bluuebunny/crossref_metadata_2025 huggingface dataset:
Electron beam pumped lasers based on II–VI compound nanostructures from the visible to UVA
Authors: Tiberi Michael D. , Kozlovsky Vladimir I. , Kuznetsov Peter I.
Published: May 2010

The latest results on electron beam pumped vertical‐cavity surface‐emitting lasers (eVCSEL) based on wide band gap II–VI compounds emitting in blue and ultraviolet (UV) (360–390 nm) ranges are presented. A typical structure consists of 20–30 quantum wells (QWs) of 5–8 nm in thickness separated by ZnMgSSe barrier layers closely lattice matched to the substrate. The structure period is tuned to the lasing wavelength achieving resonant‐periodic gain. For blue, structures were grown on GaAs substrate while for UV on GaP. ZnSe layers with the addition of Cd were used for blue. In contrast, ZnSSe QWs were best suited for UV. All structures were grown by MOVPE at a temperature range of 430–470 °C. Up to 10 W in output power in blue and 2.8 W in the UV range at room temperature (RT) in scanning mode was achieved.
Physicochemical properties of high amylose rice starches purified from Korean cultivars
Authors: Kim Ji‐Myoung , Song Ji‐Young , Shin Malshick
Published: May 2010

The physicochemical and pasting properties of high amylose rice starches isolated using alkaline steeping method from different Korean rice cultivars, Goamy2 and Goamy, and from imported Thai rice were examined. The protein and lipid contents of the Goamy2 starch were higher than those of the other two starches. The amylose and total dietary fiber contents were ranged from 31.4 to 36.8% and from 6.3 to 8.6%, respectively. Total dietary fiber was positively correlated to amylose content. Water binding capacity was higher in the Goamy2 starch (172.2%) than in the Goamy and Thai rice starches (112.7–115.6%). The swelling power of the Goamy2 starch showed lower values, but its value at 95°C was similar to others because of its rapid increment at 85°C. The granular size of Goamy2 starch was widely distributed compared to those of others. The Goamy2 starch showed a high initial pasting temperature (92.0°C) and low breakdown and setback viscosities. The Goamy and Thai rice starch granules were polygonal‐shaped with A‐type crystals, whereas the Goamy2 starch granules were round‐shaped with B‐type crystals. Goamy and Goamy2 starches showed a single endotherm at 60.8 and 76.0°C for peak temperature and 10.0 and 11.5 J/g for gelatinization enthalpies, respectively. The Thai rice starch presented an endotherm with a shoulder peak at 68.3°C (75.3°C for the main peak) and a gelatinization enthalpy of 12.4 J/g.
The Seniors Health Research Transfer Network Knowledge Network Model: System-Wide Implementation for Health and Healthcare of Seniors
Authors: Chambers Larry W. , Luesby Deirdre , Brookman Catherine , Harris Megan , Lusk Elizabeth
Published: May 2010

The Ontario Seniors Health Research Transfer Network (SHRTN) aims to improve the health of older adults through increasing the knowledge capacity of 850 community care agencies and 620 long-term care homes. The SHRTN includes caregivers, researchers, policy makers, administrators, educators, and organizations. The SHRTN comprises communities of practice, a library service, a network of 7 research institutes, and local implementation teams. The SHRTN combines face-to-face meetings with information technology to promote change at the client care level in organizational and provincial policies and in the promotion of health services research.
Exponential Diophantine Equations
Authors: Shorey T. N. , Tijdeman R.
Published: May 2010

This is a integrated presentation of the theory of exponential diophantine equations. The authors present, in a clear and unified fashion, applications to exponential diophantine equations and linear recurrence sequences of the Gelfond-Baker theory of linear forms in logarithms of algebraic numbers. Topics covered include the Thue equations, the generalised hyperelliptic equation, and the Fermat and Catalan equations. The necessary preliminaries are given in the first three chapters. Each chapter ends with a section giving details of related results.
The Letters of Thomas Babington MacAulay
Authors: MacAulay Thomas
Published: May 2010

The fourth volume of Thomas Pinney's acclaimed edition of Macaulay's letters covers the period between September 1841 and December 1848, in which Macaulay is shown keeping up an active political life as MP for Edinburgh and member of Lord John Russell's Whig Cabinet. At the same time his literary reputation is extended by The Lays of Ancient Rome, the collected Essays, and, at the end of the period spanned by this volume, the triumphant publication of the first two volumes of the History of England. In the same years Macaulay was enjoying perhaps the most satisfactory period of his private life: we see him comfortably established in the Albany, enjoying the society of his sister and her family, taking part as a leading figure in Whig political and literary circles, and confidently at work on the book which was to crown his fame.
Preference, Production and Capital
Authors: Uzawa Hirofumi , Arrow Kenneth J.
Published: May 2010

This volume contains a selection of Professor Uzawa's important contributions to mathematical economics. Subjects covered by these nineteen essays include consumption, production, equilibrium, capital, growth, planning, international trade, and the theory of social overhead capital. Written in the 1960s and early 1970s, the papers form a basis upon which economic theory has developed over the last twenty years. The collection includes some of Uzawa's classic contributions, such as 'Preference and Rational Choice in the Theory of Consumption' (presented at the First Stanford Symposium), 'Time Preference, the Consumption Function, and Optimum Asset Holdings', 'Neutral Inventions and the Stability of Growth Equilibrium', 'On a Two-Sector Model of Economic Growth', 'Time Preference and the Penrose Effect in a Two-Class Model of Economic Growth', and 'On the Economics of Social Overhead Capital'. The collection will be useful not only in understanding the nature of the development in economic theory today, but also in reflecting upon the direction toward which economic theory will be advancing in the future.
Local Analysis for the Odd Order Theorem
Authors: Bender Helmut , Glauberman George
Published: May 2010

In 1963 Walter Feit and John G. Thompson published a proof of a 1911 conjecture by Burnside that every finite group of odd order is solvable. This proof, which ran for 255 pages, was a tour-de-force of mathematics and inspired intense effort to classify finite simple groups. This book presents a revision and expansion of the first half of the proof of the Feit–Thompson theorem. Simpler, more detailed proofs are provided for some intermediate theorems. Recent results are used to shorten other proofs. The book will make the first half of this remarkable proof accessible to readers familiar with just the rudiments of group theory.
The Art of Euripides
Authors: Mastronarde Donald J.
Published: May 2010

In this book Professor Mastronarde draws on the seventeen surviving tragedies of Euripides, as well as the fragmentary remains of his lost plays, to explore key topics in the interpretation of the plays. It investigates their relation to the Greek poetic tradition and to the social and political structures of their original setting, aiming both to be attentive to the great variety of the corpus and to identify commonalities across it. In examining such topics as genre, structural strategies, the chorus, the gods, rhetoric, and the portrayal of women and men, this study highlights the ways in which audience responses are manipulated through the use of plot structures and the multiplicity of viewpoints expressed. It argues that the dramas of Euripides, through their dramatic technique, pose a strong challenge to simple formulations of norms, to the reading of consistent human character, and to the quest for certainty and closure.
The Decline of Sterling
Authors: Schenk Catherine R.
Published: May 2010

The demise of sterling as an international currency was widely predicted after 1945, but the process took thirty years to complete. Why was this demise so prolonged? Traditional explanations emphasize British efforts to prolong sterling's role because it increased the capacity to borrow, enhanced prestige, or supported London as a centre for international finance. This book challenges this view by arguing that sterling's international role was prolonged by the weakness of the international monetary system and by collective global interest in its continuation. Using the archives of Britain's partners in Europe, the USA and the Commonwealth, Catherine Schenk shows how the UK was able to convince other governments that sterling's international role was critical for the stability of the international economy and thereby attract considerable support to manage its retreat. This revised view has important implications for current debates over the future of the US dollar as an international currency.
Justifying Ballistic Missile Defence
Authors: Peoples Columba
Published: May 2010

Technology is championed as the solution to modern security problems, but also blamed as their cause. This book assesses the way in which these two views collide in the debate over ballistic missile defence: a complex, costly and controversial system intended to defend the United States from nuclear missile attacks. Columba Peoples shows how, in the face of strong scientific and strategic critique, advocates of missile defence seek to justify its development by reference to broader culturally embedded perceptions of the promises and perils of technological development. Unpacking the assumptions behind the justification of missile defence initiatives, both past and present, this book illustrates how common-sense understandings of technology are combined and used to legitimate this controversial and costly defence programme. In doing so it engages fundamental debates over understandings of technological development, human agency and the relationship between technology and security.
The Politics of Property Rights Institutions in Africa
Authors: Onoma Ato Kwamena
Published: May 2010

Why do some political leaders create and strengthen institutions like title registries and land tribunals that secure property rights to land while others neglect these institutions or destroy those that already exist? How do these institutions evolve once they have been established? This book answers these questions through spatial and temporal comparison of national and subnational cases from Botswana, Ghana, and Kenya and, to a lesser extent, Zimbabwe. Onoma argues that the level of property rights security that leaders prefer depends on how they use land. However, the extent to which leaders' institutional preferences are translated into actual institutions depends on the level of leaders' capacity. Further, once established, these institutions through their very working can contribute to their own decline over time. This book is unique in revealing the political and economic reasons why some leaders unlike others prefer an environment of insecure rights even as land prices increase.
Phases of Economic Growth, 1850–1973
Authors: Solomou Solomos
Published: May 2010

Solomos Solomou presents a clear and systematic examination of the evidence for long-term patterns of economic growth. Using data on Britain, France, Germany, the USA and the world economy between 1850 and 1973 he refutes the existence of long (Kondratieff) waves in the course of economic development. Instead he presents persuasive evidence for a growth pattern characterised by shock-induced, long-term variations in growth at the level of the world economy. The findings show that national patterns of growth did not necessarily coincide with those of the world economy, but followed episodic long swing fluctuations of twenty to thirty years before the Second World War and trend-accelerated growth in the post-war period. The author provides new historical perspectives on the pre-1913 era, the inter-war years and the post-war boom.
Multiple Forcing
Authors: Jech T.
Published: May 2010

In this 1987 text Professor Jech gives a unified treatment of the various forcing methods used in set theory, and presents their important applications. Product forcing, iterated forcing and proper forcing have proved powerful tools when studying the foundations of mathematics, for instance in consistency proofs. The book is based on graduate courses though some results are also included, making the book attractive to set theorists and logicians.
The River of Time
Authors: Novikov Igor D.
Published: May 2010

Can we change the past? The surprising answer to this question can be found in the final chapters of this book. Examining the history of the study of time and presenting in detail the modern state of physical research on the subject, this book is a superb overview of a fascinating subject. The figures who have helped to shape our views on time are presented as real people, in the context of their own times and struggles: from Socrates' troubles in Athens, to the experiences of physicists under the former Soviet Union. In addition Novikov details his own experiences with great Russian and Western physicists, such as Sakharov, Zeldovich, Rees and Hawking. Details of modern theories in fields such as the possibility of time machines, anomalous flows of time (at black or white holes) and the possible source of The River of Time are described with authority and clarity.
Teaching Large Multilevel Classes
Authors: Hess Natalie
Published: May 2010

This book provides practical advice for teachers who work with large, mixed-ability classes. It offers a wide variety of activities to develop student motivation, interest, participation and responsibility.
Rethinking Cambodian political discourse on territory: Genealogy of the Buddhist ritual boundary (sīmā)
Authors: Harris Ian
Published: May 2010

Despite their profound differences all of Cambodia's post-independence regimes have exhibited a unique obsession with protecting the country's borders from the depredations of neighbouring states. Some of this is fall-out from the colonial inheritance but this paper argues that older indigenous categories related to Theravada Buddhism have also played a significant role in the aetiology of modern Khmer territorialism. By showing how the traditional maṇḍala arrangement of space was being eroded at around the same time as the old monastic conception of a ritual boundary was purified, rationalised and extended under the influence of Buddhism modernism the author seeks to provide a Southeast Asian illustration of Carl Schmitt's insight that certain important elements of the modern state are, in fact, secularised religious concepts.
God's Kingdom on Earth? Politics of Islam in Pakistan, 1947–1969
Authors: QASMI ALI USMAN
Published: May 2010

This paper evaluates in detail the policies adopted and the religious ideas held by the power elite of Pakistan during the years from 1947 to 1969. It has been argued that the religious worldview of the power elite was shaped by the discourse of Islamic modernism which allowed envisioning of a state in which (at least theoretically) democracy, rights of minorities, sovereignty of the parliament and flexibility of Islamic laws could be propagated as the guiding principles of the state. Also, by focusing on the life and ideas of Ghulam Ahmad Parvez and by disclosing the details of his close connivance with General Ayyub Khan during the 1960s, the paper will highlight the steps taken to institutionalize Islamic modernism in Pakistan.
Bariatric surgery: a cost-effective intervention for morbid obesity; functional and nutritional outcomes
Authors: Welbourn Richard , Pournaras Dimitri
Published: May 2010

Obesity has been described as the health crisis of the 21st century. It is a chronic lifelong medical condition, whose pattern often starts in childhood, and is demographically worsening in every developed country. The cost of treating the many medical conditions associated with obesity threatens to overwhelm healthcare resources. Medical treatments produce at most no more than 10% weight loss in the severely obese, with high failure rates. In this article, we review the available evidence regarding long-term reduction in weight, reduced mortality and improvement in most, if not all, obesity-related comorbidities. There is a need for daily multivitamins and extra minerals, especially with gastric bypass, and nutritional deficiencies of vitamins D and B12, Ca, Fe and folate need monitoring and prevention. Currently there is no medical therapy on the near horizon that will match the effect of surgery, which, if done safely, remains the only effective therapy. Bariatric surgery is cost effective, and health providers should embrace the development and rapid expansion of services.
Economic collaboration of family members within and beyond households in English society, 1600–2000
Authors: WALL RICHARD
Published: May 2010

This article evaluates the extent of economic support provided by the family in English society. The first issue addressed is the importance given to relationships between family members both by contemporaries and by historians when attempting to distinguish different types of household. Following sections of the article discuss the role of households in redistributing income from the better-paid to the less well-paid or non-earners and the significance of economic support received from members of the family living elsewhere relative to that provided from within the household and from other outside sources, such as the community, employers and neighbours. A further section then assesses the impact of demographic change on the size and composition of the kin group and the extent to which population mobility made regular contact with close kin more difficult.
Early modern English kinship in the long run: reflections on continuity and change
Authors: TADMOR NAOMI
Published: May 2010

The article highlights the significance of alliances of blood and marriage in early modern England and beyond, including both positive and negative relations among kin. Examining different historiographical approaches, it emphasizes the role of kinship in explanations of historical change and continuity. Rather than focusing on the isolated nuclear family or, conversely, on an alleged decline of kinship, it highlights the importance of enmeshed patterns of kinship and connectedness. Such patterns were not only important in themselves (whether culturally, socially, economically, or politically), it is suggested, but they also invite new comparisons with other early modern societies, and in the long run. Even patterns typical of present-day ‘new families’ and ‘families of choice’, or aspects of the present-day language of kinship may bring to mind some similarities with notions of kinship and related ‘household-family’ ties characteristic of the early modern period, the article proposes.
Seeking connections between kinship and the law in early modern England
Authors: BONFIELD LLOYD
Published: May 2010

This article observes the ways in which the law mediated kinship relations in early modern England in three contexts: inheritance, marital property law, and provisions for the financially distressed. An enquiry into statutory law adopted during the period indicates that Parliament was not active in legislating in the area of family law. The courts, however, were actively involved in determining the validity of property settlements, thereby setting their temporal bounds. Both the jurisprudence and the settlements themselves illustrate that families became more interested in providing maintenance within the nuclear family (for children and widows) than they were in fostering patrilineal continuity. Likewise, an obligation to support financially needy kin was required from only a relatively small universe of family members.
Tuberculosis and the older patient
Authors: Haney S , Stenton SC
Published: May 2010

Tuberculosis (TB) rates in the UK have increased by about 25% over the last 20 years. About 12% of cases occur in those over 65. Their diagnosis and treatment is similar to that of younger patients, but their presentation is often atypical, diagnosis is often delayed, there is a higher frequency of treatment side-effects and there is greater potential for drug interactions. Mortality increases markedly with age and more than half of those aged 80 years or more die before completing treatment. About 75% of TB in older patients is due to reactivation of latent disease acquired in childhood. The risk of reactivation is particularly increased by human immunodeficiency virus (HIV) infection and anti-tumour necrosis factor (anti-TNF) medication. Active disease spreads by the inhalation of airborne droplets, particularly in enclosed environments such as nursing homes. Interferon gamma release assays (IGRAs) are an important new development in recognizing latent infection. They should allow better targeting of treatment in those with recently acquired infection, or who are at risk of reactivation. With appropriate effort it should be possible to substantially reduce TB rates to fewer than 1 per million per year, the current US target.
The Foundations of Morality
Authors: Warnock Mary
Published: May 2010

I might have entitled this lecture ‘The origins of morality’ or, ‘Where does morality come from?’. These titles sound vaguely historical, and would therefore have been misleading; whereas I suppose ‘The Foundations of Morality’ sounds in some sense analytic, and therefore more familiarly, perhaps painfully, philosophical. But I do not think that these different titles would mark a substantial difference in what I aim to explore, albeit superficially, in what follows. What interests me is the question how, or on what, is the moral sense of any individual founded?
Has Philosophy Made a Difference and Could it be Expected To?
Authors: Haldane John
Published: May 2010

In 1989 Oxford University Press launched a new programme of monographs in moral philosophy entitled the ‘Oxford Ethics Series’. Given that the series' editor is Derek Parfit it is unsurprising that the books published to date feature rigorous analysis and argumentation regarding the nature of reasons and requirements. Perhaps by way of intended commitment to this profile, the following brief statement appears on the cover of the first volume (Shelly Kagan'sThe Limits of Morality): ‘The books in the series will contain philosophical arguments about morality or rationality. The aim will be to make undeniable progress’.
The Future of Ideals
Authors: Skorupski John
Published: May 2010

The early part of the twentieth century was as revolutionary in the domain of ethical ideas as in other realms. An ethical culture inherited from the preceding century was to all appearance destroyed. This culture, the high-bourgeois culture of the nineteenth century, had emerged gradually from years of revolution and counter-revolution, and seemed then to be developing steadily and expanding its reach towards the end of the century and up to the first world war. Yet what followed it, and in fact overlapped with it, being already presaged well before the war, was quite other: the mainly 20th century phase we call ‘Modernism’, acutely fragmented not only in aesthetic but also in ethical terms, marked in politics by nationalist, collectivist and populist clashes. However, Modernism too, and in particular, many of the ideas in ethics which were characteristic of it, now belongs to history. That much has for some time been clear; the change is complicated, confused, hard to outline; discernibly though, we're in a new period and have been for perhaps a third of a century—quite how long depends on which aspect of change one considers, and on how one interprets its character.
Electr(on)ic palpitations: a visitors' pavilion for the Bieudron power plant, Switzerland
Authors: Guerreiro Nuno Mateus , Infantes Carlos , Jakob Michael
Published: May 2010

The electric power system has often been compared to a circulatory system, and telecommunication and informational complexes likened to nervous systems. Such characterisations are rigorous only for those aspects that bring the utility system closer to a living system: its mechanisms of control and regulation.
Moral theories, Homeric questions – and the shaft graves of Mycenae. A response
Authors: Voutsaki Sofia
Published: May 2010

I would like to thank Silvia Tomášková, Christoph Ulf and James Wright for their comments, which allow me to clarify and expand my argument. As I cannot address all the points they raise in this response, I have decided to concentrate on three themes: (i) the application of moral theory, (ii) Homeric questions and (iii) the focus on the shaft graves of Mycenae.
Encapsulated activated charcoal as a potent agent for improving taxane synthesis and recovery from cultures
Authors: Kajani Abolghasem Abbasi , Mofid Mohammad Reza , Abolfazli Kambiz , Tafreshi Sayed Ali Hosseini
Published: May 2010

The ability of a potent hydrophobic adsorbent, AC (activated charcoal), to induce total taxane synthesis and to improve the recovery of the products from suspension culture of Taxus baccata L. was examined. The results strongly showed that the application of encapsulated AC as an adsorbent not only led to improvement of in situ recover but also led to enhancement in taxane synthesis within the cells as well as having no inhibitory effects on the cell growth. The maximum yields for 10‐deacetyl baccatin III, baccatin III and taxol were achieved by adding 1 g·l−1 adsorbent as alginate beads to the culture and culturing for 21 days and these were 3.5‐, 4‐ and 2‐fold respectively of that for the control. We demonstrated that the late exponential phase of the cell growth (day 14) could be the best time to add the adsorbent for maximizing the yield of taxol. Adding 1 g·l−1 AC resulted in maximum extracellular taxol (5.584 mg·l−1); this value was 2.19‐fold higher than that in the control. According to the present results, AC is a powerful adsorbent that efficiently adsorbs the taxane compounds from a medium. We suggested that encapsulated AC could be used as a promising adsorbent agent for large‐scale taxane production when it is added in combination with proper elicitors.
Oct-4B isoform is differentially expressed in breast cancer cells: hypermethylation of regulatory elements of Oct-4A suggests an alternative promoter and transcriptional start site for Oct-4B transcription
Authors: Wang Yajuan , Meng Lu , Hu Hongyu , Zhang Ying , Zhao Chenfu , Li Qianqian , Shi Fangyu , Wang Xudong , Lin Aixing
Published: May 2010

The human Oct-4 gene has three isoforms, Oct-4A, Oct-4B and Oct-4B1, which are thought to be derived from alternative splicing. It remains controversial whether the Oct-4 gene is expressed in cancer cells. Expression of Oct-4A is regulated by two elements, the PE (proximal enhancer) and DE (distal enhancer), but the expression and regulation of Oct-4B are not well known. Here, we firstly report that Oct-4B is expressed at low levels in MCF-7 cells, while the Oct-4A gene is inactivated. By analysing the function of different promoter constructs and the DNA methylation status of three regulatory regions, we demonstrate that the Oct-4A gene in MCF-7 cells is repressed by epigenetic control rather than transcriptional control. In addition, we speculate that the transcription of Oct-4B in MCF-7 cells is differentially regulated by additional regulatory elements. This work will enhance the understanding of Oct-4 gene in differential regulation.
Ecological Modernisation and the Scalar Level of Contradictions in Southern European Water Politics: The Case of the Odelouca Dam in Portugal
Authors: Thiel Andreas
Published: May 2010

The author reconstructs the history of the implementation of the Odelouca Dam in the Algarve in a Natura 2000 area, viewing it in the context of Southern European coastal development. He looks at the dynamics leading up to the construction of the dam, and illustrates the persistence of the hydraulic paradigm in Portugal and the way it has been moulded by shifting European policymaking paradigms—namely, ecological modernisation (EM). Political aspects of EM are discussed because they seem to play an important role in legitimising the construction of the dam at a European level. The author assesses the policy measures and the policy outcome of the policy package associated with the Odelouca Dam and discusses whether EM in this case can be considered to have reached the stage of ecological structural policy. At the systemic level, the analysis shows deliberate, symbolic, and unintended policy contradictions. Assessment of EM policies requires careful attention to the scale of assessment, as partial EM runs the risk of contributing to aggravating overall resource pressure, as the case study illustrates. The Portuguese National Water Authority is the dominant actor in the implementation of the dam. The European Union's Regional Funding facilitated its construction, and European environmental policy provided checks and balances that were exploited by environmental NGOs. Nevertheless, the key to success of the EM—to turn around resource-use patterns in the long run—lies with national actors. In the case of the Algarve, they seem to have failed.
Magnetic field changes activate the trigeminal brainstem complex in a migratory bird
Authors: Heyers Dominik , Zapka Manuela , Hoffmeister Mara , Wild John Martin , Mouritsen Henrik
Published: May 2010

The upper beak of birds, which contains putative magnetosensory ferro-magnetic structures, is innervated by the ophthalmic branch of the trigeminal nerve (V1). However, because of the absence of replicable neurobiological evidence, a general acceptance of the involvement of the trigeminal nerve in magnetoreception is lacking in birds. Using an antibody to ZENK protein to indicate neuronal activation, we here document reliable magnetic activation of neurons in and near the principal (PrV) and spinal tract (SpV) nuclei of the trigeminal brainstem complex, which represent the two brain regions known to receive primary input from the trigeminal nerve. Significantly more neurons were activated in PrV and in medial SpV when European robins (
Erithacus rubecula
) experienced a magnetic field changing every 30 seconds for a period of 3 h (CMF) than when robins experienced a compensated, zero magnetic field condition (ZMF). No such differences in numbers of activated neurons were found in comparison structures. Under CMF conditions, sectioning of V1 significantly reduced the number of activated neurons in and near PrV and medial SpV, but not in lateral SpV or in the optic tectum. Tract tracing of V1 showed spatial proximity and regional overlap of V1 nerve endings and ZENK-positive (activated) neurons in SpV, and partly in PrV, under CMF conditions. Together, these results suggest that magnetic field changes activate neurons in and near the trigeminal brainstem complex and that V1 is necessary for this activation. We therefore suggest that V1 transmits magnetic information to the brain in this migratory passerine bird.
Pleistocene to historic shifts in bald eagle diets on the Channel Islands, California
Authors: Newsome Seth D. , Collins Paul W. , Rick Torben C. , Guthrie Daniel A. , Erlandson Jon M. , Fogel Marilyn L.
Published: May 2010

Studies of current interactions among species, their prey, and environmental factors are essential for mitigating immediate threats to population viability, but the true range of behavioral and ecological flexibility can be determined only through research on deeper timescales. Ecological data spanning centuries to millennia provide important contextual information for long-term management strategies, especially for species that now are living in relict populations. Here we use a variety of methods to reconstruct bald eagle diets and local abundance of their potential prey on the Channel Islands from the late Pleistocene to the time when the last breeding pairs disappeared from the islands in the mid-20th century. Faunal and isotopic analysis of bald eagles shows that seabirds were important prey for immature/adult eagles for millennia before the eagles’ local extirpation. In historic times (A.D. 1850–1950), however, isotopic and faunal data show that breeding bald eagles provisioned their chicks with introduced ungulates (e.g., sheep), which were locally present in high densities. Today, bald eagles are the focus of an extensive conservation program designed to restore a stable breeding population to the Channel Islands, but native and nonnative prey sources that were important for bald eagles in the past are either diminished (e.g., seabirds) or have been eradicated (e.g., introduced ungulates). In the absence of sufficient resources, a growing bald eagle population on the Channel Islands could expand its prey base to include carrion from local pinniped colonies, exert predation pressure on a recovering seabird population, and possibly prey on endangered island foxes.
Kif26b
, a kinesin family gene, regulates adhesion of the embryonic kidney mesenchyme
Authors: Uchiyama Yukako , Sakaguchi Masaji , Terabayashi Takeshi , Inenaga Toshiaki , Inoue Shuji , Kobayashi Chiyoko , Oshima Naoko , Kiyonari Hiroshi , Nakagata Naomi , Sato Yuya , Sekiguchi Kiyotoshi , Miki Hiroaki , Araki Eiichi , Fujimura Sayoko , Tanaka Satomi S. , Nishinakamura Ryuichi
Published: May 2010

The kidney develops through reciprocal interactions between two precursor tissues: the metanephric mesenchyme and the ureteric bud. We previously demonstrated that the zinc finger protein Sall1 is essential for ureteric bud attraction toward the mesenchyme. Here, we show that
Kif26b
, a kinesin family gene, is a downstream target of
Sall1
and that disruption of this gene causes kidney agenesis because of impaired ureteric bud attraction. In the
Kif26b
-null metanephros, compact adhesion between mesenchymal cells adjacent to the ureteric buds and the polarized distribution of integrin α8 were impaired, resulting in failed maintenance of
Gdnf
, a critical ureteric bud attractant. Overexpression of Kif26b in vitro caused increased cell adhesion through interactions with nonmuscle myosin. Thus, Kif26b is essential for kidney development because it regulates the adhesion of mesenchymal cells in contact with ureteric buds.
C/EBPδ targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression
Authors: Pawar Snehalata A. , Sarkar Tapasree Roy , Balamurugan Kuppusamy , Sharan Shikha , Wang Jun , Zhang Youhong , Dowdy Steven F. , Huang A-Mei , Sterneck Esta
Published: May 2010

The transcription factor CCAAT/enhancer binding protein δ (C/EBPδ, CEBPD, NFIL-6β) has tumor suppressor function; however, the molecular mechanism(s) by which C/EBPδ exerts its effect are largely unknown. Here, we report that C/EBPδ induces expression of the Cdc27 (APC3) subunit of the anaphase promoting complex/cyclosome (APC/C), which results in the polyubiquitination and degradation of the prooncogenic cell cycle regulator cyclin D1, and also down-regulates cyclin B1, Skp2, and Plk-1. In C/EBPδ knockout mouse embryo fibroblasts (MEF) Cdc27 levels were reduced, whereas cyclin D1 levels were increased even in the presence of activated GSK-3β. Silencing of C/EBPδ, Cdc27, or the APC/C coactivator Cdh1 (FZR1) in MCF-10A breast epithelial cells increased cyclin D1 protein expression. Like C/EBPδ, and in contrast to cyclin D1, Cdc27 was down-regulated in several breast cancer cell lines, suggesting that Cdc27 itself may be a tumor suppressor. Cyclin D1 is a known substrate of polyubiquitination complex SKP1/CUL1/F-box (SCF), and our studies show that Cdc27 directs cyclin D1 to alternative degradation by APC/C. These findings shed light on the role and regulation of APC/C, which is critical for most cellular processes.
Cotranslational structure acquisition of nascent polypeptides monitored by NMR spectroscopy
Authors: Eichmann Cédric , Preissler Steffen , Riek Roland , Deuerling Elke
Published: May 2010

The folding of proteins in living cells may start during their synthesis when the polypeptides emerge gradually at the ribosomal exit tunnel. However, our current understanding of cotranslational folding processes at the atomic level is limited. We employed NMR spectroscopy to monitor the conformation of the SH3 domain from α-spectrin at sequential stages of elongation via in vivo ribosome-arrested
15
N,
13
C-labeled nascent polypeptides. These nascent chains exposed either the entire SH3 domain or C-terminally truncated segments thereof, thus providing snapshots of the translation process. We show that nascent SH3 polypeptides remain unstructured during elongation but fold into a compact, native-like
β
-sheet assembly when the entire sequence information is available. Moreover, the ribosome neither imposes major conformational constraints nor significantly interacts with exposed unfolded nascent SH3 domain moieties. Our data provide evidence for a domainwise folding of the SH3 domain on ribosomes without significant population of folding intermediates. The domain follows a thermodynamically favorable pathway in which sequential folding units are stabilized, thus avoiding kinetic traps during the process of cotranslational folding.
Brain diversity evolves via differences in patterning
Authors: Sylvester Jonathan B. , Rich Constance A. , Loh Yong-Hwee E. , van Staaden Moira J. , Fraser Gareth J. , Streelman J. Todd
Published: May 2010

Differences in brain region size among species are thought to arise late in development via adaptive control over neurogenesis, as cells of previously patterned compartments proliferate, die, and/or differentiate into neurons. Here we investigate comparative brain development in ecologically distinct cichlid fishes from Lake Malawi and demonstrate that brains vary among recently evolved lineages because of early patterning. Divergence among rock-dwellers and sand-dwellers in the relative size of the telencephalon versus the thalamus is correlated with gene expression variation in a regulatory circuit (composed of
six3
,
fezf2
,
shh
,
irx1b
, and
wnt1
) known from model organisms to specify anterior-posterior (AP) brain polarity and position the
shh
-positive signaling boundary zona limitans intrathalamica (ZLI) in the forebrain. To confirm that changes in this coexpression network are sufficient to produce the differences we observe, we manipulated WNT signaling in vivo by treating rock-dwelling cichlid embryos with temporally precise doses of LiCl. Chemically treated rock-dwellers develop gene expression patterns, ZLIs, and forebrains distinct from controls and untreated conspecifics, but strongly resembling those of sand-dwellers. Notably, endemic Malawi rock- and sand-dwelling lineages are alternately fixed for an SNP in
irx1b
, a mediator of WNT signaling required for proper thalamus and ZLI. Together, these natural experiments in neuroanatomy, development, and genomics suggest that evolutionary changes in AP patterning establish ecologically relevant differences in the elaboration of cichlid forebrain compartments. In general, variation in developmental patterning might lay the foundations on which neurogenesis erects diverse brain architectures.
Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for
Mycobacterium tuberculosis
to establish and maintain infection
Authors: Marrero Joeli , Rhee Kyu Y. , Schnappinger Dirk , Pethe Kevin , Ehrt Sabine
Published: May 2010

Metabolic adaptation to the host niche is a defining feature of the pathogenicity of
Mycobacterium tuberculosis (Mtb)
. In vitro,
Mtb
is able to grow on a variety of carbon sources, but mounting evidence has implicated fatty acids as the major source of carbon and energy for
Mtb
during infection. When bacterial metabolism is primarily fueled by fatty acids, biosynthesis of sugars from intermediates of the tricarboxylic acid cycle is essential for growth. The role of gluconeogenesis in the pathogenesis of
Mtb
however remains unaddressed. Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the first committed step of gluconeogenesis. We applied genetic analyses and
13
C carbon tracing to confirm that PEPCK is essential for growth of
Mtb
on fatty acids and catalyzes carbon flow from tricarboxylic acid cycle–derived metabolites to gluconeogenic intermediates. We further show that PEPCK is required for growth of
Mtb
in isolated bone marrow–derived murine macrophages and in mice. Importantly,
Mtb
lacking PEPCK not only failed to replicate in mouse lungs but also failed to survive, and PEPCK depletion during the chronic phase of infection resulted in mycobacterial clearance.
Mtb
thus relies on gluconeogenesis throughout the infection. PEPCK depletion also attenuated
Mtb
in IFNγ-deficient mice, suggesting that this enzyme represents an attractive target for chemotherapy.
Core 1-derived O-glycans are essential E-selectin ligands on neutrophils
Authors: Yago Tadayuki , Fu Jianxin , McDaniel J. Michael , Miner Jonathan J. , McEver Rodger P. , Xia Lijun
Published: May 2010

Neutrophils roll on E-selectin in inflamed venules through interactions with cell-surface glycoconjugates. The identification of physiologic E-selectin ligands on neutrophils has been elusive. Current evidence suggests that P-selectin glycoprotein ligand-1 (PSGL-1), E-selectin ligand-1 (ESL-1), and CD44 encompass all glycoprotein ligands for E-selectin; that ESL-1 and CD44 use N-glycans to bind to E-selectin; and that neutrophils lacking core 2 O-glycans have partially defective interactions with E-selectin. These data imply that N-glycans on ESL-1 and CD44 and O-glycans on PSGL-1 constitute all E-selectin ligands, with neither glycan subset having a dominant role. The enzyme T-synthase transfers Gal to GalNAcα1-Ser/Thr to form the core 1 structure Galβ1–3GalNAcα1-Ser/Thr, a precursor for core 2 and extended core 1 O-glycans that might serve as selectin ligands. Here, using mice lacking T-synthase in endothelial and hematopoietic cells, we found that E-selectin bound to CD44 and ESL-1 in lysates of T-synthase–deficient neutrophils. However, the cells exhibited markedly impaired rolling on E-selectin in vitro and in vivo, failed to activate β2 integrins while rolling, and did not emigrate into inflamed tissues. These defects were more severe than those of neutrophils lacking PSGL-1, CD44, and the mucin CD43. Our results demonstrate that core 1-derived O-glycans are essential E-selectin ligands; that some of these O-glycans are on protein(s) other than PSGL-1, CD44, and CD43; and that PSGL-1, CD44, and ESL-1 do not constitute all glycoprotein ligands for E-selectin.
Recombinant yeast screen for new inhibitors of human acetyl-CoA carboxylase 2 identifies potential drugs to treat obesity
Authors: Marjanovic Jasmina , Chalupska Dominika , Patenode Caroline , Coster Adam , Arnold Evan , Ye Alice , Anesi George , Lu Ying , Okun Ilya , Tkachenko Sergey , Haselkorn Robert , Gornicki Piotr
Published: May 2010

Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism with multiple isozymes often expressed in different eukaryotic cellular compartments. ACC-made malonyl-CoA serves as a precursor for fatty acids; it also regulates fatty acid oxidation and feeding behavior in animals. ACC provides an important target for new drugs to treat human diseases. We have developed an inexpensive nonradioactive high-throughput screening system to identify new ACC inhibitors. The screen uses yeast gene-replacement strains depending for growth on cloned human ACC1 and ACC2. In “proof of concept” experiments, growth of such strains was inhibited by compounds known to target human ACCs. The screen is sensitive and robust. Medium-size chemical libraries yielded new specific inhibitors of human ACC2. The target of the best of these inhibitors was confirmed with in vitro enzymatic assays. This compound is a new drug chemotype inhibiting human ACC2 with 2.8 μM IC
50
and having no effect on human ACC1 at 100 μM.
Vaccinia virus strains use distinct forms of macropinocytosis for host-cell entry
Authors: Mercer Jason , Knébel Stephan , Schmidt Florian I. , Crouse Josh , Burkard Christine , Helenius Ari
Published: May 2010

To enter host cells, vaccinia virus, a prototype poxvirus, can induce transient macropinocytosis followed by endocytic internalization and penetration through the limiting membrane of pinosomes by membrane fusion. Although mature virions (MVs) of the Western reserve (WR) strain do this in HeLa cells by activating transient plasma membrane blebbing, MVs from the International Health Department-J strain were found to induce rapid formation (and lengthening) of filopodia. When the signaling pathways underlying these responses were compared, differences were observed at the level of Rho GTPases. Key to the filopodial formation was the virus-induced activation of Cdc42, and for the blebbing response the activation of Rac1. In addition, unlike WR, International Health Department-J MVs did not rely on genistein-sensitive tyrosine kinase and PI(3)K activities. Only WR MVs had membrane fusion activity at low pH. Inhibitor profiling showed that MVs from both strains entered cells by macropinocytosis and that this was induced by virion-exposed phosphatidylserine. Both MVs relied on the activation of epidermal growth factor receptor, on serine/threonine kinases, protein kinase C, and p21-activated kinase 1. The results showed that different strains of the same virus can elicit dramatically different responses in host cells during entry, and that different macropinocytic mechanisms are possible in the same cell line through subtle differences in the activating ligand.
Stochastic and reversible assembly of a multiprotein DNA repair complex ensures accurate target site recognition and efficient repair
Authors: Luijsterburg Martijn S. , von Bornstaedt Gesa , Gourdin Audrey M. , Politi Antonio Z. , Moné Martijn J. , Warmerdam Daniël O. , Goedhart Joachim , Vermeulen Wim , van Driel Roel , Höfer Thomas
Published: May 2010

To understand how multiprotein complexes assemble and function on chromatin, we combined quantitative analysis of the mammalian nucleotide excision DNA repair (NER) machinery in living cells with computational modeling. We found that individual NER components exchange within tens of seconds between the bound state in repair complexes and the diffusive state in the nucleoplasm, whereas their net accumulation at repair sites evolves over several hours. Based on these in vivo data, we developed a predictive kinetic model for the assembly and function of repair complexes. DNA repair is orchestrated by the interplay of reversible protein-binding events and progressive enzymatic modifications of the chromatin substrate. We demonstrate that faithful recognition of DNA lesions is time consuming, whereas subsequently, repair complexes form rapidly through random and reversible assembly of NER proteins. Our kinetic analysis of the NER system reveals a fundamental conflict between specificity and efficiency of chromatin-associated protein machineries and shows how a trade off is negotiated through reversibility of protein binding.
Lack of Apobec2-related proteins causes a dystrophic muscle phenotype in zebrafish embryos
Authors: Etard Christelle , Roostalu Urmas , Strähle Uwe
Published: May 2010

The chaperones Unc45b and Hsp90a are essential for folding of myosin in organisms ranging from worms to humans. We show here that zebrafish Unc45b, but not Hsp90a, binds to the putative cytidine deaminase Apobec2 (Apo2) in an interaction that requires the Unc45/Cro1p/She4p-related (UCS) and central domains of Unc45b. Morpholino oligonucleotide-mediated knockdown of the two related proteins Apo2a and Apo2b causes a dystrophic phenotype in the zebrafish skeletal musculature and impairs heart function. These phenotypic traits are shared with mutants of unc45b, but not with hsp90a mutants. Apo2a and -2b act nonredundantly and bind to each other in vitro, which suggests a heteromeric functional complex. Our results demonstrate that Unc45b and Apo2 proteins act in a Hsp90a-independent pathway that is required for integrity of the myosepta and myofiber attachment. Because the only known function of Unc45b is that of a chaperone, Apo2 proteins may be clients of Unc45b but other yet unidentified processes cannot be excluded.