bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarker-free dielectrophoretic sorting of differentiating myoblast multipotent progenitor cells and their membrane analysis by Raman spectroscopy
Authors: Muratore Massimo , Srsen Vlastimil , Waterfall Martin , Downes Andrew , Pethig Ronald
Published: August 2012

Myoblasts are muscle derived mesenchymal stem cell progenitors that have great potential for use in regenerative medicine, especially for cardiomyogenesis grafts and intracardiac cell transplantation. To utilise such cells for pre-clinical and clinical applications, and especially for personalized medicine, it is essential to generate a synchronised, homogenous, population of cells that display phenotypic and genotypic homogeneity within a population of cells. We demonstrate that the biomarker-free technique of dielectrophoresis (DEP) can be used to discriminate cells between stages of differentiation in the C2C12 myoblast multipotent mouse model. Terminally differentiated myotubes were separated from C2C12 myoblasts to better than 96% purity, a result validated by flow cytometry and Western blotting. To determine the extent to which cell membrane capacitance, rather than cell size, determined the DEP response of a cell, C2C12 myoblasts were co-cultured with GFP-expressing MRC-5 fibroblasts of comparable size distributions (mean diameter ∼10 μm). A DEP sorting efficiency greater than 98% was achieved for these two cell types, a result concluded to arise from the fibroblasts possessing a larger membrane capacitance than the myoblasts. It is currently assumed that differences in membrane capacitance primarily reflect differences in the extent of folding or surface features of the membrane. However, our finding by Raman spectroscopy that the fibroblast membranes contained a smaller proportion of saturated lipids than those of the myoblasts suggests that the membrane chemistry should also be taken into account.
The role of alkaloids in conferring aphid resistance in yellow lupin (Lupinus luteus L.)
Authors: Adhikari Kedar Nath , Edwards Owain Rhys , Wang Shaofang , Ridsdill-Smith Thomas James , Buirchell Bevan
Published: August 2012

A key goal in the breeding for aphid resistance of cultivated lupins is to manipulate the levels and distributions of alkaloids. Lupin alkaloids are known to be responsible for resistance to herbivorous insects, but the total seed alkaloid level must remain under 0.02% for animal and human consumption. Yellow lupin (Lupinus luteus L.) is being investigated as a new legume crop for Western Australia (WA), but most lines produced to date have been very susceptible to aphids. In contrast, breeders in WA have had ongoing success releasing narrow-leafed lupin (L. angustifolius L.) cultivars with adequate resistance to aphids. In this study, aphid performance was evaluated on yellow lupin plants in the glasshouse from an F2 population derived from a cross between Teo, a yellow lupin cultivar resistant to aphids and with high total alkaloid levels, and Wodjil, a single plant selection from Teo that is susceptible to aphids and has low total alkaloid levels, and their parents. Resistance in Teo and the F2 progeny was strongly associated with the alkaloids gramine and a gramine analogue. The absence of plants with intermediate levels of these alkaloids in progeny of this cross makes it unlikely that aphid-resistant lines can be generated using Teo as the resistance source. On the other hand, different alkaloids were correlated with aphid resistance in the narrow-leafed lupin cultivar Kalya, and aphid resistance was more evenly distributed among progeny of a cross of the resistant cultivar Kalya with the susceptible cultivar Tallerack. For this reason, additional yellow lupin lines with a more diverse alkaloid profile were selected for further study from the Australian lupin breeding program. A wide variation in the aphid tolerance among lines was observed and aphid tolerance was positively correlated with alkaloid content. However, four lines were identified with moderate levels of aphid resistance in a low alkaloid background. These lines had varying alkaloid profiles, but as expected none were dominated by gramine and its analogues. We believe these lines offer a greater opportunity for aphid resistance breeding in yellow lupins.
A bi-polar theory of nominal and clause structure and function
Authors: Ball Jerry T.
Published: August 2012

A bi-polar theory of the structure and function of nominals and clauses is presented in which a specifier, functioning as a referential pole, and a head, functioning as a relational pole, combine to form a referring expression. The theory applies to both object referring expressions, in the case of nominals, and situation referring expressions, in the case of clauses. The bi-polar theory is contrasted with X-Bar Theory — a uni-polar theory in which the head uniquely determines the type of the larger expression in which it occurs. Uni-polar theories adopt a strong notion of endocentricity, which is rejected in the bi-polar theory, where both the specifier and the head make significant and meaningful contributions to the larger expressions in which they occur. The bi-polar theory is also contrasted with Langacker’s conception of the basic structure and function of nominals and clauses.
Italian split intransitivity and image schemas
Authors: Stolova Natalya I.
Published: August 2012

This paper explores the choice between the auxiliaries BE and HAVE with Italian intransitive verbs. Most attempts to account for split intransitivity in Italian, as well as in other Romance languages, can be roughly grouped into two categories: the syntactic perspective and the semantic view. In this article I propose that instead of attempting to identify one single parameter responsible for the choice between BE and HAVE, the Romanists should, as our colleagues in other language families have already done, consider the auxiliary selection in terms of a combination of motivations related to the speakers’ conceptualization of the event and to their access to the relevant image schema. This proposition prompts us to reassess the conclusions previously reached by researchers working with aphasic subjects. In addition, it fosters integration between cognitive linguistics and neuroscience by providing a solution to the so-called “Granularity Mismatch Problem.”
Confrontation or complementarity?
Authors: Cameron Lynne
Published: August 2012

Theoretical and methodological challenges presented by studying metaphor in its discourse environment are addressed. Complex dynamic systems theory provides a theoretical ‘discourse dynamics’ framework for describing metaphor in face-to-face conversation, and more generally, as a phenomenon that is at once linguistic, cognitive, affective and socio-cultural. Empirical data from post-conflict reconciliation conversations illustrate the procedures of metaphor-led discourse analysis, using metaphor to investigate patterns of talking and thinking. Identification of linguistic metaphors is followed by the extraction of patterns of metaphor use, which include metaphor clusters and ‘systematic metaphors’. Connections are made between metaphor in on-line talk, patterns of metaphor use in discourse events and metaphor in socio-cultural life. The final section of this article discusses whether the differences found between metaphor as hypothesised in conceptual metaphor theory and metaphor in real-world discourse reflect an essential incompatibility or can be used more positively in developing cognitive approaches to metaphor.
Lexical templates within a functional cognitive theory of meaning
Authors: Mairal-Usón Ricardo , Faber Pamela
Published: August 2012

Within the context of the Lexical Constructional Model, which provides a comprehensive account of the relationship between syntax and all facets on meaning construction, this paper is concerned with one of the major representational modules of the model, viz. a lexical template. It is claimed that a lexical template consists of a semantic specification plus a logical structure. The logical structure formalism is constructed on the basis of Aktionsart distinctions proposed in Role and Reference Grammar (Van Valin & Lapolla, 1997; Van Valin, 2005). Aktionsart regularities are captured by the external variables of the template, specified in Roman characters, and by a set of high-level elements of structure that function as semantic primitives. Lexical templates also contain internal variables, marked with Arabic numerals, and formally expressed in terms of a catalogue of lexical functions. These variables capture world-knowledge elements that relate in a way specific to the predicate defined by the lexical template. In order to test the viability of lexical templates, a detailed analysis of a set of verbs within the lexical domain of cognition is included.
“Image” metaphors and connotations in everyday language
Authors: Deignan Alice
Published: August 2012

In this paper, I argue that the general notion of an image metaphor, which has been traditionally confined to so-called “one-shot metaphors”, as used in literary and poetic language, could be expanded to describe many expressions that are found in everyday language. Following Caballero (2003a), I argue that the division in cognitive linguistics of metaphors into “image” and “conceptual” is over-simplistic. I show that many of the most frequent metaphors in my data have characteristics which would qualify them for inclusion in both categories. I also argue that connotational meaning is an important characteristic of these expressions, unifying their literal and non-literal meanings. A detailed analysis of the Bank of English corpus concordance for heel shows the numerical importance of such metaphors. I refer to research into metaphor that takes an emergentist perspective, and which has led a number of other existing distinctions to be questioned. I argue that these expressions, termed “metaphoremes”, which are difficult to classify using existing distinctions, should be regarded as prototypical on the grounds of their frequency, rather than as anomalous.
‘Saved by the reflexive’
Authors: Gonzálvez-García Francisco
Published: August 2012

This paper argues for the existence of a dynamic interaction between constructional polysemy and coercion in shaping lower-level configurations of the subjective-transitive construction in English and Spanish. In particular, a fine-grained analysis is provided of those configurations featuring coercion via a reflexive pronoun in the object slot. The corpus-based analysis provided here shows that the verbs in question, regardless of their inherent lexical semantics, are construed in this construction as expressing a personal assessment by the subject/speaker about himself/herself, thus providing incontrovertible evidence for a constructionist analysis of the type invoked here. Moreover, the coercion effects examined here lend further credence to the construction-specific and also language-specific nature of constructions, especially in the light of instances of the reflexive subjective-transitive construction after saber (‘know’) in Spanish. This paper also suggests that the explanatory power of the anatomy of a given construction can be further maximized if the morphosyntactic properties of the XPCOMP are mapped onto their inherent meaning properties.
Light and heavy reflexive marking
Authors: Calude Andreea S.
Published: August 2012

In Romanian, the middle marker se is employed to encode five distinct situation types: reflexive, reciprocal, (medio-)passive, inchoative and impersonal. This work identifies the relationships among the different uses of the marker and puts forward explanations for them within a cognitive, functional framework. Following studies such as those by Faltz (1985), Haiman (1983), Haspelmath (2005), Kemmer (1993ab), Lakoff (1977), Manoliu-Manea (1994, 2000), Maldonado (1992, 1999), Manney (2000), and Yoshimura and Taylor (2004), the current paper gives a synchronic account of the Romanian Middle Domain, its organization and the relationships between the various middle constructions found inside it. Findings suggest that the semantic property of low elaboration of events (introduced by Kemmer, 1993ab) constitutes the common denominator among the different uses explored. This work provides an insight into Romanian itself, as well as a contribution to cognitive theories of human language and responds to the call for more data and further investigations of middles cross-linguistically (see Smith, 2004).
Hacer sociolingüística etnográfica en un mundo cambiante
Authors: Codó Eva , Patiño Santos Adriana , Unamuno Virginia
Published: August 2012

Este volumen reúne un grupo de trabajos de jóvenes sociolingüistas del mundo hispano que reflexionan, a través de su experiencia investigadora, sobre la metodología etnográfica, sus retos y confines epistemológicos, así como la configuración de nuevas posibilidades y formas de investigación para el estudio situado de los usos lingüísticos en los contextos plurilingües y multiculturales del mundo actual. Si bien se trata de seis artículos con temáticas muy diferentes entre sí, todos ellos tienen en común el plantearse un trabajo sociolingüístico que conjuga el análisis de los usos verbales con el reto de lograr la comprensión de dichos usos desde una perspectiva etnográfica que los sitúa histórica, social, política y económicamente, y que pone en un lugar central la reflexividad metodológica como parte del trabajo investigador. Por su parte, esta introducción reflexiona sobre los retos conceptuales y metodológicos a los que se enfrenta la sociolingüística actual y sugiere que el mundo hispano y sus contextos ofrecen una mirada sociolingüística propia que cuestiona y complejiza viejas dicotomías y ciertos sentidos comunes en la disciplina.
Aportaciones de la etnografía de red al estudio de un locutorio
Authors: Sabaté Dalmau Maria
Published: August 2012

Este estudio analiza las aportaciones de la etnografía de red a la investigación de un grupo de migrantes multilingües que gestionan sus trayectorias transnacionales en torno a un locutorio de Barcelona. En primer lugar, se contextualiza la móvil-ización de estas redes en Cataluña, y se presenta un negocio étnico, el locutorio, como una institución de la migración y un espacio de socialización que sirve de punto de partida para teorizar sobre esta metodología. Se indaga también en el cambio de paradigma metodológico dentro de la sociología, la sociolingüística y la antropología lingüística (y disciplinas afines) que a partir del análisis de redes sociales clásico dio fruto a la etnografía de red. A continuación se explica en qué consiste esta praxis y, con ejemplos concretos del trabajo de campo en un locutorio, se argumenta que, aunque aún nos plantea algunos retos, ésta es una herramienta privilegiada para adentrarnos en las redes sociales actuales y entender qué significa ser una persona migrada en la sociedad en red de la era global.
“Ah! Spain, that’s far away from China”
Authors: Pérez Milans Miguel
Published: August 2012

Este artículo reflexiona sobre las potencialidades y limitaciones del método etnográfico para el estudio sociolingüístico de los procesos de movilidad asociados a la nueva economía globalizada. En particular, se analizan los dilemas metodológicos derivados de un viaje de investigación entre el ámbito educativo español y el de la República Popular China que se llevó a cabo con el fin de seguir la trayectoria de movilidad realizada por unos estudiantes chinos que habían sido previamente observados en un aula de enlace de la Comunidad de Madrid. Estos dilemas indexan procesos de transformación local que las instituciones educativas están experimentando de modo específico en cada contexto, en vinculación con procesos sociales más amplios de cambio derivados de la globalización económica. Sin embargo, también descubren el propio desafío que el estudio de estos procesos de supone para el análisis situado de las prácticas sociolingüísticas.
La socialización lingüística en La Clase Mágica
Authors: Relaño Pastor Ana María
Published: August 2012

Este artículo analiza la socialización lingüística que tiene lugar en La Clase Mágica (Vásquez 2003), un programa extracurricular de carácter bilingüe y bicultural, dirigido a satisfacer las necesidades lingüísticas y culturales de la comunidad latina, mayoritariamente de origen mexicano, en el condado de San Diego (California). Siguiendo los parámetros metodológicos de la socialización lingüística, los datos emergen de la observación participante, grabaciones de audio y vídeo de las distintas interacciones en La Clase Mágica, así como notas etnográficas y entrevistas a madres, profesores y coordinadores del programa. El artículo analiza las distintas prácticas de socialización lingüística en este programa y discute las implicaciones sociopolíticas y educativas de las mismas en el contexto de racialización de la comunidad latina/mexicana en California.
Entre silencios presentidos y voces anheladas
Authors: Hecht Ana Carolina
Published: August 2012

Este artículo indaga en torno a las ideologías lingüísticas sobre el reemplazo de la lengua toba (qom) por el español entre los niños y las niñas de un grupo de familias indígenas de un asentamiento urbano en las afueras de la ciudad de Buenos Aires (Argentina). En este contexto, se vislumbran dos tipos de ideologías lingüísticas contrapuestas: una porción minoritaria considera al desplazamiento como un proceso casi irreversible, mientras que la mayoría confía en la vitalidad futura del idioma de sus ancestros. A partir de una mirada etnográfica, se comprenden los sentidos y valoraciones culturales implícitas y explícitas a las prácticas de habla bilingües que moldean dichas ideologías, así como también se analizan las relaciones entre ser niño, ser adulto y saber toba en el marco de un proceso de desplazamiento lingüístico.
Feminism, Pragmatism or Both? Czech Radical Nationalism and the Woman Question, 1898–1914
Authors: Kelly T. Mills
Published: August 2012

During a debate on the franchise reform bill in the Austrian Reichsrat on 12 September 1906, the Czech National Socialist Party deputy Václav Choc demanded that suffrage be extended to women as well as men. Otherwise, Choc asserted, the women of Austria would be consigned to the same status as “criminals and children.” Choc was certainly not the only Austrian parliamentarian to voice his support for votes for women during the debates on franchise reform. However, his party, the most radical of all the Czech nationalist political factions, was unique in that it not only included women's suffrage in its official program, as the Social Democrats had done a decade earlier, but also worked hard to change the political status of women in the Monarchy while the Social Democrats generally paid only lip service to this goal. Moreover, Choc and his colleagues in the National Socialist Party helped change the terms of the debate about women's rights by explicitly linking the “woman question” to the “national question” in ways entirely different from the prevailing discourse of liberalism infin-de-siècleAustria. In the last decades of the nineteenth century, liberal reformers, whether German or Czech, tried to mold the participation of women in political life to fit the liberal view of a woman's “proper” role in society. By contrast, the radical nationalists who rose to prominence in Czech political culture only after 1900, attempted to recast the debate over women's rights as central to their two-pronged discourse of social and national emancipation, while at the same time pressing for the complete democratization of Czech political life at all levels, not merely in the imperial parliament. In so doing, and with the active but often necessarily covert collaboration of women associated with the party, these radical nationalists helped extend the parameters of the debate over the place Czech women had in the larger national society.
Mihiz in the Sixties: Politics and Drama between Nationalism and Authoritarianism
Authors: Miller Nick
Published: August 2012

Between 1981 and 1991, Serbian intellectual and political life were energized by a movement to overcome the legacies of the Tito regime. Tito himself had died in 1980, but his political heirs, insecure and unimaginative, had proclaimed that even though Tito was gone, his image would continue to guide and bind the peoples of Yugoslavia: “After Tito—Tito!” In Belgrade, the anti-Titoist movement began as a struggle for free expression. As Borislav Mihajlović Mihiz, one of the leaders of the Committee for the Protection of Artistic Freedom (founded in 1982), said later, all political freedom flows from the right to free speech. Mihiz's commitment to the defense and nurturing of this right was consistent with values he had expressed throughout his career as a literary critic, playwright, and theater director. Yet the movement that he helped found in 1982 would be transformed after 1986 into something less obviously principled and much more visceral, as the issue of Kosovo's fate came to consume Serbia's intellectual elite. The movement for free speech segued into a movement to reclaim Kosovo for Serbia without missing a beat, thanks to the ability of Serbian intellectuals to frame the Kosovo problem as a product of the suppression of open dialogue in Yugoslavia. Kosovo replaced Gojko Djogo, Jovan Radulović, Dušan Jovanović, and other censored Serbian writers as the emotive fulcrum of the anti-Titoist movement in Serbia. The free speech movement was transformed into a movement of rage at the Tito regime's allegedly systematic injustices towards Serbs. Since the wars of Yugoslav succession began in 1991, commentators have conveniently forgotten that what ended up a violent and irrational movement in the late 1980s began in such a reasonable fashion. Borislav Mihajlović Mihiz was the face of the early free speech movement.
POLITICAL AND ECONOMIC ELITES IN SWITZERLAND
Authors: Bühlmann Felix , David Thomas , Mach André
Published: August 2012

As a legacy of the early stages of its state building process, Switzerland continues to be characterised by a cohesive elite whose members simultaneously occupy political and economic positions. Whereas sectoral analyses of the economic or political elite are widespread, few researchers have scrutinised the connections between business and politics. Therefore, this paper focuses on the linkages between the economic and political fields. Based on a joint multiple correspondence analysis of the CEOs and board members of the 110 largest Swiss companies in 2000 and 256 parliamentary members, we examine the interactional and objective relations between the fields through an analysis of personal interchange, participation in meeting places and structural homology of educational capital. It appears that the connections between elites are cumulative: in each field, the dominant faction shares a background in law or engineering, participates in meeting places, and personally moves between the fields. Reversely, the dominated, which come from a rather heterogeneous educational background, are excluded from interactional relations and moves between the two fields. That the two forms of elite coordination coincide and reinforce each other could be typical for a small country with little differentiated fields, where elite members quickly get to know each other and can easily meet on a regular basis.
Designating Critical Habitat for Juvenile Endangered Smalltooth Sawfish in the United States
Authors: Norton Shelley L. , Wiley Tonya R. , Carlson John K. , Frick Amanda L. , Poulakis Gregg R. , Simpfendorfer Colin A.
Published: August 2012

In 2003, the U.S. distinct population segment of smalltooth sawfish Pristis pectinata was listed as endangered under the U.S. Endangered Species Act (ESA). At that time, little was known about its habitat use patterns and, although required as part of the ESA, critical habitat could not be officially designated. Subsequently, studies were conducted that identified some of the specific habitats and environmental conditions important for the species. Facilitating recruitment into the adult population by protecting the species’ nurseries was identified in the recovery plan as the key conservation objective, which would be supported by the designation of critical habitat. The location of nurseries was determined by applying published criteria developed for identifying elasmobranch nursery areas to a decade of encounter data. These largely nontraditional data were composed primarily of encounters voluntarily reported by the public to members of the recovery team. The nursery habitats essential to the conservation of the species were identified as those adjacent to red mangroves Rhizophora mangle and euryhaline habitats with water depths ≤0.9 m. Ultimately, two broad areas in southwest Florida that contain these habitats were designated as critical habitat for juvenile smalltooth sawfish: the Charlotte Harbor Estuary unit (896 km2) and the Ten Thousand Islands/Everglades unit (2,505 km2).

Received June 23, 2011; accepted March 12, 2012
Phase Shift in an Estuarine Finfish Community Associated with Warming Temperatures
Authors: Howell Penelope , Auster Peter J.
Published: August 2012

Finfish abundance indices, produced from seasonal trawl survey data collected in Long Island Sound, were examined for changes in community composition related to the dynamics of water temperature from 1984 to 2008. In general, seasonal mean catch of species identified a priori as cold adapted significantly decreased while warm-adapted and subtropical species significantly increased over the time series. Bottom water temperature also significantly increased. As a group, annual abundance of cold-adapted species exhibited significant negative correlation with mean bottom water temperatures while warm-adapted species, but not subtropical species, exhibited significant positive correlation. Multivariate analyses identified a shift in community structure producing two primary year-groupings. Spring groupings were clearly delineated as 1984–1998 (cold period) and 1999–2008 (warm period). Autumn groupings were temporally discontinuous in the 1990s with group membership shifting between cold and warm periods, although the distal ends of the time series were clearly divided. These patterns aligned with deviations from the 1984 to 2008 mean bottom water temperature, indicating that this estuary is experiencing a relatively rapid shift consistent with a response to climate warming. The more distinct delineation of community structure in spring suggests that the lack of advantageous spring conditions was a more important factor in the decline of cold-adapted species than increasingly stressful conditions in autumn.

Received August 30, 2011; accepted April 7, 2012
Structural and mechanistic insights into the bifunctional enzyme isocitrate dehydrogenase kinase/phosphatase AceK
Authors: Zheng Jimin , Yates Susan P. , Jia Zongchao
Published: August 2012

The switch between the Krebs cycle and the glyoxylate bypass is controlled by isocitrate dehydrogenase kinase/phosphatase (AceK). AceK, a bifunctional enzyme, phosphorylates and dephosphorylates isocitrate dehydrogenase (IDH) with its unique active site that harbours both the kinase and ATP/ADP-dependent phosphatase activities. AceK was the first example of prokaryotic phosphorylation identified, and the recent characterization of the structures of AceK and its complex with its protein substrate, IDH, now offers a new understanding of both previous and future endeavours. AceK is structurally similar to the eukaryotic protein kinase superfamily, sharing many of the familiar catalytic and regulatory motifs, demonstrating a close evolutionary relationship. Although the active site is shared by both the kinase and phosphatase functions, the catalytic residues needed for phosphatase function are readily seen when compared with the DXDX(T/V) family of phosphatases, despite the fact that the phosphatase function of AceK is strictly ATP/ADP-dependent. Structural analysis has also allowed a detailed look at regulation and its stringent requirements for interacting with IDH.
Protein kinases display minimal interpositional dependence on substrate sequence: potential implications for the evolution of signalling networks
Authors: Joughin Brian A. , Liu Chengcheng , Lauffenburger Douglas A. , Hogue Christopher W. V. , Yaffe Michael B.
Published: August 2012

Characterization of
in vitro
substrates of protein kinases by peptide library screening provides a wealth of information on the substrate specificity of kinases for amino acids at particular positions relative to the site of phosphorylation, but provides no information concerning interdependence among positions. High-throughput techniques have recently made it feasible to identify large numbers of
in vivo
kinase substrates. We used data from experiments on the kinases ATM/ATR and CDK1, and curated CK2 substrates to evaluate the prevalence of interactions between substrate positions within a motif and the utility of these interactions in predicting kinase substrates. Among these data, evidence of interpositional sequence dependencies is strikingly rare, and what dependency exists does little to aid in the prediction of novel kinase substrates. Significant increases in the ability of models to predict kinase–substrate specificity beyond position-independent models must come largely from inclusion of elements of biological and cellular context, rather than further analysis of substrate sequences alone. Our results suggest that, evolutionarily, kinase substrate fitness exists in a smooth energetic landscape. Taken with results from others indicating that phosphopeptide-binding domains do exhibit interpositional dependence, our data suggest that incorporation of new substrate molecules into phospho-signalling networks may be rate-limited by the evolution of suitability for binding by phosphopeptide-binding domains.
Evolution of the eukaryotic protein kinases as dynamic molecular switches
Authors: Taylor Susan S. , Keshwani Malik M. , Steichen Jon M. , Kornev Alexandr P.
Published: August 2012

Protein kinases have evolved in eukaryotes to be highly dynamic molecular switches that regulate a plethora of biological processes. Two motifs, a dynamic activation segment and a GHI helical subdomain, distinguish the eukaryotic protein kinases (EPKs) from the more primitive eukaryotic-like kinases. The EPKs are themselves highly regulated, typically by phosphorylation, and this allows them to be rapidly turned on and off. The EPKs have a novel hydrophobic architecture that is typically regulated by the dynamic assembly of two hydrophobic spines that is usually mediated by the phosphorylation of an activation loop phosphate. Cyclic AMP-dependent protein kinase (protein kinase A (PKA)) is used as a prototype to exemplify these features of the PKA superfamily. Specificity in PKA signalling is achieved in large part by packaging the enzyme as inactive tetrameric holoenzymes with regulatory subunits that then are localized to macromolecular complexes in close proximity to dedicated substrates by targeting scaffold proteins. In this way, the cell creates discrete foci that most likely represent the physiological environment for cyclic AMP-mediated signalling.
Evolution of SH2 domains and phosphotyrosine signalling networks
Authors: Liu Bernard A. , Nash Piers D.
Published: August 2012

Src homology 2 (SH2) domains mediate selective protein–protein interactions with tyrosine phosphorylated proteins, and in doing so define specificity of phosphotyrosine (pTyr) signalling networks. SH2 domains and protein-tyrosine phosphatases expand alongside protein-tyrosine kinases (PTKs) to coordinate cellular and organismal complexity in the evolution of the unikont branch of the eukaryotes. Examination of conserved families of PTKs and SH2 domain proteins provides fiduciary marks that trace the evolutionary landscape for the development of complex cellular systems in the proto-metazoan and metazoan lineages. The evolutionary provenance of conserved SH2 and PTK families reveals the mechanisms by which diversity is achieved through adaptations in tissue-specific gene transcription, altered ligand binding, insertions of linear motifs and the gain or loss of domains following gene duplication. We discuss mechanisms by which pTyr-mediated signalling networks evolve through the development of novel and expanded families of SH2 domain proteins and the elaboration of connections between pTyr-signalling proteins. These changes underlie the variety of general and specific signalling networks that give rise to tissue-specific functions and increasingly complex developmental programmes. Examination of SH2 domains from an evolutionary perspective provides insight into the process by which evolutionary expansion and modification of molecular protein interaction domain proteins permits the development of novel protein-interaction networks and accommodates adaptation of signalling networks.
Determinants of Electricity Consumption Intensity in China: Analysis of Cities at Subprovince and Prefecture Levels in 2009
Authors: Xia X. H. , Hu Yi
Published: August 2012

China has experienced great social and economic vicissitudes that caused the vast complexity and uncertainty for electricity consumption. This paper attempts to identify the main determinants of the electricity consumption intensity by using the data from Chinese cities at subprovince and prefecture levels in 2009. The key category factors, including urban morphology, industrial structure, regulation context, urbanization degree, price, natural condition, and resource endowment, are abstracted and the influence of these determinants is evaluated by adopting the finite mixture models. The variation of each determinant across regions, the comparative weights of all the factors, and the detailed classifications of the cities are reported for facilitating the understanding of electricity consumption in China. The corresponding policies for electricity administration are addressed as well.
In VitroAntilisterial Properties of Crude Methanol Extracts ofGarcinia kola(Heckel) Seeds
Authors: Penduka Dambudzo , Okoh Anthony I.
Published: August 2012

Crude methanol extracts ofGarcinia kola(Heckel) seeds were screened for their antilisterial activities against 42Listeriabacteria isolated from wastewater effluents. The extract had activity against 45% of the test bacteria and achieved minimum inhibitory concentrations (MICs) ranging between 0.157 and 0.625 mg/mL. The rate of kill of the extract was determined against four representativeListeriaspecies in the study, and the results showed that the highest percentage of bacteria cells were killed after the maximum exposure time of 2 h at the highest concentration of4×MICvalue, with the maximum number of bacteria cells killed being forL. ivanovii(LEL 30) 100%,L. monocytogenes(LAL 8) 94.686%,L. ivanovii(LEL 18) 60.330%, andL. grayi(LAL 15) 56.071% We therefore conclude that the nature of inhibition of the crude methanol extracts ofGarcinia kolaseeds can be either bactericidal or bacteriostatic depending on the targetListeriaspecies and can also differ among same species as evidenced byL. ivanoviistrains LEL 30 and LEL 18.
Design, Kinematic Optimization, and Evaluation of a Teleoperated System for Middle Ear Microsurgery
Authors: Miroir Mathieu , Nguyen Yann , Szewczyk Jérôme , Sterkers Olivier , Bozorg Grayeli Alexis
Published: August 2012

Middle ear surgery involves the smallest and the most fragile bones of the human body. Since microsurgical gestures and a submillimetric precision are required in these procedures, the outcome can be potentially improved by robotic assistance. Today, there is no commercially available device in this field. Here, we describe a method to design a teleoperated assistance robotic system dedicated to the middle ear surgery. Determination of design specifications, the kinematic structure, and its optimization are detailed. The robot-surgeon interface and the command modes are provided. Finally, the system is evaluated by realistic tasks in experimental dedicated settings and in human temporal bone specimens.
Association of the miR‐146aC>G, miR‐149T>C, miR‐196a2T>C, and miR‐499A>G Polymorphisms with Risk of Spontaneously Aborted Fetuses
Authors: Jeon Young Joo , Kim Su Yeoun , Rah HyungChul , Choi Dong Hee , Cha Sun Hee , Yoon Tae Ki , Lee Woo Sik , Shim Sung Han , Kim Nam Keun
Published: August 2012

Problem

The miR‐196a2T>C and miR‐499A>G polymorphisms have been reported to be genetic risk factors for recurrent spontaneous abortion; however, that previous study focused on the genetic analyses of pregnant women rather than aborted fetuses. Because annexin A1 is a target of miR‐196a2 and is related to anti‐inflammation, miR‐196a2 may be immunologically important. Moreover, miR‐146a, miR‐149, miR‐196a2, and miR‐499 have shown associations with immune responses.

Method of study

One hundred and eighty‐two spontaneously aborted fetuses (SAFs) were <20 weeks of gestational age. The control subjects were 101 healthy children and 302 adults collected from a convenience sample. Polymerase chain reaction and restriction fragment length polymorphism analysis was performed to identify the miR‐146aC>G, miR‐149T>C, miR‐196a2T>C, and miR‐499A>G genotypes.

Results

Chromosomally normal SAFs had significantly different frequencies of the miR‐196a2CC, miR‐146aCC/miR‐196a2CC, and miR‐149TT/miR‐196a2CC genotypes compared with control subjects.

Conclusions

miR‐196a2CC, miR‐146aCC/miR‐196a2CC, and miR‐149TT/miR‐196a2CC in fetuses are possible risk factors for spontaneous abortion.
The future role of monoclonal antibody therapy in childhood acute leukaemias
Authors: Barth Matthew , Raetz Elizabeth , Cairo Mitchell S.
Published: August 2012

Leukaemia is the single most common childhood malignancy. With modern treatment regimens, survival in acute lymphoblastic leukaemia (ALL) approaches 90%. Only about 70% of children with acute myeloid leukaemia (AML) achieve long term survival. Patients who relapse have a dismal prognosis. Novel therapeutic approaches are needed to improve treatment outcomes in newly‐diagnosed patients with a poor prognosis and for patients with relapsed/refractory disease that have limited treatment options. One promising approach in treating haematological malignancies has been the use of monoclonal antibodies to target cell surface antigens expressed on malignant cells. Most success with monoclonal antibody therapy in the treatment of haematological malignancies has come in the setting of adult B‐cell non‐Hodgkin lymphoma with the addition of the anti‐CD20 monoclonal antibody rituximab to standard treatment regimens. In order to further advance treatment of haematological malignancies, novel monoclonal antibodies continue to be developed that target a variety of cell surface antigens. Several antibodies continue to be investigated in childhood leukaemias. This review will discuss the development of monoclonal antibodies that target a variety of cell surface antigens for the treatment of childhood ALL and the use of the anti‐CD33 antibody gemtuzumab ozogamicin in the treatment of childhood AML.
Randomized trial of the effectiveness of combined behavioral/pharmacological smoking cessation treatment in Syrian primary care clinics
Authors: Ward Kenneth D. , Asfar Taghrid , Al Ali Radwan , Rastam Samer , Weg Mark W. Vander , Eissenberg Thomas , Maziak Wasim
Published: August 2012

Aims

Effectiveness of nicotine replacement therapy (NRT) for smoking cessation has not been evaluated in low income countries, such as Syria, where it is expensive and not widely available. We evaluated whether nicotine patch boosts smoking cessation rates when used in conjunction with behavioral support in primary care clinics in Aleppo, Syria.

Design

Two arm, parallel group, randomized, placebo controlled, double‐blinded multi‐site trial.

Setting

Four primary care clinics in Aleppo, Syria.

Participants

 Two hundred and sixty‐nine adult primary care patients received behavioral cessation counseling from a trained primary care physician and were randomized to receive six weeks of treatment with nicotine versus placebo patch.

Measurements

Primary end‐points were prolonged abstinence (no smoking after a 2‐week grace period) at end of treatment, and 6 and 12 months post‐quit day, assessed by self‐report and exhaled carbon monoxide levels of <10 p.p.m.

Findings

Treatment adherence was excellent and nicotine patch produced expected reductions in urges to smoke and withdrawal symptoms, but no treatment effect was observed. The proportion of patients in the nicotine and placebo groups with prolonged abstinence was 21.6% and 20.0%, respectively, at end of treatment, 13.4% and 14.1% at 6 months, and 12.7% and 11.9% at 12 months.

Conclusions

 Nicotine patches may not be effective in helping smokers in low‐income countries to stop when given as an adjunct to behavioural support.
Current and emerging antiviral treatments for hepatitis C infection
Authors: Doyle Joseph S. , Aspinall Esther , Liew Danny , Thompson Alexander J. , Hellard Margaret E.
Published: August 2012

Newly licensed direct acting antivirals for hepatitis C virus HCV are able to cure up to 75% of patients chronically infected with genotype‐1 infection, which is the predominant HCV strain in Europe and North America. Emerging antiviral therapies promise further increases in virological response, as well as improved tolerability, reduced duration of therapy, and will potentially eliminate the need for interferon use. This review highlights the main therapeutic agents used in current standard of care, including telaprevir and boceprevir. It goes on to evaluate the mechanisms of emerging drugs, their stage of development and response rates seen in research to date. Finally, it projects into the not too distant future to consider treatment strategies involving combinations of agents and interferon‐free therapies, and in which patients they might prove most successful.
Selective resection of dorsal nerves of penis for premature ejaculation
Authors: Zhang G.‐X. , Yu L.‐P. , Bai W.‐J. , Wang X.‐F.
Published: August 2012

Premature ejaculation (PE) is one of the most prevalent male sexual dysfunctions. Selective resection of the dorsal nerve (SRDN) of penis has recently been used for the treatment of PE and has shown some efficacy. To further clarify the efficacy and safety of SRDN on PE, we performed a preliminary, randomized, placebo‐controlled clinical observational study. Persons with the complaints of rapid ejaculation, asking for circumcision because of redundant foreskin, intravaginal ejaculation latency time (IELT) within 2 min, not responding to antidepressant medication or disliking oral medication were randomly enrolled in two groups. From April 2007 to August 2010, a total of 101 eligible persons were enrolled, 40 of them received SRDN which dorsal nerves of the penis were selectively resected, and those (n = 61) enrolled in the control group were circumcised only. IELT and the Brief Male Sexual Function Inventory (BMSFI) questionnaire were implemented pre‐ and post‐operatively for the evaluation of the effect and safety of the surgery. There are no statistically significant differences in the baseline data including mean ages, mean IELTs, perceived control abilities and the BMSFI mean scores between the two groups. With regard to the post‐operative data of the surgery, both IELTs and perceived control abilities were significantly increased after SRDN (1.1 ± 0.9 min vs. 3.8 ± 3.1 min for pre‐ and post‐operative IELT, respectively, p < 0.01),whereas the post‐operative results were not significantly improved for the control group (1.2 ± 0.7 min vs. 1.5 ± 1.1 min, p > 0.05). Also, there were no statistically significant differences both in BMSFI composite and subscale scores between the two groups after surgery. Hence, we conclude that SRDN is effective in delaying ejaculation and improving ejaculatory control, whereas erectile function is not affected. The results imply that SRDN may be an alternative method for the treatment of PE for some patients.
Insights into type IV pilus biogenesis and dynamics from genetic analysis of a C‐terminally tagged pilin: a role for O‐linked glycosylation
Authors: Vik Åshild , Aspholm Marina , Anonsen Jan Haug , Børud Bente , Roos Norbert , Koomey Michael
Published: August 2012

Type IV pili are surface organelles essential for pathogenicity of many Gram‐negative bacteria. In Neisseria gonorrhoeae, the major subunit of type IV pili, PilE, is a target of its general O‐linked glycosylation system. This system modifies a diverse set of periplasmic and extracellular gonococcal proteins with a variable set of glycans. Here we show that expression of a particular hexa‐histidine‐tagged PilE was associated with growth arrest. By studying intra‐ and extragenic suppressors, we found that this phenotype was dependent on pilus assembly and retraction. Based on these results, we developed a sensitive tool to identify factors with subtle effects on pilus dynamics. Using this approach, we found that glycan chain length has differential effects on the growth arrest that appears to be mediated at the level of pilin subunit–subunit interactions and bidirectional remodelling of pilin between its membrane‐associated and assembled states. Gonococcal pilin glycosylation thus plays both an intracellular role in pilus dynamics and potential extracellular roles mediated through type IV pili. In addition to demonstrating the effect of glycosylation on pilus dynamics, the study provides a new way of identifying factors with less dramatic effects on processes involved in type IV pilus biogenesis.
The opening of the Magellan Strait and its geodynamic implications
Authors: Ghiglione Matías C. , Navarrete‐Rodríguez Angela Teresa , González‐Guillot Mauricio , Bujalesky Gustavo
Published: August 2012

Terra Nova, 25, 13–20, 2013

The existence of a Neogene‐Quaternary rift system responsible for the opening of the eastern Magellan strait has been one of the more peculiar tectonic features of the southernmost Andes since its discovery more than a decade ago. However, until now there has been no explanation pinpointing the specific tectonic factors that led to the development of the rift. This work focuses on the interaction between the fault systems and the tectonic regimes that have affected Tierra del Fuego north of the South America–Scotia left lateral strike‐slip plate boundary. Due to a good match between a Jurassic extensional fault array orientation and the principal stress directions related to the strike‐slip plate boundary, we conclude that Jurassic transfer faults reactivated extensionally generating the Magellan rift system. This process was enhanced by northward continental drift, and has implications for the geodynamic behind the separation of South America from Antarctica.