bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Negation in Conditional Inference
Authors: Evans Jonathan St.B.T. , Handley Simon J.
Published: September 2011

This paper addresses the issue of how negative components affect people's ability to draw conditional inferences. The study was motivated by an attempt to resolve a difficulty for the mental models theory of Johnson-Laird and Byrne, whose account of matching bias in the selection task is apparently inconsistent with Johnson-Laird's explanation of the double negation effects in conditional inference reported by Evans, Clibbens, and Rood (1995). Two experiments are reported, which investigate frequencies of conditional inferences with task presentation similar to that of the selection task in two respects: the presence of a picture of four cards and the use of implicit negations in the premises. The latter variable was shown to be critical and demonstrated a new phenomenon: Conditional inferences of all kinds are substantially suppressed when based on implicitly negative premises. This phenomenon was shown to operate independently of and in addition to the double negation effect. A third experiment showed that the implicit negation effect could be extended to the paradigm in which people are asked to produce their own conclusions. It is argued that these two effects can be explained within either the mental models theory or the inference rule theory, of propositional reasoning, but that each will require some revision in order to offer a convincing account.
Isolating Unconscious Influences: The Neutral Parameter Procedure
Authors: Vinter Annie , Perruchet Pierre
Published: September 2011

Earlier demonstrations of unconscious learning have been regularly challenged. In this paper, we suggest that earlier demonstrations were not compelling due to certain properties of the experimental situations, and notably that conscious exploitation of explicit knowledge, if present, would coincide or conflict with the results of unconscious processing. We designed a method consisting of inducing a neutral behavioural change in the way subjects drew geometric figures. Two experiments showed that important and long-lasting modifications of drawing behaviour were obtained following specially devised practice, although these modifications could not be expected from deliberate adaptive strategies. In addition, we showed that subjects were unaware of the manipulation to which they had been exposed. The study provides striking evidence for unconscious learning and offers insights for the design of suitable new tools to investigate unconscious cognition.
p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis
Authors: Fessing Michael Y. , Mardaryev Andrei N. , Gdula Michal R. , Sharov Andrey A. , Sharova Tatyana Y. , Rapisarda Valentina , Gordon Konstantin B. , Smorodchenko Anna D. , Poterlowicz Krzysztof , Ferone Giustina , Kohwi Yoshinori , Missero Caterina , Kohwi-Shigematsu Terumi , Botchkarev Vladimir A.
Published: September 2011

During development, multipotent progenitor cells establish tissue-specific programs of gene expression. In this paper, we show that p63 transcription factor, a master regulator of epidermal morphogenesis, executes its function in part by directly regulating expression of the genome organizer Satb1 in progenitor cells. p63 binds to a proximal regulatory region of the Satb1 gene, and p63 ablation results in marked reduction in the Satb1 expression levels in the epidermis. Satb1−/− mice show impaired epidermal morphology. In Satb1-null epidermis, chromatin architecture of the epidermal differentiation complex locus containing genes associated with epidermal differentiation is altered primarily at its central domain, where Satb1 binding was confirmed by chromatin immunoprecipitation–on-chip analysis. Furthermore, genes within this domain fail to be properly activated upon terminal differentiation. Satb1 expression in p63+/− skin explants treated with p63 small interfering ribonucleic acid partially restored the epidermal phenotype of p63-deficient mice. These data provide a novel mechanism by which Satb1, a direct downstream target of p63, contributes in epidermal morphogenesis via establishing tissue-specific chromatin organization and gene expression in epidermal progenitor cells.
TOR kinase complexes and cell migration
Authors: Liu Lunhua , Parent Carole A.
Published: September 2011

Cell migration is a fundamental process in a wide array of biological and pathological responses. It is regulated by complex signal transduction pathways in response to external cues that couple to growth factor and chemokine receptors. In recent years, the target of rapamycin (TOR) kinase, as part of either TOR complex 1 (TORC1) or TOR complex 2 (TORC2), has been shown to be an important signaling component linking external signals to the cytoskeletal machinery in a variety of cell types and organisms. Thus, these complexes have emerged as key regulators of cell migration and chemotaxis.
Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology
Authors: Lippi Giordano , Steinert Joern R. , Marczylo Emma L. , D’Oro Sabina , Fiore Roberto , Forsythe Ian D. , Schratt Gerhard , Zoli Michele , Nicotera Pierluigi , Young Kenneth W.
Published: September 2011

Previous studies have demonstrated that microribonucleic acids (miRs) are key regulators of protein expression in the brain and modulate dendritic spine morphology and synaptic activity. To identify novel miRs involved in neuronal plasticity, we exposed adult mice to chronic treatments with nicotine, cocaine, or amphetamine, which are psychoactive drugs that induce well-documented neuroadaptations. We observed brain region– and drug-specific changes in miR expression levels and identified miR-29a/b as regulators of synaptic morphology. In vitro imaging experiments indicated that miR-29a/b reduce mushroom-shaped dendritic spines on hippocampal neurons with a concomitant increase in filopodial-like outgrowths, suggesting an effect on synapse formation via actin cytoskeleton remodeling. We identified Arpc3, a component of the ARP2/3 actin nucleation complex, as a bona fide target for down-regulation by miR-29a/b. This work provides evidence that targeting of Arpc3 by miR-29a/b fine tunes structural plasticity by regulating actin network branching in mature and developing spines.
GRK5 promotes F-actin bundling and targets bundles to membrane structures to control neuronal morphogenesis
Authors: Chen Yuejun , Wang Feifei , Long Hui , Chen Ying , Wu Ziyan , Ma Lan
Published: September 2011

Neuronal morphogenesis requires extensive membrane remodeling and cytoskeleton dynamics. In this paper, we show that GRK5, a G protein–coupled receptor kinase, is critically involved in neurite outgrowth, dendrite branching, and spine morphogenesis through promotion of filopodial protrusion. Interestingly, GRK5 is not acting as a kinase but rather provides a key link between the plasma membrane and the actin cytoskeleton. GRK5 promoted filamentous actin (F-actin) bundling at the membranes of dynamic neuronal structures by interacting with both F-actin and phosphatidylinositol-4,5-bisphosphate. Moreover, separate domains of GRK5 mediated the coupling of actin cytoskeleton dynamics and membrane remodeling and were required for its effects on neuronal morphogenesis. Accordingly, GRK5 knockout mice exhibited immature spine morphology and deficient learning and memory. Our findings identify GRK5 as a critical mediator of dendritic development and suggest that coordinated actin cytoskeleton and membrane remodeling mediated by bifunctional actin-bundling and membrane-targeting molecules, such as GRK5, is crucial for proper neuronal morphogenesis and the establishment of functional neuronal circuitry.
Profit or access: which is more important for Chinese medical journals?
Authors: Xiao‐jun HE , Zhen‐ying CHEN
Published: September 2011

The Chinese Medical Association, one of the largest and most influential medical journal publishers in China, signed an exclusive copyright transfer agreement with Beijing Wanfang Data Co. Ltd in 2006, which ended the era of cheap transfer of copyrights from journals to full‐text databases. Since then, many journals have chosen the same route to earn more money. However, without generally recognized databases that offer free access to medical abstracts in China, many potential readers are lost. In addition, many Chinese readers do not have adequate literature retrieval skills: more convenient access to journals is therefore far more important than earning immediate profits. Goods in exclusive shops are more expensive than those in ordinary shops. That is why many journals sell exclusive copyrights to databases. However, while obtaining more profits by exclusive copyright transfer, journals may actually lose a large proportion of readers.
Slow decay for a linearized model of the solar wind
Authors: Schaeffer Jack
Published: September 2011

The solar wind interacting with a magnetized obstacle is modelled with the steady Vlasov-Poisson system in the plane. The system is linearized for the (given) magnetic field of the obstacle being small. The main focus is on the rate of decay of the spatial charge density “downwind” of the obstacle. A special case that admits an explicit solution is presented. It is also shown that when the background particle distribution is compactly supported in velocity, that the spatial charge density cannot, in general, decay faster than

x
1

−

1
2

x^{-\frac {1}{2}}_1

, where

x
1

x_1

is the downwind distance.
The Influence of Roman Law
Authors: Kelley Donald R.
Published: September 2011

Centuries of Roman jurisprudence were assembled in the great Byzantine collection, the Digest, by Tribonian and the other editors. Roman law became more formal when during the Renaissance of the twelfth century it came to be taught in the first universities, starting with Bologna and the teaching of Irnerius. The main channels of expansion were through the Glossators and post-Glossators, who commented on the main texts and on later legislation by the Holy Roman Emperors, which included “feudal law,” but also by notaries and other proto-lawyers. Christian doctrine also became part of the “Roman” tradition, and canon and civil law were taught together in the universities as “civil science.” According to the ancient Roman jurist Gaius, “all the law which we use pertains either to persons or to things or to actions,” three categories that exhaust the external human condition—personality, reality, and action. In the nineteenth century, the study of Roman law lost its ideological power and became part of philology and history, at least so concludes James Whitman.
Absolutism
Authors: Goldie Mark
Published: September 2011

Absolutism is a nineteenth-century term designed precisely to address the mismatch between doctrine and power. The intellectual resources of absolutism were far older than the Renaissance and Reformation. The absolutism of monarchs was a contingent and temporary corollary of the principal juridical development of the early modern period: the emergence of the concept of sovereignty. Absolute monarchy was a free rider on a concept that would later unseat it. Theorists of absolute sovereignty drew heavily on Roman law, and often invoked the idea of the translatio imperii, the inheritance by modern monarchies of Roman imperial authority. The sovereignty of kings, seeking to trump the divine imperium of the papacy, masqueraded its jurisprudence as the divinity of kings. The “divine right of kings” was a theological meditation on a juridical concept, not a species of mysticism, and rarely did absolutists endow monarchs with magical or sacerdotal attributes. Absolutism conspicuously appropriated religious form when expressed as a theory of obedience. Absolutist theory offered an account of the origins of civil authority.
Enlightenment Political Philosophy
Authors: Whatmore Richard
Published: September 2011

Toleration, secularization, and an associated critique of confessional religion might have served previous generations as organizing themes for an account of political philosophy during the Enlightenment. Two prominent attempts have been made in recent years to bring clarity to the political philosophies of the enlightenment era. The first is Jonathan Israel's assertion of a radical enlightenment critical of state and clerical authority, and of social hierarchies, which he traces from rebellions such as the Fronde in France (1648–1653), the Masaniello revolt in Naples (1647), and the civil wars in England, Scotland, and Ireland between 1638 and 1660, up to their culmination in the French Revolution (1789–1799). A sense of the contrasting scholarly perception of enlightenment political philosophy is evident by comparing Israel's views with those of John Robertson's The Case for the Enlightenment: Scotland and Naples 1680–1760 (2005). This article explores Enlightenment political philosophy and discusses the absolute monarchy of France, political philosophy in Britain and in Europe's small states, and philosophies of despotism.
The Scottish Enlightenment
Authors: McArthur Neil
Published: September 2011

Scotland made a significant contribution to the intellectual and artistic life of Enlightenment Europe despite having a small population. In philosophy, the Scottish Enlightenment can be seen as beginning in 1725 with the publication of a series of treatises by Francis Hutcheson. David Hume published the first volumes of his Treatise of Human Nature in 1739, Adam Ferguson's Essay on the History of Civil Society appeared in 1769 while Adam Smith's Theory of Moral Sentiments and Inquiry into the Wealth of Nations in 1759 and 1776, respectively. These extraordinary masterpieces are only the most enduring testaments to the vitality of an intellectual community whose members were deeply engaged with the politics of the time, and the problems of political philosophy were of central concern to them. This article discusses the Scottish Enlightenment, focusing on justice, allegiance, and the moral sentiments; liberty, equality, and forms of government; the development of political economy; skepticism, conservatism, and reform; and philosophical history.
The Idea of the Welfare State
Authors: Moon Donald
Published: September 2011

The welfare state rests upon a commitment to equality, such that the provision of services, and the type and quality of services that are provided, are not differentiated by class or other markers of unequal status. This article outlines the history of welfare state theorizing, beginning with a discourse that is likely to be most familiar to Anglophone audiences, which view the welfare state as emerging from a critical, and largely internal, interrogation of liberalism, with its commitment to juridical equality, individualism, and liberty. In much of continental Europe, where liberal ideas were less established, the idea of a welfare state emerged from a critical, and again largely internal, interrogation of socialism—more particularly, Marxism—with its commitment to solidarity, science, and positive freedom. Although discourse about the scope and structure of social policy continued to engage large issues of political philosophy, social scientists began to raise narrower and more technical questions about the effectiveness of the policies and programs of the welfare state.
Libertarianism
Authors: Mack Eric
Published: September 2011

The core prescriptive postulate of libertarianism is that individuals have strong moral claims to the peaceful enjoyment of their own persons and their own legitimate extra-personal possessions along with similarly strong claims to the fulfillment of their voluntary agreements with others. All (non-pacifist) libertarians take these moral claims to be so strong and salient that force and the threat of force may permissibly be employed to defend against and to rectify their infringement. On the other hand, only infringements of these core claims trigger the permissible use or threat of force. Other deployments of force or the threat of force are taken themselves to be violations of the moral claims asserted by the prescriptive postulate. This article presents a brief history of libertarian political philosophy, focusing on six hard-core libertarian theorists of the nineteenth and twentieth centuries: Herbert Spencer, Lysander Spooner, Gustav de Molinari, Ayn Rand, Murray Rothbard, and Robert Nozick.
Religious Toleration
Authors: Zagorin Perez
Published: September 2011

The fullest development of the concept of religious toleration in the West occurred in Christian Europe between the sixteenth and eighteenth centuries. The emergence and establishment of religious pluralism in modern societies, and most notably in the Western world, has been very largely the result of the evolution and gradual victory of the principle of religious toleration on a variety of grounds. Among the world's great monotheistic religions, Christianity has been the most intolerant. Early Christianity was intolerant of Judaism, from which it had to separate itself, and of ancient paganism, whose suppression it demanded. The New Testament recognized heresy as a danger to religious truth and the Christian communities. Heresy entailed the existence of its opposite, orthodoxy, which meant right thinking and true belief. Following World War II, the United Nations Universal Declaration of Human Rights of 1948 named freedom of religion, conscience, and thought as basic human rights.
Presentism and the Space‐Time Manifold
Authors: Zimmerman Dean W.
Published: September 2011

This chapter seeks to defend a version of presentism. Presentism faces a conflict with relativity theory in physics. Relativity theory affirms the relativity of simultaneity, a thesis that immediately threatens presentism. The chapter develops a theory that aims to escape this difficulty. The main problems for presentism it discusses are: Theodore Sider's argument that presentists lack adequate grounds for physically important cross-temporal relations involving motion; and objections based on inconsistency with relativity, especially those based on alleged inconsistency with special relativity.
Time in Action
Authors: Gallagher Shaun
Published: September 2011

This chapter links phenomenology with cognitive science. It deals with the “intrinsic temporality” in both bodily movement and action, some of which is experienced, but some of which happens at the subpersonal levels of analysis. The chapter begins with Husserl's dynamic model of retention and protention, extending it to unconscious motor processes too. Bringing empirical studies to support the claims throughout, the discussion then focuses on various timescales in an effort to show how the concept of free will becomes important.
Time in the Special Theory of Relativity
Authors: Savitt Steven
Published: September 2011

Restricted to special relativity, this chapter observes that the most significant change in the concept of time is certainly the relativity of simultaneity. What events are simultaneous with some event for one observer are different from those that are simultaneous with respect to an object traveling in a different inertial frame. Many believe that this relativity can play a role in an argument for eternalism. This chapter critically surveys these arguments before taking on the implications of relativity for the metaphysics of time. It also tackles the conventionality of simultaneity. Many philosophers of science, especially during the early days of relativity, felt that simultaneity is not only relative but also conventional—there is a crucial element of choice in deciding what events are simultaneous for any other in a given inertial reference frame, so that there is no fact of the matter about what is simultaneous.
Time Travel and Time Machines
Authors: Smeenk Chris , Wüthrich Christian
Published: September 2011

This chapter examines the logical, metaphysical, and physical possibility of time travel understood in the sense of the existence of closed worldlines that can be traced out by physical objects, arguing that none of the purported paradoxes rule out time travel on the grounds of either logic or metaphysics. More relevantly, modern space–time theories such as general relativity seem to permit models that feature closed worldlines. The chapter discusses what this apparent physical possibility of time travel means, and, furthermore, reviews the recent literature on so-called time machines, of devices that produce closed worldlines where none would have existed otherwise. Finally, it investigates what the implications of the quantum behavior of matter might be for the possibility of time travel, and explicates in what sense time travel might be possible according to leading contenders for full quantum theories of gravity such as string theory and loop quantum gravity.
Time in Quantum Gravity
Authors: Kiefer Claus
Published: September 2011

This chapter notes that quantum gravity places the concept of time on a new level. In the absence of experimental hints, mathematical and conceptual issues must be chosen as the guides in the search for such a theory. Just as reconceiving classical notions of time was key for Einstein, in his discovery of special relativity, so too many believe that time will again hold the clue for theoretical advancement, but this time with quantum gravity. The chapter details the challenge of reconciling quantum theory with relativity, concentrating especially on why time in particular causes trouble. It describes a result in canonical quantum gravity which is possibly of signal importance, namely, that fundamentally there is no time at all, and discusses the problem of time, quantization, semiclassical time, loop quantum gravity, and string theory.
A Possible Next Frontier in Political Communication Research
Authors: Gaines Brian J. , Kuklinski James H.
Published: September 2011

This chapter examines the future of political communication research, reviewing the last three generations of research, which lasted for over ninety years. It then discusses the problem of separating the effects of media, information, and statements from politicians in political communication studies. Finally, the chapter suggests including some previous techniques into the present study of political communication, in order to cover a few gaps in existing research.
Campaigning, Debating, Advertising
Authors: Bishop Bradford H. , Hillygus D. Sunshine
Published: September 2011

This chapter studies debating, advertising, and campaigning, the latter playing an important role in American democracy, first discussing the development of political campaigns and summarizing the broad theoretical perspectives that have directed scholarly thinking and research on campaign effects. Next, it examines the findings of modern research on the effects of the different sources of campaign information, along with their implications for the democratic process. The chapter ends with a discussion of the opportunities and challenges for future research.
The Effect of Media on Public Knowledge
Authors: Jamieson Kathleen Hall , Hardy Bruce W.
Published: September 2011

This chapter takes a look at the effect of media on public knowledge, studying the knowledge on the candidates' issue stands and endorsements, and then introducing the concept of the Gas Tax Holiday. It also discusses the effects of partisan media and selective avoidance, along with the informing effect of the Internet.
News Polls
Authors: Bennett W. Lance
Published: September 2011

This chapter investigates the reasons why producing good news stories usually gets the better of more measured assessments of poll results, briefly discussing the construction of an imagined engaged public, which can be a lasting media project. It then looks at some fixed methodological cautions in interpreting polls, along with an analysis of why the news media routinely ignore these cautions. The last part of the chapter studies the importance of creating a news public that conveniently gathers around supposedly clear support and opposition to elite policy frames, thus making a dramatic news narrative on representative democracy.
Political Socialization
Authors: Stoker Laura , Bass Jackie
Published: September 2011

This chapter discusses political socialization and summarizes some of the primary research threads in the field, studying the civic orientations and political attitudes of American youths today in order to differentiate them from the previous generations. It then considers the transformative potential of new media, discussing the influence of biology and genetics on political behaviour and attitudes, and finally presents some directions for future research.
Latino Public Opinion
Authors: de la Garza Rodolfo O. , Jang Seung‐Jin
Published: September 2011

This chapter discusses Latino public opinion, which was closely monitored since the 1990s through a series of successive large-scale opinion polls, first taking a look at the general form and patterns that help characterize Latino public opinion. It then examines the continuities and changes that occurred between the Latino National Political Survey and the Latino National Survey, in order to provide some insight to understanding the components and evolution of current Latino public opinion. The chapter also discusses transnationalism and the views of Latinos on foreign policies, as well as the effects of Latino public opinion.
Assignment of quantities to biological medicines: an old problem re-discovered
Authors: Bristow Adrian F.
Published: September 2011

A distinction exists between ‘chemical’ and ‘biological’ medicines. While, from antiquity, both organic and inorganic substances had been used in therapy, developing chemical sciences were inapplicable to materials extracted from natural sources, and the active principles could be neither identified nor characterized. The distinction between biological medicines or ‘biologicals’ grew out of this realization. Such ‘biologicals’ in clinical use were, however, variable in efficacy and in safety, and controlling the strength or quality was necessary. Without information on what biological medicines
are
, it was necessary to quantify what they
do
, and such medicines were quantified using systems based on biological responses (bioassays) in animals, organs or cells. Bioassays are defined in terms of an external standard rather than in absolute terms, and depend on a number of key assumptions: the need to assay ‘like against like’, the desirability of making the assay principle relevant to the intended clinical effect in man, and the importance of appropriate statistical models of design and analysis. The science of ‘biological standardization’ has kept pace with developments in medicine and continues to allow the use of biological medicines in man to be controlled on the basis of common measurement systems.
Determination of the Boltzmann constant using a quasi-spherical acoustic resonator
Authors: Pitre Laurent , Sparasci Fernando , Truong Daniel , Guillou Arnaud , Risegari Lara , Himbert Marc E.
Published: September 2011

The paper reports a new experiment to determine the value of the Boltzmann constant,

, with a relative standard uncertainty of 1.2 parts in 10
6
.
k
B
was deduced from measurements of the velocity of sound in argon, inside a closed quasi-spherical cavity at a temperature of the triple point of water. The shape of the cavity was achieved using an extremely accurate diamond turning process. The traceability of temperature measurements was ensured at the highest level of accuracy. The volume of the resonator was calculated from measurements of the resonance frequencies of microwave modes. The molar mass of the gas was determined by chemical and isotopic composition measurements with a mass spectrometer. Within combined uncertainties, our new value of
k
B
is consistent with the 2006 Committee on Data for Science and Technology (CODATA) value: (
k
new
B
/
k
B_CODATA
−1)=−1.96×10
−6
, where the relative uncertainties are

and
u
r
(
k
B_CODATA
)=1.7×10
−6
. The new relative uncertainty approaches the target value of 1×10
−6
set by the Consultative Committee on Thermometry as a precondition for redefining the unit of the thermodynamic temperature, the kelvin.
Accurate radiometry from space: an essential tool for climate studies
Authors: Fox Nigel , Kaiser-Weiss Andrea , Schmutz Werner , Thome Kurtis , Young Dave , Wielicki Bruce , Winkler Rainer , Woolliams Emma
Published: September 2011

The Earth's climate is undoubtedly changing; however, the time scale, consequences and causal attribution remain the subject of significant debate and uncertainty. Detection of subtle indicators from a background of natural variability requires measurements over a time base of decades. This places severe demands on the instrumentation used, requiring measurements of sufficient accuracy and sensitivity that can allow reliable judgements to be made decades apart. The International System of Units (SI) and the network of National Metrology Institutes were developed to address such requirements. However, ensuring and maintaining SI traceability of sufficient accuracy in instruments orbiting the Earth presents a significant new challenge to the metrology community. This paper highlights some key measurands and applications driving the uncertainty demand of the climate community in the solar reflective domain, e.g. solar irradiances and reflectances/radiances of the Earth. It discusses how meeting these uncertainties facilitate significant improvement in the forecasting abilities of climate models. After discussing the current state of the art, it describes a new satellite mission, called TRUTHS, which enables, for the first time, high-accuracy SI traceability to be established in orbit. The direct use of a ‘primary standard’ and replication of the terrestrial traceability chain extends the SI into space, in effect realizing a ‘metrology laboratory in space’.
Serpentinite and the dawn of life
Authors: Sleep Norman H. , Bird Dennis K. , Pope Emily C.
Published: September 2011

Submarine hydrothermal vents above serpentinite produce chemical potential gradients of aqueous and ionic hydrogen, thus providing a very attractive venue for the origin of life. This environment was most favourable before Earth's massive CO2atmosphere was subducted into the mantle, which occurred tens to approximately 100 Myr after the moon-forming impact; thermophile to clement conditions persisted for several million years while atmospheric pCO2dropped from approximately 25 bar to below 1 bar. The ocean was weakly acid (pH ∼ 6), and a large pH gradient existed for nascent life with pH 9–11 fluids venting from serpentinite on the seafloor. Total CO2in water was significant so the vent environment was not carbon limited. Biologically important phosphate and Fe(II) were somewhat soluble during this period, which occurred well before the earliest record of preserved surface rocks approximately 3.8 billion years ago (Ga) when photosynthetic life teemed on the Earth and the oceanic pH was the modern value of approximately 8. Serpentinite existed by 3.9 Ga, but older rocks that might retain evidence of its presence have not been found. Earth's sequesters extensive evidence of Archaean and younger subducted biological material, but has yet to be exploited for the Hadean record.
An optimal degree of physical and chemical heterogeneity for the origin of life?
Authors: Szostak Jack W.
Published: September 2011

The accumulation of pure, concentrated chemical building blocks, from which the essential components of protocells could be assembled, has long been viewed as a necessary, but extremely difficult step on the pathway to the origin of life. However, recent experiments have shown that moderately increasing the complexity of a set of chemical inputs can in some cases lead to a dramatic simplification of the resulting reaction products. Similarly, model protocell membranes composed of certain mixtures of amphiphilic molecules have superior physical properties than membranes composed of single amphiphiles. Moreover, membrane self-assembly under simple and natural conditions gives rise to heterogeneous mixtures of large multi-lamellar vesicles, which are predisposed to a robust pathway of growth and division that simpler and more homogeneous small unilamellar vesicles cannot undergo. Might a similar relaxation of the constraints on building block purity and homogeneity actually facilitate the difficult process of nucleic acid replication? Several arguments suggest that mixtures of monomers and short oligonucleotides may enable the chemical copying of polynucleotides of sufficient length and sequence complexity to allow for the emergence of the first nucleic acid catalysts. The question of the origin of life may become less daunting once the constraints of overly well-defined laboratory experiments are appropriately relaxed.
Crystal structure of an RNA polymerase ribozyme in complex with an antibody fragment
Authors: Piccirilli Joseph A. , Koldobskaya Yelena
Published: September 2011

All models of the RNA world era invoke the presence of ribozymes that can catalyse RNA polymerization. The class I ligase ribozyme selected
in vitro
15 years ago from a pool of random RNA sequences catalyses formation of a 3′,5′-phosphodiester linkage analogous to a single step of RNA polymerization. Recently, the three-dimensional structure of the ligase was solved in complex with U1A RNA-binding protein and independently in complex with an antibody fragment. The RNA adopts a tripod arrangement and appears to use a two-metal ion mechanism similar to protein polymerases. Here, we discuss structural implications for engineering a true polymerase ribozyme and describe the use of the antibody framework both as a portable chaperone for crystallization of other RNAs and as a platform for exploring steps in evolution from the RNA world to the RNA–protein world.
Genotypic and phenotypic evaluation of Rutilus spp. from Skadar, Ohrid and Prespa Lakes supports revision of endemic as well as taxonomic status of several taxa
Authors: Milošević D. , Winkler K. A. , Marić D. , Weiss S.
Published: September 2011

One mtDNA gene (cytochrome b), one nuclear DNA fragment, five microsatellites and a suite of morphological characters were evaluated in samples of Rutilus spp. from Skadar, Ohrid and Prespa Lakes. Both genetic and phenotypic data supported two sympatric taxa in Lake Skadar, whereby Prespa and Ohrid Lakes revealed only a single taxon each. One of the taxa from Lake Skadar was similar to samples from Lake Prespa, whereas the second taxon was the most divergent in the data set. The estimated time to the most recent common ancestor of these two sympatric taxa in Lake Skadar was between 125 000 and 500 000 years. The data did not support existing taxonomic schemes for Rutilus in these lakes. This study poses the following working hypothesis: (1) Rutilus prespensis lives both in Lake Prespa and Lake Skadar and therefore is not endemic to Lake Prespa, (2) Rutilus ohridanus lives in Lake Ohrid only and therefore could be considered an endemic if its species status is retained and (3) a third recently described taxon (Rutilus albus) sympatric to R. prespensis lives in Lake Skadar.
Haplotypic variation and characteristics across the toll‐like receptor 3 locus in chickens
Authors: Huang Y. Q. , Chen W. , Huang Y. H. , Shi X. W. , Deng X. M. , Kang X. T. , Li N.
Published: September 2011

Toll‐like receptor 3 (TLR3) has an important protective function against viral infection. The ability of an individual to respond properly to TLR ligands may be impaired by variants located in the TLR genes. By directly PCR sequencing four exons and their flanking sequence of chicken TLR3, a total of 50 nucleotide variants were identified from five breeds. Tibetan chickens and Silkies exhibited more abundant variation sites and rare alleles. Thirty haplotypes were reconstructed, with 31 variants whose minor allelic frequency was above 5% in five breeds, which revealed four divergent clades. Chicken TLR3 was partitioned into three haplotype blocks by the htSNPer program, and six tag SNPs could be used to distinguish these 30 haplotypes. Thirty variants were located in the coding sequence of chicken TLR3, and 16 of them were non‐synonymous substitutions. It is predicted that p.Ser180Gly amino substitution could form an N‐myristoylation site; the p.Lys240Thr amino substitution in chicken TLR3 could result in the loss of one protein kinase C phosphorylation site. These data provide a basic understanding of chicken TLR3 sequence variation and provide haplotypic markers for disease association studies.
An ABC estimate of pedigree error rate: application in dog, sheep and cattle breeds
Authors: Leroy G. , Danchin‐Burge C. , Palhiere I. , Baumung R. , Fritz S. , Mériaux J. C. , Gautier M.
Published: September 2011

On the basis of correlations between pairwise individual genealogical kinship coefficients and allele sharing distances computed from genotyping data, we propose an approximate Bayesian computation (ABC) approach to assess pedigree file reliability through gene‐dropping simulations. We explore the features of the method using simulated data sets and show precision increases with the number of markers. An application is further made with five dog breeds, four sheep breeds and one cattle breed raised in France and displaying various characteristics and population sizes, using microsatellite or SNP markers. Depending on the breeds, pedigree error estimations range between 1% and 9% in dog breeds, 1% and 10% in sheep breeds and 4% in cattle breeds.
Promising therapy results for lymphoid malignancies in children with chromosomal breakage syndromes (Ataxia teleangiectasia or Nijmegen‐breakage syndrome): a retrospective survey
Authors: Bienemann Klaus , Burkhardt Birgit , Modlich Simon , Meyer Ulrike , Möricke Anja , Bienemann Kirsten , Mauz‐Körholz Christine , Escherich Gabriele , Zimmermann Martin , Körholz Dieter , Janka‐Schaub Gritta , Schrappe Martin , Reiter Alfred , Borkhardt Arndt
Published: September 2011

Children with chromosomal instability syndromes have an increased risk of developing lymphoma and leukaemia. The treatment of these malignancies is hampered by therapy‐associated toxicity and infectious complications. This retrospective analysis evaluated the therapy outcome of 38 children with Ataxia teleangiectasia or Nijmegen‐breakage syndrome with acute lymphoblastic leukaemia (ALL, n = 9), Non‐Hodgkin lymphoma (NHL, n = 28) and Hodgkin lymphoma (HL, n = 1). All patients with NHL or ALL were treated in accordance to Berlin‐Frankfurt‐Münster (BFM)‐ or Co‐operative study group for childhood ALL (CoALL)‐oriented chemotherapy schedules. 22 patients received significantly reduced‐intensity chemotherapy. After a median follow‐up of 3·7 years the 10‐year overall survival was 58%. Dosage‐reduction of chemotherapeutic drugs seemed to have no disadvantages and reduced toxic side effects. On the other hand, reduced‐intensity chemotherapy did not prevent second malignancies, which occurred in ten patients with a 10‐year incidence of 25%. After individual treatment approaches three of these patients with second malignancies were in complete clinical remission for more than 5 years. We conclude that BFM‐ or CoALL‐oriented chemotherapy is effective and can be administered in children with AT or NBS. Moreover, we show that even second lymphoid malignancies can successfully be treated in these patients.
Aberrant T‐cell antigen expression in B lymphoblastic leukaemia
Authors: Hussein Shafinaz , Gill Kamraan Z. , Sireci Anthony N. , Colovai Adriana I. , Small Tania , Emmons Foxwell N. , Murty Vundavalli V. , Bhagat Govind , Alobeid Bachir
Published: September 2011

B lymphoblastic leukaemia (B‐ALL) cells are characterized by the expression of various B‐cell antigens. Expression of T/Natural Killer‐cell antigens, however, has rarely been reported in B‐ALL (TAg+ B‐ALL), and the significance of this aberrant antigen expression is unclear. We thus analysed the frequency of TAg+ B‐ALL at our institution and investigated its significance in the context of immunophenotypes, cytogenetic/molecular findings, and prognosis. We reviewed 134 consecutive cases of B‐ALL and found 18 cases (13·4%) of TAg+ B‐ALL. The most common aberrant T‐cell antigens expressed were CD2, CD5, and CD7 at equivalent rates (each in six cases), CD4 (two cases), and CD56 (three cases). Adverse cytogenetic abnormalities were seen in a significantly larger proportion of the TAg+ cases (72·2%) than the TAg− cases (32·2%; P = 0·003). Multivariate Cox‐regression analysis showed that the risk of relapse over time was higher in the TAg+ cases, independent of high risk status (based on age and white blood cell count) and the presence of adverse cytogenetic abnormalities (hazard ratio = 2·256, P = 0·065). These findings suggest that T‐cell antigen expression in B‐ALL may be an independent predictor of poor prognosis, and a useful marker to identify patients at increased risk for relapse and for harbouring adverse cytogenetic abnormalities.
Burkitt lymphoma in adults
Authors: Linch David C.
Published: September 2011

The diagnosis of Burkitt Lymphoma (BL) and B‐cell lymphomas unclassifiable with features intermediate between Diffuse Large B‐cell Lymphoma and BL (BLU) in adults remains problematic even with immunophenotyping andMYCgene analysis. Gene expression profiling may improve categorization but is not routinely available. BL and its variants should be treated with specific regimens incorporating intensive courses of chemotherapy with fractionated alkylating agents and cell cycle phase‐specific agents that readily cross the blood brain barrier. Subsequent courses should be given as soon as haematological recovery occurs, with the whole course completed within a few months. A number of regimens have been developed that encompass these principles but there have been no comparative randomized trials. The results from several studies suggest that the addition of rituximab is highly efficacious and this may be particularly valuable in older patients. It is usual to employ ‘risk‐adapted’ strategies in the treatment of BL but these must be continually re‐evaluated, and ‘response‐adapted’ approaches should be explored. The role of transplantation is limited and largely confined to autologous transplants in patients who only achieve a partial response on front‐line therapy or who have a chemosensitive relapse. Further advances will be greatly facilitated by randomized trials, which will require international collaboration.
TheDualArrhenius andMichaelis–Menten kinetics model for decomposition of soil organic matter at hourly to seasonal time scales
Authors: Davidson Eric A. , Samanta Sudeep , Caramori Samantha S. , Savage Kathleen
Published: September 2011

Decomposition of soil carbon stocks is one of the largest potential biotic feedbacks to climate change. Models of decomposition of soil organic matter and of soil respiration rely on empirical functions that relate variation in temperature and soil water content to rates of microbial metabolism using soil‐Csubstrates. Here, we describe a unifying modeling framework to combine the effects of temperature, soil water content, and soluble substrate supply on decomposition of soluble soil‐Csubstrates using simple functions based on process concepts. The model's backbone is the Michaelis–Menten equation, which describes the relationship between reaction velocity and soluble organic‐CandO2substrate concentrations at an enzyme's reactive site, which are determined by diffusivity functions based on soil water content. Temperature sensitivity is simulated by allowing the maximum velocity of the reaction (Vmax) to vary according toArrhenius function. TheDualArrhenius andMichaelis–Menten kinetics (DAMM) model core was able to predict effectively observations from of laboratory enzyme assays of β‐glucosidase and phenol‐oxidase across a range of substrate concentrations and incubation temperatures. The model also functioned as well or better than purely empirical models for simulating hourly and seasonal soil respiration data from a trenched plot in a deciduous forest at theHarvard Forest, in northeasternUnitedStates. TheDAMMmodel demonstrates that enzymatic processes can be intrinsically temperature sensitive, but environmental constrains of substrate supply under soil moisture extremes can prevent that response to temperature from being observed. We discuss howDAMMcould serve as a core module that is informed by other modules regarding microbial dynamics and supply of soluble‐Csubstrates from plant inputs and from desorption of physically stabilized soil‐Cpools. Most importantly, it presents a way forward from purely empirical representation of temperature and moisture responses and integrates temperature‐sensitive enzymatic processes with constraints of substrate supply.
Overexpression of a cytochrome P450 monooxygenase, CYP6ER1, is associated with resistance to imidacloprid in the brown planthopper, Nilaparvata lugens
Authors: Bass C. , Carvalho R. A. , Oliphant L. , Puinean A. M. , Field L. M. , Nauen R. , Williamson M. S. , Moores G. , Gorman K.
Published: September 2011

The brown planthopper, Nilaparvata lugens, is an economically significant pest of rice throughout Asia and has evolved resistance to many insecticides including the neonicotinoid imidacloprid. The resistance of field populations of N. lugens to imidacloprid has been attributed to enhanced detoxification by cytochrome P450 monooxygenases (P450s), although, to date, the causative P450(s) has (have) not been identified. In the present study, biochemical assays using the model substrate 7‐ethoxycoumarin showed enhanced P450 activity in several resistant N. lugens field strains when compared with a susceptible reference strain. Thirty three cDNA sequences encoding tentative unique P450s were identified from two recent sequencing projects and by degenerate PCR. The mRNA expression level of 32 of these was examined in susceptible, moderately resistant and highly resistant N. lugens strains using quantitative real‐time PCR. A single P450 gene (CYP6ER1) was highly overexpressed in all resistant strains (up to 40‐fold) and the level of expression observed in the different N. lugens strains was significantly correlated with the resistance phenotype. These results provide strong evidence for a role of CYP6ER1 in the resistance of N. lugens to imidacloprid.