launch a detailed structural and functional characterization of Sfh3, the recombinant protein was purified to homogeneity, diffraction-quality crystals were produced and a native X-ray data set was collected to 2.2 {angstrom} resolution. To aid in phasing, SAD X-ray diffraction data were collected to 1.93 {angstrom} resolution from an SeMet-labeled crystal at the Southeast Regional Collaborative Access Team at the Advanced Photon Source. Here, the cloning and purification of Sfh3 and the preliminary diffraction of Sfh3 crystals are reported, enabling structural analyses that are expected to reveal novel principles governing ligand binding and functional specificity for Sec14-superfamily proteins.

  13. A Survey of the ATP-Binding Cassette (ABC Gene Superfamily in the Salmon Louse (Lepeophtheirus salmonis.

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    Greta Carmona-Antoñanzas

    Full Text Available Salmon lice, Lepeophtheirus salmonis (Krøyer, 1837, are fish ectoparasites causing significant economic damage in the mariculture of Atlantic salmon, Salmo salar Linnaeus, 1758. The control of L. salmonis at fish farms relies to a large extent on treatment with anti-parasitic drugs. A problem related to chemical control is the potential for development of resistance, which in L. salmonis is documented for a number of drug classes including organophosphates, pyrethroids and avermectins. The ATP-binding cassette (ABC gene superfamily is found in all biota and includes a range of drug efflux transporters that can confer drug resistance to cancers and pathogens. Furthermore, some ABC transporters are recognised to be involved in conferral of insecticide resistance. While a number of studies have investigated ABC transporters in L. salmonis, no systematic analysis of the ABC gene family exists for this species. This study presents a genome-wide survey of ABC genes in L. salmonis for which, ABC superfamily members were identified through homology searching of the L. salmonis genome. In addition, ABC proteins were identified in a reference transcriptome of the parasite generated by high-throughput RNA sequencing (RNA-seq of a multi-stage RNA library. Searches of both genome and transcriptome allowed the identification of a total of 33 genes / transcripts coding for ABC proteins, of which 3 were represented only in the genome and 4 only in the transcriptome. Eighteen sequences were assigned to ABC subfamilies known to contain drug transporters, i.e. subfamilies B (4 sequences, C (11 and G (2. The results suggest that the ABC gene family of L. salmonis possesses fewer members than recorded for other arthropods. The present survey of the L. salmonis ABC gene superfamily will provide the basis for further research into potential roles of ABC transporters in the toxicity of salmon delousing agents and as potential mechanisms of drug resistance.

  14. Genome-wide analysis of the expansin gene superfamily reveals grapevine-specific structural and functional characteristics.

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    Silvia Dal Santo

    Full Text Available BACKGROUND: Expansins are proteins that loosen plant cell walls in a pH-dependent manner, probably by increasing the relative movement among polymers thus causing irreversible expansion. The expansin superfamily (EXP comprises four distinct families: expansin A (EXPA, expansin B (EXPB, expansin-like A (EXLA and expansin-like B (EXLB. There is experimental evidence that EXPA and EXPB proteins are required for cell expansion and developmental processes involving cell wall modification, whereas the exact functions of EXLA and EXLB remain unclear. The complete grapevine (Vitis vinifera genome sequence has allowed the characterization of many gene families, but an exhaustive genome-wide analysis of expansin gene expression has not been attempted thus far. METHODOLOGY/PRINCIPAL FINDINGS: We identified 29 EXP superfamily genes in the grapevine genome, representing all four EXP families. Members of the same EXP family shared the same exon-intron structure, and phylogenetic analysis confirmed a closer relationship between EXP genes from woody species, i.e. grapevine and poplar (Populus trichocarpa, compared to those from Arabidopsis thaliana and rice (Oryza sativa. We also identified grapevine-specific duplication events involving the EXLB family. Global gene expression analysis confirmed a strong correlation among EXP genes expressed in mature and green/vegetative samples, respectively, as reported for other gene families in the recently-published grapevine gene expression atlas. We also observed the specific co-expression of EXLB genes in woody organs, and the involvement of certain grapevine EXP genes in berry development and post-harvest withering. CONCLUSION: Our comprehensive analysis of the grapevine EXP superfamily confirmed and extended current knowledge about the structural and functional characteristics of this gene family, and also identified properties that are currently unique to grapevine expansin genes. Our data provide a model for the

  15. Genome-wide identification and phylogenetic analysis of the AP2/ERF gene superfamily in sweet orange (Citrus sinensis).

    Science.gov (United States)

    Ito, T M; Polido, P B; Rampim, M C; Kaschuk, G; Souza, S G H

    2014-09-26

    Sweet orange (Citrus sinensis) plays an important role in the economy of more than 140 countries, but it is grown in areas with intermittent stressful soil and climatic conditions. The stress tolerance could be addressed by manipulating the ethylene response factor (ERF) transcription factors because they orchestrate plant responses to environmental stress. We performed an in silico study on the ERFs in the expressed sequence tag database of C. sinensis to identify potential genes that regulate plant responses to stress. We identified 108 putative genes encoding protein sequences of the AP2/ERF superfamily distributed within 10 groups of amino acid sequences. Ninety-one genes were assembled from the ERF family containing only one AP2/ERF domain, 13 genes were assembled from the AP2 family containing two AP2/ERF domains, and four other genes were assembled from the RAV family containing one AP2/ERF domain and a B3 domain. Some conserved domains of the ERF family genes were disrupted into a few segments by introns. This irregular distribution of genes in the AP2/ERF superfamily in different plant species could be a result of genomic losses or duplication events in a common ancestor. The in silico gene expression revealed that 67% of AP2/ERF genes are expressed in tissues with usual plant development, and 14% were expressed in stressed tissues. Because the AP2/ERF superfamily is expressed in an orchestrated way, it is possible that the manipulation of only one gene may result in changes in the whole plant function, which could result in more tolerant crops.

  16. The cys-loop ligand-gated ion channel gene superfamily of the red flour beetle, Tribolium castaneum

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    Sattelle David B

    2007-09-01

    Full Text Available Abstract Background Members of the cys-loop ligand-gated ion channel (cys-loop LGIC superfamily mediate chemical neurotransmission and are studied extensively as potential targets of drugs used to treat neurological disorders such as Alzheimer's disease. Insect cys-loop LGICs are also of interest as they are targets of highly successful insecticides. The red flour beetle, Tribolium castaneum, is a major pest of stored agricultural products and is also an important model organism for studying development. Results As part of the T. castaneum genome sequencing effort, we have characterized the beetle cys-loop LGIC superfamily which is the third insect superfamily to be described after those of Drosophila melanogaster and Apis mellifera, and also the largest consisting of 24 genes. As with Drosophila and Apis, Tribolium possesses ion channels gated by acetylcholine, γ-amino butyric acid (GABA, glutamate and histamine as well as orthologs of the Drosophila pH-sensitive chloride channel subunit (pHCl, CG8916 and CG12344. Similar to Drosophila and Apis, Tribolium cys-loop LGIC diversity is broadened by alternative splicing although the beetle orthologs of RDL and GluCl possess more variants of exon 3. Also, RNA A-to-I editing was observed in two Tribolium nicotinic acetylcholine receptor subunits, Tcasα6 and Tcasβ1. Editing in Tcasα6 is evolutionarily conserved with D. melanogaster, A. mellifera and Heliothis virescens, whereas Tcasβ1 is edited at a site so far only observed in the beetle. Conclusion Our findings reveal that in diverse insect species the cys-loop LGIC superfamily has remained compact with only minor changes in gene numbers. However, alternative splicing, RNA editing and the presence of divergent subunits broadens the cys-loop LGIC proteome and generates species-specific receptor isoforms. These findings on Tribolium castaneum enhance our understanding of cys-loop LGIC functional genomics and provide a useful basis for the

  17. Involvement of major facilitator superfamily proteins SfaA and SbnD in staphyloferrin secretion in Staphylococcus aureus.

    Science.gov (United States)

    Hannauer, Mélissa; Sheldon, Jessica R; Heinrichs, David E

    2015-03-12

    A paucity of information exists concerning the mechanism(s) by which bacteria secrete siderophores into the extracellular compartment. We investigated the role of SfaA and SbnD, two major facilitator superfamily (MFS)-type efflux proteins, in the secretion of the Staphylococcus aureus siderophores staphyloferrin A (SA) and staphyloferrin B (SB), respectively. Deletion of sfaA resulted in a drastic reduction of SA secreted into the supernatant with a corresponding accumulation of SA in the cytoplasm and a significant growth defect in cells devoid of SB synthesis. In contrast, sbnD mutants showed transiently lowered levels of secreted SB, suggesting the involvement of additional efflux mechanisms.

  18. Complement system proteins which interact with C3b or C4b A superfamily of structurally related proteins

    DEFF Research Database (Denmark)

    Reid, K B M; Bentley, D R; Campbell, R D;

    1986-01-01

    , while the precise number of units in CR1 is not known yet. These structurally homologous complement proteins are also functionally related as they all interact with C3b and C4b during activation of the cascade. The repeating units also occur in the functionally unrelated proteins subcomponent C1r, β2......-glycoprotein 1, blood clotting factor XIII and interleukin-2 receptor. In this review Ken Reid and his colleagues propose that this could be a general feature of a superfamily of structurally related proteins....

  19. Use of RNA Interference by In Utero Electroporation to Study Cortical Development: The Example of the Doublecortin Superfamily

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    Raanan Greenman

    2012-11-01

    Full Text Available The way we study cortical development has undergone a revolution in the last few years following the ability to use shRNA in the developing brain of the rodent embryo. The first gene to be knocked-down in the developing brain was doublecortin (Dcx. Here we will review knockdown experiments in the developing brain and compare them with knockout experiments, thus highlighting the advantages and disadvantages using the different systems. Our review will focus on experiments relating to the doublecortin superfamily of proteins.

  20. Subdivision of the MDR superfamily of medium-chain dehydrogenases/reductases through iterative hidden Markov model refinement

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    Persson Bengt

    2010-10-01

    Full Text Available Abstract Background The Medium-chain Dehydrogenases/Reductases (MDR form a protein superfamily whose size and complexity defeats traditional means of subclassification; it currently has over 15000 members in the databases, the pairwise sequence identity is typically around 25%, there are members from all kingdoms of life, the chain-lengths vary as does the oligomericity, and the members are partaking in a multitude of biological processes. There are profile hidden Markov models (HMMs available for detecting MDR superfamily members, but none for determining which MDR family each protein belongs to. The current torrential influx of new sequence data enables elucidation of more and more protein families, and at an increasingly fine granularity. However, gathering good quality training data usually requires manual attention by experts and has therefore been the rate limiting step for expanding the number of available models. Results We have developed an automated algorithm for HMM refinement that produces stable and reliable models for protein families. This algorithm uses relationships found in data to generate confident seed sets. Using this algorithm we have produced HMMs for 86 distinct MDR families and 34 of their subfamilies which can be used in automated annotation of new sequences. We find that MDR forms with 2 Zn2+ ions in general are dehydrogenases, while MDR forms with no Zn2+ in general are reductases. Furthermore, in Bacteria MDRs without Zn2+ are more frequent than those with Zn2+, while the opposite is true for eukaryotic MDRs, indicating that Zn2+ has been recruited into the MDR superfamily after the initial life kingdom separations. We have also developed a web site http://mdr-enzymes.org that provides textual and numeric search against various characterised MDR family properties, as well as sequence scan functions for reliable classification of novel MDR sequences. Conclusions Our method of refinement can be readily applied to

  1. Molecular phylogeny of the kelch-repeat superfamily reveals an expansion of BTB/kelch proteins in animals

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    Adams Josephine C

    2003-09-01

    Full Text Available Abstract Background The kelch motif is an ancient and evolutionarily-widespread sequence motif of 44–56 amino acids in length. It occurs as five to seven repeats that form a β-propeller tertiary structure. Over 28 kelch-repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain kelch-repeats. In general, kelch-repeat β-propellers are involved in protein-protein interactions, however the modest sequence identity between kelch motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the kelch-repeat domain and the kelch-repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of kelch-repeat proteins encoded in the human genome and have made comparisons to the kelch-repeat proteins encoded in other sequenced genomes. Results We identified 71 kelch-repeat proteins encoded in the human genome, whereas 5 or 8 members were identified in yeasts and around 18 in C. elegans, D. melanogaster and A. gambiae. Multiple domain architectures were identified in each organism, including previously unrecognised forms. The vast majority of kelch-repeat domains are predicted to form six-bladed β-propellers. The most prevalent domain architecture in the metazoan animal genomes studied was the BTB/kelch domain organisation and we uncovered 3 subgroups of human BTB/kelch proteins. Sequence analysis of the kelch-repeat domains of the most robustly-related subgroups identified differences in β-propeller organisation that could provide direction for experimental study of protein-binding characteristics. Conclusion The kelch-repeat superfamily constitutes a

  2. Normalization of Complete Genome Characteristics: Application to Evolution from Primitive Organisms to Homo sapiens.

    Science.gov (United States)

    Sorimachi, Kenji; Okayasu, Teiji; Ohhira, Shuji

    2015-04-01

    Normalized nucleotide and amino acid contents of complete genome sequences can be visualized as radar charts. The shapes of these charts depict the characteristics of an organism's genome. The normalized values calculated from the genome sequence theoretically exclude experimental errors. Further, because normalization is independent of both target size and kind, this procedure is applicable not only to single genes but also to whole genomes, which consist of a huge number of different genes. In this review, we discuss the applications of the normalization of the nucleotide and predicted amino acid contents of complete genomes to the investigation of genome structure and to evolutionary research from primitive organisms to Homo sapiens. Some of the results could never have been obtained from the analysis of individual nucleotide or amino acid sequences but were revealed only after the normalization of nucleotide and amino acid contents was applied to genome research. The discovery that genome structure was homogeneous was obtained only after normalization methods were applied to the nucleotide or predicted amino acid contents of genome sequences. Normalization procedures are also applicable to evolutionary research. Thus, normalization of the contents of whole genomes is a useful procedure that can help to characterize organisms.

  3. Building the genomic nation: 'Homo Brasilis' and the 'Genoma Mexicano' in comparative cultural perspective.

    Science.gov (United States)

    Kent, Michael; García-Deister, Vivette; López-Beltrán, Carlos; Santos, Ricardo Ventura; Schwartz-Marín, Ernesto; Wade, Peter

    2015-12-01

    This article explores the relationship between genetic research, nationalism and the construction of collective social identities in Latin America. It makes a comparative analysis of two research projects--the 'Genoma Mexicano' and the 'Homo Brasilis'--both of which sought to establish national and genetic profiles. Both have reproduced and strengthened the idea of their respective nations of focus, incorporating biological elements into debates on social identities. Also, both have placed the unifying figure of the mestizo/mestiço at the heart of national identity constructions, and in so doing have displaced alternative identity categories, such as those based on race. However, having been developed in different national contexts, these projects have had distinct scientific and social trajectories: in Mexico, the genomic mestizo is mobilized mainly in relation to health, while in Brazil the key arena is that of race. We show the importance of the nation as a frame for mobilizing genetic data in public policy debates, and demonstrate how race comes in and out of focus in different Latin American national contexts of genomic research, while never completely disappearing.

  4. Spatial construction skills of chimpanzees (Pan troglodytes) and young human children (Homo sapiens sapiens).

    Science.gov (United States)

    Potì, Patrizia; Hayashi, Misato; Matsuzawa, Tetsuro

    2009-07-01

    Spatial construction tasks are basic tests of visual-spatial processing. Two studies have assessed spatial construction skills in chimpanzees (Pan troglodytes) and young children (Homo sapiens sapiens) with a block modelling task. Study 1a subjects were three young chimpanzees and five adult chimpanzees. Study 1b subjects were 30 human children belonging to five age groups (24, 30, 36, 42, 48 months). Subjects were given three model constructions to reproduce: Line, Cross-Stack and Arch, which differed in type and number of spatial relations and dimensions, but required comparable configurational understanding. Subjects' constructions were rated for accuracy. Our results show that: (1) chimpanzees are relatively advanced in constructing in the vertical dimension; (2) Among chimpanzees only adults make accurate copies of constructions; (3) Chimpanzees do not develop in the direction of constructing in two dimensions as human children do starting from age 30 months. The pattern of development of construction skills in chimpanzees partially diverges from that of human children and indicates that spatial analysis and spatial representation are partially different in the two species.

  5. Age estimation in fossil hominins: comparing dental development in early Homo with modern humans.

    Science.gov (United States)

    Dean, M Christopher; Liversidge, Helen M

    2015-01-01

    Previous studies have used molar tooth eruption as a comparative marker of maturation in early fossil hominins. However, tooth eruption and tooth formation are independent maturational processes. To determine whether estimates of age for entering a stage of dental development in three early hominin fossils fell within the distribution of a modern human sample. This study used a comparative model of dental development to identify the stages of dental development most likely to provide information about length of the growth period in early fossil hominins. Age estimates for stages of dental development in fossils were superimposed onto a normal distribution of the same radiographically defined stages derived from a sample of 6540 children of diverse geographical origin. Both within the dentition of S7-37, from Sangiran, Java, but also for stages of two other specimens (KNM-WT 15000 from Kenya and StW 151 from South Africa), all age estimates for later stages of tooth formation fell within the modern sample range. A pattern appears to exist in early Homo where, both within and between developing dentitions, age estimates for stages of P4, M2 and M3 tooth formation fell consistently among the more advanced individuals of the modern human sample.

  6. Cold Spring Harbor symposia on quantitative biology: Volume 51, Molecular biology of Homo sapiens

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    Thirteen years marked the time between the discovery of the double helix in 1953 and the elucidation of the genetic code in 1966. A similar interval has now passed since the development by Cohen and Boyer of a simple procedure for the cloning of selective DNA fragments. The scientific advances made possible by the subsequent modification and elaboration of these original cloning procedures now amaze, stimulate, and increasingly often overwhelm us. Facts that until recently were virtually unobtainable now flow forth almost effortlessly. Most excitingly, the frenetic pace of these new discoveries, instead of marking the impending end of a glorious moment of learning, give every indication of opening up scientific frontiers that will take hundreds if not thousands of years to explore thoroughly. This new era of enlightenment is nowhere more apparent than in our newfound ability to study ourselves at the molecular level. This volume is the first of two collections of papers submitted by the contributors to the Cold Spring Harbor symposia on quantitative biology for 1986 - molecular biology of Homo sapiens. Contained in this collection are 80 papers grouped into sessions entitled Human Gene Map, Genetic Diagnosis, Human Evolution, and Drugs Made Off Human Genes.

  7. Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment.

    Science.gov (United States)

    Klein, Christian L; Rovelli, Giorgio; Springer, Wolfdieter; Schall, Christoph; Gasser, Thomas; Kahle, Philipp J

    2009-11-01

    Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most common cause of autosomal-dominant familial and late-onset sporadic Parkinson's disease (PD). LRRK2 is a large multi-domain protein featuring a GTP-binding C-terminal of Ras of complex proteins (ROC) (ROCO) domain combination unique for the ROCO protein family, directly followed by a kinase domain. Dimerization is a well-established phenomenon among protein kinases. Here, we confirm LRRK2 self-interaction, and provide evidence for general homo- and heterodimerization potential among the ROCO kinase family (LRRK2, LRRK1, and death-associated protein kinase 1). The ROCO domain was critically, though not exclusively involved in dimerization, as a LRRK2 deletion mutant lacking the ROCO domain retained dimeric properties. GTP binding did not appear to influence ROCO(LRRK2) self-interaction. Interestingly, ROCO(LRRK2) fragments exerted an inhibitory effect on both wild-type and the elevated G2019S LRRK2 autophosphorylation activity. Insertion of PD mutations into ROCO(LRRK2) reduced self-interaction and led to a reduction of LRRK2 kinase inhibition. Collectively, these results suggest a functional link between ROCO interactions and kinase activity of wild-type and mutant LRRK2. Importantly, our finding of ROCO(LRRK2) fragment-mediated LRRK2 kinase inhibition offers a novel lead for drug design and thus might have important implications for new therapeutic avenues in PD.

  8. Ligand Dependent Switch from RXR Homo- to RXR-NURR1 Heterodimerization.

    Science.gov (United States)

    Scheepstra, Marcel; Andrei, Sebastian A; de Vries, Rens M J M; Meijer, Femke A; Ma, Jian-Nong; Burstein, Ethan S; Olsson, Roger; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, Luc

    2017-09-20

    Retinoid X receptors (RXRs) play key roles in many physiological processes in both the periphery and central nervous system. In addition, RXRs form heterodimers with other nuclear receptors to exert their physiological effects. The nuclear receptor related 1 protein (NURR1) is particularly interesting because of its role in promoting differentiation and survival of dopamine neurons. However, only a small number of RXR-heterodimer selective modulators are available, with limited chemical diversity. This work describes the synthesis, biochemical evaluation, and structural elucidation of a novel series of RXR ligands with strongly biased interactions with RXRα-NURR1 heterodimers. Targeted modifications to the small molecule biaryl scaffold caused local RXRα side-chain disturbances and displacement of secondary structural elements upon ligand binding. This resulted in the repositioning of protein helices in the heterodimer interface of RXRα, alterations in homo- versus heterodimer formation, and modulation of activation function 2 (AF2). The data provide a rationale for the design of RXR ligands consisting of a highly conserved hydrophilic region, strongly contributing to the ligand affinity, and a variable hydrophobic region, which efficiently probes the effects of structural changes at the level of the ligand on co-regulator recruitment or the RXRα-NURR1 dimerization interface.

  9. Experimental studies illuminate the cultural transmission of percussive technologies in Homo and Pan.

    Science.gov (United States)

    Whiten, Andrew

    2015-11-19

    The complexity of Stone Age tool-making is assumed to have relied upon cultural transmission, but direct evidence is lacking. This paper reviews evidence bearing on this question provided through five related empirical perspectives. Controlled experimental studies offer special power in identifying and dissecting social learning into its diverse component forms, such as imitation and emulation. The first approach focuses on experimental studies that have discriminated social learning processes in nut-cracking by chimpanzees. Second come experiments that have identified and dissected the processes of cultural transmission involved in a variety of other force-based forms of chimpanzee tool use. A third perspective is provided by field studies that have revealed a range of forms of forceful, targeted tool use by chimpanzees, that set percussion in its broader cognitive context. Fourth are experimental studies of the development of flint knapping to make functional sharp flakes by bonobos, implicating and defining the social learning and innovation involved. Finally, new and substantial experiments compare what different social learning processes, from observational learning to teaching, afford good quality human flake and biface manufacture. Together these complementary approaches begin to delineate the social learning processes necessary to percussive technologies within the Pan-Homo clade. © 2015 The Author(s).

  10. Silicon homo-heterojunction solar cells: A promising candidate to realize high performance more stably

    Directory of Open Access Journals (Sweden)

    Miao Tan

    2017-08-01

    Full Text Available We have investigated the influences of diverse physical parameters on the performances of a silicon homo-heterojunction (H-H solar cell, which encompasses both homojunction and heterojunction, together with their underlying mechanisms by the aid of AFORS-HET simulation. It is found that the performances of H-H solar cell are less sensitive to (i the work function of the transparent conductive oxide layer, (ii the interfacial density of states at the front hydrogenated amorphous silicon/crystalline silicon (a-Si:H/c-Si interface, (iii the peak dangling bond defect densities within the p-type a-Si:H (p-a-Si:H layer, and (iv the doping concentration of the p-a-Si:H layer, when compared to that of the conventional heterojunction with intrinsic thin layer (HIT counterparts. These advantages are due to the fact that the interfacial recombination and the recombination within the a-Si:H region are less affected by all the above parameters, which fundamentally benefit from the field-effect passivation of the homojunction. Therefore, the design of H-H structure can provide an opportunity to produce high-efficiency solar cells more stably.

  11. Silicon homo-heterojunction solar cells: A promising candidate to realize high performance more stably

    Science.gov (United States)

    Tan, Miao; Zhong, Sihua; Wang, Wenjie; Shen, Wenzhong

    2017-08-01

    We have investigated the influences of diverse physical parameters on the performances of a silicon homo-heterojunction (H-H) solar cell, which encompasses both homojunction and heterojunction, together with their underlying mechanisms by the aid of AFORS-HET simulation. It is found that the performances of H-H solar cell are less sensitive to (i) the work function of the transparent conductive oxide layer, (ii) the interfacial density of states at the front hydrogenated amorphous silicon/crystalline silicon (a-Si:H/c-Si) interface, (iii) the peak dangling bond defect densities within the p-type a-Si:H (p-a-Si:H) layer, and (iv) the doping concentration of the p-a-Si:H layer, when compared to that of the conventional heterojunction with intrinsic thin layer (HIT) counterparts. These advantages are due to the fact that the interfacial recombination and the recombination within the a-Si:H region are less affected by all the above parameters, which fundamentally benefit from the field-effect passivation of the homojunction. Therefore, the design of H-H structure can provide an opportunity to produce high-efficiency solar cells more stably.

  12. The type specimen (LB1) of Homo floresiensis did not have Laron syndrome.

    Science.gov (United States)

    Falk, Dean; Hildebolt, Charles; Smith, Kirk; Jungers, William; Larson, Susan; Morwood, Michael; Sutikna, Thomas; Jatmiko; Saptomo, E Wahyu; Prior, Fred

    2009-09-01

    The type specimen (LB1) of Homo floresiensis has been hypothesized to be a pathological human afflicted with Laron Syndrome (LS), a type of primary growth hormone insensitivity (Hershkovitz et al.: Am J Phys Anthropol 134 [2007] 198-208). Comparing measurements, photographs and three-dimensional, computed-tomography reconstructions of LB1 with data and diagnoses from the literature on LS, we critically evaluate numerous skull and postcranial traits that Hershkovitz et al. identified as being shared by LB1 and patients with LS. The statements regarding most of these traits are new to the clinical literature and lack quantitative support. LB1 and patients with LS differ markedly in the size and shape of the cranium; thickness and pneumatization of cranial bones; morphology of the face, mandible, teeth, and chin; form of the shoulder, wrist, and pelvis; and general body proportions including relative foot size. Claims that patients with LS are similar to LB1 in displaying protracted scapulae, short clavicles, low degrees of humeral torsion, flaring ilia, and curved tibiae are not supported by data or corroborating images. Some points of similarity (e.g., femoral neck-shaft angle, femoral bicondylar angle, and estimated stature) can be found in other hominins, and cannot be considered diagnostic. From our review and analysis, we conclude that LB1 did not suffer from LS.

  13. Reconstruction of Protein-Protein Interaction Network of Insulin Signaling in Homo Sapiens

    Directory of Open Access Journals (Sweden)

    Saliha Durmuş Tekir

    2010-01-01

    Full Text Available Diabetes is one of the most prevalent diseases in the world. Type 1 diabetes is characterized by the failure of synthesizing and secreting of insulin because of destroyed pancreatic β-cells. Type 2 diabetes, on the other hand, is described by the decreased synthesis and secretion of insulin because of the defect in pancreatic β-cells as well as by the failure of responding to insulin because of malfunctioning of insulin signaling. In order to understand the signaling mechanisms of responding to insulin, it is necessary to identify all components in the insulin signaling network. Here, an interaction network consisting of proteins that have statistically high probability of being biologically related to insulin signaling in Homo sapiens was reconstructed by integrating Gene Ontology (GO annotations and interactome data. Furthermore, within this reconstructed network, interacting proteins which mediate the signal from insulin hormone to glucose transportation were identified using linear paths. The identification of key components functioning in insulin action on glucose metabolism is crucial for the efforts of preventing and treating type 2 diabetes mellitus.

  14. New interpretation of the Gran Dolina-TD6 bearing Homo antecessor deposits through sedimentological analysis

    Science.gov (United States)

    Campaña, I.; Pérez-González, A.; Benito-Calvo, A.; Rosell, J.; Blasco, R.; de Castro, J. M. Bermúdez; Carbonell, E.; Arsuaga, J. L.

    2016-10-01

    Gran Dolina is a cavity infilled by at least 25 m of Pleistocene sediments. This sequence contains the TD6 stratigraphic unit, whose records include around 170 hominin bones that have allowed the definition of a new species, Homo antecessor. This fossil accumulation was studied as a single assemblage and interpreted as a succession of several human home bases. We propose a complete stratigraphic context and sedimentological interpretation for TD6, analyzing the relationships between the sedimentary facies, the clasts and archaeo-palaeontological remains. The TD6 unit has been divided into three sub-units and 13 layers. Nine sedimentary facies have been defined. Hominin remains appear related to three different sedimentary facies: debris flow facies, channel facies and floodplain facies. They show three kinds of distribution: first a group of scattered fossils, then a group with layers of fossils in fluvial facies, and third a group with a layer of fossils in mixed fluvial and gravity flow facies. The results of this work suggest that some of these hominin remains accumulated in the cave by geological processes, coming from the adjacent slope above the cave or the cave entry, as the palaeogeography and sedimentary characteristics of these allochthonous facies suggest.

  15. Pair-bonding, romantic love, and evolution: the curious case of Homo sapiens.

    Science.gov (United States)

    Fletcher, Garth J O; Simpson, Jeffry A; Campbell, Lorne; Overall, Nickola C

    2015-01-01

    This article evaluates a thesis containing three interconnected propositions. First, romantic love is a "commitment device" for motivating pair-bonding in humans. Second, pair-bonding facilitated the idiosyncratic life history of hominins, helping to provide the massive investment required to rear children. Third, managing long-term pair bonds (along with family relationships) facilitated the evolution of social intelligence and cooperative skills. We evaluate this thesis by integrating evidence from a broad range of scientific disciplines. First, consistent with the claim that romantic love is an evolved commitment device, our review suggests that it is universal; suppresses mate-search mechanisms; has specific behavioral, hormonal, and neuropsychological signatures; and is linked to better health and survival. Second, we consider challenges to this thesis posed by the existence of arranged marriage, polygyny, divorce, and infidelity. Third, we show how the intimate relationship mind seems to be built to regulate and monitor relationships. Fourth, we review comparative evidence concerning links among mating systems, reproductive biology, and brain size. Finally, we discuss evidence regarding the evolutionary timing of shifts to pair-bonding in hominins. We conclude there is interdisciplinary support for the claim that romantic love and pair-bonding, along with alloparenting, played critical roles in the evolution of Homo sapiens.

  16. Homo- and heterofermentative lactobacilli differently affect sugarcane-based fuel ethanol fermentation.

    Science.gov (United States)

    Basso, Thiago Olitta; Gomes, Fernanda Sgarbosa; Lopes, Mario Lucio; de Amorim, Henrique Vianna; Eggleston, Gillian; Basso, Luiz Carlos

    2014-01-01

    Bacterial contamination during industrial yeast fermentation has serious economic consequences for fuel ethanol producers. In addition to deviating carbon away from ethanol formation, bacterial cells and their metabolites often have a detrimental effect on yeast fermentative performance. The bacterial contaminants are commonly lactic acid bacteria (LAB), comprising both homo- and heterofermentative strains. We have studied the effects of these two different types of bacteria upon yeast fermentative performance, particularly in connection with sugarcane-based fuel ethanol fermentation process. Homofermentative Lactobacillus plantarum was found to be more detrimental to an industrial yeast strain (Saccharomyces cerevisiae CAT-1), when compared with heterofermentative Lactobacillus fermentum, in terms of reduced yeast viability and ethanol formation, presumably due to the higher titres of lactic acid in the growth medium. These effects were only noticed when bacteria and yeast were inoculated in equal cell numbers. However, when simulating industrial fuel ethanol conditions, as conducted in Brazil where high yeast cell densities and short fermentation time prevail, the heterofermentative strain was more deleterious than the homofermentative type, causing lower ethanol yield and out competing yeast cells during cell recycle. Yeast overproduction of glycerol was noticed only in the presence of the heterofermentative bacterium. Since the heterofermentative bacterium was shown to be more deleterious to yeast cells than the homofermentative strain, we believe our findings could stimulate the search for more strain-specific antimicrobial agents to treat bacterial contaminations during industrial ethanol fermentation.

  17. Greater Emphasis on Female Attractiveness in Homo Sapiens: A Revised Solution to an Old Evolutionary Riddle

    Directory of Open Access Journals (Sweden)

    Jonathan Gottschall

    2007-04-01

    Full Text Available Substantial evidence from psychology and cross-cultural anthropology supports a general rule of greater emphasis on female physical attractiveness in Homo sapiens. As sensed by Darwin (1871 and clarified by Trivers (1972, generally higher female parental investment is a key determinant of a common pattern of sexual selection in which male animals are more competitive, more eager sexually and more conspicuous in courtship display, ornamentation, and coloration. Therefore, given the larger minimal and average parental investment of human females, keener physical attractiveness pressure among women has long been considered an evolutionary riddle. This paper briefly surveys previous thinking on the question, before offering a revised explanation for why we should expect humans to sharply depart from general zoological pattern of greater emphasis on male attractiveness. This contribution hinges on the argument that humans have been seen as anomalies mainly because we have been held up to the wrong zoological comparison groups. I argue that humans are a partially sex-role reversed species, and more emphasis on female physical attractiveness is relatively common in such species. This solution to the riddle, like those of other evolutionists, is based on peculiarities in human mating behavior, so this paper is also presented as a refinement of current thinking about the evolution of human mating preferences.

  18. Similar Efficacies of Selection Shape Mitochondrial and Nuclear Genes in Both Drosophila melanogaster and Homo sapiens.

    Science.gov (United States)

    Cooper, Brandon S; Burrus, Chad R; Ji, Chao; Hahn, Matthew W; Montooth, Kristi L

    2015-08-21

    Deleterious mutations contribute to polymorphism even when selection effectively prevents their fixation. The efficacy of selection in removing deleterious mitochondrial mutations from populations depends on the effective population size (Ne) of the mitochondrial DNA and the degree to which a lack of recombination magnifies the effects of linked selection. Using complete mitochondrial genomes from Drosophila melanogaster and nuclear data available from the same samples, we reexamine the hypothesis that nonrecombining animal mitochondrial DNA harbor an excess of deleterious polymorphisms relative to the nuclear genome. We find no evidence of recombination in the mitochondrial genome, and the much-reduced level of mitochondrial synonymous polymorphism relative to nuclear genes is consistent with a reduction in Ne. Nevertheless, we find that the neutrality index, a measure of the excess of nonsynonymous polymorphism relative to the neutral expectation, is only weakly significantly different between mitochondrial and nuclear loci. This difference is likely the result of the larger proportion of beneficial mutations in X-linked relative to autosomal loci, and we find little to no difference between mitochondrial and autosomal neutrality indices. Reanalysis of published data from Homo sapiens reveals a similar lack of a difference between the two genomes, although previous studies have suggested a strong difference in both species. Thus, despite a smaller Ne, mitochondrial loci of both flies and humans appear to experience similar efficacies of purifying selection as do loci in the recombining nuclear genome.

  19. Temporal coherence for pure tones in budgerigars (Melopsittacus undulatus) and humans (Homo sapiens).

    Science.gov (United States)

    Neilans, Erikson G; Dent, Micheal L

    2015-02-01

    Auditory scene analysis has been suggested as a universal process that exists across all animals. Relative to humans, however, little work has been devoted to how animals perceptually isolate different sound sources. Frequency separation of sounds is arguably the most common parameter studied in auditory streaming, but it is not the only factor contributing to how the auditory scene is perceived. Researchers have found that in humans, even at large frequency separations, synchronous tones are heard as a single auditory stream, whereas asynchronous tones with the same frequency separations are perceived as 2 distinct sounds. These findings demonstrate how both the timing and frequency separation of sounds are important for auditory scene analysis. It is unclear how animals, such as budgerigars (Melopsittacus undulatus), perceive synchronous and asynchronous sounds. In this study, budgerigars and humans (Homo sapiens) were tested on their perception of synchronous, asynchronous, and partially overlapping pure tones using the same psychophysical procedures. Species differences were found between budgerigars and humans in how partially overlapping sounds were perceived, with budgerigars more likely to segregate overlapping sounds and humans more apt to fuse the 2 sounds together. The results also illustrated that temporal cues are particularly important for stream segregation of overlapping sounds. Lastly, budgerigars were found to segregate partially overlapping sounds in a manner predicted by computational models of streaming, whereas humans were not.

  20. Gracility of the modern Homo sapiens skeleton is the result of decreased biomechanical loading.

    Science.gov (United States)

    Ryan, Timothy M; Shaw, Colin N

    2015-01-13

    The postcranial skeleton of modern Homo sapiens is relatively gracile compared with other hominoids and earlier hominins. This gracility predisposes contemporary humans to osteoporosis and increased fracture risk. Explanations for this gracility include reduced levels of physical activity, the dissipation of load through enlarged joint surfaces, and selection for systemic physiological characteristics that differentiate modern humans from other primates. This study considered the skeletal remains of four behaviorally diverse recent human populations and a large sample of extant primates to assess variation in trabecular bone structure in the human hip joint. Proximal femur trabecular bone structure was quantified from microCT data for 229 individuals from 31 extant primate taxa and 59 individuals from four distinct archaeological human populations representing sedentary agriculturalists and mobile foragers. Analyses of mass-corrected trabecular bone variables reveal that the forager populations had significantly higher bone volume fraction, thicker trabeculae, and consequently lower relative bone surface area compared with the two agriculturalist groups. There were no significant differences between the agriculturalist and forager populations for trabecular spacing, number, or degree of anisotropy. These results reveal a correspondence between human behavior and bone structure in the proximal femur, indicating that more highly mobile human populations have trabecular bone structure similar to what would be expected for wild nonhuman primates of the same body mass. These results strongly emphasize the importance of physical activity and exercise for bone health and the attenuation of age-related bone loss.

  1. Evolutionary genetic analyses of MEF2C gene: implications for learning and memory in Homo sapiens.

    Science.gov (United States)

    Kalmady, Sunil V; Venkatasubramanian, Ganesan; Arasappa, Rashmi; Rao, Naren P

    2013-02-01

    MEF2C facilitates context-dependent fear conditioning (CFC) which is a salient aspect of hippocampus-dependent learning and memory. CFC might have played a crucial role in human evolution because of its advantageous influence on survival of species. In this study, we analyzed 23 orthologous mammalian gene sequences of MEF2C gene to examine the evidence for positive selection on this gene in Homo sapiens using Phylogenetic Analysis by Maximum Likelihood (PAML) and HyPhy software. Both PAML Bayes Empirical Bayes (BEB) and HyPhy Fixed Effects Likelihood (FEL) analyses supported significant positive selection on 4 codon sites in H. sapiens. Also, haplotter analysis revealed significant ongoing positive selection on this gene in Central European population. The study findings suggest that adaptive selective pressure on this gene might have influenced human evolution. Further research on this gene might unravel the potential role of this gene in learning and memory as well as its pathogenetic effect in certain hippocampal disorders with evolutionary basis like schizophrenia.

  2. The Homo sapiens 'hemibun': its developmental pattern and the problem of homology.

    Science.gov (United States)

    Nowaczewska, W; Kuźmiński, L

    2009-01-01

    The occipital bun is widely considered a Neanderthal feature. Its homology to the 'hemibun' observed in some European Upper Palaeolithic anatomically modern humans is a current problem. This study quantitatively evaluates the degree of occipital plane convexity in African and Australian modern human crania to analyse a relationship between this feature and some neurocranial variables. Neanderthal and European Upper Palaeolithic Homo sapiens crania were included in the analysis as well. The results of this study indicated that there is a significant relationship between the degree of occipital plane convexity and the following two features in the examined crania of modern humans: the ratio of the maximum neurocranial height to the maximum width of the vault and the ratio of bregma-lambda chord to bregma-lambda arc. The results also revealed that some H. sapiens crania (modern and fossil) show the Neanderthal shape of the occipital plane and that the neurocranial height and shape of parietal midsagittal profile has an influence on occipital plane convexity in the hominins included in this study. This study suggests that the occurrence of the great convexity of the occipital plane in the Neanderthals and H. sapiens is a "by-product" of the relationship between the same neurocranial features and there is no convincing evidence that the Neanderthal occipital bun and the similar structure in H. sapiens develop during ontogeny in the same way.

  3. Vibrational spectra, NBO, HOMO-LUMO and conformational stability studies of 4-hydroxythiobenzamide.

    Science.gov (United States)

    Sambathkumar, Kuppusamy

    2015-08-05

    In this work, the experimental and theoretical study on molecular structure, vibrational spectral analysis of 4-hydroxythiobenzamide (HTB) have been reported. The solid phase FTIR (4000-400 cm(-1)) and FT-Raman spectra (3500-50 cm(-1)) were recorded. The molecular geometry, harmonic vibrational frequencies and bonding features of HTB in the ground-state have been calculated by the density functional method (B3LYP) with 6-311+G(d,p) and 6-311++G(d,p) as basis sets. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of the fundamental modes of the compound were carried out. Stability of the molecule arising from hyperconjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The results show that the value of electron density (ED) in the σ(∗) antibonding orbitals and E((2)) energies confirms the occurrence of ICT (intra-molecular charge transfer) within the molecule. The UV spectrum was measured in ethanol solution. The energy and oscillator strength calculated by time-dependent density functional theory (TD-DFT) correlates with the experimental findings. The calculated molecular electrostatic potential (MESP), HOMO and LUMO energies show that charge transfer occurs within the molecule. Besides, the simulated infrared and Raman spectra of the title compound which show good agreement with observed spectra. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Understanding chemical reactivity for homo- and heterobifunctional protein cross-linking agents.

    Science.gov (United States)

    Chen, Fan; Nielsen, Simone; Zenobi, Renato

    2013-07-01

    Chemical cross-linking, combined with mass spectrometry, has been applied to map three-dimensional protein structures and protein-protein interactions. Proper choice of the cross-linking agent, including its reactive groups and spacer arm length, is of great importance. However, studies to understand the details of reactivity of the chemical cross-linkers with proteins are quite sparse. In this study, we investigated chemical cross-linking from the aspects of the protein structures and the cross-linking reagents involved, by using two structurally well-known proteins, glyceraldehyde 3-phosohate dehydrogenase and ribonuclease S. Chemical cross-linking reactivity was compared using a series of homo- and hetero-bifunctional cross-linkers, including bis(sulfosuccinimidyl) suberate, dissuccinimidyl suberate, bis(succinimidyl) penta (ethylene glycol), bis(succinimidyl) nona (ethylene glycol), m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester, 2-pyridyldithiol-tetraoxaoctatriacontane-N-hydrosuccinimide and succinimidyl-[(N-maleimidopropionamido)-tetracosaethyleneglycol]ester. The protein structure itself, especially the distances between target amino acid residues, was found to be a determining factor for the cross-linking efficiency. Moreover, the reactive groups of the chemical cross-linker also play an important role; a higher cross-linking reaction efficiency was found for maleimides compared to 2-pyrimidyldithiols. The reaction between maleimides and sulfhydryl groups is more favorable than that between N-hydroxysuccinimide esters and amine groups, although cysteine residues are less abundant in proteins compared to lysine residues. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Uncovering homo-and hetero-interactions on the cell membrane using single particle tracking approaches

    Science.gov (United States)

    Torreno-Pina, Juan A.; Manzo, Carlo; Garcia-Parajo, Maria F.

    2016-03-01

    The plasma membrane of eukaryotic cells is responsible for a myriad of functions that regulate cell physiology and plays a crucial role in a multitude of processes that include adhesion, migration, signaling recognition and cell-cell communication. This is accomplished by specific interactions between different membrane components such as lipids and proteins on the lipid bilayer but also through interactions with the underlying cortical actin cytoskeleton on the intracellular side and the glycocalyx matrix in close proximity to the extracellular side. Advanced biophysical techniques, including single particle tracking (SPT) have revealed that the lateral diffusion of molecular components on the plasma membrane represents a landmark manifestation of such interactions. Indeed, by studying changes in the diffusivity of individual membrane molecules, including sub-diffusion, confined diffusion and/or transient arrest of molecules in membrane compartments, it has been possible to gain insight on the nature of molecular interactions and to infer on its functional role for cell response. In this review, we will revise some exciting results where SPT has been crucial to reveal homo- and hetero-interactions on the cell membrane.

  6. Female-directed violence as a form of sexual coercion in humans (Homo sapiens).

    Science.gov (United States)

    Barbaro, Nicole; Shackelford, Todd K

    2016-11-01

    Male-perpetrated female-directed violence (FDV) may be associated with greater sexual access to a female. Accordingly, FDV is expected to be associated with greater copulation frequency. Research on nonhuman primates affirms this hypothesis, but no previous research has investigated this relationship in humans (Homo sapiens). The current research tests the hypothesis that FDV is associated with in-pair copulation frequency and, thus, may function as a form of sexual coercion. It was predicted that men who perpetrate FDV will secure more in-pair copulations than men who do not perpetrate violence (Prediction 1a), and that average monthly rates of FDV would positively correlate with in-pair copulation frequency (Prediction 1b). Male participants (n = 355) completed a survey, reporting limited demographic information (e.g., age, relationship length), in-pair copulation frequency, and history of physical violence perpetration. As predicted, violent men secured more in-pair copulations, on average, than nonviolent men, and monthly rates of violence positively correlated with in-pair copulation frequency. In humans, as in nonhuman primates, FDV by males may facilitate greater sexual access to a female. We discuss the implications of the current research for an evolutionary perspective on partner violence, and draw on research on nonhuman primates to highlight profitable avenues of research on FDV in humans. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. The Arrival of Homo sapiens into the Southern Cone at 14,000 Years Ago

    Science.gov (United States)

    Politis, Gustavo G.; Gutiérrez, María A.; Blasi, Adriana

    2016-01-01

    The Arroyo Seco 2 site contains a rich archaeological record, exceptional for South America, to explain the expansion of Homo sapiens into the Americas and their interaction with extinct Pleistocene mammals. The following paper provides a detailed overview of material remains found in the earliest cultural episodes at this multi-component site, dated between ca. 12,170 14C yrs B.P. (ca. 14,064 cal yrs B.P.) and 11,180 14C yrs B.P. (ca. 13,068 cal yrs B.P.). Evidence of early occupations includes the presence of lithic tools, a concentration of Pleistocene species remains, human-induced fractured animal bones, and a selection of skeletal parts of extinct fauna. The occurrence of hunter-gatherers in the Southern Cone at ca. 14,000 cal yrs B.P. is added to the growing list of American sites that indicate a human occupation earlier than the Clovis dispersal episode, but posterior to the onset of the deglaciation of the Last Glacial Maximum (LGM) in the North America. PMID:27683248

  8. Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia.

    Science.gov (United States)

    Sutikna, Thomas; Tocheri, Matthew W; Morwood, Michael J; Saptomo, E Wahyu; Jatmiko; Awe, Rokus Due; Wasisto, Sri; Westaway, Kira E; Aubert, Maxime; Li, Bo; Zhao, Jian-xin; Storey, Michael; Alloway, Brent V; Morley, Mike W; Meijer, Hanneke J M; van den Bergh, Gerrit D; Grün, Rainer; Dosseto, Anthony; Brumm, Adam; Jungers, William L; Roberts, Richard G

    2016-04-21

    Homo floresiensis, a primitive hominin species discovered in Late Pleistocene sediments at Liang Bua (Flores, Indonesia), has generated wide interest and scientific debate. A major reason this taxon is controversial is because the H. floresiensis-bearing deposits, which include associated stone artefacts and remains of other extinct endemic fauna, were dated to between about 95 and 12 thousand calendar years (kyr) ago. These ages suggested that H. floresiensis survived until long after modern humans reached Australia by ~50 kyr ago. Here we report new stratigraphic and chronological evidence from Liang Bua that does not support the ages inferred previously for the H. floresiensis holotype (LB1), ~18 thousand calibrated radiocarbon years before present (kyr cal. BP), or the time of last appearance of this species (about 17 or 13-11 kyr cal. BP). Instead, the skeletal remains of H. floresiensis and the deposits containing them are dated to between about 100 and 60 kyr ago, whereas stone artefacts attributable to this species range from about 190 to 50 kyr in age. Whether H. floresiensis survived after 50 kyr ago--potentially encountering modern humans on Flores or other hominins dispersing through southeast Asia, such as Denisovans--is an open question.

  9. The frontal bone in the genus Homo: a survey of functional and phylogenetic sources of variation.

    Science.gov (United States)

    Athreya, Sheela

    2012-01-01

    The frontal bone is a useful aspect of the craniofacial skeleton to study in physical anthropology because it contains several characters considered to be important for both population- and species-level distinctions. These include forehead (frontal squama) inclination and supraorbital morphology. Because it lies at the interface between the anterior neurocranium and the upper face, it is also informative about the evolution of both of these regions of the skull. Previous research on frontal bone morphology can be grouped into two broad categories. One set of studies explored the relationship between craniofacial structure and function in an attempt to explain biological sources of variation in the torus development of various extant primate species, including modern humans. The second group of studies examined geographical and temporal patterns of variation in frontal morphology to make inferences about the phylogenetic relationship relationships among fossil hominin populations in the Pleistocene. This paper offers a review of both phylogenetic and functional studies of variation in frontal bone morphology, and synthesizes them to offer a comprehensive understanding of what the frontal bone can tell us about bio-behavioral and evolutionary differences both among extant and extinct members of the genus Homo.

  10. Emprego de catalisadores à base de níquel para homo- e copolimerização de estireno The use of nickel-based catalysts for homo-and copolymerization of styrene

    Directory of Open Access Journals (Sweden)

    Luis Carlos Ferreira Jr.

    2004-12-01

    Full Text Available This review deals with the homo- and copolymerization of styrene with nickel catalysts. The catalytic activity, polymer stereoregularity, polymer molecular weight and polydispersity are dependent upon nickel ligands and reaction parameters. Catalysts supported on silica, treated with methylaluminoxane (MAO, have shown higher stereospecificity and activity compared to homogeneous ones. The influence of these parameters is discussed focusing on the elucidation of some aspects of the polymerization mechanism.

  11. Homo-FRET Based Biosensors and Their Application to Multiplexed Imaging of Signalling Events in Live Cells

    Science.gov (United States)

    Warren, Sean C.; Margineanu, Anca; Katan, Matilda; Dunsby, Chris; French, Paul M. W.

    2015-01-01

    Multiplexed imaging of Förster Resonance Energy Transfer (FRET)-based biosensors potentially presents a powerful approach to monitoring the spatio-temporal correlation of signalling pathways within a single live cell. Here, we discuss the potential of homo-FRET based biosensors to facilitate multiplexed imaging. We demonstrate that the homo-FRET between pleckstrin homology domains of Akt (Akt-PH) labelled with mCherry may be used to monitor 3′-phosphoinositide accumulation in live cells and show how global analysis of time resolved fluorescence anisotropy measurements can be used to quantify this accumulation. We further present multiplexed imaging readouts of calcium concentration, using fluorescence lifetime measurements of TN-L15-a CFP/YFP based hetero-FRET calcium biosensor-with 3′-phosphoinositide accumulation. PMID:26133241

  12. Study on Tonghaosu and Its Analogs:Isolation, Structure Identification and Synthesis of Antifeedant B-ring-homo-tonghaosu

    Institute of Scientific and Technical Information of China (English)

    CHEN,Li(陈立); YIN,Biao-Lin(尹标林); XU,Han-Hong(徐汉虹); CHIU,Ming-Hua(邱明华); WU,Yu-Lin(吴毓林)

    2004-01-01

    The methanolic extract from a Chinese endemic Chrysanthemum plant, Dendranthema indicum var. aromaticum, was found to show high antifeeding activity against Pieris brassicae L., and by bioassay-guided separation, the active component, B-ring-homo-tonghaosu, 2-(2',4'-hexadiynylidene)-1,6-dioxaspiro-[4,5]-dec-3-ene (2) was isolated. Its structure was elucidated by comparing its spectroscopic data with those of 2 reported in the literatures. Furthermore new convenient total synthesis methods of B-ring-homo-tonghaosu were also developed to confirm its structure and make its further application in crop protection available. In addition, extensive comparison of spectroscopic data showed that the structure of compound 21 reported in literature should be revised to 2.

  13. Anti-tumor Activities of Novel Estrogen Compound 17aα-D-Homo-Ethynylestradiol-3-Acetate

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ze-wei; TANG Wei-sheng; SHEN Xiu; HAN Ying; WANG Xiao-xue; ZHANG Liang-an

    2008-01-01

    Objective:To study the anti-tumor activities of novel estrogen compound 17a α-D-homo-ethvnvlestradiol-3-acetate in vitro and in vivo. Methods:In vitro anti-tumor activity was assayed in adenoma cells A549 and human liver cancer cells Bel-7402 using MTT method,and half-inhibitory concentration (IC50)were observed. In vivo the pulmonary adenoma LA795 cells was selected and the conventional assay method of anti-tumor activity was employed.5,7.5,10 mg/kg of 17a α-D-homo-ethynylestradiol-3-acetate was administered by i.P., and tumor-inhibitory rate, thymus and spleen indexes,bone marrow cells(BMC)were observed. Results:IC50 of 17a α-D-homo-ethynylestradiol-3-acetate in vitro for A549 and Bel-7402 cells were 12.28 μg/ml and 17.79 μg/ml, respectively.In vivo the highest tumor-inhibitory rates for LA795 was 60.0%(P<0.01).The drug had hardly any side-effect in spleen indexes,thymus indexes,and BMC compared with control mice. Nevertheless,compared with the positive control drug cyclophosphamide(CY),thymus and spleen indexes,BMC showed obvious diffefences(P<0.01). Conclusion:17a α-D-homo-ethynylestradiol-3-acetate has obvious anti-tumor activities in vitro and in vivo with low side-effect, thus worth further investigation.

  14. FOSSIL REPTILES FROM THE PLEISTOCENE HOMO-BEARING LOCALITY OF BUIA (ERITREA, NORTHERN DANAKIL DEPRESSION)

    OpenAIRE

    2004-01-01

    The early to early-Middle Pleistocene fossil assemblage form the Buia area (Northern Danakil Depression, Eritrea) hosts, along with Homo and several other large mammal taxa, the following reptiles: Nile Crocodile, Crocodylus niloticus, Serrated Hinged Terrapin, Pelusios cf. P. sinuatus, Nile Monitor, Varanus niloticus and African Rock Python, Python gr. sebae. All the identified taxa belong to living species. At present, these taxa do not occur in the Northern Danakil depression since it is a...

  15. Tube-in-tube reactor as a useful tool for homo- and heterogeneous olefin metathesis under continuous flow mode.

    Science.gov (United States)

    Skowerski, Krzysztof; Czarnocki, Stefan J; Knapkiewicz, Paweł

    2014-02-01

    A tube-in-tube reactor was successfully applied in homo- and heterogeneous olefin metathesis reactions under continuous flow mode. It was shown that the efficient removal of ethylene facilitated by connection of the reactor with a vacuum pump significantly improves the outcome of metathesis reactions. The beneficial aspects of this approach are most apparent in reactions performed at low concentration, such as macrocyclization reactions. The established system allows achievement of both improved yield and selectivity, and is ideal for industrial applications.

  16. Inhibition of Homo-coupling of Arylboronic Acids in Ligand Free Pd(Ⅱ)-Catalyzed Suzuki Reaction

    Institute of Scientific and Technical Information of China (English)

    TAO,Xiao-Chun; ZHANG,Yue-Ping; HE,Tian-Xiong; SHEN,Dong

    2007-01-01

    A series of solvents were examined for the ligand free Pd(Ⅱ)-catalyzed Suzuki reaction of 4-bromotoluene with phenylboronic acid. It was found that the PdCl2/i-PrOH system could efficiently inhibit the homo-coupling of phenylboronic acid and give a cross-coupling product in high yields. The substrates with a wide variety of functional groups were tolerated in the system. A possible mechanism for this system was proposed.

  17. The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases (PDE4s).

    Science.gov (United States)

    Xie, Moses; Blackman, Brigitte; Scheitrum, Colleen; Mika, Delphine; Blanchard, Elise; Lei, Tao; Conti, Marco; Richter, Wito

    2014-05-01

    PDE4s (type 4 cyclic nucleotide phosphodiesterases) are divided into long and short forms by the presence or absence of conserved N-terminal domains termed UCRs (upstream conserved regions). We have shown previously that PDE4D2, a short variant, is a monomer, whereas PDE4D3, a long variant, is a dimer. In the present study, we have determined the apparent molecular masses of various long and short PDE4 variants by size-exclusion chromatography and sucrose density-gradient centrifugation. Our results indicate that dimerization is a conserved property of all long PDE4 forms, whereas short forms are monomers. Dimerization is mediated by the UCR domains. Given their high sequence conservation, the UCR domains mediate not only homo-oligomerization, but also hetero-oligomerization of distinct PDE4 long forms as detected by co-immunoprecipitation assays and FRET microscopy. Endogenous PDE4 hetero-oligomers are, however, low in abundance compared with homo-dimers, revealing the presence of mechanisms that predispose PDE4s towards homo-oligomerization. Oligomerization is a prerequisite for the regulatory properties of the PDE4 long forms, such as their PKA (protein kinase A)-dependent activation, but is not necessary for PDE4 protein-protein interactions. As a result, individual PDE4 protomers may independently mediate protein-protein interactions, providing a mechanism whereby PDE4s contribute to the assembly of macromolecular signalling complexes.

  18. Penicillin-binding protein 5 can form a homo-oligomeric complex in the inner membrane of Escherichia coli.

    Science.gov (United States)

    Skoog, Karl; Bruzell, Filippa Stenberg; Ducroux, Aurélie; Hellberg, Mårten; Johansson, Henrik; Lehtiö, Janne; Högbom, Martin; Daley, Daniel O

    2011-09-01

    Penicillin-binding protein 5 (PBP5) is a DD-carboxypeptidase, which cleaves the terminal D-alanine from the muramyl pentapeptide in the peptidoglycan layer of Escherichia coli and other bacteria. In doing so, it varies the substrates for transpeptidation and plays a key role in maintaining cell shape. In this study, we have analyzed the oligomeric state of PBP5 in detergent and in its native environment, the inner membrane. Both approaches indicate that PBP5 exists as a homo-oligomeric complex, most likely as a homo-dimer. As the crystal structure of the soluble domain of PBP5 (i.e., lacking the membrane anchor) shows a monomer, we used our experimental data to generate a model of the homo-dimer. This model extends our understanding of PBP5 function as it suggests how PBP5 can interact with the peptidoglycan layer. It suggests that the stem domains interact and the catalytic domains have freedom to move from the position observed in the crystal structure. This would allow the catalytic domain to have access to pentapeptides at different distances from the membrane. Copyright © 2011 The Protein Society.

  19. Out of Africa: new hypotheses and evidence for the dispersal of Homo sapiens along the Indian Ocean rim.

    Science.gov (United States)

    Petraglia, Michael D; Haslam, Michael; Fuller, Dorian Q; Boivin, Nicole; Clarkson, Chris

    2010-06-01

    The dispersal of Homo sapiens out of Africa is a significant topic in human evolutionary studies. Most investigators agree that our species arose in Africa and subsequently spread out to occupy much of Eurasia. Researchers have argued that populations expanded along the Indian Ocean rim at ca 60,000 years ago during a single rapid dispersal event, probably employing a coastal route towards Australasia. Archaeologists have been relatively silent about the movement and expansion of human populations in terrestrial environments along the Indian Ocean rim, although it is clear that Homo sapiens reached Australia by ca 45,000 years ago. Here, we synthesize and document current genetic and archaeological evidence from two major landmasses, the Arabian peninsula and the Indian subcontinent, regions that have been underplayed in the story of out of Africa dispersals. We suggest that modern humans were present in Arabia and South Asia earlier than currently believed, and probably coincident with the presence of Homo sapiens in the Levant between ca 130 and 70,000 years ago. We show that climatic and environmental fluctuations during the Late Pleistocene would have had significant demographic effects on Arabian and South Asian populations, though indigenous populations would have responded in different ways. Based on a review of the current genetic, archaeological and environmental data, we indicate that demographic patterns in Arabia and South Asia are more interesting and complex than surmised to date.

  20. A Profile of an ‘A’ List Homo –Habitus, Attitude, Boredom and The End of Enjoyment

    Directory of Open Access Journals (Sweden)

    Sasho Alexander Lambevski

    2015-05-01

    Full Text Available Embodying signifiers of silent suffering, frequently envenomed by envy disguised as patronising pity, enraged as a result of admiration never returned, duped by their naïve belief in gay (capitalist Eden, stress-ridden, moving through a psychosocial reality that almost never fails to disappoint, split between a deadly wish to speak in monotone with their larynxes, bodies and dicks, and a little flicker that tells them to resists this urge, too many homo men express, in the guise of the composite character I describe below, the emotional battleground created by the new bourgeoisie’s deployment of the breathtakingly beautiful masculine homo male body as a sign/image vehicle in asserting its own social domination in a late capitalist society. The character I develop here can be read as a simulation and fabulation of the homonormative new bourgeois self as a syndrome with a range of affective cripplings coming from the technologically assisted channelling of homosexual desire via the mass circulation of the imaginary of the homo new bourgeoisie. 

  1. A Profile of an ‘A’ List Homo –Habitus, Attitude, Boredom and The End of Enjoyment

    Directory of Open Access Journals (Sweden)

    Sasho Alexander Lambevski

    2015-04-01

    Full Text Available Embodying signifiers ofsilentsuffering, frequently envenomed by envy disguised as patronising pity, enraged as a result of admiration never returned, duped by their naïve belief in gay (capitalist Eden, stress-ridden, moving through a psychosocial reality that almost never fails to disappoint, split between a deadly wish to speak in monotone with their larynxes, bodies and dicks, and a little flicker that tells them to resists this urge, too many homo men express, in the guise of the composite character I describe below, the emotional battleground created by the new bourgeoisie’s deployment of the breathtakingly beautiful masculine homo male body as a sign/image vehicle in asserting its own social domination in a late capitalist society. The character I develop here can be read as a simulation and fabulation of the homonormative new bourgeoisself as a syndrome with a range of affective cripplings coming from the technologically assisted channelling of homosexual desire via the mass circulation of the imaginary of the homo new bourgeoisie.

  2. The homo-oligomerisation of both Sas-6 and Ana2 is required for efficient centriole assembly in flies.

    Science.gov (United States)

    Cottee, Matthew A; Muschalik, Nadine; Johnson, Steven; Leveson, Joanna; Raff, Jordan W; Lea, Susan M

    2015-05-23

    Sas-6 and Ana2/STIL proteins are required for centriole duplication and the homo-oligomerisation properties of Sas-6 help establish the ninefold symmetry of the central cartwheel that initiates centriole assembly. Ana2/STIL proteins are poorly conserved, but they all contain a predicted Central Coiled-Coil Domain (CCCD). Here we show that the Drosophila Ana2 CCCD forms a tetramer, and we solve its structure to 0.8 Å, revealing that it adopts an unusual parallel-coil topology. We also solve the structure of the Drosophila Sas-6 N-terminal domain to 2.9 Å revealing that it forms higher-order oligomers through canonical interactions. Point mutations that perturb Sas-6 or Ana2 homo-oligomerisation in vitro strongly perturb centriole assembly in vivo. Thus, efficient centriole duplication in flies requires the homo-oligomerisation of both Sas-6 and Ana2, and the Ana2 CCCD tetramer structure provides important information on how these proteins might cooperate to form a cartwheel structure.

  3. Mutations in a Conserved Domain of E. coli MscS to the Most Conserved Superfamily Residue Leads to Kinetic Changes.

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    Hannah R Malcolm

    Full Text Available In Escherichia coli (E. coli the mechanosensitive channel of small conductance, MscS, gates in response to membrane tension created from acute external hypoosmotic shock, thus rescuing the bacterium from cell lysis. E. coli MscS is the most well studied member of the MscS superfamily of channels, whose members are found throughout the bacterial and plant kingdoms. Homology to the pore lining helix and upper vestibule domain of E. coli MscS is required for inclusion into the superfamily. Although highly conserved, in the second half of the pore lining helix (TM3B, E. coli MscS has five residues significantly different from other members of the superfamily. In superfamilies such as this, it remains unclear why variations within such a homologous region occur: is it tolerance of alternate residues, or does it define functional variance within the superfamily? Point mutations (S114I/T, L118F, A120S, L123F, F127E/K/T and patch clamp electrophysiology were used to study the effect of changing these residues in E. coli MscS on sensitivity and gating. The data indicate that variation at these locations do not consistently lead to wildtype channel phenotypes, nor do they define large changes in mechanosensation, but often appear to effect changes in the E. coli MscS channel gating kinetics.

  4. Mutations in a Conserved Domain of E. coli MscS to the Most Conserved Superfamily Residue Leads to Kinetic Changes.

    Science.gov (United States)

    Malcolm, Hannah R; Blount, Paul

    2015-01-01

    In Escherichia coli (E. coli) the mechanosensitive channel of small conductance, MscS, gates in response to membrane tension created from acute external hypoosmotic shock, thus rescuing the bacterium from cell lysis. E. coli MscS is the most well studied member of the MscS superfamily of channels, whose members are found throughout the bacterial and plant kingdoms. Homology to the pore lining helix and upper vestibule domain of E. coli MscS is required for inclusion into the superfamily. Although highly conserved, in the second half of the pore lining helix (TM3B), E. coli MscS has five residues significantly different from other members of the superfamily. In superfamilies such as this, it remains unclear why variations within such a homologous region occur: is it tolerance of alternate residues, or does it define functional variance within the superfamily? Point mutations (S114I/T, L118F, A120S, L123F, F127E/K/T) and patch clamp electrophysiology were used to study the effect of changing these residues in E. coli MscS on sensitivity and gating. The data indicate that variation at these locations do not consistently lead to wildtype channel phenotypes, nor do they define large changes in mechanosensation, but often appear to effect changes in the E. coli MscS channel gating kinetics.

  5. Melanophore migration and survival during zebrafish adult pigment stripe development require the immunoglobulin superfamily adhesion molecule Igsf11.

    Directory of Open Access Journals (Sweden)

    Dae Seok Eom

    Full Text Available The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11. We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation.

  6. Proteins with an alpha/beta hydrolase fold: Relationships between subfamilies in an ever-growing superfamily.

    Science.gov (United States)

    Lenfant, Nicolas; Hotelier, Thierry; Bourne, Yves; Marchot, Pascale; Chatonnet, Arnaud

    2013-03-25

    Alpha/beta hydrolases function as hydrolases, lyases, transferases, hormone precursors or transporters, chaperones or routers of other proteins. The amount of structural and functional available data related to this protein superfamily expands exponentially, as does the number of proteins classified as alpha/beta hydrolases despite poor sequence similarity and lack of experimental data. However the superfamily can be rationally divided according to sequence or structural homologies, leading to subfamilies of proteins with potentially similar functions. Since the discovery of proteins homologous to cholinesterases but devoid of enzymatic activity (e.g., the neuroligins), divergent functions have been ascribed to members of other subfamilies (e.g., lipases, dipeptidylaminopeptidase IV, etc.). To study the potentially moonlighting properties of alpha/beta hydrolases, the ESTHER database (for ESTerase and alpha/beta Hydrolase Enzymes and Relatives; http://bioweb.ensam.inra.fr/esther), which collects, organizes and disseminates structural and functional information related to alpha/beta hydrolases, has been updated with new tools and the web server interface has been upgraded. A new Overall Table along with a new Tree based on HMM models has been included to tentatively group subfamilies. These tools provide starting points for phylogenetic studies aimed at pinpointing the origin of duplications leading to paralogous genes (e.g., acetylcholinesterase versus butyrylcholinesterase, or neuroligin versus carboxylesterase). Another of our goals is to implement new tools to distinguish catalytically active enzymes from non-catalytic proteins in poorly studied or annotated subfamilies.

  7. Evolution of plant virus movement proteins from the 30K superfamily and of their homologs integrated in plant genomes

    Energy Technology Data Exchange (ETDEWEB)

    Mushegian, Arcady R., E-mail: mushegian2@gmail.com [Division of Molecular and Cellular Biosciences, National Science Foundation, 4201 Wilson Boulevard, Arlington, VA 22230 (United States); Elena, Santiago F., E-mail: sfelena@ibmcp.upv.es [Instituto de Biología Molecular y Celular de Plantas, CSIC-UPV, 46022 València (Spain); The Santa Fe Institute, Santa Fe, NM 87501 (United States)

    2015-02-15

    Homologs of Tobacco mosaic virus 30K cell-to-cell movement protein are encoded by diverse plant viruses. Mechanisms of action and evolutionary origins of these proteins remain obscure. We expand the picture of conservation and evolution of the 30K proteins, producing sequence alignment of the 30K superfamily with the broadest phylogenetic coverage thus far and illuminating structural features of the core all-beta fold of these proteins. Integrated copies of pararetrovirus 30K movement genes are prevalent in euphyllophytes, with at least one copy intact in nearly every examined species, and mRNAs detected for most of them. Sequence analysis suggests repeated integrations, pseudogenizations, and positive selection in those provirus genes. An unannotated 30K-superfamily gene in Arabidopsis thaliana genome is likely expressed as a fusion with the At1g37113 transcript. This molecular background of endopararetrovirus gene products in plants may change our view of virus infection and pathogenesis, and perhaps of cellular homeostasis in the hosts. - Highlights: • Sequence region shared by plant virus “30K” movement proteins has an all-beta fold. • Most euphyllophyte genomes contain integrated copies of pararetroviruses. • These integrated virus genomes often include intact movement protein genes. • Molecular evidence suggests that these “30K” genes may be selected for function.

  8. A putative cell surface receptor for white spot syndrome virus is a member of a transporter superfamily.

    Directory of Open Access Journals (Sweden)

    Huai-Ting Huang

    Full Text Available White spot syndrome virus (WSSV, a large enveloped DNA virus, can cause the most serious viral disease in shrimp and has a wide host range among crustaceans. In this study, we identified a surface protein, named glucose transporter 1 (Glut1, which could also interact with WSSV envelope protein, VP53A. Sequence analysis revealed that Glut1 is a member of a large superfamily of transporters and that it is most closely related to evolutionary branches of this superfamily, branches that function to transport this sugar. Tissue tropism analysis showed that Glut1 was constitutive and highly expressed in almost all organs. Glut1's localization in shrimp cells was further verified and so was its interaction with Penaeus monodon chitin-binding protein (PmCBP, which was itself identified to interact with an envelope protein complex formed by 11 WSSV envelope proteins. In vitro and in vivo neutralization experiments using synthetic peptide contained WSSV binding domain (WBD showed that the WBD peptide could inhibit WSSV infection in primary cultured hemocytes and delay the mortality in shrimps challenged with WSSV. These findings have important implications for our understanding of WSSV entry.

  9. Evolution of plant virus movement proteins from the 30K superfamily and of their homologs integrated in plant genomes.

    Science.gov (United States)

    Mushegian, Arcady R; Elena, Santiago F

    2015-02-01

    Homologs of Tobacco mosaic virus 30K cell-to-cell movement protein are encoded by diverse plant viruses. Mechanisms of action and evolutionary origins of these proteins remain obscure. We expand the picture of conservation and evolution of the 30K proteins, producing sequence alignment of the 30K superfamily with the broadest phylogenetic coverage thus far and illuminating structural features of the core all-beta fold of these proteins. Integrated copies of pararetrovirus 30K movement genes are prevalent in euphyllophytes, with at least one copy intact in nearly every examined species, and mRNAs detected for most of them. Sequence analysis suggests repeated integrations, pseudogenizations, and positive selection in those provirus genes. An unannotated 30K-superfamily gene in Arabidopsis thaliana genome is likely expressed as a fusion with the At1g37113 transcript. This molecular background of endopararetrovirus gene products in plants may change our view of virus infection and pathogenesis, and perhaps of cellular homeostasis in the hosts.

  10. Crystal structure and potential physiological role of zebra fish thioesterase superfamily member 2 (fTHEM2).

    Science.gov (United States)

    Yu, Shanshan; Li, Han; Gao, Feng; Zhou, Ying

    2015-08-07

    Thioesterase superfamily member 2 (THEM2) is an essential protein for mammalian cell proliferation. It belongs to the hotdog-fold thioesterase superfamily and catalyzes hydrolysis of thioester bonds of acyl-CoA in vitro, while its in vivo function remains unrevealed. In this study, Zebra fish was selected as a model organism to facilitate the investigations on THEM2. First, we solved the crystal structure of recombinant fTHEM2 at the resolution of 1.80 Å, which displayed a similar scaffolding as hTHEM2. Second, functional studies demonstrated that fTHEM2 is capable of hydrolyzing palmitoyl-CoA in vitro. In addition, injection of morpholino against fTHEM2 at one-cell stage resulted in distorted early embryo development, including delayed cell division, retarded development and increased death rate. The above findings validated our hypothesis that fTHEM2 could serve as an ideal surrogate for studying the physiological functions of THEM2.

  11. Structure of the stress response protein DR1199 from Deinococcus radiodurans: a member of the DJ-1 superfamily.

    Science.gov (United States)

    Fioravanti, Emanuela; Durá, M Asunción; Lascoux, David; Micossi, Elena; Franzetti, Bruno; McSweeney, Sean

    2008-11-01

    The expression level of protein DR1199 is observed to increase considerably in the radio-resistant bacterium Deinococcus radiodurans following irradiation. This protein belongs to the DJ-1 superfamily, which includes proteins with diverse functions, such as the archaeal proteases PhpI and PfpI, the bacterial chaperone Hsp31 and hyperosmotic stress protein YhbO, and the human Parkinson's disease-related protein DJ-1. All members of the superfamily are oligomeric, and the oligomerization interface varies from protein to protein. Although for many of these proteins, their function remains obscure, most of them are involved in cellular protection against environmental stresses. We have determined the structure of DR1199 to a resolution of 2.15 A, and we have tested its function and studied its role in the response to irradiation and more generally to oxidative stress in D. radiodurans. The protein is a dimer displaying an oligomerization interface similar to that observed for the YhbO and PhpI proteins. The cysteine in the catalytic triad (Cys 115) is oxidized in our structure, similar to modifications seen in the corresponding cysteine of the DJ-1 protein. The oxidation occurs spontaneously in DR1199 crystals. In solution, no proteolytic or chaperone activity was detected. On the basis of our results, we suggest that DR1199 might work as a general stress protein involved in the detoxification of the cell from oxygen reactive species, rather than as a peptidase in D. radiodurans.

  12. Why is the GMN motif conserved in the CorA/Mrs2/Alr1 superfamily of magnesium transport proteins?

    Science.gov (United States)

    Palombo, Isolde; Daley, Daniel O; Rapp, Mikaela

    2013-07-16

    Members of the CorA/Mrs2/Alr1 superfamily of transport proteins mediate magnesium uptake in all kingdoms of life. Family members have a low degree of sequence conservation but are characterized by a conserved extracellular loop. While the degree of sequence conservation in the loop deviates to some extent between family members, the GMN family signature motif is always present. Structural and functional data imply that the loop plays a central role in magnesium selectivity, and recent biochemical data suggest it is crucial for stabilizing the pentamer in the magnesium-free (putative open) conformation. In this study, we present a detailed structure-function analysis of the extracellular loop of CorA from Thermotoga maritima, which provides molecular insight into how the loop mediates these two functions. The data show that loop residues outside of the GMN motif can be substituted if they support the pentameric state, but the residues of the GMN motif are intolerant to substitution. We conclude that G(312) is absolutely required for magnesium uptake, M(313) is absolutely required for pentamer integrity in the putative open conformation, and N(314) plays a role in both of these functions. These observations suggest a molecular reason why the GMN motif is conserved throughout the CorA/Mrs2/Alr1 superfamily.

  13. The enzymatic nature of an anonymous protein sequence cannot reliably be inferred from superfamily level structural information alone.

    Science.gov (United States)

    Roche, Daniel Barry; Brüls, Thomas

    2015-05-01

    As the largest fraction of any proteome does not carry out enzymatic functions, and in order to leverage 3D structural data for the annotation of increasingly higher volumes of sequence data, we wanted to assess the strength of the link between coarse grained structural data (i.e., homologous superfamily level) and the enzymatic versus non-enzymatic nature of protein sequences. To probe this relationship, we took advantage of 41 phylogenetically diverse (encompassing 11 distinct phyla) genomes recently sequenced within the GEBA initiative, for which we integrated structural information, as defined by CATH, with enzyme level information, as defined by Enzyme Commission (EC) numbers. This analysis revealed that only a very small fraction (about 1%) of domain sequences occurring in the analyzed genomes was found to be associated with homologous superfamilies strongly indicative of enzymatic function. Resorting to less stringent criteria to define enzyme versus non-enzyme biased structural classes or excluding highly prevalent folds from the analysis had only modest effect on this proportion. Thus, the low genomic coverage by structurally anchored protein domains strongly associated to catalytic activities indicates that, on its own, the power of coarse grained structural information to infer the general property of being an enzyme is rather limited.

  14. Two major facilitator superfamily sugar transporters from Trichoderma reesei and their roles in induction of cellulase biosynthesis.

    Science.gov (United States)

    Zhang, Weixin; Kou, Yanbo; Xu, Jintao; Cao, Yanli; Zhao, Guolei; Shao, Jing; Wang, Hai; Wang, Zhixing; Bao, Xiaoming; Chen, Guanjun; Liu, Weifeng

    2013-11-15

    Proper perception of the extracellular insoluble cellulose is key to initiating the rapid synthesis of cellulases by cellulolytic Trichoderma reesei. Uptake of soluble oligosaccharides derived from cellulose hydrolysis represents a potential point of control in the induced cascade. In this study, we identified a major facilitator superfamily sugar transporter Stp1 capable of transporting cellobiose by reconstructing a cellobiose assimilation system in Saccharomyces cerevisiae. The absence of Stp1 in T. reesei resulted in differential cellulolytic response to Avicel versus cellobiose. Transcriptional profiling revealed a different expression profile in the Δstp1 strain from that of wild-type strain in response to Avicel and demonstrated that Stp1 somehow repressed induction of the bulk of major cellulase and hemicellulose genes. Two other putative major facilitator superfamily sugar transporters were, however, up-regulated in the profiling. Deletion of one of them identified Crt1 that was required for growth and enzymatic activity on cellulose or lactose, but was not required for growth or hemicellulase activity on xylan. The essential role of Crt1 in cellulase induction did not seem to rely on its transporting activity because the overall uptake of cellobiose or sophorose by T. reesei was not compromised in the absence of Crt1. Phylogenetic analysis revealed that orthologs of Crt1 exist in the genomes of many filamentous ascomycete fungi capable of degrading cellulose. These data thus shed new light on the mechanism by which T. reesei senses and transmits the cellulose signal and offers potential strategies for strain improvement.

  15. CD177: A member of the Ly-6 gene superfamily involved with neutrophil proliferation and polycythemia vera

    Directory of Open Access Journals (Sweden)

    Bettinotti Maria

    2004-03-01

    Full Text Available Abstract Genes in the Leukocyte Antigen 6 (Ly-6 superfamily encode glycosyl-phosphatidylinositol (GPI anchored glycoproteins (gp with conserved domains of 70 to 100 amino acids and 8 to 10 cysteine residues. Murine Ly-6 genes encode important lymphocyte and hematopoietic stem cell antigens. Recently, a new member of the human Ly-6 gene superfamily has been described, CD177. CD177 is polymorphic and has at least two alleles, PRV-1 and NB1. CD177 was first described as PRV-1, a gene that is overexpressed in neutrophils from approximately 95% of patients with polycythemia vera and from about half of patients with essential thrombocythemia. CD177 encodes NB1 gp, a 58–64 kD GPI gp that is expressed by neutrophils and neutrophil precursors. NB1 gp carries Human Neutrophil Antigen (HNA-2a. Investigators working to identify the gene encoding NB1 gp called the CD177 allele they described NB1. NB1 gp is unusual in that neutrophils from some healthy people lack the NB1 gp completely and in most people NB1 gp is expressed by a subpopulation of neutrophils. The function of NB1 gp and the role of CD177 in the pathogenesis and clinical course of polycythemia vera and essential thrombocythemia are not yet known. However, measuring neutrophil CD177 mRNA levels has become an important marker for diagnosing the myeloproliferative disorders polycythemia vera and essential thrombocythemia.

  16. Crystal structure and potential physiological role of zebra fish thioesterase superfamily member 2 (fTHEM2)

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Shanshan; Li, Han; Gao, Feng; Zhou, Ying, E-mail: zhouying@moon.ibp.ac.cn

    2015-08-07

    Thioesterase superfamily member 2 (THEM2) is an essential protein for mammalian cell proliferation. It belongs to the hotdog-fold thioesterase superfamily and catalyzes hydrolysis of thioester bonds of acyl-CoA in vitro, while its in vivo function remains unrevealed. In this study, Zebra fish was selected as a model organism to facilitate the investigations on THEM2. First, we solved the crystal structure of recombinant fTHEM2 at the resolution of 1.80 Å, which displayed a similar scaffolding as hTHEM2. Second, functional studies demonstrated that fTHEM2 is capable of hydrolyzing palmitoyl-CoA in vitro. In addition, injection of morpholino against fTHEM2 at one-cell stage resulted in distorted early embryo development, including delayed cell division, retarded development and increased death rate. The above findings validated our hypothesis that fTHEM2 could serve as an ideal surrogate for studying the physiological functions of THEM2. - Highlights: • The crystal structure of recombinant fTHEM2 is presented. • fTHEM2 is capable of hydrolyzing palmitoyl-CoA. • The influence of fTHEM2 on early embryo development is demonstrated.

  17. The mitogenome of a 35,000-year-old Homo sapiens from Europe supports a Palaeolithic back-migration to Africa

    National Research Council Canada - National Science Library

    Hervella, M; Svensson, E M; Alberdi, A; Günther, T; Izagirre, N; Munters, A R; Alonso, S; Ioana, M; Ridiche, F; Soficaru, A; Jakobsson, M; Netea, M G; de-la-Rua, C

    2016-01-01

    After the dispersal of modern humans (Homo sapiens) Out of Africa, hominins with a similar morphology to that of present-day humans initiated the gradual demographic expansion into Eurasia. The mitogenome (33-fold coverage...

  18. Functional inositol 1,4,5-trisphosphate receptors assembled from concatenated homo- and heteromeric subunits.

    Science.gov (United States)

    Alzayady, Kamil J; Wagner, Larry E; Chandrasekhar, Rahul; Monteagudo, Alina; Godiska, Ronald; Tall, Gregory G; Joseph, Suresh K; Yule, David I

    2013-10-11

    Vertebrate genomes code for three subtypes of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R1, -2, and -3). Individual IP3R monomers are assembled to form homo- and heterotetrameric channels that mediate Ca(2+) release from intracellular stores. IP3R subtypes are regulated differentially by IP3, Ca(2+), ATP, and various other cellular factors and events. IP3R subtypes are seldom expressed in isolation in individual cell types, and cells often express different complements of IP3R subtypes. When multiple subtypes of IP3R are co-expressed, the subunit composition of channels cannot be specifically defined. Thus, how the subunit composition of heterotetrameric IP3R channels contributes to shaping the spatio-temporal properties of IP3-mediated Ca(2+) signals has been difficult to evaluate. To address this question, we created concatenated IP3R linked by short flexible linkers. Dimeric constructs were expressed in DT40-3KO cells, an IP3R null cell line. The dimeric proteins were localized to membranes, ran as intact dimeric proteins on SDS-PAGE, and migrated as an ∼1100-kDa band on blue native gels exactly as wild type IP3R. Importantly, IP3R channels formed from concatenated dimers were fully functional as indicated by agonist-induced Ca(2+) release. Using single channel "on-nucleus" patch clamp, the channels assembled from homodimers were essentially indistinguishable from those formed by the wild type receptor. However, the activity of channels formed from concatenated IP3R1 and IP3R2 heterodimers was dominated by IP3R2 in terms of the characteristics of regulation by ATP. These studies provide the first insight into the regulation of heterotetrameric IP3R of defined composition. Importantly, the results indicate that the properties of these channels are not simply a blend of those of the constituent IP3R monomers.

  19. Homo acrobaticus et corps des extrémités

    Directory of Open Access Journals (Sweden)

    Myriam Peignist

    2009-10-01

    Full Text Available Qui dit «Acrobate», voit souvent un héros ou un champion qui «en impose» par ses tours spectaculaires. Des spectateurs distants s’avouent sidérés et impressionnés par les exploits des «casse-cou» et les envolées du corps en tous sens: à travers une telle représentation, c’est un cliché nostalgique de l’homo acrobaticus réduit, de façon sommaire à un hercule aux «gros bras», à un «Monsieur muscle» de cirque ou à un athlète spectaculaire qui enchaîne des figures extrêmes, porté par une «passion du risque», du «dépassement de soi»… Les discours boursouflés de la prouesse et de la performance, leur jargon bien rôdé et reconnu, empêchent presque d’aborder la question autrement. Or, triste est la théorie qui ignore les plaisirs sensuels du corps, car «ils forment une large part de ce qui donne une valeur à la vie [et] peuvent être cultivés pour rendre la vie plus riche. […] Et si nous pouvons émanciper et transformer le moi à travers un nouveau langage, nous pouvons aussi le libérer et le transfigurer à travers de nouvelles pratiques corporelles». Une somatique qualitative permet de prendre la chose par un autre bout.

  20. Brain size and thermoregulation during the evolution of the genus Homo.

    Science.gov (United States)

    Naya, Daniel E; Naya, Hugo; Lessa, Enrique P

    2016-01-01

    Several hypotheses have been proposed to explain the evolution of an energetically costly brain in the genus Homo. Some of these hypotheses are based on the correlation between climatic factors and brain size recorded for this genus during the last millions of years. In this study, we propose a complementary climatic hypothesis that is based on the mechanistic connection between temperature, thermoregulation, and size of internal organs in endothermic species. We hypothesized that global cooling during the last 3.2 my may have imposed an increased energy expenditure for thermoregulation, which in the case of hominids could represent a driver for the evolution of an expanded brain, or at least, it could imply the relaxation of a negative selection pressure acting upon this costly organ. To test this idea, here we (1) assess variation in the energetic costs of thermoregulation and brain maintenance for the last 3.2 my, and (2) evaluate the relationship between Earth temperature and brain maintenance cost for the same period, taking into account the effects of body mass and fossil age. We found that: (1) the energetic cost associated with brain enlargement represents an important fraction (between 47.5% and 82.5%) of the increase in energy needed for thermoregulation; (2) fossil age is a better predictor of brain maintenance cost than Earth temperature, suggesting that (at least) another factor correlated with time was more relevant than ambient temperature in brain size evolution; and (3) there is a significant negative correlation between the energetic cost of brain and Earth temperature, even after accounting for the effect of body mass and fossil age. Thus, our results expand the current energetic framework for the study of brain size evolution in our lineage by suggesting that a fall in Earth temperature during the last millions of years may have facilitated brain enlargement.

  1. Homo sapiens as physician and patient: a view from Darwinian medicine.

    Science.gov (United States)

    Román-Franco, Angel A

    2013-09-01

    Medicine's cardinal diagnostic and therapeutic resource is the clinical encounter. Over the last two centuries and particularly over the last five decades the function of the clinical encounter has been eroded to the point of near irrelevance because of the atomized and atomizing influence of technology and microspecialization. Meanwhile, over the past five decades the exceptionalist view of Homo sapiens inherent in the social and religious traditions of the West has similarly undergone radical changes. H. sapiens is now best understood as a microecosystem integrated into a much broader ecosystem: the biosphere. That human microecosystem is composed of constituents derived from the archaeal, bacterial, and eukaryan domains via endosymbiotic, commensalistic and mutualistic interactions. This amalgamation of 100 trillion cells and viral elements is regulated by a composite genome aggregated over the 3.8 billion years of evolutionary history of organic life. No component of H. sapiens or its genome can be identified as irreducibly and exclusively human. H. sapiens' humanity is an emergent property of the microecosystem. Ironically as H. sapiens is viewed by evolutionary science in a highly integrated manner medicine approaches it as a balkanized, deaggregated entity through the eye of 150 different specialties. To effectively address the needs of H sapiens in its role as patient by the same species in its role as physician the disparate views must be harmonized. Here I review some conceptual elements that would assist a physician in addressing the needs of the patient in integrum, as a microecosystem, by the former address the latter as a historical gestalt being. The optimal way to recover the harmony between patient and physician is through a revitalization of the clinical encounter via an ecological and Darwinian epistemology.

  2. Forearm articular proportions and the antebrachial index in Homo sapiens, Australopithecus afarensis and the great apes.

    Science.gov (United States)

    Williams, Frank L'Engle; Cunningham, Deborah L; Amaral, Lia Q

    2015-12-01

    When hominin bipedality evolved, the forearms were free to adopt nonlocomotor tasks which may have resulted in changes to the articular surfaces of the ulna and the relative lengths of the forearm bones. Similarly, sex differences in forearm proportions may be more likely to emerge in bipeds than in the great apes given the locomotor constraints in Gorilla, Pan and Pongo. To test these assumptions, ulnar articular proportions and the antebrachial index (radius length/ulna length) in Homo sapiens (n=51), Gorilla gorilla (n=88), Pan troglodytes (n=49), Pongo pygmaeus (n=36) and Australopithecus afarensis A.L. 288-1 and A.L. 438-1 are compared. Intercept-adjusted ratios are used to control for size and minimize the effects of allometry. Canonical scores axes show that the proximally broad and elongated trochlear notch with respect to size in H. sapiens and A. afarensis is largely distinct from G. gorilla, P. troglodytes and P. pygmaeus. A cluster analysis of scaled ulnar articular dimensions groups H. sapiens males with A.L. 438-1 ulna length estimates, while one A.L. 288-1 ulna length estimate groups with Pan and another clusters most closely with H. sapiens, G. gorilla and A.L. 438-1. The relatively low antebrachial index characterizing H. sapiens and non-outlier estimates of A.L. 288-1 and A.L. 438-1 differs from those of the great apes. Unique sex differences in H. sapiens suggest a link between bipedality and forearm functional morphology.

  3. Evaluating the transitional mosaic: frameworks of change from Neanderthals to Homo sapiens in eastern Europe

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    Davies, William; White, Dustin; Lewis, Mark; Stringer, Chris

    2015-06-01

    Defining varying spatial and temporal analytical scales is essential before evaluating the responses of late Neanderthals and early Homo sapiens to Abrupt Environmental Transitions (AETs) and environmental disasters for the period 130-25 ka. Recent advances in addressing the population histories and interactions (using both genetic and archaeological evidence) of Neanderthals and H. sapiens have encouraged consideration of more subtle dynamics of archaeological change. Descriptions of change based on methodologies pioneered some 160 years ago are no longer adequate to explain the patterning we now see in the record. New chronological results, using multiple dating methods, allow us to begin to unpick the spatial and temporal scales of change. Isochronic markers (such as specific volcanic eruptions) can be used to create temporal frameworks (lattices), and results from other dating techniques compared against them. A combination of chronological lattices and direct dating of diagnostic artefacts and human fossils permits us, for the first time, to have greater confidence in connecting human (recent hominin) species and their behavioural responses to environmental conditions, and in quantifying scales of change over time and space (time-transgression). The timing of innovations, particularly those in bone, antler and ivory, can be directly quantified and tested, and used to re-evaluate longstanding models of cultural change. This paper also uses these new chronologies to explore the ecologies of late Neanderthals and early H. sapiens: their population densities, mobilities, resources exploited and possible interactions. Environmental productivity estimates are used to generate new questions of potential population densities and mobilities, and thus the sensitivity of these groups to environmental perturbations. Scales and intensities of effect on environments from natural disasters and AETs (notably Heinrich Events and the Campanian Ignimbrite eruption) are defined

  4. The origins and persistence of Homo floresiensis on Flores: biogeographical and ecological perspectives

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    Dennell, Robin W.; Louys, Julien; O'Regan, Hannah J.; Wilkinson, David M.

    2014-07-01

    The finding of archaeological evidence predating 1 Ma and a small hominin species (Homo floresiensis) on Flores, Indonesia, has stimulated much research on its origins and ancestry. Here we take a different approach and examine two key questions - 1) how did the ancestors of H. floresiensis reach Flores and 2) what are the possibilities for estimating the likelihood of hominin persistence for over 1 million years on a small island? With regard to the first question, on the basis of the biogeography we conclude that the mammalian, avian, and reptilian fauna on Flores arrived from a number of sources including Java, Sulawesi and Sahul. Many of the terrestrial taxa were able to float or swim (e.g. stegodons, giant tortoises and the Komodo dragon), while the rodents and hominins probably accidentally rafted from Sulawesi, following the prevailing currents. The precise route by which hominins arrived on Flores cannot at present be determined, although a route from South Asia through Indochina, Sulawesi and hence Flores is tentatively supported on the basis of zoogeography. With regards to the second question, we find the archaeological record equivocal. A basic energetics model shows that a greater number of small-bodied hominins could persist on Flores than larger-bodied hominins (whether H. floresiensis is a dwarfed species or a descendent of an early small-bodied ancestor is immaterial here), which may in part explain their apparent long-term success. Yet the frequent tsunamis and volcanic eruptions in the region would certainly have affected all the taxa on the island, and at least one turnover event is recorded, when Stegodon sondaari became extinct. The question of the likelihood of persistence may be unanswerable until we know much more about the biology of H. floresiensis.

  5. The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport.

    Science.gov (United States)

    Alva, Vikram; Lupas, Andrei N

    2016-08-01

    The tubular lipid-binding (TULIP) superfamily has emerged in recent years as a major mediator of lipid sensing and transport in eukaryotes. It currently encompasses three protein families, SMP-like, BPI-like, and Takeout-like, which share a common fold. This fold consists of a long helix wrapped in a highly curved anti-parallel β-sheet, enclosing a central, lipophilic cavity. The SMP-like proteins, which include subunits of the ERMES complex and the extended synaptotagmins (E-Syts), appear to be mainly located at membrane contacts sites (MCSs) between organelles, mediating inter-organelle lipid exchange. The BPI-like proteins, which include the bactericidal/permeability-increasing protein (BPI), the LPS (lipopolysaccharide)-binding protein (LBP), the cholesteryl ester transfer protein (CETP), and the phospholipid transfer protein (PLTP), are either involved in innate immunity against bacteria through their ability to sense lipopolysaccharides, as is the case for BPI and LBP, or in lipid exchange between lipoprotein particles, as is the case for CETP and PLTP. The Takeout-like proteins, which are comprised of insect juvenile hormone-binding proteins and arthropod allergens, transport, where known, lipid hormones to target tissues during insect development. In all cases, the activity of these proteins is underpinned by their ability to bind large, hydrophobic ligands in their central cavity and segregate them away from the aqueous environment. Furthermore, where they are involved in lipid exchange, recent structural studies have highlighted their ability to establish lipophilic, tubular channels, either between organelles in the case of SMP domains or between lipoprotein particles in the case of CETP. Here, we review the current knowledge on the structure, versatile functions, and evolution of the TULIP superfamily. We propose a deep evolutionary split in this superfamily, predating the Last Eukaryotic Common Ancestor, between the SMP-like proteins, which act on

  6. Computational Identification of the Paralogs and Orthologs of Human Cytochrome P450 Superfamily and the Implication in Drug Discovery

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    Shu-Ting Pan

    2016-06-01

    Full Text Available The human cytochrome P450 (CYP superfamily consisting of 57 functional genes is the most important group of Phase I drug metabolizing enzymes that oxidize a large number of xenobiotics and endogenous compounds, including therapeutic drugs and environmental toxicants. The CYP superfamily has been shown to expand itself through gene duplication, and some of them become pseudogenes due to gene mutations. Orthologs and paralogs are homologous genes resulting from speciation or duplication, respectively. To explore the evolutionary and functional relationships of human CYPs, we conducted this bioinformatic study to identify their corresponding paralogs, homologs, and orthologs. The functional implications and implications in drug discovery and evolutionary biology were then discussed. GeneCards and Ensembl were used to identify the paralogs of human CYPs. We have used a panel of online databases to identify the orthologs of human CYP genes: NCBI, Ensembl Compara, GeneCards, OMA (“Orthologous MAtrix” Browser, PATHER, TreeFam, EggNOG, and Roundup. The results show that each human CYP has various numbers of paralogs and orthologs using GeneCards and Ensembl. For example, the paralogs of CYP2A6 include CYP2A7, 2A13, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 2R1, 2S1, 2U1, and 2W1; CYP11A1 has 6 paralogs including CYP11B1, 11B2, 24A1, 27A1, 27B1, and 27C1; CYP51A1 has only three paralogs: CYP26A1, 26B1, and 26C1; while CYP20A1 has no paralog. The majority of human CYPs are well conserved from plants, amphibians, fishes, or mammals to humans due to their important functions in physiology and xenobiotic disposition. The data from different approaches are also cross-validated and validated when experimental data are available. These findings facilitate our understanding of the evolutionary relationships and functional implications of the human CYP superfamily in drug discovery.

  7. Enantiomeric self-recognition in homo- and heterodinuclear macrocyclic lanthanide(III) complexes.

    Science.gov (United States)

    Lisowski, Jerzy

    2011-06-20

    The controlled formation of lanthanide(III) dinuclear μ-hydroxo-bridged [Ln(2)L(2)(μ-OH)(2)X(2)](n+) complexes (where X = H(2)O, NO(3)(-), or Cl(-)) of the enantiopure chiral macrocycle L is reported. The (1)H and (13)C NMR resonances of these complexes have been assigned on the basis of COSY, NOESY, TOCSY, and HMQC spectra. The observed NOE connectivities confirm that the dimeric solid-state structure is retained in solution. The enantiomeric nature of the obtained chiral complexes and binding of hydroxide anions are reflected in their CD spectra. The formation of the dimeric complexes is accompanied by a complete enantiomeric self-recognition of the chiral macrocyclic units. The reaction of NaOH with a mixture of two different mononuclear lanthanide(III) complexes, [Ln(1)L](3+) and [Ln(2)L](3+), results in formation of the heterodinuclear [Ln(1)Ln(2)L(2)(μ-OH)(2)X(2)](n+) complexes as well as the corresponding homodinuclear complexes. The formation of the heterodinuclear complex is directly confirmed by the NOESY spectra of [EuLuL(2)(μ-OH)(2)(H(2)O)(2)](4+), which reveal close contacts between the macrocyclic unit containing the Eu(III) ion and the macrocyclic unit containing the Lu(III) ion. While the relative amounts of homo- and heterodinuclear complexes are statistical for the two lanthanide(III) ions of similar radii, a clear preference for the formation of heterodinuclear species is observed when the two mononuclear complexes contain lanthanide(III) ions of markedly different sizes, e.g., La(III) and Yb(III). The formation of heterodinuclear complexes is accompanied by the self-sorting of the chiral macrocyclic units based on their chirality. The reactions of NaOH with a pair of homochiral or racemic mononuclear complexes, [Ln(1)L(RRRR)](3+)/[Ln(2)L(RRRR)](3+), [Ln(1)L(SSSS)](3+)/[Ln(2)L(SSSS)](3+), or [Ln(1)L(rac)](3+)/[Ln(2)L(rac)](3+), results in mixtures of homochiral, homodinuclear and homochiral, heterodinuclear complexes. On the contrary, no

  8. The rhizome of Reclinomonas americana, Homo sapiens, Pediculus humanus and Saccharomyces cerevisiae mitochondria

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    Raoult Didier

    2011-10-01

    Full Text Available Abstract Background Mitochondria are thought to have evolved from eubacteria-like endosymbionts; however, the origin of the mitochondrion remains a subject of debate. In this study, we investigated the phenomenon of chimerism in mitochondria to shed light on the origin of these organelles by determining which species played a role in their formation. We used the mitochondria of four distinct organisms, Reclinomonas americana, Homo sapiens, Saccharomyces cerevisiae and multichromosome Pediculus humanus, and attempted to identify the origin of each mitochondrial gene. Results Our results suggest that the origin of mitochondrial genes is not limited to the Rickettsiales and that the creation of these genes did not occur in a single event, but through multiple successive events. Some of these events are very old and were followed by events that are more recent and occurred through the addition of elements originating from current species. The points in time that the elements were added and the parental species of each gene in the mitochondrial genome are different to the individual species. These data constitute strong evidence that mitochondria do not have a single common ancestor but likely have numerous ancestors, including proto-Rickettsiales, proto-Rhizobiales and proto-Alphaproteobacteria, as well as current alphaproteobacterial species. The analysis of the multichromosome P. humanus mitochondrion supports this mechanism. Conclusions The most plausible scenario of the origin of the mitochondrion is that ancestors of Rickettsiales and Rhizobiales merged in a proto-eukaryotic cell approximately one billion years ago. The fusion of the Rickettsiales and Rhizobiales cells was followed by gene loss, genomic rearrangements and the addition of alphaproteobacterial elements through ancient and more recent recombination events. Each gene of each of the four studied mitochondria has a different origin, while in some cases, multichromosomes may allow for

  9. Is Homo heidelbergensis a distinct species? New insight on the Mauer mandible.

    Science.gov (United States)

    Mounier, Aurélien; Marchal, François; Condemi, Silvana

    2009-03-01

    The discovery of new fossils in Africa, Asia, and Europe, and the recognition of a greater diversity in the middle Pleistocene fossil record, has led to a reconsideration of the species Homo heidelbergensis. This nomen, formulated by Schoetensack in 1908 to describe the Mauer jaw (Germany), was almost forgotten during most of the past century. Numerous fossils have been attributed to it but no consensus has arisen concerning their classification. The holotype anatomical traits are still poorly understood, and numerous fossils with no mandibular remains have been placed in the taxon. Some researchers propose H. heidelbergensis as an Afro-European taxon that is ancestral to both modern humans and Neandertals whereas others think it is a strictly European species that is part of the Neandertal lineage. We focus on the validity of H. heidelbergensis, using the traditional basis of species recognition: anatomical description. We provide a comparative morphological analysis using 47 anatomical traits of 36 Pleistocene fossils from Africa, Asia, and Europe and 35 extant human mandibles. We re-examine the mandibular features of Mauer and discuss the specimen's inclusion in H. heidelbergensis, as well as alternative evolutionary theories. To lend objectivity to specimen grouping, we use multiple correspondence analysis associated with hierarchical classification that creates clusters corresponding to phenetic similarities between jaws. Our phenetic and comparative morphological analyses support the validity of H. heidelbergensis as a taxon. A set of morphological features can be statistically identified for the definition of the species. Some traits can be used to delimit H. heidelbergensis in an evolutionary framework (e.g., foramina mentale posteriorly positioned, horizontal retromolar surface). Those traits are also present on African (e.g., Tighenif) and European (e.g., Sima de los Huesos) specimens that show a close relationship with the Mauer mandible. Therefore, the

  10. TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator.

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    Vicky Wang-Wei Tsai

    Full Text Available The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1(-/- weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1(-/- mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1(-/- mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.

  11. Fumarate reductase superfamily: A diverse group of enzymes whose evolution is correlated to the establishment of different metabolic pathways.

    Science.gov (United States)

    Jardim-Messeder, Douglas; Cabreira-Cagliari, Caroline; Rauber, Rafael; Turchetto-Zolet, Andreia Carina; Margis, Rogério; Margis-Pinheiro, Márcia

    2017-05-01

    Fumarate and succinate are known to be present in prebiotic systems essential for the origin of life. The fumarate and succinate interconversion reactions have been conserved throughout evolution and are found in all living organisms. The fumarate and succinate interconversion is catalyzed by the enzymes succinate dehydrogenase (SDH) and fumarate reductase (FRD). In this work we show that SDH and FRD are part of a group of enzymes that we propose to designate "fumarate reductase superfamily". Our results demonstrate that these enzymes emerged from a common ancestor and were essential in the development of metabolic pathways involved in energy transduction. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  12. The evolutionary ecology of biotic association in a megadiverse bivalve superfamily: sponsorship required for permanent residency in sediment.

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    Jingchun Li

    Full Text Available BACKGROUND: Marine lineage diversification is shaped by the interaction of biotic and abiotic factors but our understanding of their relative roles is underdeveloped. The megadiverse bivalve superfamily Galeommatoidea represents a promising study system to address this issue. It is composed of small-bodied clams that are either free-living or have commensal associations with invertebrate hosts. To test if the evolution of this lifestyle dichotomy is correlated with specific ecologies, we have performed a statistical analysis on the lifestyle and habitat preference of 121 species based on 90 source documents. METHODOLOGY/PRINCIPAL FINDINGS: Galeommatoidea has significant diversity in the two primary benthic habitats: hard- and soft-bottoms. Hard-bottom dwellers are overwhelmingly free-living, typically hidden within crevices of rocks/coral heads/encrusting epifauna. In contrast, species in soft-bottom habitats are almost exclusively infaunal commensals. These infaunal biotic associations may involve direct attachment to a host, or clustering around its tube/burrow, but all commensals locate within the oxygenated sediment envelope produced by the host's bioturbation. CONCLUSIONS/SIGNIFICANCE: the formation of commensal associations by Galeommatoidean clams is robustly correlated with an abiotic environmental setting: living in sediments (P < 0.001. Sediment-dwelling bivalves are exposed to intense predation pressure that drops markedly with depth of burial. Commensal galeommatoideans routinely attain depth refuges many times their body lengths, independent of siphonal investment, by virtue of their host's burrowing and bioturbation. In effect, they use their much larger hosts as giant auto-irrigating siphon substitutes. The evolution of biotic associations with infaunal bioturbating hosts may have been a prerequisite for the diversification of Galeommatoidea in sediments and has likely been a key factor in the success of this exceptionally diverse

  13. Analysis of the Active-Site Mechanism of Tyrosyl-DNA Phosphodiesterase I: A Member of the Phospholipase D Superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Gajewski, Stefan; Comeaux, Evan Q.; Jafari, Nauzanene; Bharatham, Nagakumar; Bashford, Donald; White, Stephen W.; van Waardenburg, Robert C.A.M. (UAB); (SJCH)

    2012-03-15

    Tyrosyl-DNA phosphodiesterase I (Tdp1) is a member of the phospholipase D superfamily that hydrolyzes 3'-phospho-DNA adducts via two conserved catalytic histidines - one acting as the lead nucleophile and the second acting as a general acid/base. Substitution of the second histidine specifically to arginine contributes to the neurodegenerative disease spinocerebellar ataxia with axonal neuropathy (SCAN1). We investigated the catalytic role of this histidine in the yeast protein (His432) using a combination of X-ray crystallography, biochemistry, yeast genetics, and theoretical chemistry. The structures of wild-type Tdp1 and His432Arg both show a phosphorylated form of the nucleophilic histidine that is not observed in the structure of His432Asn. The phosphohistidine is stabilized in the His432Arg structure by the guanidinium group that also restricts the access of nucleophilic water molecule to the Tdp1-DNA intermediate. Biochemical analyses confirm that His432Arg forms an observable and unique Tdp1-DNA adduct during catalysis. Substitution of His432 by Lys does not affect catalytic activity or yeast phenotype, but substitutions with Asn, Gln, Leu, Ala, Ser, and Thr all result in severely compromised enzymes and DNA topoisomerase I-camptothecin dependent lethality. Surprisingly, His432Asn did not show a stable covalent Tdp1-DNA intermediate that suggests another catalytic defect. Theoretical calculations revealed that the defect resides in the nucleophilic histidine and that the pK{sub a} of this histidine is crucially dependent on the second histidine and on the incoming phosphate of the substrate. This represents a unique example of substrate-activated catalysis that applies to the entire phospholipase D superfamily.

  14. Identification and characterization of RBEL1 subfamily of GTPases in the Ras superfamily involved in cell growth regulation.

    Science.gov (United States)

    Montalbano, JoAnne; Lui, Ki; Sheikh, M Saeed; Huang, Ying

    2009-07-03

    Recently, we reported the identification of a novel gene named RBEL1 (Rab-like protein 1) and characterized its two encoded isoforms, RBEL1A and RBEL1B, that function as novel GTPases of Ras superfamily. Here we report the identification of two additional splice variants of RBEL1 that we have named RBEL1C and -D. All four RBEL1 isoforms (A, B, C, and D) have identical N termini harboring the Rab-like GTPase domains but contain variable C termini. Although all isoforms can be detected in both cytoplasm and nucleus, RBEL1A is predominantly cytoplasmic, whereas RBEL1B is mostly nuclear. RBEL1C and -D, by contrast, are evenly distributed between the cytoplasm and nucleus. Furthermore, all four RBEL1 proteins are also capable of associating with cellular membrane. The RBEL1 proteins also exhibit a unique nucleotide-binding potential and, whereas the larger A and B isoforms are mainly GTP-bound, the smaller C and D variants bind to both GTP and GDP. Furthermore, a regulatory region at amino acid position 236-302 immediately adjacent to the GTP-binding domain is important for GTP-binding potential of RBEL1A, because deletion of this region converts RBEL1A from predominantly GTP-bound to GDP-bound. RBEL1 knockdown via RNA interference results in marked cell growth suppression, which is associated with morphological and biochemical features of apoptosis as well as inhibition of extracellular signal-regulated kinase phosphorylation. Taken together, our results indicate that RBEL1 proteins are linked to cell growth and survival and possess unique biochemical, cellular, and functional characteristics and, therefore, appear to form a novel subfamily of GTPases within the Ras superfamily.

  15. The Catalytic Scaffold fo the Haloalkanoic Acid Dehalogenase Enzyme Superfamily Acts as a Mold for the Trigonal Bipyramidal Transition State

    Energy Technology Data Exchange (ETDEWEB)

    Lu,Z.; Dunaway-Mariano, D.; Allen, K.

    2008-01-01

    The evolution of new catalytic activities and specificities within an enzyme superfamily requires the exploration of sequence space for adaptation to a new substrate with retention of those elements required to stabilize key intermediates/transition states. Here, we propose that core residues in the large enzyme family, the haloalkanoic acid dehalogenase enzyme superfamily (HADSF) form a 'mold' in which the trigonal bipyramidal transition states formed during phosphoryl transfer are stabilized by electrostatic forces. The vanadate complex of the hexose phosphate phosphatase BT4131 from Bacteroides thetaiotaomicron VPI-5482 (HPP) determined at 1.00 Angstroms resolution via X-ray crystallography assumes a trigonal bipyramidal coordination geometry with the nucleophilic Asp-8 and one oxygen ligand at the apical position. Remarkably, the tungstate in the complex determined to 1.03 Angstroms resolution assumes the same coordination geometry. The contribution of the general acid/base residue Asp-10 in the stabilization of the trigonal bipyramidal species via hydrogen-bond formation with the apical oxygen atom is evidenced by the 1.52 Angstroms structure of the D10A mutant bound to vanadate. This structure shows a collapse of the trigonal bipyramidal geometry with displacement of the water molecule formerly occupying the apical position. Furthermore, the 1.07 Angstroms resolution structure of the D10A mutant complexed with tungstate shows the tungstate to be in a typical 'phosphate-like' tetrahedral configuration. The analysis of 12 liganded HADSF structures deposited in the protein data bank (PDB) identified stringently conserved elements that stabilize the trigonal bipyramidal transition states by engaging in favorable electrostatic interactions with the axial and equatorial atoms of the transferring phosphoryl group.

  16. A novel inhibitor of α9α10 nicotinic acetylcholine receptors from Conus vexillum delineates a new conotoxin superfamily.

    Directory of Open Access Journals (Sweden)

    Sulan Luo

    Full Text Available Conotoxins (CTxs selectively target a range of ion channels and receptors, making them widely used tools for probing nervous system function. Conotoxins have been previously grouped into superfamilies according to signal sequence and into families based on their cysteine framework and biological target. Here we describe the cloning and characterization of a new conotoxin, from Conus vexillum, named αB-conotoxin VxXXIVA. The peptide does not belong to any previously described conotoxin superfamily and its arrangement of Cys residues is unique among conopeptides. Moreover, in contrast to previously characterized conopeptide toxins, which are expressed initially as prepropeptide precursors with a signal sequence, a ''pro'' region, and the toxin-encoding region, the precursor sequence of αB-VxXXIVA lacks a ''pro'' region. The predicted 40-residue mature peptide, which contains four Cys, was synthesized in each of the three possible disulfide arrangements. Investigation of the mechanism of action of αB-VxXXIVA revealed that the peptide is a nicotinic acetylcholine receptor (nAChR antagonist with greatest potency against the α9α10 subtype. (1H nuclear magnetic resonance (NMR spectra indicated that all three αB-VxXXIVA isomers were poorly structured in aqueous solution. This was consistent with circular dichroism (CD results which showed that the peptides were unstructured in buffer, but adopted partially helical conformations in aqueous trifluoroethanol (TFE solution. The α9α10 nAChR is an important target for the development of analgesics and cancer chemotherapeutics, and αB-VxXXIVA represents a novel ligand with which to probe the structure and function of this protein.

  17. Ag(I)-mediated homo and hetero pairs of guanosine and cytidine: Monitoring by circular dichroism spectroscopy

    Science.gov (United States)

    Goncharova, Iryna

    2014-01-01

    Ag(I)-containing compounds are attractive as antibacterial and antifungal agents. The renewed interest in the application of silver(I) compounds has led to the need for detailed knowledge of the mechanism of their action. One of the possible ways is the coordination of Ag(I) to G-C pairs of DNA, where Ag+ ions form Ag(I)-mediated base pairs and inhibit the transcription. Herein, a systematic chiroptical study on silver(I)-mediated homo and mixed pairs of the C-G complementary-base derivatives cytidine(C) and 5‧-guanosine monophosphate(G) in water is presented. Ag(I)-mediated homo and hetero pairs of G and C and their self-assembled species were studied under two pH levels (7.0 and 10.0) by vibrational (VCD) and electronic circular dichroism(ECD). VCD was used for the first time in this field and showed itself to be a powerful method for obtaining specific structural information in solution. Based on results of the VCD experiments, the different geometries of the homo pairs were proposed under pH 7.0 and 10.0. ECD was used as a diagnostic tool to characterize the studied systems and as a contact point between the previously defined structures of the metal or proton mediated pairs of nucleobases and the systems studied here. On the basis of the obtained data, the formation of the self-assembled species of cytidine with a structure similar to the i-motif structure in DNA was proposed at pH 10.0.

  18. Homo- and heterodinuclear coordination polymers based on a tritopic cyclam bis-terpyridine unit: Structure and rheological properties

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Li; Fan, Jiangxia; Ren, Yong; Xiong, Kun [State Key Laboratory Cultivation Base for Nonmetal Composites and Functional Materials, School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010 (China); Yan, Minhao, E-mail: yanminhao@swust.edu.cn [State Key Laboratory Cultivation Base for Nonmetal Composites and Functional Materials, School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010 (China); Tuo, Xianguo, E-mail: tuoxg@swust.edu.cn [Laboratory of National Defense for Radioactive Waste and Environmental Security, Southwest University of Science and Technology, Mianyang 621010 (China); Terech, Pierre [SPrAM, UMR CEA/CNRS/UJF-Grenoble 1, INAC, Grenoble F-38054 (France); Royal, Guy [Université Joseph Fourier Grenoble I, Département de Chimie Moléculaire, UMR CNRS-5250, Institut de Chimie Moléculaire de Grenoble, FR CNRS-2607, BP 53, 38041 Grenoble Cedex 9 (France)

    2015-03-01

    An innovative coordination polymer based on a tritopic ligand having the bis-terpyridine cyclam (CHTT) unit is explored. Homo- or heteronuclear 1D coordination polymers can be formed with bivalent metal ions such as Co(II) and Ni(II) in solvent DMF. Creep-recovery curves of the (Co{sup II}){sub 2}CHTT gels formed from 1D coordination polymers were analyzed with the Burgers model and demonstrated an original self-healing property, unusual in the class of molecular gels. The influence of the metal type was studied through the structural features using small-angle neutron scattering (SANS) experiments. In gels, the corresponding network involves genuine fibers (R ≈ 35 Å), bundles of these fibers and also a fraction of finite size aggregates (rods with aspect ratio f ≈ 3–5). We found that the distribution of these latter structural components is sensitive to the metal ions type. Such tritopic 1D coordination polymers exhibit a range of original structural features and a facile control of the developed structures in solutions and gels by tuning their thermodynamic parameters. The versatility associated to the intrinsic dynamic ability of the systems should pave the way to original properties for molecular devices. - Graphical abstract: A tritopic ligand with a bis-terpyridine cyclam (CHTT) unit can form homo- and heterobinuclear coordination polymers with bivalent metal ions in DMF. Gels exhibit a remarkable self-healing property while structures of solutions and gels are studied by small-angle neutron scattering. - Highlights: • Homo- and heteronuclear coordination polymers based on innovative tritopic ligand. • The gels formed from the coordination polymers demonstrated self-healing property. • Influence of the metal type was studied through the structural properties by SANS. • Versatility of the singular system present original properties for molecular device.

  19. Tyrosine Phosphorylation Based Homo-dimerization of Arabidopsis RACK1A Proteins Regulates Oxidative Stress Signaling Pathways in Yeast.

    Science.gov (United States)

    Sabila, Mercy; Kundu, Nabanita; Smalls, Deana; Ullah, Hemayet

    2016-01-01

    Scaffold proteins are known as important cellular regulators that can interact with multiple proteins to modulate diverse signal transduction pathways. RACK1 (Receptor for Activated C Kinase 1) is a WD-40 type scaffold protein, conserved in eukaryotes, from Chlamydymonas to plants and humans, plays regulatory roles in diverse signal transduction and stress response pathways. RACK1 in humans has been implicated in myriads of neuropathological diseases including Alzheimer and alcohol addictions. Model plant Arabidopsis thaliana genome maintains three different RACK1 genes termed RACK1A, RACK1B, and RACK1C with a very high (85-93%) sequence identity among them. Loss of function mutation in Arabidopsis indicates that RACK1 proteins regulate diverse environmental stress signaling pathways including drought and salt stress resistance pathway. Recently deduced crystal structure of Arabidopsis RACK1A- very first among all of the RACK1 proteins, indicates that it can potentially be regulated by post-translational modifications, like tyrosine phosphorylations and sumoylation at key residues. Here we show evidence that RACK1A proteins, depending on diverse environmental stresses, are tyrosine phosphorylated. Utilizing site-directed mutagenesis of key tyrosine residues, it is found that tyrosine phosphorylation can potentially dictate the homo-dimerization of RACK1A proteins. The homo-dimerized RACK1A proteins play a role in providing UV-B induced oxidative stress resistance. It is proposed that RACK1A proteins ability to function as scaffold protein may potentially be regulated by the homo-dimerized RACK1A proteins to mediate diverse stress signaling pathways.

  20. Large-scale identification of coevolution signals across homo-oligomeric protein interfaces by direct coupling analysis.

    Science.gov (United States)

    Uguzzoni, Guido; John Lovis, Shalini; Oteri, Francesco; Schug, Alexander; Szurmant, Hendrik; Weigt, Martin

    2017-03-28

    Proteins have evolved to perform diverse cellular functions, from serving as reaction catalysts to coordinating cellular propagation and development. Frequently, proteins do not exert their full potential as monomers but rather undergo concerted interactions as either homo-oligomers or with other proteins as hetero-oligomers. The experimental study of such protein complexes and interactions has been arduous. Theoretical structure prediction methods are an attractive alternative. Here, we investigate homo-oligomeric interfaces by tracing residue coevolution via the global statistical direct coupling analysis (DCA). DCA can accurately infer spatial adjacencies between residues. These adjacencies can be included as constraints in structure prediction techniques to predict high-resolution models. By taking advantage of the ongoing exponential growth of sequence databases, we go significantly beyond anecdotal cases of a few protein families and apply DCA to a systematic large-scale study of nearly 2,000 Pfam protein families with sufficient sequence information and structurally resolved homo-oligomeric interfaces. We find that large interfaces are commonly identified by DCA. We further demonstrate that DCA can differentiate between subfamilies with different binding modes within one large Pfam family. Sequence-derived contact information for the subfamilies proves sufficient to assemble accurate structural models of the diverse protein-oligomers. Thus, we provide an approach to investigate oligomerization for arbitrary protein families leading to structural models complementary to often-difficult experimental methods. Combined with ever more abundant sequential data, we anticipate that this study will be instrumental to allow the structural description of many heteroprotein complexes in the future.

  1. Similarity analysis between chromosomes of Homo sapiens and monkeys with correlation coefficient, rank correlation coefficient and cosine similarity measures.

    Science.gov (United States)

    Someswara Rao, Chinta; Viswanadha Raju, S

    2016-03-01

    In this paper, we consider correlation coefficient, rank correlation coefficient and cosine similarity measures for evaluating similarity between Homo sapiens and monkeys. We used DNA chromosomes of genome wide genes to determine the correlation between the chromosomal content and evolutionary relationship. The similarity among the H. sapiens and monkeys is measured for a total of 210 chromosomes related to 10 species. The similarity measures of these different species show the relationship between the H. sapiens and monkey. This similarity will be helpful at theft identification, maternity identification, disease identification, etc.

  2. Short communication: Traits unique to genus Homo within primates at the cervical spine (C2-C7).

    Science.gov (United States)

    Rios, Luis; Muñoz, Alexandra; Cardoso, Hugo; Pastor, Francisco

    2014-05-01

    From a comparative study of 222 human and 261 nonhuman primates complete cervical spines, two bony variants associated to the course of the vertebral artery are proposed as unique to genus Homo within primates. First, the opening of the foramen transversarium at C2, a trait present at low frequency in humans (3 to 5.6%). Second, the presence of a bipartite foramen transversarium in the cervical segment C3-C6, a trait that can be observed fully formed in human fetal skeletons, with a clear frequency pattern along the cervical spine (C3>C4>C5>C6primate cervical spine.

  3. Bcmfs1, a novel major facilitator superfamily transporter from Botrytis cinerea, provides tolerance towards the natural toxic compounds camptothecin and cercosporin and towards fungicides

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Waard, De M.A.

    2002-01-01

    Bcmfs1, a novel major facilitator superfamily gene from Botrytis cinerea, was cloned, and replacement and overexpression mutants were constructed to study its function. Replacement mutants showed increased sensitivity to the natural toxic compounds camptothecin and cercosporin, produced by the plant

  4. Aspergillus niger protein estA defines a new class of fungal esterases within the alfa/beta hydrolase fold superfamily of proteins

    NARCIS (Netherlands)

    Bourne, Y.; Hasper, A.A.; Chahinian, H.; Juin, M.; Graaff, de L.H.

    2004-01-01

    From the fungus Aspergillus niger, we identified a new gene encoding protein EstA, a member of the alpha/beta-hydrolase fold superfamily but of unknown substrate specificity. EstA was overexpressed and its crystal structure was solved by molecular replacement using a lipaseacetylcholinesterase chime

  5. Secretion of natural and synthetic toxic compounds from filamentous fungi by membrane transporters of the ATP-binding cassette and major facilitator superfamily

    NARCIS (Netherlands)

    Stergiopoulos, I.; Zwiers, L.H.; Waard, De M.A.

    2002-01-01

    This review provides an overview of members of the ATP-binding cassette (ABC) and major facilitator superfamily (MFS) of transporters identified in filamentous fungi. The most common function of these membrane proteins is to provide protection against natural toxic compounds present in the environme

  6. Entre vapores & vídeos pornôs: dissidências homo/eróticas na trama discursiva do envelhecimento masculino Through steams & porno videos: homo/erotic dissident threads in the discoursive tapestry of aging men

    Directory of Open Access Journals (Sweden)

    Fernando Altair Pocahy

    2012-08-01

    Full Text Available Este artigo analisa formas de regulação do gênero e da sexualidade em sua articulação com os discursos normativos acionados na produção discursiva do envelhecimento. Buscando problematizar os jogos de verdade que cercam as experimentações de homens idosos em práticas homo/eróticas, tratou-se neste estudo (resultado de uma tese de doutorado em Educação de compreender como algo em torno de uma forma que o corpo toma é fabricado e descrito como verdade, produzindo sua materialidade (discursiva 'abjeta'.This article analyzes forms of regulation of gender and sexuality in their relationship with the normative discourses triggered by the discursive production of the 'aging'. Seeking the games of truth that surround the experience of elderly men with homo erotic practices, this study (the result of a doctoral thesis in Education tried to understand how the modern discursive practices can build and materialize the aging body as "abject".

  7. Filling the gap. Human cranial remains from Gombore II (Melka Kunture, Ethiopia; ca. 850 ka) and the origin of Homo heidelbergensis.

    Science.gov (United States)

    Profico, Antonio; Di Vincenzo, Fabio; Gagliardi, Lorenza; Piperno, Marcello; Manzi, Giorgio

    2016-06-20

    African archaic humans dated to around 1,0 Ma share morphological affinities with Homo ergaster and appear distinct in cranio-dental morphology from those of the Middle Pleistocene that are referred to Homo heidelbergensis. This observation suggests a taxonomic and phylogenetic discontinuity in Africa that ranges across the Matuyama/Brunhes reversal (780 ka). Yet, the fossil record between roughly 900 and 600 ka is notoriously poor. In this context, the Early Stone Age site of Gombore II, in the Melka Kunture formation (Upper Awash, Ethiopia), provides a privileged case-study. In the Acheulean layer of Gombore II, somewhat more recent than 875 ±10 ka, two large cranial fragments were discovered in 1973 and 1975 respectively: a partial left parietal (Melka Kunture 1) and a right portion of the frontal bone (Melka Kunture 2), which probably belonged to the same cranium. We present here the first detailed description and computer-assisted reconstruction of the morphology of the cranial vault pertaining to these fossil fragments. Our analysis suggest that the human fossil specimen from Gombore II fills a phenetic gap between Homo ergaster and Homo heidelbergensis. This appears in agreement with the chronology of such a partial cranial vault, which therefore represents at present one of the best available candidates (if any) for the origin of Homo heidelbergensis in Africa.

  8. Synthesis of gastrin antagonists, analogues of the C-terminal tetrapeptide of gastrin, by introduction of a beta-homo residue.

    Science.gov (United States)

    Rodriguez, M; Fulcrand, P; Laur, J; Aumelas, A; Bali, J P; Martinez, J

    1989-03-01

    A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.

  9. Crystal structure of homo-DNA and nature's choice of pentose over hexose in the genetic system

    Energy Technology Data Exchange (ETDEWEB)

    Egli, Martin; Pallan, Pradeep S.; Pattanayek, Rekha; Wilds, Christopher J.; Lubini, Paolo; Minasov, George; Dobler, Max; Leumann, Christian J.; Eschenmoser, Albert (Bern); (Vanderbilt); (Scripps); (NWU); (Biographics Laboratory 3R); (Alta)

    2010-03-05

    An experimental rationalization of the structure type encountered in DNA and RNA by systematically investigating the chemical and physical properties of alternative nucleic acids has identified systems with a variety of sugar-phosphate backbones that are capable of Watson-Crick base pairing and in some cases cross-pairing with the natural nucleic acids. The earliest among the model systems tested to date, (4{prime} {yields} 6{prime})-linked oligo(2{prime},3{prime}-dideoxy-{beta}-d-glucopyranosyl)nucleotides or homo-DNA, shows stable self-pairing, but the pairing rules for the four natural bases are not the same as those in DNA. However, a complete interpretation and understanding of the properties of the hexapyranosyl (4{prime} {yields} 6{prime}) family of nucleic acids has been impeded until now by the lack of detailed 3D-structural data. We have determined the crystal structure of a homo-DNA octamer. It reveals a weakly twisted right-handed duplex with a strong inclination between the hexose-phosphate backbones and base-pair axes, and highly irregular values for helical rise and twist at individual base steps. The structure allows a rationalization of the inability of allo-, altro-, and glucopyranosyl-based oligonucleotides to form stable pairing systems.

  10. Spectroscopic investigation, vibrational assignments, HOMO-LUMO, NBO, MEP analysis and molecular docking studies of oxoaporphine alkaloid liriodenine

    Science.gov (United States)

    Costa, Renyer A.; Pitt, Priscilla Olliveira; Pinheiro, Maria Lucia B.; Oliveira, Kelson M. T.; Salomé, Kahlil Schwanka; Barison, Andersson; Costa, Emmanoel Vilaça

    2017-03-01

    A combined experimental and theoretical DFT study of the structural, vibrational and electronic properties of liriodenine is presented using B3LYP function with 6-311G (2d, p) basis set. The theoretical geometry optimization data were compared with the X-ray data for a similar structure in the associated literature, showing similar values. In addition, natural bond orbitals (NBOs), HOMO-LUMO energy gap, mapped molecular Electrostatic Potential (MEP) surface calculation, first and second order hyperpolarizabilities were also performed with the same calculation level. Theoretical UV spectrum agreed well with the measured experimental data, with transitions assigned. The molecular electrostatic potential map shows opposite potentials regions that forms hydrogen bonds that stabilize the dimeric form, which were confirmed by the close values related to the C dbnd O bond stretching between the dimeric form and the experimental IR spectra (1654 cm- 1 for the experimental, 1700 cm- 1 for the dimer form). Calculated HOMO/LUMO gaps shows the excitation energy for Liriodenine, justifying its stability and kinetics reaction. Molecular docking studies with Candida albicans dihydrofolate reductase (DHFR) and Candida albicans secreted aspartic protease (SAP) showed binding free energies values of - 8.5 and - 8.3 kcal/mol, suggesting good affinity between the liriodenine and the target macromolecules.

  11. Analysis of Three Sugarcane Homo/Homeologous Regions Suggests Independent Polyploidization Events of Saccharum officinarum and Saccharum spontaneum

    Science.gov (United States)

    Vilela, Mariane de Mendonça; Del Bem, Luiz Eduardo; Van Sluys, Marie-Anne; de Setta, Nathalia; Kitajima, João Paulo; Cruz, Guilherme Marcelo Queiroga; Sforça, Danilo Augusto; de Souza, Anete Pereira; Ferreira, Paulo Cavalcanti Gomes; Grativol, Clícia; Cardoso-Silva, Claudio Benicio; Vicentini, Renato

    2017-01-01

    Whole genome duplication has played an important role in plant evolution and diversification. Sugarcane is an important crop with a complex hybrid polyploid genome, for which the process of adaptation to polyploidy is still poorly understood. In order to improve our knowledge about sugarcane genome evolution and the homo/homeologous gene expression balance, we sequenced and analyzed 27 BACs (Bacterial Artificial Chromosome) of sugarcane R570 cultivar, containing the putative single-copy genes LFY (seven haplotypes), PHYC (four haplotypes), and TOR (seven haplotypes). Comparative genomic approaches showed that these sugarcane loci presented a high degree of conservation of gene content and collinearity (synteny) with sorghum and rice orthologous regions, but were invaded by transposable elements (TE). All the homo/homeologous haplotypes of LFY, PHYC, and TOR are likely to be functional, because they are all under purifying selection (dN/dS ≪ 1). However, they were found to participate in a nonequivalently manner to the overall expression of the corresponding gene. SNPs, indels, and amino acid substitutions allowed inferring the S. officinarum or S. spontaneum origin of the TOR haplotypes, which further led to the estimation that these two sugarcane ancestral species diverged between 2.5 and 3.5 Ma. In addition, analysis of shared TE insertions in TOR haplotypes suggested that two autopolyploidization may have occurred in the lineage that gave rise to S. officinarum, after its divergence from S. spontaneum. PMID:28082603

  12. Human species and mating systems: Neandertal-Homo sapiens reproductive isolation and the archaeological and fossil records.

    Science.gov (United States)

    Overmann, Karenleigh; Coolidge, Frederick

    2013-01-01

    The present paper examined the assumption of strong reproductive isolation (RI) between Homo neanderthalensis and Homo sapiens, as well as the question of what form it might have taken, using insights from the parallel case of chimpanzee–bonobo hybridization. RI from hybrid sterility or inviability was thought unlikely based on the short separation-to-introgression timeline. The forms of RI that typically develop in primates have relatively short timelines (especially for partial implementation); they generally preclude mating or influence hybrid survival and reproduction in certain contexts, and they have the potential to skew introgression directionality. These RI barriers are also consistent with some interpretations of the archaeological and fossil records, especially when behavioral, cognitive, morphological, and genetic differences between the two human species are taken into consideration. Differences potentially influencing patterns of survival and reproduction include interspecies violence, Neandertal xenophobia, provisioning behavior, and ontogenetic, morphological, and behavioral differences affecting matters such as kin and mate recognition, infanticide, and sexual selection. These factors may have skewed the occurrence of interbreeding or the survival and reproduction of hybrids in a way that might at least partially explain the pattern of introgression.

  13. The Sima de los Huesos (Burgos, northern Spain): palaeoenvironment and habitats of Homo heidelbergensis during the Middle Pleistocene

    Science.gov (United States)

    García, Nuria; Arsuaga, Juan Luis

    2011-06-01

    Interpreting how environmental dynamics respond to global climate change and how this has affected human evolution and dispersal is an on-going topic of debate. During the early Middle Pleistocene (˜0.6-0.4 Ma), as compared to earlier, environmental conditions were relatively more stable, with longer climatic cycles alternating between open and forested landscapes. During this interval, humans spread successfully providing an important number of fossil sites where fossils or tools are reported. The Atapuerca-Sima de los Huesos (Burgos, northern Spain) site (Atapuerca-SH) is one of the earliest localities with hominin evidence in the European Middle Pleistocene, with the most important accumulation of Homo heidelbergensis so far. We have analyzed the abundant faunal record from Sima de los Huesos, which is mainly comprised of carnivores, in order to approach an interpretation of the palaeoenvironmental circumstances where these hominids inhabited within the Sierra. Other sites from Sierra de Atapuerca referred to the same Faunal Unit (FU 6), are roughly contemporaneous, and include important ungulates, which are here analyzed with Atapuerca-SH. Additional information provided by isotopic analysis helps elucidate the ancient ecology of taxa present in Sima de los Huesos allowing for an accurate portrayal of the setting in which humans lived. The timing of the spread of Homo heidelbergensis is dominated by a relative climatic and environmental stability and points to a landscape dominated by savannah-like open woodland.

  14. HS3D, A Dataset of Homo Sapiens Splice Regions, and its Extraction Procedure from a Major Public Database

    Science.gov (United States)

    Pollastro, Pasquale; Rampone, Salvatore

    The aim of this work is to describe a cleaning procedure of GenBank data, producing material to train and to assess the prediction accuracy of computational approaches for gene characterization. A procedure (GenBank2HS3D) has been defined, producing a dataset (HS3D - Homo Sapiens Splice Sites Dataset) of Homo Sapiens Splice regions extracted from GenBank (Rel.123 at this time). It selects, from the complete GenBank Primate Division, entries of Human Nuclear DNA according with several assessed criteria; then it extracts exons and introns from these entries (actually 4523 + 3802). Donor and acceptor sites are then extracted as windows of 140 nucleotides around each splice site (3799 + 3799). After discarding windows not including canonical GT-AG junctions (65 + 74), including insufficient data (not enough material for a 140 nucleotide window) (686 + 589), including not AGCT bases (29 + 30), and redundant (218 + 226), the remaining windows (2796 + 2880) are reported in the dataset. Finally, windows of false splice sites are selected by searching canonical GT-AG pairs in not splicing positions (271 937 + 332 296). The false sites in a range +/- 60 from a true splice site are marked as proximal. HS3D, release 1.2 at this time, is available at the Web server of the University of Sannio: http://www.sci.unisannio.it/docenti/rampone/.

  15. Gold(I) NHC-based homo- and heterobimetallic complexes: synthesis, characterization and evaluation as potential anticancer agents.

    Science.gov (United States)

    Bertrand, Benoît; Citta, Anna; Franken, Inge L; Picquet, Michel; Folda, Alessandra; Scalcon, Valeria; Rigobello, Maria Pia; Le Gendre, Pierre; Casini, Angela; Bodio, Ewen

    2015-09-01

    While N-heterocyclic carbenes (NHC) are ubiquitous ligands in catalysis for organic or industrial syntheses, their potential to form transition metal complexes for medicinal applications has still to be exploited. Within this frame, we synthesized new homo- and heterobimetallic complexes based on the Au(I)-NHC scaffold. The compounds were synthesized via a microwave-assisted method developed in our laboratories using Au(I)-NHC complexes carrying a pentafluorophenol ester moiety and another Au(I) phosphane complex or a bipyridine ligand bearing a pendant amine function. Thus, we developed two different methods to prepare homo- and heterobimetallic complexes (Au(I)/Au(I) or Au(I)/Cu(II), Au(I)/Ru(II), respectively). All the compounds were fully characterized by several spectroscopic techniques including far infrared, and were tested for their antiproliferative effects in a series of human cancer cells. They showed moderate anticancer properties. Their toxic effects were also studied ex vivo using the precision-cut tissue slices (PCTS) technique and initial results concerning their reactivity with the seleno-enzyme thioredoxin reductase were obtained.

  16. Sinorhizobium meliloti Phage ΦM9 Defines a New Group of T4 Superfamily Phages with Unusual Genomic Features but a Common T=16 Capsid

    Science.gov (United States)

    Johnson, Matthew C.; Tatum, Kelsey B.; Lynn, Jason S.; Brewer, Tess E.; Lu, Stephen; Washburn, Brian K.

    2015-01-01

    ABSTRACT Relatively little is known about the phages that infect agriculturally important nitrogen-fixing rhizobial bacteria. Here we report the genome and cryo-electron microscopy structure of the Sinorhizobium meliloti-infecting T4 superfamily phage ΦM9. This phage and its close relative Rhizobium phage vB_RleM_P10VF define a new group of T4 superfamily phages. These phages are distinctly different from the recently characterized cyanophage-like S. meliloti phages of the ΦM12 group. Structurally, ΦM9 has a T=16 capsid formed from repeating units of an extended gp23-like subunit that assemble through interactions between one subunit and the adjacent E-loop insertion domain. Though genetically very distant from the cyanophages, the ΦM9 capsid closely resembles that of the T4 superfamily cyanophage Syn9. ΦM9 also has the same T=16 capsid architecture as the very distant phage SPO1 and the herpesviruses. Despite their overall lack of similarity at the genomic and structural levels, ΦM9 and S. meliloti phage ΦM12 have a small number of open reading frames in common that appear to encode structural proteins involved in interaction with the host and which may have been acquired by horizontal transfer. These proteins are predicted to encode tail baseplate proteins, tail fibers, tail fiber assembly proteins, and glycanases that cleave host exopolysaccharide. IMPORTANCE Despite recent advances in the phylogenetic and structural characterization of bacteriophages, only a small number of phages of plant-symbiotic nitrogen-fixing soil bacteria have been studied at the molecular level. The effects of phage predation upon beneficial bacteria that promote plant growth remain poorly characterized. First steps in understanding these soil bacterium-phage dynamics are genetic, molecular, and structural characterizations of these groups of phages. The T4 superfamily phages are among the most complex phages; they have large genomes packaged within an icosahedral head and a long

  17. Most probable distance between the nucleus and HOMO electron: the latent meaning of atomic radius from the product of chemical hardness and polarizability.

    Science.gov (United States)

    Szarek, Paweł; Grochala, Wojciech

    2014-11-06

    The simple relationship between size of an atom, the Pearson hardness, and electronic polarizability is described. The estimated atomic radius correlates well with experimental as well as theoretical covalent radii reported in the literature. Furthermore, the direct connection of atomic radius to HOMO electron density and important notions of conceptual DFT (such as frontier molecular orbitals and Fukui function) has been shown and interpreted. The radial maximum of HOMO density distribution at (αη)(1/2) minimizes the system energy. Eventually, the knowledge of the Fukui function of an atom is sufficient to estimate its electronic polarizability, chemical potential, and hardness.

  18. Acetatos homo e heterotrinucleares de ferro: um experimento para o laboratório de química de coordenação Homo and heterotrinuclear iron acetates: an experiment for the coordination chemistry laboratory

    Directory of Open Access Journals (Sweden)

    Reginaldo da Silva Santos

    2010-01-01

    Full Text Available Homo and heterotrinuclear acetates are unique compounds having μ3-oxo bridge and many interesting properties of such compounds are derived from this structure. Some undergraduate inorganic textbooks discuss several aspects of these compounds and we present here an undergraduate experiment for the high-yield synthesis of [Fe2MO(CH3CO26(H 2O3], with M = Fe3+, Co2+ and Ni2+, as well as their characterization using infrared spectroscopy and cyclic voltametry. The proposed experiment gives the opportunity to discuss several concepts of coordination chemistry that follow the characterization techniques, such as: types of acetate coordination, reversibility of electrochemical processes, quelate and trans effects and lability.

  19. Extracellular Ribonuclease from Bacillus licheniformis (Balifase, a New Member of the N1/T1 RNase Superfamily

    Directory of Open Access Journals (Sweden)

    Yulia Sokurenko

    2016-01-01

    Full Text Available The N1/T1 RNase superfamily comprises enzymes with well-established antitumor effects, such as ribotoxins secreted by fungi, primarily by Aspergillus and Penicillium species, and bacterial RNase secreted by B. pumilus (binase and B. amyloliquefaciens (barnase. RNase is regarded as an alternative to classical chemotherapeutic agents due to its selective cytotoxicity towards tumor cells. New RNase with a high degree of structural similarity with binase (73% and barnase (74% was isolated and purified from Bacillus licheniformis (balifase, calculated molecular weight 12421.9 Da, pI 8.91. The protein sample with enzymatic activity of 1.5 × 106 units/A280 was obtained. The physicochemical properties of balifase are similar to those of barnase. However, in terms of its gene organization and promoter activity, balifase is closer to binase. The unique feature of balifase gene organization consists in the fact that genes of RNase and its inhibitor are located in one operon. Similarly to biosynthesis of binase, balifase synthesis is induced under phosphate starvation; however, in contrast to binase, balifase does not form dimers under natural conditions. We propose that the highest stability of balifase among analyzed RNase types allows the protein to retain its structure without oligomerization.

  20. A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria.

    Science.gov (United States)

    Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Iñigo; Novick, Richard P; Christie, Gail E; Penadés, José R

    2013-08-01

    The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria.