bluuebunny/crossref_metadata_2025 huggingface dataset:
Policy Adjustment by Parties in Response to Rival Parties’ Policy Shifts: Spatial Theory and the Dynamics of Party Competition in Twenty-Five Post-War Democracies
Authors: Adams James , Somer-Topcu Zeynep
Published: April 2009

Although spatial theory posits that political parties adjust their policies in response to rival parties’ policy strategies, there is little comparative research that evaluates this hypothesis. Using the Comparative Manifesto Project data, we analyse the relationship between parties’ policy programmes and the policies of their opponents in twenty-five post-war democracies. The authors conclude that parties tended to shift their policy positions in the same direction that their opponents had shifted their policies at the previous election; furthermore, parties were particularly responsive to policy shifts by other members of their ‘ideological families’, i.e. leftist parties responded to other leftist parties while right-wing parties responded to right-wing parties. Their findings have important implications for spatial models of elections, for the dynamics of party systems and for political representation.
Interest Group Adaptations to Campaign Finance Reform in Canada and the United States
Authors: Boatright Robert G.
Published: April 2009

Abstract.The United States and Canada enacted similar campaign finance reforms in the early 2000s. This article draws upon interviews with leaders of the major Canadian interest groups to explore similarities and differences in the responses of Canadian and American interest groups to reform. While groups in both countries shared an increased emphasis on mobilization and communication with members, the Canadian reforms were more effective at removing many groups from political campaigns entirely. This difference is primarily a result of differences in the two nations' party systems and the historical development of interest groups in the two countries.

Résumé.Au début des années 2000, les États-Unis et le Canada ont promulgué des lois similaires visant la réforme du financement des campagnes électorales. Cet article est basé sur des entretiens avec les chefs des principaux groupes d'intérêt canadiens. Il étudie les ressemblances et les différences entre leurs réponses à ces réformes et celles des groupes d'intérêt américains. Même si les groupes des deux pays ont tous insisté sur la communication et la mobilisation de leurs membres, les réformes canadiennes ont mieux réussi à éliminer entièrement plusieurs groupes des campagnes électorales. Cette différence s'explique surtout par la structure différente des deux systèmes de partis politiques et par l'évolution historique des groupes d'intérêt dans ces deux pays.
The Unanimous Decisions of the Supreme Court of Canada as a Test of the Attitudinal Model
Authors: Songer Donald R. , Siripurapu Julia
Published: April 2009

Abstract.Most of the empirical work on the decision making of justices on the Supreme Court of Canada has taken as its exclusive focus the divided decisions of the Court. In contrast to this extensive body of research on divided decision, the much more limited knowledge of unanimous decisions is troubling because such decisions constitute nearly three-quarters of all of the formal decisions of the Court. The analysis reported below provides a first step towards understanding the neglected nature of unanimous decisions. This investigation of the nature and causes of unanimity in the Supreme Court of Canada explores two competing explanations: one drawn from the most widely accepted general explanation of judicial voting (that is, the attitudinal model) and the other from the perspectives of the justices themselves. To determine that perspective, the author interviewed ten of the current or recent justices on the Court. After describing these two alternative accounts of unanimity, empirical tests are conducted of the implications of each view. We find substantially more support for the perspectives of the justices than for the perspective derived from the attitudinal model on unanimity.

Résumé.La majeure partie du travail de recherche empirique portant sur la manière dont les juges de la Cour suprême du Canada prennent leurs décisions se concentre exclusivement sur les décisions divisées de cette institution. En contraste avec cette foison d'études sur les décisions divisées, le corpus beaucoup plus limité de connaissances sur les décisions unanimes pose un problème important, car celles-ci représentent presque les trois quarts de la totalité des décisions formelles de la Cour suprême. L'analyse présentée ci-dessous se veut un premier pas vers une meilleure connaissance de la nature, trop négligée jusqu'à présent, de ces décisions unanimes. Cette investigation sur la nature et les causes de l'unanimité dans les décisions de la Cour suprême du Canada explore deux voies se trouvant en compétition : l'une qui résulte de l'explication la plus largement acceptée du vote judiciaire (soit le modèle attitudinal), et l'autre qui découle de la perspective personnelle des juges. Pour élucider cette perspective propre des juges, les auteurs ont interviewé dix juges actuels et récents de la Cour suprême du Canada. Après avoir décrit ces deux explications alternatives de l'unanimité, ils effectuent des tests empiriques sur les implications respectives du modèle attitudinal et des perspectives propres des juges. L'étude révèle que les perspectives propres des juges ont beaucoup plus de poids que la perspective dérivée du modèle attitudinal en ce qui concerne l'unanimité.
Voter Heterogeneity: Informational Differences and Voting
Authors: Roy Jason
Published: April 2009

Abstract.Do differences in levels of political information affect the vote calculus? Do differences in the decision process along informational divides affect vote choice? Using data from the 2004 Canadian Election Study this research tests the influence of political information on both the vote decision process and incumbent vote shares through a series of analyses that compare actual and simulated behaviour across information levels. The proposition being tested contends that information heterogeneity produces differences in the vote calculus that in turn lead to systematic and significant variation in vote choice. The results suggest that information does indeed affect the decision calculus and outcome, but not necessarily as one might expect.

Résumé.Le niveau d'information politique des électeurs a-t-il une incidence sur leur vote? Les différences dans le processus décisionnel associées au niveau d'information influent-elles sur les électeurs? Grâce aux données tirées de l'édition 2004 de l'Étude électorale canadienne et à une série d'estimations et de simulations statistiques, cet article propose de tester l'influence du niveau d'information politique sur le processus décisionnel des électeurs et sur le soutien accordé aux urnes au parti sortant. La proposition testée ici stipule que la présence d'hétérogénéité dans l'information politique des électeurs influe sur leurs mécanismes de décision, ce qui entraîne une variation systématique et significative dans le choix du vote. Les résultats suggèrent que l'information politique a une incidence sur le processus décisionnel des électeurs et sur leur vote, bien que cet impact n'aille pas nécessairement dans le sens attendu.
Birds of a Feather? Citizenship Norms, Group Identity, and Political Participation in Western Canada
Authors: Raney Tracey , Berdahl Loleen
Published: April 2009

Abstract.This paper explores how citizenship norms of duty to vote and to volunteer in one's community influence political participation, and the role of group identities in producing these norms. By showing how citizenship norms influence an array of political activities, and by drawing on social psychology literature that shows how citizenship norms are shaped by group identifications, the paper offers a more complete picture of the relationship between citizenship norms and political participation beyond traditional civic duty/federal vote models that currently dominate Canadian political research. The central argument forwarded is that not only do citizenship norms matter to political participation, but that group identities matter, too.

Résumé.Cette étude explore les effets sur la participation politique des normes relatives au devoir du citoyen de voter et de contribuer à sa communauté, de même que le rôle des identités de groupe dans la production de ces normes. En montrant comment les normes de citoyenneté influencent une foule d'activités politiques et en puisant dans la littérature en psychologie sociale, qui montre comment ces normes sont formées par des identifications de groupe, cette étude aide à mieux comprendre la relation entre ces normes et la participation politique au-delà du cadre traditionnel devoir civique / vote fédéral qui domine actuellement la recherche en politique canadienne. La thèse avancée est que les normes de citoyenneté jouent effectivement un rôle important dans la participation politique, tout comme les identités de groupe.
Pratiques des artistes en arts visuels : un terrain fécond pour une réflexion sur les contours actuels de l'engagement
Authors: Lamoureux Eve
Published: April 2009

Résumé. À partir d'une recherche sur l'art engagé des artistes québécois en arts visuels, nous analysons ce que ce type particulier de contestation sociopolitique nous apprend sur les transformations qu'a subies l'engagement depuis la fin des années 1970. Nous explorons ainsi la représentation sociale de l'engagement dit passé ainsi que les caractéristiques actuelles des pratiques artisticopolitiques. Ce choix d'étudier l'engagement à partir d'une forme située hors du cadre strict de l'action usuelle, dans un espace ouvert (au sens où il ne correspond pas aux lieux, aux institutions et aux façons d'agir reconnus comme politiques), permet d'accéder à la diversité des configurations de l'engagement présent et aux déplacements et transgressions opérés quant à sa représentation plus classique.

Abstract. Based on research on the politically committed art of Québécois visual artists, we analyze what this particular form of socio-political contestation teaches us about the changes which political involvement has seen since the end of the 1970s. We explore the social representation of involvement said to be that of the past, as well as the characteristics of present day artistic-political practices. The choice made to study involvement from a perspective outside of the framework of usual political action, in an open space (open in the sense of lacking correspondence with the spaces, institutions and ways of acting usually recognized as political), opens on the diversity of current forms of involvement and on the changes and transgressions which have occurred with regard to the more classical social representation of involvement.
Why and How Should Middle East and African Studies Be Connected? (posed by Mervat Hatem)
Authors: Hatem Mervat
Published: April 2009

For years, I struggled with the presentation of the category of “Middle East” to my students at Howard University, a historically black college. Like many of their professors, my students did not consider North Africa to be part of Africa. The reason was simple: the study of the continent was bifurcated between two fields, African and Middle East studies. African studies focused on sub-Saharan Africa; North Africa was the purview of Middle East studies.
Pensée 2: The “African” in Africana/Black/African and African American Studies
Authors: Somerville Carolyn
Published: April 2009

In Pensée 1, “Africa on My Mind,” Mervat Hatem questions the perceived wisdom of creating the African Studies Association (focused on sub-Saharan Africa) and the Middle East Studies Association a decade later, which “institutionalized the political bifurcation of the African continent into two academic fields.” The cleaving of Africa into separate and distinct parts—a North Africa/Middle East and a sub-Saharan Africa—rendered a great disservice to all Africans: it has fractured dialogue, research, and policy while preventing students and scholars of Africa from articulating a coherent understanding of the continent.
Pensée 3: Reconceptualizing the “Regions” in “Area Studies”
Authors: Voll John O.
Published: April 2009

“Area studies” as a way of trying to understand human experience is undergoing a major transition. Questioning the connection between Middle East and African studies highlights important dimensions of the changing nature of area studies at the beginning of the 21st century.
Pensée 4: The Fruit of the Africanist Contribution
Authors: Walz Terence
Published: April 2009

Recently I completed an initial foray into the underutilized 1848 census of Egypt that was commissioned by Muhammad ʿAli in the last years of his long rule. This enormous unpublished document provides a fascinating bird's-eye view of Cairo in the middle of the 19th century, permitting one to snoop into thousands of households, great and small, in Egypt's greatest and largest city to see a population undergoing profound social transformation. Here we find ordinary Egyptians, each identified by gender, age, nationality, civil status, occupation, religion, and relationship to the head of the household, living in houses, tenements,wakalas (caravansaries/residential hotels), mosques, and slums in a fantastic maze of streets, alleys, and byways. Here may be located various nationalities that contributed to the city's rich tapestry: Turks, Armenians, Syrians, Nubians, Sudanese, and Maghribis; Christians as well as Muslims and Jews; merchants and artisans; and soldiers, servants, and slaves.
JOURNEYMEN, MIDDLEMEN: TRAVEL, TRANSCULTURE, AND TECHNOLOGY IN THE ORIGINS OF MUSLIM PRINTING
Authors: Green Nile
Published: April 2009

Within a few years of 1820, Muslim-owned printing presses were established under state sponsorship in Iran, Egypt, and India, marking the true beginning of printing in the Islamic world. Printing projects had been initiated before this period—most famously by Ibrahim Müteferrika (1674–1745) in Istanbul—but these were isolated and unsustained ventures. None gathered the joint momentum of state support and technological transfer to compare with what emerged simultaneously in Tabriz, Cairo, and Lucknow. In attempting to understand the common processes behind this “triplet” birth of Muslim printing, this article reconstructs the small circle of individuals whose at times discordant projects collided in creating a sustainable Muslim print tradition in several distinct centers around 1820.
REGIME LOYALTY ANDBĀZĀRĪREPRESENTATION UNDER THE ISLAMIC REPUBLIC OF IRAN: DILEMMAS OF THE SOCIETY OF ISLAMIC COALITION
Authors: Keshavarzian Arang
Published: April 2009

The prevailing perception within the academy, policy circles, and the media inside and outside Iran has been that the members of bazaars are a unified social class engaged in a symbiotic relationship with the political elite of the Islamic republic and the conservative faction in particular. This approach is largely built on the perspective that there is a historic predilection forbāzārīs and clerics to cooperate (“mosque–bazaar alliance”), and thus ideological compatibility and familial ties between the clergy andbāzārīs have continued and developed into an alliance under the current regime headed by segments of the clergy. For instance, one of the leading experts on 20th-century Iran, Nikki Keddie, comments that, despite Mohammad Khatami's reformist agenda, “the ruling elite, who represent an alliance between the commercial bazaar bourgeoisie and conservative clerics, resist giving up their economic privileges as they do their political ones.”
A REPLY TO MICHAEL GUNTER (IJMES 40 [2008]: 728–29)
Authors: Dadrian Vahakn N.
Published: April 2009

While avowing his concern for the “scholarly reputation of IJMES,” Michael Gunter is denouncing my lack of “common sense” and my “audacity to argue incongruously” in the debate about the general validity of the Naim-Andonian documents. To substantiate his argument Gunter once more resorts to the method of truncation through deletions; the essential part of my phrase is deliberately excised from the quotation he used.
JOURNEYMEN, MIDDLEMEN: TRAVEL, TRANSCULTURE, AND TECHNOLOGY IN THE ORIGINS OF MUSLIM PRINTING
Authors: Green Nile
Published: April 2009

This essay offers a reinterpretation of the origins of Islamic printing as part of the new global technological and cultural exchanges of the early 19th century. With a special focus on Iranian printers, it reconstructs the interactions of the individual agents of this technological transfer with their European partners. In particular, it traces the emergence of cultural and technological “middlemen” in government employment who traveled to European cities to acquire printing. The “transculturalism” that these middlemen developed was a necessary qualification for success, and here their interaction with missionary organizations and their Arabic typographers proved crucial. They accessed the mass-produced, portable iron handpress, the global proliferation of which in the early 1800s linked pioneer Iranian as well as Indian and Egyptian printers to contemporary developments in England, New Zealand, and America. Islamic printing emerged as less a “late development” than part of the wider globalization of printing that accompanied the Industrial Revolution.
Dynamic simulation of a parallel robot: Coulomb friction and stick–slip in robot joints
Authors: Farhat Nidal , Mata Vicente , Page Álvaro , Díaz-Rodríguez Miguel
Published: April 2009

Dynamic simulation in robotic systems can be considered as a useful tool not only for the design of both mechanical and control systems, but also for planning the tasks of robotic systems. Usually, the dynamic model suffers from discontinuities in some parts of it, such as the use of Coulomb friction model and the contact problem. These discontinuities could lead to stiff differential equations in the simulation process. In this paper, we present an algorithm that solves the discontinuity problem of the Coulomb friction model without applying any normalization. It consists of the application of an external switch that divides the integration interval into subintervals, the calculation of the friction force in the stick phase, and further improvements that enhance its stability. This algorithm can be implemented directly in the available commercial integration routines with event-detecting capability. Results are shown by a simulation process of a simple 1-DoF oscillator and a 3-DoF parallel robot prototype considering Coulomb friction in its joints. Both simulations show that the stiffness problem has been solved. This algorithm is presented in the form of a flowchart that can be extended to solve other types of discontinuity.
On the relationship between diurnal temperature range and surface solar radiation in Europe
Authors: Makowski Knut , Jaeger Eric B. , Chiacchio Marc , Wild Martin , Ewen Tracy , Ohmura Atsumu
Published: April 2009

The surface solar radiation (SSR) is an important factor influencing the local and global energy budget. However, information on the spatial and temporal variation of SSR is limited. A more commonly available measure, which may provide such information, is the diurnal temperature range (DTR). In this study we analyze the relationship between DTR and SSR in Europe between 1970 and 2005 on seasonal and decadal scale. When comparing the mean anomalies time series composed of 31 pairs of sites with long‐term SSR and DTR measurements, we found a correlation coefficient of 0.87 in the annual mean and between 0.61 and 0.92 in the seasonal mean anomalies. When investigating the individual pairs of SSR and DTR individually, we found that local correlations are mostly lower than the European mean and that they decrease rapidly in seasons and latitudes with low incident angles and at high alpine altitude. The highest correlation on local and seasonal scales seems to be connected with the variability of the large‐scale circulation in Europe. The output of 11 simulations of current generation regional climate models over Europe confirms the strong relationship between SSR and DTR. The seasonal dependence of the relationship is well reproduced, but the absolute values of DTR and SSR are mostly too low. The pattern of decrease (dimming) and increase (brightening) in SSR and DTR was not reproduced in the modeled time series. There is still strong evidence from both models and observations that DTR is a reliable representative of SSR.
Significant decadal brightening of downwelling shortwave in the continental United States
Authors: Long C. N. , Dutton E. G. , Augustine J. A. , Wiscombe W. , Wild M. , McFarlane S. A. , Flynn C. J.
Published: April 2009

We conduct analyses of all‐sky and clear‐sky surface downwelling shortwave radiation and bulk cloud properties using data from several Department of Energy Atmospheric Radiation Measurement (ARM) Program and National Oceanic and Atmospheric Administration Surface Radiation (SURFRAD) network sites spanning the years 1995 through 2007. Five ARM sites are aggregated to study downwelling shortwave tendencies on global circulation model grid scales, and then six SURFRAD sites plus the central ARM site are aggregated to study the wider scale of the continental United States. We show that widespread brightening has occurred over the continental United States as represented by these measurements over the 12 years of the study, averaging about 8 W m−2/decade for the all‐sky shortwave and 5 W m−2/decade for the clear‐sky shortwave. This all‐sky increase is substantially greater than the 2 W m−2/decade previously reported over much more of the globe as represented by data from the Global Energy Balance Archive spanning 1986–2000 and is more than twice the magnitude of the corresponding 1986–2000 2–3 W m−2/decade increase in downwelling longwave. Our results show that changes in dry aerosols and/or direct aerosol effects alone cannot explain the observed changes in surface shortwave (SW) radiation, but it is likely that changes in cloudiness play a significant role. These SW increases are accompanied by decreasing tendencies in cloudiness, and an increasing tendency in the clear‐sky SW diffuse/direct ratio that is often associated with atmospheric turbidity. However, given the many local influences, evidence presented here suggests that the determination of the causes of decadal changes in the downwelling solar radiation at the surface are better studied locally and regionally, rather than on a global or continental scale.
Measurements of volatile organic compounds during the 2006 TexAQS/GoMACCS campaign: Industrial influences, regional characteristics, and diurnal dependencies of the OH reactivity
Authors: Gilman Jessica B. , Kuster William C. , Goldan Paul D. , Herndon Scott C. , Zahniser Mark S. , Tucker Sara C. , Brewer W. Alan , Lerner Brian M. , Williams Eric J. , Harley Robert A. , Fehsenfeld Fred C. , Warneke Carsten , de Gouw Joost A.
Published: April 2009

An extensive set of volatile organic compounds (VOCs) and other gas phase species were measured in situ aboard the NOAA R/V Ronald H. Brown as the ship sailed in the Gulf of Mexico and the Houston and Galveston Bay (HGB) area as part of the Texas Air Quality (TexAQS)/Gulf of Mexico Atmospheric Composition and Climate Study (GoMACCS) conducted from July–September 2006. The magnitudes of the reactivities of CH4, CO, VOCs, and NO2 with the hydroxyl radical, OH, were determined in order to quantify the contributions of these compounds to potential ozone formation. The average total OH reactivity (ROH,TOTAL) increased from 1.01 s−1 in the central gulf to 10.1 s−1 in the HGB area as a result of the substantial increase in the contribution from VOCs and NO2. The increase in the measured concentrations of reactive VOCs in the HGB area compared to the central gulf was explained by the impact of industrial emissions, the regional distribution of VOCs, and the effects of local meteorology. By compensating for the effects of boundary layer mixing, the diurnal profiles of the OH reactivity were used to characterize the source signatures and relative magnitudes of biogenic, anthropogenic (urban + industrial), and oxygenated VOCs as a function of the time of day. The source of reactive oxygenated VOCs (e.g., formaldehyde) was determined to be almost entirely from secondary production. The secondary formation of oxygenated VOCs, in addition to the continued emissions of reactive anthropogenic VOCs, served to sustain elevated levels of OH reactivity throughout the time of peak ozone production.
Molecular fossil evidence for anaerobic ammonium oxidation in the Arabian Sea over the last glacial cycle
Authors: Jaeschke Andrea , Ziegler Martin , Hopmans Ellen C. , Reichart Gert‐Jan , Lourens Lucas J. , Schouten Stefan , Sinninghe Damsté Jaap S.
Published: April 2009

Anaerobic ammonium oxidation (anammox) has been recognized as an important process converting fixed nitrogen to N2 in many marine environments, thereby having a major impact on the present‐day marine nitrogen cycle. However, essentially nothing is known about the importance of anammox in past marine nitrogen cycles. In this study, we analyzed the distribution of fossil ladderane lipids, derived from bacteria performing anammox, in a sediment core from the northern Arabian Sea. Concentrations of ladderane lipids varied between 0.3 and 5.3 ng g−1 sediment during the past 140 ka, with high values observed during the Holocene, intervals during the last glacial, and during the penultimate interglacial. Maxima in ladderane lipid abundances correlate with high total organic carbon (4–6%) and elevated δ15N (>8‰) values. Anammox activity, therefore, seems enhanced during periods characterized by an intense oxygen minimum zone (OMZ). Low concentrations of ladderanes (<0.5 ng g−1 sediment), indicating low‐anammox activity, coincide with periods during which the OMZ was severely diminished. Since anammox activity covaried with OMZ intensity, it may play an important role in the loss of fixed inorganic nitrogen from the global ocean on glacial‐interglacial timescales, which was so far attributed only to heterotrophic denitrification.
Momentum balance and gravity wave forcing in the mesosphere and lower thermosphere
Authors: Liu H.‐L. , Marsh D. R. , She C.‐Y. , Wu Q. , Xu J.
Published: April 2009

Gravity wave forcing (GWF), which is the primary driver of the mesospheric and lower thermospheric (MLT) circulation, is difficult to measure directly. In this work, the zonal mean GWF at extratropical MLT is deduced from measured winds using momentum balance. With the GWF dominating in the MLT, the zonally averaged zonal momentum equation can be simplified to a balance relation between the GWF and the Coriolis force in the extratropics. The meridional advection of zonal momentum makes a higher order contribution to the momentum balance, especially at places where the GWF maximizes. This method is tested with WACCM3 model and preliminary results are obtained from wind measurements by CSU Na lidar and TIMED/TIDI.
TB vaccines: current status and future perspectives
Authors: Aagaard Claus , Dietrich Jes , Doherty Mark , Andersen Peter
Published: April 2009

Vaccines against intracellular pathogens such as Mycobacterium tuberculosis need to induce strong cellular immune responses. Antigen discovery programs have exploited this and used proteome studies and T‐cell recognition in PPD‐positive individuals to select proteins and after testing for protective efficacy in animals the most promising proteins have been put together in fusion molecules. Three such fusion proteins are currently in clinical trials, the two most advanced have already passed phase I trials and are entering phase II.
Differing effects of exogenous or endogenous cathelicidin on macrophage toll‐like receptor signaling
Authors: Pinheiro da Silva Fabiano , Gallo Richard L , Nizet Victor
Published: April 2009

Cathelicidins are mammalian defense peptides with direct antimicrobial activity and the potential to exert other immunomodulatory effects during the innate immune response. One such function of human cathelicidin is direct binding and inhibition of bacterially derived lipopolysaccharide (LPS), a ligand of toll‐like receptor 4 (TLR4) . Here, we show that physiological concentrations of exogenous murine cathelicidin blunt activation of p38 and ERK mitogen‐activated protein kinases (MAPKs) and decrease tumor necrosis factor‐α (TNFα) release in murine macrophages exposed to LPS, but also other TLR agonists such as lipoteichoic acid and flagellin. In this context, CRAMP is capable of aborting MyD88 synthesis and MyD88/IRAK (interleukin‐1 receptor‐associated kinase)‐4 association in the stimulated macrophages. Exogenous CRAMP can reverse diminished MAPK activation associated with LPS tolerance. By analyzing macrophages from CRAMP−/− mice, we find their endogenous production of cathelicidin does not inhibit LPS MAPK and cytokine activation, rather CRAMP−/− cells show slightly diminished responses. CRAMP deficiency does not render mice more susceptible to lethal LPS challenge. These studies indicate the immunomodulatory effects of cathelicidin on macrophage TLR response may vary both on the exogenous vs endogenous origin of peptide and the prior activation state of the cell.
Two-dimensional IR spectroscopy and isotope labeling defines the pathway of amyloid formation with residue-specific resolution
Authors: Shim Sang-Hee , Gupta Ruchi , Ling Yun L. , Strasfeld David B. , Raleigh Daniel P. , Zanni Martin T.
Published: April 2009

There is considerable interest in uncovering the pathway of amyloid formation because the toxic properties of amyloid likely stems from prefibril intermediates and not the fully formed fibrils. Using a recently invented method of collecting 2-dimensional infrared spectra and site-specific isotope labeling, we have measured the development of secondary structures for 6 residues during the aggregation process of the 37-residue polypeptide associated with type 2 diabetes, the human islet amyloid polypeptide (hIAPP). By monitoring the kinetics at 6 different labeled sites, we find that the peptides initially develop well-ordered structure in the region of the chain that is close to the ordered loop of the fibrils, followed by formation of the 2 parallel β-sheets with the N-terminal β-sheet likely forming before the C-terminal sheet. This experimental approach provides a detailed view of the aggregation pathway of hIAPP fibril formation as well as a general methodology for studying other amyloid forming proteins without the use of structure-perturbing labels.
Bistable switches control memory and plasticity in cellular differentiation
Authors: Wang Lei , Walker Brandon L. , Iannaccone Stephen , Bhatt Devang , Kennedy Patrick J. , Tse William T.
Published: April 2009

Development of stem and progenitor cells into specialized tissues in multicellular organisms involves a series of cell fate decisions. Cellular differentiation in higher organisms is generally considered irreversible, and the idea of developmental plasticity in postnatal tissues is controversial. Here, we show that inhibition of mitogen-activated protein kinase (MAPK) in a human bone marrow stromal cell-derived myogenic subclone suppresses their myogenic ability and converts them into satellite cell-like precursors that respond to osteogenic stimulation. Clonal analysis of the induced osteogenic response reveals ultrasensitivity and an “all-or-none” behavior, hallmarks of a bistable switch mechanism with stochastic noise. The response demonstrates cellular memory, which is contingent on the accumulation of an intracellular factor and can be erased by factor dilution through cell divisions or inhibition of protein synthesis. The effect of MAPK inhibition also exhibits memory and appears to be controlled by another bistable switch further upstream that determines cell fate. Once the memory associated with osteogenic differentiation is erased, the cells regain their myogenic ability. These results support a model of cell fate decision in which a network of bistable switches controls inducible production of lineage-specific differentiation factors. A competitive balance between these factors determines cell fate. Our work underscores the dynamic nature of cellular differentiation and explains mechanistically the dual properties of stability and plasticity associated with the process.
Gcm protein degradation suppresses proliferation of glial progenitors
Authors: Ho Margaret Su-chun , Chen Hungwen , Chen Minghan , Jacques Cécile , Giangrande Angela , Chien Cheng-Ting
Published: April 2009

Gliogenesis in animal development is spatiotemporally regulated so that correct numbers of glia are present to support various neuronal functions. During
Drosophila
embryonic development, the glial regulatory gene,
glial cell missing/glial cell deficient
(
gcm/glide
), promotes glial cell fate and differentiation. Here we describe the ubiquitin–proteasome regulation of the Gcm protein and the consequence in gliogenesis without timely degradation of Gcm. Gcm binds to 2 F-box proteins, Supernumerary limbs (Slimb) and Archipelago (Ago), adaptors of SCF E3 ubiquitin ligases. Ubiquitination and proteasomal degradation of Gcm depend on
slimb
and
ago
. In
slimb
and
ago
double mutants, Gcm protein levels are enhanced. Concomitantly, glial cell numbers increase owing to proliferation, which can be phenocopied by Gcm overexpression only at the onset of glial differentiation. The glial lineage 5–6A in
slimb ago
mutants displays excess glial progenies and enhanced Gcm protein levels. We propose that downregulation of Gcm protein levels by Slimb and Ago is required for glial progenitors to exit the cell cycle for differentiation.
Independent gene duplications of the YidC/Oxa/Alb3 family enabled a specialized cotranslational function
Authors: Funes Soledad , Hasona Adnan , Bauerschmitt Heike , Grubbauer Caroline , Kauff Frank , Collins Ryan , Crowley Paula J. , Palmer Sara R. , Brady L. Jeannine , Herrmann Johannes M.
Published: April 2009

YidC/Oxa/Alb3 family proteins catalyze the insertion of integral membrane proteins in bacteria, mitochondria, and chloroplasts, respectively. Unlike gram-negative organisms, gram-positive bacteria express 2 paralogs of this family, YidC1/SpoIIIJ and YidC2/YgjG. In
Streptococcus mutans
, deletion of
yidC2
results in a stress-sensitive phenotype similar to that of mutants lacking the signal recognition particle (SRP) protein translocation pathway, while deletion of
yidC1
has a less severe phenotype. In contrast to eukaryotes and gram-negative bacteria, SRP-deficient mutants are viable in
S. mutans
; however, double SRP-
yidC2
mutants are severely compromised. Thus, YidC2 may enable loss of the SRP by playing an independent but overlapping role in cotranslational protein insertion into the membrane. This is reminiscent of the situation in mitochondria that lack an SRP pathway and where Oxa1 facilitates cotranslational membrane protein insertion by binding directly to translation-active ribosomes. Here, we show that
OXA1
complements a lack of
yidC2
in
S. mutans
. YidC2 also functions reciprocally in
oxa1
-deficient
Saccharomyces cerevisiae
mutants and mediates the cotranslational insertion of mitochondrial translation products into the inner membrane. YidC2, like Oxa1, contains a positively charged C-terminal extension and associates with translating ribosomes. Our results are consistent with a gene-duplication event in gram-positive bacteria that enabled the specialization of a YidC isoform that mediates cotranslational activity independent of an SRP pathway.
Historical forest baselines reveal potential for continued carbon sequestration
Authors: Rhemtulla Jeanine M. , Mladenoff David J. , Clayton Murray K.
Published: April 2009

One-third of net CO2emissions to the atmosphere since 1850 are the result of land-use change, primarily from the clearing of forests for timber and agriculture, but quantifying these changes is complicated by the lack of historical data on both former ecosystem conditions and the extent and spatial configuration of subsequent land use. Using fine-resolution historical survey records, we reconstruct pre-EuroAmerican settlement (1850s) forest carbon in the state of Wisconsin, examine changes in carbon after logging and agricultural conversion, and assess the potential for future sequestration through forest recovery. Results suggest that total above-ground live forest carbon (AGC) fell from 434 TgC before settlement to 120 TgC at the peak of agricultural clearing in the 1930s and has since recovered to approximately 276 TgC. The spatial distribution of AGC, however, has shifted significantly. Former savanna ecosystems in the south now store more AGC because of fire suppression and forest ingrowth, despite the fact that most of the region remains in agriculture, whereas northern forests still store much less carbon than before settlement. Across the state, continued sequestration in existing forests has the potential to contribute an additional 69 TgC. Reforestation of agricultural lands, in particular, the formerly high C-density forests in the north-central region that are now agricultural lands less optimal than those in the south, could contribute 150 TgC. Restoring historical carbon stocks across the landscape will therefore require reassessing overall land-use choices, but a range of options can be ranked and considered under changing needs for ecosystem services.
Species abundance distribution results from a spatial analogy of central limit theorem
Authors: Šizling Arnošt L. , Storch David , Šizlingová Eva , Reif Jiří , Gaston Kevin J.
Published: April 2009

The frequency distribution of species abundances [the species abundance distribution (SAD)] is considered to be a fundamental characteristic of community structure. It is almost invariably strongly right-skewed, with most species being rare. There has been much debate as to its exact properties and the processes from which it results. Here, we contend that an SAD for a study plot must be viewed as spliced from the SADs of many smaller nonoverlapping subplots covering that plot. We show that this splicing, if applied repeatedly to produce subplots of progressively larger size, leads to the observed shape of the SAD for the whole plot regardless of that of the SADs of those subplots. The widely reported shape of an SAD is thus likely to be driven by a spatial parallel of the central limit theorem, a statistically convergent process through which the SAD arises from small to large scales. Exact properties of the SAD are driven by species spatial turnover and the spatial autocorrelation of abundances, and can be predicted using this information. The theory therefore provides a direct link between SADs and the spatial correlation structure of species distributions, and thus between several fundamental descriptors of community structure. Moreover, the statistical process described may lie behind similar frequency distributions observed in many other scientific fields.
Crystal structure of full-length KcsA in its closed conformation
Authors: Uysal Serdar , Vásquez Valeria , Tereshko Valentina , Esaki Kaori , Fellouse Frederic A. , Sidhu Sachdev S. , Koide Shohei , Perozo Eduardo , Kossiakoff Anthony
Published: April 2009

KcsA is a proton-activated, voltage-modulated K
+
channel that has served as the archetype pore domain in the Kv channel superfamily. Here, we have used synthetic antigen-binding fragments (Fabs) as crystallographic chaperones to determine the structure of full-length KcsA at 3.8 Å, as well as that of its isolated C-terminal domain at 2.6 Å. The structure of the full-length KcsA–Fab complex reveals a well-defined, 4-helix bundle that projects ≈70 Å toward the cytoplasm. This bundle promotes a ≈15° bending in the inner bundle gate, tightening its diameter and shifting the narrowest point 2 turns of helix below. Functional analysis of the full-length KcsA–Fab complex suggests that the C-terminal bundle remains whole during gating. We suggest that this structure likely represents the physiologically relevant closed conformation of KcsA.
Localized delivery of fibroblast growth factor–2 and brain-derived neurotrophic factor reduces spontaneous seizures in an epilepsy model
Authors: Paradiso Beatrice , Marconi Peggy , Zucchini Silvia , Berto Elena , Binaschi Anna , Bozac Aleksandra , Buzzi Andrea , Mazzuferi Manuela , Magri Eros , Mora Graciela Navarro , Rodi Donata , Su Tao , Volpi Ilaria , Zanetti Lara , Marzola Andrea , Manservigi Roberto , Fabene Paolo F. , Simonato Michele
Published: April 2009

A loss of neurons is observed in the hippocampus of many patients with epilepsies of temporal lobe origin. It has been hypothesized that damage limitation or repair, for example using neurotrophic factors (NTFs), may prevent the transformation of a normal tissue into epileptic (epileptogenesis). Here, we used viral vectors to locally supplement two NTFs, fibroblast growth factor–2 (FGF-2) and brain-derived neurotrophic factor (BDNF), when epileptogenic damage was already in place. These vectors were first characterized in vitro, where they increased proliferation of neural progenitors and favored their differentiation into neurons, and they were then tested in a model of status epilepticus-induced neurodegeneration and epileptogenesis. When injected in a lesioned hippocampus, FGF-2/BDNF expressing vectors increased neuronogenesis, embanked neuronal damage, and reduced epileptogenesis. It is concluded that reduction of damage reduces epileptogenesis and that supplementing specific NTFs in lesion areas represents a new approach to the therapy of neuronal damage and of its consequences.
The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons
Authors: Chameau Pascal , Inta Dragos , Vitalis Tania , Monyer Hannah , Wadman Wytse J. , van Hooft Johannes A.
Published: April 2009

Cajal-Retzius cells, located in layer I of the cortex, synthesize and secrete the glycoprotein reelin, which plays a pivotal role in neuronal migration during embryonic development. Cajal-Retzius cells persist after birth, but their postnatal role is unknown. Here we show that Cajal-Retzius cells receive a major excitatory synaptic input via serotonin 5-HT
3
receptors. Blocking this input using pharmacological tools or neutralization of reelin signaling results in hypercomplexity of apical, but not basal, dendrites of cortical layer II/III pyramidal neurons. A similar hypercomplexity is observed in the cortex of the 5-HT
3A
receptor knockout mouse. The increased dendritic complexity can be rescued by application of recombinant full-length reelin or its N-terminal fragment, but not by the central fragment of reelin, and involves a signal transduction pathway independent of the activation of the canonical reelin receptors. Taken together, our results reveal a novel role of serotonin, Cajal-Retzius cells, and reelin in the postnatal maturation of the cortex.
Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p
Authors: Moxley Joel F. , Jewett Michael C. , Antoniewicz Maciek R. , Villas-Boas Silas G. , Alper Hal , Wheeler Robert T. , Tong Lily , Hinnebusch Alan G. , Ideker Trey , Nielsen Jens , Stephanopoulos Gregory
Published: April 2009

Genome sequencing dramatically increased our ability to understand cellular response to perturbation. Integrating system-wide measurements such as gene expression with networks of protein–protein interactions and transcription factor binding revealed critical insights into cellular behavior. However, the potential of systems biology approaches is limited by difficulties in integrating metabolic measurements across the functional levels of the cell despite their being most closely linked to cellular phenotype. To address this limitation, we developed a model-based approach to correlate mRNA and metabolic flux data that combines information from both interaction network models and flux determination models. We started by quantifying 5,764 mRNAs, 54 metabolites, and 83 experimental
13
C-based reaction fluxes in continuous cultures of yeast under stress in the absence or presence of global regulator Gcn4p. Although mRNA expression alone did not directly predict metabolic response, this correlation improved through incorporating a network-based model of amino acid biosynthesis (from
r
= 0.07 to 0.80 for mRNA-flux agreement). The model provides evidence of general biological principles: rewiring of metabolic flux (i.e., use of different reaction pathways) by transcriptional regulation and metabolite interaction density (i.e., level of pairwise metabolite-protein interactions) as a key biosynthetic control determinant. Furthermore, this model predicted flux rewiring in studies of follow-on transcriptional regulators that were experimentally validated with additional
13
C-based flux measurements. As a first step in linking metabolic control and genetic regulatory networks, this model underscores the importance of integrating diverse data types in large-scale cellular models. We anticipate that an integrated approach focusing on metabolic measurements will facilitate construction of more realistic models of cellular regulation for understanding diseases and constructing strains for industrial applications.
Kinetochore asymmetry defines a single yeast lineage
Authors: Thorpe Peter H. , Bruno Joanne , Rothstein Rodney
Published: April 2009

Asymmetric cell division is of fundamental importance in biology as it allows for the establishment of separate cell lineages during the development of multicellular organisms. Although microbial systems, including the yeast
Saccharomyces cerevisiae
, are excellent models of asymmetric cell division, this phenotype occurs in all cell divisions; consequently, models of lineage-specific segregation patterns in these systems do not exist. Here, we report the first example of lineage-specific asymmetric division in yeast. We used fluorescent tags to show that components of the yeast kinetochore, the protein complex that anchors chromosomes to the mitotic spindle, divide asymmetrically in a single postmeiotic lineage. This phenotype is not seen in vegetatively dividing haploid or diploid cells. This kinetochore asymmetry suggests a mechanism for the selective segregation of sister centromeres to daughter cells to establish different cell lineages or fates. These results provide a mechanistic link between lineage-defining asymmetry of metazoa with unicellular eukaryotes.