bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pinch Technique and its Applications to Non-Abelian Gauge Theories
Authors: Cornwall John M. , Papavassiliou Joannis , Binosi Daniele
Published: February 2011

Non-Abelian gauge theories, such as quantum chromodynamics (QCD) or electroweak theory, are best studied with the aid of Green's functions that are gauge-invariant off-shell, but unlike for the photon in quantum electrodynamics, conventional graphical constructions fail. The Pinch Technique provides a systematic framework for constructing such Green's functions, and has many useful applications. Beginning with elementary one-loop examples, this book goes on to extend the method to all orders, showing that the Pinch Technique is equivalent to calculations in the background field Feynman gauge. The Pinch Technique Schwinger-Dyson equations are derived, and used to show how a dynamical gluon mass arises in QCD. Applications are given to the center vortex picture of confinement, the gauge-invariant treatment of resonant amplitudes, the definition of non-Abelian effective charges, high-temperature effects, and even supersymmetry. This book is ideal for elementary particle theorists and graduate students.
The Foundations of British Maritime Ascendancy
Authors: Morriss Roger
Published: February 2011

British power and global expansion between 1755 and 1815 have mainly been attributed to the fiscal-military state and the achievements of the Royal navy at sea. Roger Morriss here sheds new light on the broader range of developments in the infrastructure of the state needed to extend British power at sea and overseas. He demonstrates how developments in culture, experience and control in central government affected the supply of ships, manpower, food, transport and ordnance as well as the support of the army, permitting the maintenance of armed forces of unprecedented size and their projection to distant stations. He reveals how the British state, although dependent on the private sector, built a partnership with it based on trust, ethics and the law. This book argues that Britain's military bureaucracy, traditionally regarded as inferior to the fighting services, was in fact the keystone of the nation's maritime ascendancy.
The Passing of Protestant England
Authors: Green S. J. D.
Published: February 2011

In this 2010 book S. J. D. Green offers an important account of the causes, courses and consequences of the secularisation of English society. He argues that the critical cultural transformation of modern English society was forged in the agonised abandonment of a long-domesticated Protestant, Christian tradition between 1920 and 1960. Its effects were felt across the nation and among all classes. Yet their significance in the evolution of contemporary indigenous identities remains curiously neglected in most mainstream accounts of post-Victorian Britain. Dr Green traces the decline of English ecclesiastical institutions after 1918. He also investigates the eclipse of once-common moral sensibilities during the years up to 1945. Finally, he examines why subsequent efforts to reverse these trends so comprehensively failed. His work will be of enduring interest to modern historians, sociologists of religion, and all those concerned with the future of faith in Britain and beyond.
Central Banking in the Twentieth Century
Authors: Singleton John
Published: February 2011

Central banks are powerful but poorly understood organisations. In 1900 the Bank of Japan was the only central bank to exist outside Europe but over the past century central banking has proliferated. John Singleton here explains how central banks and the profession of central banking have evolved and spread across the globe during this period. He shows that the central banking world has experienced two revolutions in thinking and practice, the first after the depression of the early 1930s, and the second in response to the high inflation of the 1970s and 1980s. In addition, the central banking profession has changed radically. In 1900 the professional central banker was a specialised type of banker, whereas today he or she must also be a sophisticated economist and a public official. Understanding these changes is essential to explaining the role of central banks during the recent global financial crisis.
Contiguity of Probability Measures
Authors: Roussas George G.
Published: February 2011

This Tract presents an elaboration of the notion of 'contiguity', which is a concept of 'nearness' of sequences of probability measures. It provides a powerful mathematical tool for establishing certain theoretical results with applications in statistics, particularly in large sample theory problems, where it simplifies derivations and points the way to important results. The potential of this concept has so far only been touched upon in the existing literature, and this book provides the first systematic discussion of it. Alternative characterizations of contiguity are first described and related to more familiar mathematical ideas of a similar nature. A number of general theorems are formulated and proved. These results, which provide the means of obtaining asymptotic expansions and distributions of likelihood functions, are essential to the applications which follow.
Antipsychotics and their Side Effects
Authors: Gardner David M. , Teehan Michael D. , Baldessarini Ross
Published: February 2011

With the remarkable expansion in the use of antipsychotics, concerns about their immediate, intermediate, and long-term adverse effects have intensified. Despite this, studies consistently show that monitoring of patients taking antipsychotics can be inadequate, haphazard, or worse. This book provides a comprehensive review of the adverse effects of this pharmacologically complex therapeutic class, covering all commonly used conventional and atypical agents. In the first section, each chapter provides background information about an adverse effect, reviews the evidence linking the effect to various antipsychotics, and provides specific detection and monitoring recommendations. The second section provides unique monitoring guides for each antipsychotic. The third section provides the clinician with a program to monitor patients over the long-term. By supporting rational treatment decisions and systematic adverse effect monitoring, Antipsychotics and their Side Effects provides the clinician with the necessary information and tools for optimizing the safe and effective long-term use of antipsychotic drugs.
The Politics of Protest in Hybrid Regimes
Authors: Robertson Graeme B.
Published: February 2011

Since the end of the Cold War, more and more countries feature political regimes that are neither liberal democracies nor closed authoritarian systems. Most research on these hybrid regimes focuses on how elites manipulate elections to stay in office, but in places as diverse as Bolivia, Georgia, Kyrgyzstan, Serbia, Thailand, Ukraine and Venezuela, protest in the streets has been at least as important as elections in bringing about political change. The Politics of Protest in Hybrid Regimes builds on previously unpublished data and extensive fieldwork in Russia to show how one high-profile hybrid regime manages political competition in the workplace and in the streets. More generally, the book develops a theory of how the nature of organizations in society, state strategies for mobilizing supporters, and elite competition shape political protest in hybrid regimes.
Studies in the Greek Historians
Authors: Kagan Donald
Published: February 2011

The historians considered in this volume lived between the fifth century BC and the third century AD. They came from areas as far apart as Syria and Sicily and they had in common the Greek language and the Greek tradition of historical writing. They include authors who, though not strictly historians, shed important light on the tradition. Some contributors consider the value of their subjects as historical sources, others deal with problems of historical method or with ideas which arise from their works.
Neurology
Authors: Tarulli Andrew
Published: February 2011

Neurology: A Clinician's Approach teaches a symptom-oriented approach to the 20 most common problems which face neurologists in training. Emphasizing the primary importance of the patient history, the reader is instructed which questions to ask in order to elicit the chief complaint, how to ask these questions, and how to interpret the answers. The neurologic examination is presented as a flexible diagnostic tool rather than as a rigid exercise to be performed by rote and without reference to the chief complaint. Each chapter integrates evidence-based and experience-based approaches to diagnostic testing and treatment. Frequently-encountered conditions, uncommon 'zebras', and non-neurologic mimics of nervous system dysfunction are all given appropriate weight. Neurology: A Clinician's Approach is essential reading for neurologists in training, including neurology residents and medical students.
Later Greek Literature
Authors: Winkler John J. , Williams Gordon
Published: February 2011

Under the Roman Empire Greek literature experienced a renaissance. This flowering of interest in the Classics was in part a revival of the traditional culture associated with the glorious past and in part a development of new forms such as the novel, the classical lecture and the erotic letter. This literature has traditionally been considerably underrated and the essays in this 1982 volume of Yale Classical Studies were collected in an attempt to draw attention to the literary excellence of some undeservedly neglected authors and to inspire more readers to take them seriously. As the editors say in their introduction: 'nowadays we look to papyrology for ocasional revelations of exciting new pieces of ancient literature, but there are masterpieces already on the shelves waiting to be noticed'. This book will be of interest to students of Greek literature and ancient hsitory, especially to those concerned with post-Hellenistic Greek culture.
International Authority and the Responsibility to Protect
Authors: Orford Anne
Published: February 2011

The idea that states and the international community have a responsibility to protect populations at risk has framed internationalist debates about conflict prevention, humanitarian aid, peacekeeping and territorial administration since 2001. This book situates the responsibility to protect concept in a broad historical and jurisprudential context, demonstrating that the appeal to protection as the basis for de facto authority has emerged at times of civil war or revolution - the Protestant revolutions of early modern Europe, the bourgeois and communist revolutions of the following centuries and the revolution that is decolonisation. This analysis, from Hobbes to the UN, of the resulting attempts to ground authority on the capacity to guarantee security and protection is essential reading for all those seeking to understand, engage with, limit or critique the expansive practices of international executive action authorised by the responsibility to protect concept.
Quantity Implicatures
Authors: Geurts Bart
Published: February 2011

In recent years, quantity implicatures - a type of pragmatic inference - have been widely debated in linguistics, philosophy, and psychology, and have been subject to an enormous variety of analyses, ranging from lexical, syntactic, semantic, and pragmatic, to various hybrid accounts. In this first book-length discussion of the topic, Bart Geurts presents a theory of quantity implicatures that is resolutely pragmatic, arguing that the orthodox Gricean approach to conversational implicature is capable of accounting for all the standard cases of quantity implicature, and more. He shows how the theory deals with free-choice inferences as merely a garden variety of quantity implicatures, and gives an in-depth treatment of so-called 'embedded implicatures'. Moreover, as well as offering a comprehensive theory of quantity implicatures, he also takes into account experimental data and processing issues. Original and pioneering, and avoiding technical terminology, this insightful study will be invaluable to linguists, philosophers, and experimental psychologists alike.
Jews and Intermarriage in Nazi Austria
Authors: Bukey Evan Burr
Published: February 2011

Evan Burr Bukey explores the experience of intermarried couples - marriages with Jewish and non-Jewish partners - and their children in Vienna after Germany's seizure of Austria in 1938. These families coped with changing regulations that disrupted family life, pitted relatives against each other, and raised profound questions about religious, ethnic, and national identity. Bukey finds that although intermarried couples lived in a state of fear and anxiety, many managed to mitigate, delay, or even escape Nazi sanctions. Drawing on extensive archival research, his study reveals how hundreds of them pursued ingenious strategies to preserve their assets, to improve their 'racial' status, and above all to safeguard the position of their children. It also analyzes cases of intermarried partners who chose divorce as well as persons involved in illicit liaisons with non-Jews. Jews and Intermarriage in Nazi Austria concludes that although most of Vienna's intermarried Jews survived the Holocaust, several hundred Jewish partners were deported to their deaths and children of such couples were frequently subjected to Gestapo harassment.
In-Vitro Fertilization
Authors: Elder Kay , Dale Brian , Ménézo Yves , Harper Joyce , Huntriss John
Published: February 2011

This fully updated new edition of a successful and popular practical guide is an indispensable account of modern in-vitro fertilization practice. Initial chapters cover theoretical aspects of gametogenesis and embryo development at the cellular and molecular level, while the latter half of the book describes the requisites for a successful IVF laboratory and the basic technologies in ART. Advanced techniques, including pre-implantation genetic diagnosis, vitrification and stem-cell technology, are comprehensively covered, providing up-to-date analyses of these groundbreaking technologies. This edition includes: • New practical techniques, including preservation of fertility for cancer patients, stem-cell biology/technology, vitrification and in-vitro maturation • A 'refresher' study review of fundamental principles of cell and molecular biology • The latest information available from animal and human research in reproductive biology Packed with a wealth of practical and scientific detail, this is a must for all IVF practitioners.
Prostitution and Female Leadership in Rural Thailand: The Story of Phayao Province
Authors: NISHIZAKI YOSHINORI
Published: February 2011

For all the attention paid to the economic, social, and moral dimensions of prostitution in Thailand, no scholar has thus far conducted an empirical study of the relationship between the vice and political change in the countryside, where most sex workers come from. Using the case of Phayao Province in northern Thailand, I attempt to redress this lacuna. I show how rampant prostitution, the most acute social issue in Phayao, has ushered in the rise to power of one virtuous woman from an ethnic minority family—Ladawan Wongsriwong. Located on the economic and social margins of Thailand, many village families in Phayao traditionally relied on prostitution for income, causing a massive influx of young girls into the lucrative sex industry in Bangkok and abroad. In the 1990s, however, AIDS started taking a heavy toll on Phayao's small population. Against this backdrop, Ladawan emerged as a prominent female leader in the male-dominant rural society of Phayao by conducting an extensive issue-oriented campaign against prostitution. This case questions much of the literature on rural politics and female leadership in democratizing Southeast Asia that underestimates the importance of social issues.
Determined to Be Free: The Meaning of Freedom in Spinoza'sTheologico-Political Treatise
Authors: Frankel Steven
Published: February 2011

The goal of this essay is to offer an alternative account to the view that political freedom and philosophical freedom are consistent, harmonious, and mutually reinforcing. Certainly, freedom is central to Spinoza's political thought, but to understand it properly, we need to explain how it alleviates, rather than encourages, superstition among the nonrational multitude. In light of his belief in the permanency of irrationality and superstition, Spinoza does not hope to expunge illusions from political life. Advocating freedom is an attempt to adapt the facts of the imagination to the needs of our political order and create stability. The belief in freedom—that is, the belief that we are individual actors who decide our actions and determine our fate—is the most powerful and abiding illusion in politics.
On Communitarian and Global Sources of Legitimacy
Authors: Etzioni Amitai
Published: February 2011

Although the concept of legitimacy is widely invoked in social science literature, political discourse, and common parlance, key empirical and normative questions about legitimacy are often left far from answered, especially “Legitimated by whom?” and “Legitimate by what criteria?” Recently these questions have been raised with particular acuteness with regard to the nascent international society, for instance, the standing of the International Criminal Court and the 2003 invasion of Iraq by the United States-led coalition.
The Morality of “Lolita”
Authors: Gold Joseph
Published: February 2011

The difference in critical response to Lolita in England and America is interesting and troubling. It cannot be dismissed without comment or merely accepted as a twentieth century phenomenon of intellectual life. It can, I believe, be explained in only one way. In the literature of the United States there is by now a well-established literary tradition which centres around the alien figure in society, the outcast, the lowly and the rejected.
Notes on American Negro Reformers in Victorian Britain
Authors: Taylor Clare
Published: February 2011

During the middle years of the nineteenth century a significant number of American Negro reformers visited Britain. Their visits have not passed unnoticed. As J. H. Franklin has remarked, “More than a score of black abolitionists went to England, Scotland, France and Germany… Almost everywhere they were received with enthusiasm and were instrumental in linking up the humanitarian movement with various reform movements on both sides of the Atlantic.” Benjamin Quarles, furthermore, has commented on some of their work in Britain.
The British Whigs on America: 1820–1860
Authors: Crook D. P.
Published: February 2011

There has been a tendency among historians of the Anglo-American connection to suggest that there was a fairly rigid dichotomy in English opinion about America in the first half of the nineteenth century. On the one hand, it is suggested, there were the Radicals, who, by tradition and in principle, favoured the United States and its institutions. This group - the Left of that period - comprised the excluded classes of society, the dissenters, the artisans and labourers, the Chartists and democrats, the utilitarians. Confronting them was the Establishment, opposed to innovation, and especially democratic innovation, embittered by memories of 1776 and 1812, and therefore thoroughly anti-American.
The Teaching of American Literature in Britian
Authors: Moore Geoffrey
Published: February 2011

I do not know how many ways of teaching American literature there are, but I can think of at least three. One can accept it as a literature in its own right and teach it for its moral and aesthetic values; one can regard it as worthy only of being treated as part of American intellectual history, or as an illustration of American life and thought; or one can make some compromise between these two methods. I should like, at the outset, to examine the practicability of the first method. George Bernard Shaw said once that an Englishman “does everything on principle. He fights you on patriotic principles; he robs you on business principles; he enslaves you on imperial principles.” If, therefore, I propose a principle for the teaching of Amerioan literature, it will perhaps be understood that, although I am not exactly announcing my deliberate perfidy, I am at least acknowledging that I am aware that the current frame of mind in Britain would suggest a certain strategy.
James Branch Cabell: a Reappraisal
Authors: Tarrant Desmond
Published: February 2011

Even today it is still possible, by the help of some such accident as censorship, for a good book actually to become widely read. This is, of course, precisely what happened to Jurgen in 1920. Yet it is tempting to believe that Jurgen was released primarily because, as Judge Charles C. Nott observed when recommending the jury to acquit the defendants, very few readers would be capable of understanding it. There seems little doubt that Cabell was suppressed for what he didn't say and exalted for what he didn't mean. This may be an inevitable penalty for creating what is, in effect, a spiritual synthesis in an age of intellectual analysis. But the wheel must turn, and with Edward Wagenknecht's fuller comprehension in his Cavalcade of the American Novel (1952) and Edmund Wilson's article in the New Yorker in April, 1956, perhaps we are now ready to honour Vernon Louis Parrington's description (in The Pacific Review of 1921) of Cabell as:
Scottish-American Cultural Connections: a Bibliographical Note
Authors: Shepperson George
Published: February 2011

When William James, at the beginning of his 1901 Gifford Lectures, The Varieties of Religious Experience, referred to Edinburgh as “sacred to the American imagination” and went on to pay tribute to its philosophical traditions, he was indulging in something much more than the customary academic pleasantries which every visiting lecturer feels obliged to make. Sir William Hamilton's lectures, he said, “were the first philosophic writings I ever forced myself to study, and after that I was inmersed in Dugald Stewart and Thomas Brown. Such juvenile emotions of reverence never get outgrown.”
“For the Good of the Association”: American Trade Unionism At the Grass Roots
Authors: Harrison J. F. C.
Published: February 2011

“If it weren't for the door prize they wouldn't come at all,” confided the president of the local. The doorkeeper stood with his bowl of dimes, religiously unlocking and relocking the door as each member presented himself for admittance, reaching at the sane time into his trousers' pocket for his ten cents contribution to the evening's sweepstake. Outside, the temperature was ten degrees below freezing; inside, the gas heater on the ceiling buzzed noisily. One by one, the members flopped into the vacant chairs, unzipped their padded jackets, and smoked and chewed and chatted happily. The room was pleasantly warm, the chairs uncomfortably hard, and the walls had the timeless dinginess of dark green paint. On a dais at one end, between the narrow trestle table covered with files, dues books, and loose papers sat the four officers of the local. To one side, leaning precariously in a wobbly standard-holder, was the Flag. From the wall behind the dais, past presidents of the International and the State Federation of Labor looked down on the meeting. Between them was the charter of the local; around the other walls, in varying degrees of ornateness, were the framed charters of different locals in the town which also used the Labor Temple. A painted piano in one corner, a refrigerator and a row of coat hangers completed the furnishings. Smiling broadly, the president rose and banged his gavel on the table gently. The hubbub subsided rapidly as he began reading the historic formula for opening, the meeting.
Three Unpublished Letters of George Ticknor and Edward Everett
Authors: Goldman Arnold
Published: February 2011

William Roscoe of Liverpool, banker, historian and man of letters, was George Ticknor and Edward Everett's “first celebrity” in their 1815–1819 European apprenticeship. Roscoe stood for them, as he does in Washington Irving's The Sketch-Book of Geoffrey Crayon, Gent. (1819–20), as “the literary landmark” of Liverpool, and more than that, a gateway to European culture. His house was open to Americans and he introduced them to and sped them on their repossessions of the heritage on which, in the previous years, the young country had turned its back.
The Conditions of Isolationism
Authors: Campbell A. E.
Published: February 2011

Recent work on American foreign policy between the two world wars has shown some dissatisfaction with the term “isolationism” as a tool for the historian. The immediate reasons for this dissatisfaction are two. First, it is remarkably difficult to identify an individual statesman firmly as an isolationist or an interventionist. Lodge, Hughes, Kellogg, Hoover, Stimson, Roosevelt, Hull – the list could be extended – all move embarrassingly from positions which can be called isolationist to others which seem to strain the term past recognition; nor are these shifts in one direction only. Second, a specific policy which can be identified as isolationist is often justified by remarkably various arguments, so that support for the policy makes some curious allies, while dividing men from others with whom they seem, in general, to have far more in common. If the term can be used neither to identify a man throughout his career, nor to identify a group of attitudes, a cast of political mind, its usefulness is certainly diminished
The Pathfinder: Leatherstocking in Love
Authors: Dekker G.
Published: February 2011

The Pathfinder (1840) is the only Leatherstocking tale in which Natty Bumppo at all resembles the wavering hero of a Scott novel. Here for the first and only time we see him waver between the life he has always led — untrammelled by property, responsible only to his own strict code and conscience, free to follow his own bent away from white European society — and the life of a border family man with all that that implies in terms of a wife who must be kept content with her lot, children.who must be properly educated, property which must be acquired and protected. Yet The Pathfinder is not in the least like a Waverley novel. It is not even very much like one of the earlier Leatherstocking tales. Why, more than a decade after burying Leatherstocking in The Prairie (1827), did Cooper revive him again? And why revive him in this particular way?
The Implementation of the Civil Rights Act of 1964: Title VI and the Use of Federal Funds
Authors: Lees John D.
Published: February 2011

The passage of the Civil Rights Act of 1964 by the United States Congress was a landmark not merely because of the manner in which Congressional opposition to the bill was overcome, but also in the potential effect of the legislation upon a variety of Federal programmes, in particular the use of Federal funds to implement such programmes. The Civil Rights Act of 1964, itself preceded by a period of intense and unprecedented civil rights agitation, in turn provoked further bouts of agitation, culminating in the attempts to register Negro voters in Selma, Alabama, and the march from Selma to Montgomery, Albama. Because of this, that section of the Act (Title 1) concerned with more effective enforcement of the right to vote in Federal elections has gained considerable prominence, especially following the presentation to Congress in March, 1965, of recommended legislation designed to enforce the 15th Amendment to the Constitution. However, one of the most significant and far-reaching sections of the Act is that relating to, and affecting, the use of Federal funds by Federal agencies. Under Title VI of the Act every Federal agency providing financial assistance through grants, loans or contracts, is required to eliminate discrimination in these programmes on the grounds of race, colour or national origin. This power could be a powerful lever for the President to force state governmental agencies to eliminate such discrimination in their programmes or risk the loss of vital Federal funds to supplement such programmes. It provides an important potential economic sanction on many Southern states and its effects may be far-reaching. The importance of Title VI can be seen by reference to particular areas where it has already been implemented.
Roosevelt and Kennedy
Authors: Adams David K.
Published: February 2011

Historical analogies are often misleading, but the character of John F. Kennedy's administration can be usefully illuminated by consideration of the points of resemblance which it bears to the peacetime administrations of Franklin D. Roosevelt. Superficially of course the influx of intellectuals into the federal capital in the winter of 1960–1961 recalls the gathering of the brain-trusters in Washington in 1933. But there are two more fundamental aspects of the Kennedy presidency which remind the observer of the Roosevelt period. These are the philosophy of the New Frontier, with its conscious overtones of the New Deal and its radical challenge to the traditions of laissez faire; and the political problem inherent in the composition of the Democratic party.
Attention et production d'autoreformulations autoamorcées en français langue seconde, quelle relation?
Authors: SIMARD DAPHNEE , FORTIER VERONIQUE , ZUNIGA MICHAEL
Published: February 2011

RESUME

Cette étude avait comme objectif de tenter d'établir un lien entre la capacité attentionnelle et les autoreformulations autoamorcées d'apprenants adultes de français langue seconde produites lors d'une tâche de narration. L'analyse des données n'a pas permis d'établir une association significative entre ces deux variables. Les résultats appuient donc ceux obtenus d'une étude antérieure (c.-à-d., Fincher, 2006) ayant examiné, de manière différente, la même question de recherche. Les résultats doivent être interprétés en fonction de la mesure de l'attention utilisée, à savoir une mesure capacitaire. Les conclusions de l'étude permettent de faire ressortir le manque de précision concernant la nature du processus attentionnel en jeu lors de production d'autoreformulations autoamorcées.
Évaluation et identification perceptives d'accents ouest-africains en français
Authors: DE MAREÜIL PHILIPPE BOULA , BOUTIN BÉATRICE AKISSI
Published: February 2011

Cette étude examine avec quel degré de granularité divers accents ouest-africains en français peuvent être distingués. Elle vise avant tout à déterminer si, en perception, des auditeurs de l'Afrique de l'Ouest sont capables d'identifier l'appartenance ethnolinguistique, le pays de résidence et le niveau d'études de locuteurs akan, bambara, sénoufo, mossi (de langue mooré) et wolof, enregistrés en Côte d'Ivoire, au Mali, au Burkina Faso et au Sénégal. Une expérience perceptive a été menée, d'où il ressort que les dimensions étudiées sont bien identifiées par les sujets. Pour les jeunes locuteurs comme pour les locuteurs plus âgés, en lecture comme en parole spontanée, les résultats sont très robustes. Ils sont de plus assez fidèles à la conscience linguistique auto-évaluée par les auditeurs: quand ceux-ci se déclaraient confiants pour reconnaître les accents en présence, tel a effectivement été le cas. Quelques indices acoustiques différenciant notamment les accents wolof (Sénégal) et akan (Côte d'Ivoire) ont finalement été dégagés.
Mini‐review series: focus on chemokines
Authors: Comerford Iain , McColl Shaun R
Published: February 2011

Our understanding of the significance and complexity of the chemokine superfamily has increased at an explosive pace over the last decade. Although this pace may be slowing down, many questions remain in this field. The February 2011 Special Feature on Chemokines reviews some of these issues: the CXCR3/CXCL9/CXCL10/CXCL11 axis; the role of chemokines in the thymus; and the function of the atypical chemokine receptors DARC and D6.
Cafeteria Diet Is a Robust Model of Human Metabolic Syndrome With Liver and Adipose Inflammation: Comparison to High‐Fat Diet
Authors: Sampey Brante P. , Vanhoose Amanda M. , Winfield Helena M. , Freemerman Alex J. , Muehlbauer Michael J. , Fueger Patrick T. , Newgard Christopher B. , Makowski Liza
Published: February 2011

Obesity has reached epidemic proportions worldwide and reports estimate that American children consume up to 25% of calories from snacks. Several animal models of obesity exist, but studies are lacking that compare high‐fat diets (HFD) traditionally used in rodent models of diet‐induced obesity (DIO) to diets consisting of food regularly consumed by humans, including high‐salt, high‐fat, low‐fiber, energy dense foods such as cookies, chips, and processed meats. To investigate the obesogenic and inflammatory consequences of a cafeteria diet (CAF) compared to a lard‐based 45% HFD in rodent models, male Wistar rats were fed HFD, CAF or chow control diets for 15 weeks. Body weight increased dramatically and remained significantly elevated in CAF‐fed rats compared to all other diets. Glucose‐ and insulin‐tolerance tests revealed that hyperinsulinemia, hyperglycemia, and glucose intolerance were exaggerated in the CAF‐fed rats compared to controls and HFD‐fed rats. It is well‐established that macrophages infiltrate metabolic tissues at the onset of weight gain and directly contribute to inflammation, insulin resistance, and obesity. Although both high fat diets resulted in increased adiposity and hepatosteatosis, CAF‐fed rats displayed remarkable inflammation in white fat, brown fat and liver compared to HFD and controls. In sum, the CAF provided a robust model of human metabolic syndrome compared to traditional lard‐based HFD, creating a phenotype of exaggerated obesity with glucose intolerance and inflammation. This model provides a unique platform to study the biochemical, genomic and physiological mechanisms of obesity and obesity‐related disease states that are pandemic in western civilization today.
Single‐Nucleotide Polymorphisms in the TNF Gene Are Associated With Obesity‐Related Phenotypes in Vervet Monkeys
Authors: Gray Stanton B. , Langefeld Carl D. , Ziegler Julie T. , Hawkins Gregory A. , Wagner Janice D. , Howard Timothy D.
Published: February 2011

Tumor necrosis factor (TNF) promoter single‐nucleotide polymorphisms (SNPs) have been extensively characterized in humans, with numerous reports of associations with obesity‐related phenotypes as well an array of infectious, immune‐mediated, and inflammatory disease phenotypes. Controlling for the multitude of environmental risk factors in human studies has been a major confounder of efforts to elucidate the role and relative contribution of TNF promoter SNPs. As part of an ongoing initiative to further genetically and phenotypically characterize the St Kitts‐origin vervet monkey (Chlorocebus aethiops ssp.) as an animal model of human obesity, we have conducted association analyses between TNF SNPs and previously defined obesity‐related phenotypes in 265 pedigreed vervets. We report eight SNPs (−809G, −756A, −352C, −322A, +1285T, +2133T, +2362A, +2405), all contained within the same haplotype block and comprising a single haplotype, to be significantly associated with BMI, waist circumference, total plasma cholesterol (P < 0.05), and high‐density lipoprotein‐cholesterol (HDL‐C) (P < 0.01). This study provides additional validation of the St Kitts‐origin vervet model of obesity by demonstrating genetic associations analogous to that shown in humans.
Neuropilin-1 mediates PDGF stimulation of vascular smooth muscle cell migration and signalling via p130Cas
Authors: Pellet-Many Caroline , Frankel Paul , Evans Ian M. , Herzog Birger , Jünemann-Ramírez Manfred , Zachary Ian C.
Published: February 2011

NRP1 (neuropilin-1) is a co-receptor for members of the VEGF (vascular endothelial growth factor) family in endothelial cells, but is increasingly implicated in signalling induced by other growth factors. NRP1 is expressed in VSMCs (vascular smooth muscle cells), but its function and the mechanisms involved are poorly understood. The present study aimed to determine the role of NRP1 in the migratory response of HCASMCs (human coronary artery smooth muscle cells) to PDGF (platelet-derived growth factor), and to identify the signalling mechanisms involved. NRP1 is highly expressed in HAoSMCs (human aortic smooth muscle cells) and HCASMCs, and modified in VSMCs by CS (chondroitin sulfate)-rich O-linked glycosylation at Ser612. HCASMC migration induced by PDGF-BB and PDGF-AA was inhibited by NRP1 siRNA (small interfering RNA), and by adenoviral overexpression of an NRP1 mutant lacking the intracellular domain (Ad.NRP1ΔC). NRP1 co-immunoprecipitated with PDGFRα (PDGF receptor α), and immunofluorescent staining indicated that NRP1 and PDGFRα co-localized in VSMCs. NRP1 siRNA also inhibited PDGF-induced PDGFRα activation. NRP1-specific siRNA, Ad.NRP1ΔC and removal of CS glycans using chondroitinase all inhibited PDGF-BB and -AA stimulation of tyrosine phosphorylation of the adapter protein, p130Cas (Cas is Crk-associated substrate), with little effect on other major signalling pathways, and p130Cas knockdown inhibited HCASMC migration. Chemotaxis and p130Cas phosphorylation induced by PDGF were inhibited by chondroitinase, and, additionally, adenoviral expression of a non-glycosylatable NRP1S612A mutant inhibited chemotaxis, but not p130Cas phosphorylation. These results indicate a role for NRP1 and NRP1 glycosylation in mediating PDGF-induced VSMC migration, possibly by acting as a co-receptor for PDGFRα and via selective mobilization of a novel p130Cas tyrosine phosphorylation pathway.
Cyclic lipopeptide antibiotics bind to the N-terminal domain of the prokaryotic Hsp90 to inhibit the chaperone activity
Authors: Minagawa Shun , Kondoh Yasumitsu , Sueoka Keigo , Osada Hiroyuki , Nakamoto Hitoshi
Published: February 2011

Chemical arrays were employed to screen ligands for HtpG, the prokaryotic homologue of Hsp (heat-shock protein) 90. We found that colistins and the closely related polymyxin B interact physically with HtpG. They bind to the N-terminal domain of HtpG specifically without affecting its ATPase activity. The interaction caused inhibition of chaperone function of HtpG that suppresses thermal aggregation of substrate proteins. Further studies were performed with one of these cyclic lipopeptide antibiotics, colistin sulfate salt. It inhibited the chaperone function of the N-terminal domain of HtpG. However, it inhibited neither the chaperone function of the middle domain of HtpG nor that of other molecular chaperones such as DnaK, the prokaryotic homologue of Hsp70, and small Hsp. The addition of colistin sulfate salt increased surface hydrophobicity of the N-terminal domain of HtpG and induced oligomerization of HtpG and its N-terminal domain. These structural changes are discussed in relation to the inhibition of the chaperone function.
UHRF1 depletion causes a G2/M arrest, activation of DNA damage response and apoptosis
Authors: Tien Amy L. , Senbanerjee Sucharita , Kulkarni Atul , Mudbhary Raksha , Goudreau Bernadette , Ganesan Shridar , Sadler Kirsten C. , Ukomadu Chinweike
Published: February 2011

UHRF1 [ubiquitin-like protein, containing PHD (plant homeodomain) and RING finger domains 1] is required for cell cycle progression and epigenetic regulation. In the present study, we show that depleting cancer cells of UHRF1 causes activation of the DNA damage response pathway, cell cycle arrest in G2/M-phase and apoptosis dependent on caspase 8. The DNA damage response in cells depleted of UHRF1 is illustrated by: phosphorylation of histone H2AX on Ser139, phosphorylation of CHK (checkpoint kinase) 2 on Thr68, phosphorylation of CDC25 (cell division control 25) on Ser216 and phosphorylation of CDK1 (cyclin-dependent kinase 1) on Tyr15. Moreover, we find that UHRF1 accumulates at sites of DNA damage suggesting that the cell cycle block in UHRF1-depleted cells is due to an important role in damage repair. The consequence of UHRF1 depletion is apoptosis; cells undergo activation of caspases 8 and 3, and depletion of caspase 8 prevents cell death induced by UHRF1 knockdown. Interestingly, the cell cycle block and apoptosis occurs in p53-containing and -deficient cells. From the present study we conclude that UHRF1 links epigenetic regulation with DNA replication.
The Arabidopsis class I TCP transcription factor AtTCP11 is a developmental regulator with distinct DNA-binding properties due to the presence of a threonine residue at position 15 of the TCP domain
Authors: Viola Ivana L. , Uberti Manassero Nora G. , Ripoll Rodrigo , Gonzalez Daniel H.
Published: February 2011

The TCP domain is a DNA-binding domain present in plant transcription factors that modulate different processes. In the present study, we show that Arabidopsis class I TCP proteins are able to interact with a dyad-symmetric sequence composed of two GTGGG half-sites. TCP20 establishes symmetric interactions with the 5′ half of each strand, whereas TCP11 interacts mainly with the 3′ half. SELEX (systematic evolution of ligands by exponential enrichment) experiments with TCP15 and TCP20 indicated that these proteins have similar, although not identical, DNA-binding preferences and are able to interact with non-palindromic binding sites of the type GTGGGNCCNN. TCP11 shows a different DNA-binding specificity, with a preference for the sequence GTGGGCCNNN. The distinct DNA-binding properties of TCP11 are due to the presence of a threonine residue at position 15 of the TCP domain, a position that is occupied by an arginine residue in most TCP proteins. TCP11 also forms heterodimers with TCP15 that have increased DNA-binding efficiency. The expression in plants of a repressor form of TCP11 demonstrated that this protein is a developmental regulator that influences the growth of leaves, stems and petioles, and pollen development. The results suggest that changes in DNA-binding preferences may be one of the mechanisms through which class I TCP proteins achieve functional specificity.
Knockdown of T-cell intracellular antigens triggers cell proliferation, invasion and tumour growth
Authors: Izquierdo José M. , Alcalde José , Carrascoso Isabel , Reyes Raquel , Ludeña María Dolores
Published: February 2011

TIA (T-cell intracellular antigen) proteins function as DNA/RNA trans-acting regulators to expand transcriptome and proteome diversity in mammals. In the present paper we report that the stable silencing of TIA1 and/or TIAR/TIAL1 (TIA1-related/like protein 1) expression in HeLa cells enhances cell proliferation, anchorage-dependent and -independent growth and invasion. HeLa cells lacking TIA1 and/or TIAR generate larger and faster-growing epithelial tumours with high rates of proliferation and angiogenesis in nude mice xenografts. Protein array analysis of a collection of human tumours shows that TIA1 and TIAR protein expression is down-regulated in a subset of epithelial tumours relative to normal tissues. Our results suggest a link between the epigenetic control exerted by TIA proteins and the transcriptional and post-transcriptional regulation of a subset of specific genes involved in tumour progression. Taken together, these results are consistent with a role for TIA proteins as growth/tumour-suppressor genes.
Identification and characterization of AtI-2, anArabidopsishomologue of an ancient protein phosphatase 1 (PP1) regulatory subunit
Authors: Templeton George W. , Nimick Mhairi , Morrice Nicholas , Campbell David , Goudreault Marilyn , Gingras Anne-Claude , Takemiya Atsushi , Shimazaki Ken-ichiro , Moorhead Greg B. G.
Published: February 2011

PP1 (protein phosphatase 1) is among the most conserved enzymes known, with one or more isoforms present in all sequenced eukaryotic genomes. PP1 dephosphorylates specific serine/threonine phosphoproteins as defined by associated regulatory or targeting subunits. In the present study we performed a PP1-binding screen to find putative PP1 interactors in Arabidopsis thaliana and uncovered a homologue of the ancient PP1 interactor, I-2 (inhibitor-2). Bioinformatic analysis revealed remarkable conservation of three regions of plant I-2 that play key roles in binding to PP1 and regulating its function. The sequence-related properties of plant I-2 were compared across eukaryotes, indicating a lack of I-2 in some species and the emergence points from key motifs during the evolution of this ancient regulator. Biochemical characterization of AtI-2 (Arabidopsis I-2) revealed its ability to inhibit all plant PP1 isoforms and inhibitory dependence requiring the primary interaction motif known as RVXF. Arabidopsis I-2 was shown to be a phosphoprotein in vivo that was enriched in the nucleus. TAP (tandem affinity purification)-tag experiments with plant I-2 showed in vivo association with several Arabidopsis PP1 isoforms and identified other potential I-2 binding proteins.
SCM, a novel M-like protein fromStreptococcus canis, binds (mini)-plasminogen with high affinity and facilitates bacterial transmigration
Authors: Fulde Marcus , Rohde Manfred , Hitzmann Angela , Preissner Klaus T. , Nitsche-Schmitz D. Patric , Nerlich Andreas , Chhatwal Gursharan Singh , Bergmann Simone
Published: February 2011

Streptococcus canis is an important zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. In the present paper we report the binding of human plasminogen to S. canis and the recruitment of proteolytically active plasmin on its surface. The binding receptor for plasminogen was identified as a novel M-like protein designated SCM (S. canis M-like protein). SPR (surface plasmon resonance) analyses, radioactive dot-blot analyses and heterologous expression on the surface of Streptococcus gordonii confirmed the plasminogen-binding capability of SCM. The binding domain was located within the N-terminus of SCM, which specifically bound to the C-terminal part of plasminogen (mini-plasminogen) comprising kringle domain 5 and the catalytic domain. In the presence of urokinase, SCM mediated plasminogen activation on the bacterial surface that was inhibited by serine protease inhibitors and lysine amino acid analogues. Surface-bound plasmin effectively degraded purified fibrinogen as well as fibrin clots, resulting in the dissolution of fibrin thrombi. Electron microscopic illustration and time-lapse imaging demonstrated bacterial transmigration through fibrinous thrombi. The present study has led, for the first time, to the identification of SCM as a novel receptor for (mini)-plasminogen mediating the fibrinolytic activity of S. canis.
ATR (ataxia telangiectasia mutated- and Rad3-related kinase) is activated by mild hypothermia in mammalian cells and subsequently activates p53
Authors: Roobol Anne , Roobol Jo , Carden Martin J. , Bastide Amandine , Willis Anne E. , Dunn Warwick B. , Goodacre Royston , Smales C. Mark
Published: February 2011

In vitro cultured mammalian cells respond to mild hypothermia (27–33 °C) by attenuating cellular processes and slowing and arresting the cell cycle. The slowing of the cell cycle at the upper range (31–33 °C) and its complete arrest at the lower range (27–28 °C) of mild hypothermia is effected by the activation of p53 and subsequent expression of p21. However, the mechanism by which cold is perceived in mammalian cells with the subsequent activation of p53 has remained undetermined. In the present paper, we report that the exposure of Chinese-hamster ovary-K1 cells to mildly hypothermic conditions activates the ATR (ataxia telangiectasia mutated- and Rad3-related kinase)–p53–p21 signalling pathway and is thus a key pathway involved in p53 activation upon mild hypothermia. In addition, we show that although p38MAPK (p38 mitogen-activated protein kinase) is also involved in activation of p53 upon mild hypothermia, this is probably the result of activation of p38MAPK by ATR. Furthermore, we show that cold-induced changes in cell membrane lipid composition are correlated with the activation of the ATR–p53–p21 pathway. Therefore we provide the first mechanistic detail of cell sensing and signalling upon mild hypothermia in mammalian cells leading to p53 and p21 activation, which is known to lead to cell cycle arrest.