bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating RD Policies for Social and Human Capital Development L’évaluation de la politique de développement rural en termes de développement du capital social et humain Die Evaluation von Politikmaßnahmen zur Entwicklung des ländlichen Raums zur Entwicklung von Sozial‐ und Humankapital
Authors: Kinsella Jim , Goetz Stephan J. , Partridge Mark D. , Deller Steven C. , Fleming David
Published: April 2010

Evaluating RD Policies for Social and Human Capital Development

In the EU, building social capital and developing human capital are increasingly seen as key to development in rural areas. Social capital is fundamentally about human interrelationships and networks. Evaluation of policy initiatives to promote social capital needs to go beyond indicators of conventional economic outcome measures such as jobs created and income generated and to encompass growth in the processes by which social capital works. Human capital in the form of education and skills possessed by individuals is linked with productivity and incomes. In the US, federal funding of human capital formation in support of rural entrepreneurship has been limited, fragmented and uncoordinated but activities in this area hold promise. The evaluation of entrepreneurial programmes needs to overcome many statistical problems such as selection bias regarding which firms received ‘treatment’ and how to identify causality. In particular there is a lack of indicators on the returns to investment in entrepreneurship. While the two case studies face their own sets of particular problems, they share the characteristic of a lack of data on relevant indicators that evaluators need in order to reach sound judgements. This points to the importance to evaluation of the design of the rural data system and scheme monitoring mechanisms.
Model‐Based Evaluation of Rural Development Policies L’évaluation de la politique de développement rural à partir de modèles Modellgestützte Evaluation von Politikmaßnahmen zur Entwicklung des ländlichen Raums
Authors: Johnson Thomas G. , Roberts Deborah , Wojan Timothy R.
Published: April 2010

Model‐Based Evaluation of Rural Development Policies

A primary concern in rural development policy is the impact of government expenditures on economic growth, income and employment. The Socio‐Economic Benefit Assessment System (SEBAS) model developed through academic/government collaboration in the United States is an example of a practical tool for assessing the impact of federal programmes on these key development indicators. The model is based on an interregional social accounting matrix (SAM) and estimates the location and impact (including displacement effects) of economic initiatives. It has been used to examine the impact of loans and grants programmes and rural energy projects on regional value‐added (GDP) and the quantity and quality of employment. Although the challenges of using model‐based assessment are greater in the European Union due to data deficiencies and a complex rural development policy framework, considerable potential exists for deepening understanding of the effectiveness of policy measures, particularly in terms of region‐specific impacts. Results obtained through modelling approaches such as computable general equilibrium (CGE) models, suggest that the impacts of programmes can be smaller than traditionally assumed and that there can also be important re‐distributional effects. There are strong arguments for making modelling a key element in a broad evaluation of rural development policy.
Evaluation of Rural Development Requires Clarity on Expected Outcomes L’évaluation du développement rural demande à ce que les résultats attendus soient clairement identifiés Die Evaluation der Entwicklung des ländlichen Raums erfordert Klarheit hinsichtlich der erwarteten Ergebnisse
Authors: Wakeford Richard
Published: April 2010

Evaluation of Rural Development Requires Clarity on Expected Outcomes

Without good evaluation, we deny ourselves the evidence that should influence choices of policy instrument in the future. Evaluation of rural development is complex. The crucial thing is to be absolutely clear about the outcome you want before starting the project. For a building, defining desired outcomes is not too difficult if the architect and partners in development work properly with the client from the start. Evaluation of whether society is achieving sustainable development is pretty near impossible, given so many competing views of what success might look like in terms of outcomes. Evaluation of rural development policy falls somewhere between these two extremes. The suspicion is that, despite Regulations agreed at Council level, the EU’s 27 ‘Rural Development’ Ministers would not reveal much consensus about the desired outcomes of the EU’s rural development policy. Ministers and officials may find it hard to bring themselves to do evaluation as it may show that their policies haven’t delivered. Nevertheless, useful evaluation can take place. It has to face a series of technical issues, such as ‘Should the evaluation be of individual programmes or combinations of programmes’. It also has to respect certain principles, such as the ‘arms length’ status of the evaluator.
The Evaluation of Rural Development Policy: Macro and Micro Perspectives L’évaluation de la politique de développement rural: perspectives macro et microéconomiques Die Evaluation der Politik zur Entwicklung des ländlichen Raums: Mikro‐ und Makroperspektiven
Authors: Midmore Peter , Partridge Mark D. , Rose Olfert M. , Ali Kamar
Published: April 2010

The Evaluation of Rural Development Policy: Macro and Micro Perspectives

Effective rural development (RD) policy requires transparent goals, specific objectives, well‐defined metrics to measure success, and rigorous evaluation to justify sound policy. Such evaluation can employ aggregate indicators of impact (a macro approach) and/or more disaggregated information (a micro approach). Each has its place. Changes in population and population structure provide a key macro indicator of the success of rural development policy, since individuals reveal the attractiveness of rural areas by ‘voting with their feet’. By using additional data on the factors that attract people to rural areas, the targeting of rural development policy can be improved. Policymakers frequently need to examine specific policy initiatives in detail to determine their impact, if any, and how and why they achieve their effects. The example of farm diversification policy in the EU illustrates that information obtained from case studies can help not only to elaborate the impact of policy but also illuminate how that impact is generated. Without complementary in‐depth inquiry, scope for making sense of quantitative indicators, which have been the primary focus of evaluation in the EU, is limited; but without a broad base of measurement, the usefulness of insights derived from case study analysis is also restricted.
Eat Local? Constructions of Place in Alternative Food Politics
Authors: Harris Edmund M.
Published: April 2010

In recent years those seeking alternatives to industrialized and globalized food systems have looked beyond organic production to develop a range of alternative food networks (AFNs). Alongside these developments in sustainable food and agriculture activism, a body of literature has emerged in rural sociology, agri‐food studies and human geography exploring the development of alternative food networks. This article explores some potential synergies between this literature and geographical theory surrounding space and place. Place has been identified as central to AFN discourse and efforts to localize food systems, and while the benefits of localized food systems can be accepted uncritically by activist communities and the media, important questions have been raised about the reflexivity of local food activism. This article argues that a closer engagement with place theory would help avoid the fetishized constructions of the local often present in alternative food politics. Drawing on geographical debates about place, this article demonstrates the ways in which geographical place theory could inform and develop literatures examining alternative food politics.
Tourism and Entrepreneurialism in Southeast Asian Cities
Authors: Gillen Jamie
Published: April 2010

This study reviews recent literatures related to entrepreneurship in the Southeast Asian urban tourism sector. The study is divided into three sections. The first section concerns urban identity. I outline recent debates surrounding the disparity between tourist stereotypes of the region’s cities and discursive attempts by the local governments to counter them. I argue that the twin themes of harmony and convergence are used by Southeast Asia’s urban governments to promote their cities as appealing, safe, and multicultural places to visit. In the second section, I present an alternative approach to traditional understandings of state–society relations in the region. Instead of explaining local resistances to a predatory state, I highlight recent research that favors a relational, cooperative reading of the production of the tourism industry in Southeast Asia. Lastly, I introduce the political implications for urban tourism growth, focusing on the desires of the Southeast Asian urban population to use tourism as a tool to expedite their political goals.
Evaluating Human Exposure to Fine Particulate Matter Part I: Measurements
Authors: Millar Gail , Abel Tyler , Allen Janice , Barn Prabjit , Noullett Melanie , Spagnol John , Jackson Peter L.
Published: April 2010

Exposure to airborne fine particulate matter has been a pressing issue since the early 1990s when several studies reported health effects at unexpectedly low ambient levels. Since this time, several reviews have addressed various aspects of this topic. This article is the first of a two‐part review of reviews. The intention of these articles is to provide a consolidated overview about fine particulate matter exposure assessment. This article, Part I, begins with a general introduction to particulate matter which includes general properties of particulate matter, how it is classified and how it is associated with health effects. Fundamental concepts related to exposure are also summarized. The remainder of the article focuses on measurement‐based methods for assessing exposure to fine particulate matter. A subsequent article, Part II, addresses modeling approaches used for particulate matter exposure assessment. Current and recommended future directions for assessing exposure to fine particulate matter are also summarized in each of these two articles.
Racism without Races: Reflections on Racialization and Racial Projects
Authors: Baber Zaheer
Published: April 2010

‘The metaphor of race is a dangerous weapon whether it is used for asserting white supremacy or for making demands on behalf of the disadvantaged groups...Treating caste as a form of race is politically mischievous; what is worse, it is scientifically nonsensical’. Andre Beteille (2004: 52)

‘…what is in fact “scientifically nonsensical” is Professor Beteille’s misunderstanding of “race”. What is mischievous is his insistence that India’s system of ascribed system of social inequality should be exempted from the provisions of a UN Convention whose sole purpose is the extension of human rights to include freedom from all forms of discrimination and intolerance – and to which India, along with most other nations, has committed itself” Gerald Berreman (cited in Thorat and Umakant 2004: xxv)

‘The possibility that the current Indian Hindu‐Muslim or upper versus lower‐caste conflict may be, in a significant sense, a variant of a modern problem of “ethnicity” or “race” is seldom entertained…”racism” is thought of as something the white people do to us. What Indians do to one another are variously described as “communalism”, “regionalism” and “casteism” but never “racism”’. Dipesh Chakrabarty (1994: 145)
World Culture and Transnational Economic Governance: Theory and Evidence
Authors: Major Aaron
Published: April 2010

The current global financial crisis has led to renewed efforts to strengthen the formal rules and organizations of transnational economic governance. A substantial body of research in sociology and related fields suggests that the informal norms, values, expectations, and ideas that make up a world culture are equally important for understanding why countries cooperate, and why those cooperative efforts sometimes fail. This article explores these insights, showing how they can be applied to current debates about transnational economic governance, by paying particular attention to the emergence, adoption, and evolution of the Basel Capital Accords.
Unbelievable Thoughts and Doxastic Oughts
Authors: PODLASKOWSKI ADAM C.
Published: April 2010

From the dictum ought implies can, it has been argued that no account of belief's normativity can avoid the unpalatable result that, for unbelievable propositions such as “It is raining and nobody believes that it is raining”, one ought not to believe them even if true. In this article, I argue that this move only succeeds on a faulty assumption about the conjunction of doxastic “oughts.”
Parity Demystified
Authors: CARLSON ERIK
Published: April 2010

Ruth Chang has defended a concept of “parity”, implying that two items may be evaluatively comparable even though neither item is better than or equally good as the other. This article takes no stand on whether there actually are cases of parity. Its aim is only to make the hitherto somewhat obscure notion of parity more precise, by defining it in terms of the standard value relations. Given certain plausible assumptions, the suggested definiens is shown to state a necessary and sufficient condition for parity, as this relation is envisaged by Chang.
The Moderate Communitarian Individual and the Primacy of Duties
Authors: FAMAKINWA J.O.
Published: April 2010

Gyekye argues for the moral supremacy of certain duties. The individual is, as a natural member of the cultural community, morally obligated to respect community values; co‐operate with fellow community members, be sensitive to the economic plight of others and morally expected to respect the elderly. Though Gyekye recognizes the moral need to respect certain individual rights, in the case of a moral clash between those rights and the values cherished by the community, the latter must be upheld. I wish to critically examine the arguments in support of this position. Contrary to Gyekye's view, I argue that the natural interpersonal bond among members of the same cultural community does not strongly support some of the duties mentioned. However, I am not arguing that the individual person is not morally obligated to the cultural community at all. I argue that natural membership of the cultural community could be a necessary condition for the justification of certain duties; it is not, morally, a sufficient condition.
Answerable to the World: Experience and Practical Intentionality in Brandom's and McDowell's “Intramural” Debate
Authors: HENDLEY STEVEN
Published: April 2010

Robert Brandom and John McDowell pursue similar, yet strikingly different approaches to a shared problem: that of how we can be answerable to the world in our beliefs about it in the wake of Sellars' critique of the myth of the given. While McDowell attempts to rehabilitate the idea that experience is capable of providing justifications for our beliefs, Brandom constructs a sophisticated social‐pragmatist account of the objectivity of our conceptual commitments in which experience is, as he says, not one of his words. In this article, I argue that McDowell is right in stressing the indispensability of the idea of experience, but that he is wrong in believing that Brandom lacks the resources for making sense of the idea of being answerable to the world in experience. Especially when we expand Brandom's account of discursive practice to include its relation to what he has called practical intentionality, his work provides the resources for an answer to McDowell's concerns, but only if it is understood not as an attempt to simply deny McDowell's claims about experience, but as an attempt to explain what we must be capable of doing in order for experience, in McDowell's sense, to be possible.
Technicity of the Body as Part of the Socio‐technical System: the Contributions of Mauss and Bourdieu
Authors: WOLFF ERNST
Published: April 2010

The aim of this article is to contribute to a philosophy of technics by proposing an answer to the following question: what is the nature of the human body as an element of technical systems? The argument focuses on an examination of the phenomenon of bodily technics. This examination is guided by the conviction that Pierre Bourdieu's social theory can be read as contributing significantly to an answer to the above question. However, since Bourdieu's project is not directly aimed at enhancing our understanding of the technicity of the human body, a reading of Marcel Mauss's seminal essay on bodily technics is also discussed to set the stage for an examination of the technicity of the body and to justify the manner in which Bourdieu's theory is read here. Through a careful study of the key notions of habitus, field, practice, time and rule, Bourdieu's social theory is systematically presented and explored for its contribution to an understanding of the question raised in this article. In conclusion, a number of remarks are made on how the relation between Mauss and Bourdieu is to be understood and on the argumentative strength of Bourdieu's work.
Partitioning of Histone H3-H4 Tetramers During DNA Replication–Dependent Chromatin Assembly
Authors: Xu Mo , Long Chengzu , Chen Xiuzhen , Huang Chang , Chen She , Zhu Bing
Published: April 2010

Histone Inheritance

Chromatin, the packaging material for eukaryotic genomes, is a potential repository for epigenetic information. The core structure of chromatin is the nucleosome, which consists of an octamer of histone proteins, two dimers each of histones H2A and H2B, and histones 3 and 4. Histones 3 and 4, in particular, carry a series of covalent modifications presumed to be passed on through cell division. Using mass spectrometry of tagged and isotope labeled histones,

Xu
et al.

(p.
94
; see the Perspective by

Ray-Gallet and Almouzni

) followed the inheritance of the histones themselves through mitosis. The H2A-H2B dimers were inherited randomly through cell division, correlating with their lack of major covalent marks. In comparison, replication-deposited H3.1-H4 dimers did not separate through cell division, implying that H3 and H4 histone modifications might be maintained by copying from neighboring preexisting histones. Intriguingly, up to one-quarter of the nonreplication-deposited H3.3-H4 dimers, which mark active chromatin, did split during cell division.
Evidence for Strong Extragalactic Magnetic Fields from Fermi Observations of TeV Blazars
Authors: Neronov Andrii , Vovk Ievgen
Published: April 2010

On the Origins of Magnetism

The magnetic fields in galaxies and galaxy clusters are thought to result from the amplification of weak primordial magnetic fields, which, according to one class of theories, should exist in the voids between galaxies and galaxy clusters.
Neronov and Vovk
(p.
73
) present evidence for the existence of intergalactic magnetic fields and derive a lower limit for their strength, based on an analysis of data from the Fermi Large Area Telescope. The results place constraints on magnetogenesis models and suggest that magnetic fields originated in the early universe before galaxy formation took place.
Orchestration of Floral Initiation by APETALA1
Authors: Kaufmann Kerstin , Wellmer Frank , Muiño Jose M. , Ferrier Thilia , Wuest Samuel E. , Kumar Vijaya , Serrano-Mislata Antonio , Madueño Francisco , Krajewski Pawel , Meyerowitz Elliot M. , Angenent Gerco C. , Riechmann José Luis
Published: April 2010

Flower Power

The transcription factor APETALA1 (AP1) controls the transition from vegetative growth to flower production in the plant
Arabidopsis
. A handful of factors that control AP1 have been identified, as well as some targets that AP1 controls.

Kaufmann
et al.

(p.
85
) now apply genome-wide microarray analysis to identify over a thousand genes whose transcription is regulated by AP1. By proximity to AP1 binding sites, over two thousand genes are implicated as putative AP1 targets. Analysis of this network of interactions indicates that AP1 functions first to repress vegetative identity, then to help establish floral primordia, and finally to shape the differentiation of floral parts.
Evasion of CD8
+
T Cells Is Critical for Superinfection by Cytomegalovirus
Authors: Hansen Scott G. , Powers Colin J. , Richards Rebecca , Ventura Abigail B. , Ford Julia C. , Siess Don , Axthelm Michael K. , Nelson Jay A. , Jarvis Michael A. , Picker Louis J. , Früh Klaus
Published: April 2010

Cytomegalovirus Immune Evasion Strategy

Cytomegalovirus (CMV) infects a large percentage of the world's population. Most of those infected are asymptomatic; however, CMV is a substantial public health concern for immunocompromised individuals and neonates. CMV is unusual in that it can superinfect: it re-infects hosts who are already infected with the virus, even in the presence of a strong, specific immune response.

Hansen
et al.

(p.
102
; see the Perspective by

Hengel and Koszinowski

) now find that in rhesus macaques, a good model for human CMV superinfection, CMV establishes superinfections by evading the immune response mediated by CD8
+
T cells. A series of viral mutants deficient in expression of the US2-11 glycoproteins, which regulate antigen presentation to CD8
+
T cells, revealed that, although able to establish the initial infection, these viral mutants were unable to superinfect. Depletion of CD8
+
T cells from the monkeys allowed infection by the mutant viruses. These results highlight the difficulties in developing an effective protective vaccine against CMV itself, but suggest that CMV-based vectors may be useful in other vaccine efforts such as those against HIV.
Empowering Young Scientists
Authors: Brück Tilman , Beaudry Catherine , Hilgenkamp Hans , Karoonuthaisiri Nitsara , Mohamed Hiba Salah-Eldin , Weiss Gregory A.
Published: April 2010

The Vancouver Olympics reveal stark differences between the worlds of sports and science. In both, young people from around the world try to surpass all previous accomplishments in pursuit of world records or scientific discoveries. Selected entirely on merit, athletes receive honor just for participating in the games, spurring the next generation of young people in each nation to excel. And as star athletes age, they often support their sport in other ways, serving as advocates, mentors, or coaches. In contrast, in too many nations, the selection and promotion processes in science involve considerations other than merit. Senior scientists receive most of the resources available for scientific research, and young scientists rarely receive societal recognition for their work. This situation is growing worse as life expectancies and retirement ages increase, along with the average age for attaining scientific independence.
*
Perhaps as one consequence, science is typically not a top career choice. How many exceptional scientists around the world thereby go unrecognized, their talents allowed to wither away untapped? In an attempt to reverse such trends, a nascent “young national academies” movement has begun across the globe, and a new international group has recently been established to promote this cause.
Fishing Antihypernuclei Out of a Quark-Gluon Soup
Authors: Cohen Thomas D.
Published: April 2010

Rare antimatter hypernuclei can form when an ultrahigh-energy plasma of quarks and gluons cools down.
Hatching a Mongrel Species
An Entirely Synthetic Fish
How Rainbow Trout Beguiled America and Overran the World

by Anders Halverson

Yale University Press, New Haven, CT, 2010. 279 pp. $26, £20. ISBN 9780300140873.
Authors: Farmer Jared
Published: April 2010

Halverson discusses the spread of our most ubiquitous stocked game fish and its unintended consequences for ecosystems and the rainbow trout itself.
A Vaccine Monkey Wrench?
Authors: Hengel Hartmut , Koszinowski Ulrich H.
Published: April 2010

The mechanism by which monkeys succumb to secondary infection by a herpesvirus may explain the difficulty in developing a human vaccine.
In the Shadow of Jane Goodall
Authors: Cohen Jon
Published: April 2010

Fifty years after Goodall arrived in Gombe, the environment has changed dramatically for both our closest relatives and the scientists who study them
Chimps Read Lips
Authors: Cohen Jon
Published: April 2010

Comparative psychologists at the Yerkes National Primate Research Center are trying to connect the puckered lips, raised eyebrows, and grins of chimpanzees with emotional states such as aggression, surprise, and lasciviousness.
Makoku at 0°30′N 30°24′E: Chimping Via GPS
Authors: Cohen Jon
Published: April 2010

With the help of satellites, a handheld GPS device, and his laptop, a Cambridge researcher has put together a map that redefines the art of charting chimpanzee life in the wild.
Species Recognition and Clinical Relevance of the Zygomycetous GenusLichtheimia(syn.Absidia Pro Parte,Mycocladus)
Authors: Alastruey-Izquierdo Ana , Hoffmann Kerstin , de Hoog G. Sybren , Rodriguez-Tudela Juan Luis , Voigt Kerstin , Bibashi Evangelia , Walther Grit
Published: April 2010

The zygomycete genusLichtheimia(syn.Absidia pro parte,Mycocladus) consists of saprotrophic fungi inhabiting soil or dead plant material.Lichtheimia corymbifera(syn.Absidia corymbifera,Mycocladus corymbifer) andLichtheimia ramosa(syn.Absidia ramosa,Mycocladus ramosus) may cause fulminant infections in patients with impaired immunity. The present study investigated the species boundaries inLichtheimiausing genealogical concordance phylogenetic species recognition (by comparison of the genealogies of the internal transcribed spacer [ITS] sequence, the D1/D2 region of the large subunit [LSU], and actin), biological species recognition by mating tests, as well as morphological and physiological characteristics. The three molecular markers used were selected by evaluating the polymorphisms and paralogies of several loci, including those for β-tubulin, translation elongation factor 1α, the two largest subunits of the RNA polymerase II (RPB1 and RPB2), the mitochondrial cytochromecoxidase subunit I (COI), and the mitochondrial small-subunit (mtSSU) rDNA, among four strains belonging to different putative species. Comparing the genealogies of the ITS, LSU, and actin genes, we recognized seven phylogenetic species. However, mating tests did not show intrinsic reproductive barriers for two pairs of the phylogenetic species. Therefore, we regard five species inLichtheimato be confirmed:Lichtheimia corymbifera,L. ornatacomb. nov.,L. ramosa,L. hyalospora, andL. sphaerocystissp. nov. Only the first three species seem to have clinical relevance.Lichtheimia blakesleeanais reduced to a synonym ofLichtheimia hyalospora. We provide a detailed description ofLichtheimia sphaerocystissp. nov. and a key for the identification of all accepted species identified in the present study on the basis of their morphological traits and growth at different temperatures.
Comparison of the Luminex Respiratory Virus Panel Fast Assay with In-House Real-Time PCR for Respiratory Viral Infection Diagnosis
Authors: Gadsby Naomi J. , Hardie Alison , Claas Eric C. J. , Templeton Kate E.
Published: April 2010

The Luminex xTAG Respiratory Virus Panel (RVP) assay has been shown to offer improved diagnostic sensitivity over traditional viral culture methods and to have a sensitivity comparable to those of individual real-time nucleic acid tests for respiratory viruses. The objective of this retrospective study was to test a new, streamlined version of this assay, the RVP Fast assay, which requires considerably less run time and operator involvement. The study compared the performance of the RVP Fast assay with those of viral culture, a direct fluorescent assay (DFA), and a panel of single and multiplex real-time PCRs in the testing of 286 respiratory specimens submitted to the Edinburgh Specialist Virology Centre for routine diagnosis of viral infection between December 2007 and February 2009. At least one respiratory viral infection was detected in 13.6% of specimens by culture and DFA combined, in 49.7% by real-time PCR, and in 46.2% by the RVP Fast assay. The sensitivity and specificity of the RVP Fast assay compared to the results of real-time PCR as the gold standard were 78.8% and 99.6%, respectively. Real-time PCR-positive specimens missed by the RVP Fast assay generally had low viral loads or were positive for adenovirus. Additionally, a small number of specimens were positive by the RVP Fast assay but were not detected by real-time PCR. For some viral targets, only a small number of positive results were found in our sample set using either method; therefore, the sensitivity of detection of the RVP Fast assay for individual targets could be investigated further with a greater number of virus-positive specimens.
Identification of a Domain of the Baculovirus
Autographa californica
Multiple Nucleopolyhedrovirus Single-Strand DNA-Binding Protein LEF-3 Essential for Viral DNA Replication
Authors: Yu Mei , Carstens Eric B.
Published: April 2010

Autographa californica
multiple nucleopolyhedrovirus (AcMNPV)
lef-3
is one of nine genes required for viral DNA replication in transient assays. LEF-3 is predicted to contain several domains related to its functions, including nuclear localization, single-strand DNA binding, oligomerization, interaction with P143 helicase, and interaction with a viral alkaline nuclease. To investigate the essential nature of LEF-3 and the roles it may play during baculovirus DNA replication, a
lef-3
null bacmid (bKO-lef3) was constructed in
Escherichia coli
and characterized in Sf21 cells. The results showed that AcMNPV
lef-3
is essential for DNA replication, budded virus production, and late gene expression
in vivo
. Cells transfected with the
lef-3
knockout bacmid produced low levels of early proteins (P143, DNA polymerase, and early GP64) and no late proteins (P47, VP39, or late GP64). To investigate the functional role of domains within the LEF-3 open reading frame in the presence of the whole viral genome, plasmids expressing various LEF-3 truncations were transfected into Sf21 cells together with bKO-lef3 DNA. The results showed that expression of AcMNPV LEF-3 amino acids 1 to 125 was sufficient to stimulate viral DNA replication and to support late gene expression. Expression of
Choristoneura fumiferana
MNPV
lef-3
did not rescue any LEF-3 functions. The construction of a LEF-3 amino acid 1 to 125 rescue bacmid revealed that this region of LEF-3, when expressed in the presence of the rest of the viral genome, stimulated viral DNA replication and late and very late protein expression, as well as budded virus production.
Combinatorial Latency Reactivation for HIV-1 Subtypes and Variants
Authors: Burnett John C. , Lim Kwang-il , Calafi Arash , Rossi John J. , Schaffer David V. , Arkin Adam P.
Published: April 2010

The eradication of HIV-1 will likely require novel clinical approaches to purge the reservoir of latently infected cells from a patient. We hypothesize that this therapy should target a wide range of latent integration sites, act effectively against viral variants that have acquired mutations in their promoter regions, and function across multiple HIV-1 subtypes. By using primary CD4+and Jurkat cell-basedin vitroHIV-1 latency models, we observe that single-agent latency reactivation therapy is ineffective against most HIV-1 subtypes. However, we demonstrate that the combination of two clinically promising drugs—namely, prostratin and suberoylanilide hydroxamic acid (SAHA)—overcomes the limitations of single-agent approaches and can act synergistically for many HIV-1 subtypes, including A, B, C, D, and F. Finally, by identifying the proviral integration position of latent Jurkat cell clones, we demonstrate that this drug combination does not significantly enhance the expression of endogenous genes nearest to the proviral integration site, indicating that its effects may be selective.
The Rab11 Pathway Is Required for Influenza A Virus Budding and Filament Formation
Authors: Bruce Emily A. , Digard Paul , Stuart Amanda D.
Published: April 2010

Influenza A virus buds through the apical plasma membrane, forming enveloped virus particles that can take the shape of pleomorphic spheres or vastly elongated filaments. For either type of virion, the factors responsible for separation of viral and cell membranes are not known. We find that cellular Rab11 (a small GTP-binding protein involved in endocytic recycling) and Rab11-family interacting protein 3 ([FIP3] which plays a role in membrane trafficking and regulation of actin dynamics) are both required to support the formation of filamentous virions, while Rab11 is additionally involved in the final budding step of spherical particles. Cells transfected with Rab11 GTP-cycling mutants or depleted of Rab11 or FIP3 content by small interfering RNA treatment lost the ability to form virus filaments. Depletion of Rab11 resulted in up to a 100-fold decrease in titer of spherical virus released from cells. Scanning electron microscopy of Rab11-depleted cells showed high densities of virus particles apparently stalled in the process of budding. Transmission electron microscopy of thin sections confirmed that Rab11 depletion resulted in significant numbers of abnormally formed virus particles that had failed to pinch off from the plasma membrane. Based on these findings, we see a clear role for a Rab11-mediated pathway in influenza virus morphogenesis and budding.
Evidence for Translational Regulation by the Herpes Simplex Virus Virion Host Shutoff Protein
Authors: Saffran Holly A. , Read G. Sullivan , Smiley James R.
Published: April 2010

The herpes simplex virus (HSV) virion host shutoff protein (vhs) encoded by gene UL41 is an mRNA-specific RNase that triggers accelerated degradation of host and viral mRNAs in infected cells. We report here that vhs is also able to modulate reporter gene expression without greatly altering the levels of the target mRNA in transient-transfection assays conducted in HeLa cells. We monitored the effects of vhs on a panel of bicistronic reporter constructs bearing a variety of internal ribosome entry sites (IRESs) located between two test cistrons. As expected, vhs inhibited the expression of the 5′ cistrons of all of these constructs; however, the response of the 3′ cistron varied with the IRES: expression driven from the wild-type EMCV IRES was strongly suppressed, while expression controlled by a mutant EMCV IRES and the cellular ApaF1, BiP, and DAP5 IRES elements was strongly activated. In addition, several HSV type 1 (HSV-1) 5′ untranslated region (5′ UTR) sequences also served as positive vhs response elements in this assay. IRES activation was also observed in 293 and HepG2 cells, but no such response was observed in Vero cells. Mutational analysis has yet to uncouple the ability of vhs to activate 3′ cistron expression from its shutoff activity. Remarkably, repression of 5′ cistron expression could be observed under conditions where the levels of the reporter RNA were not correspondingly reduced. These data provide strong evidence that vhs can modulate gene expression at the level of translation and that it is able to activate cap-independent translation through specific
cis
-acting elements.
Hepatitis C Virus Hypervariable Region 1 Modulates Receptor Interactions, Conceals the CD81 Binding Site, and Protects Conserved Neutralizing Epitopes
Authors: Bankwitz Dorothea , Steinmann Eike , Bitzegeio Julia , Ciesek Sandra , Friesland Martina , Herrmann Eva , Zeisel Mirjam B. , Baumert Thomas F. , Keck Zhen-yong , Foung Steven K. H. , Pécheur Eve-Isabelle , Pietschmann Thomas
Published: April 2010

The variability of the hepatitis C virus (HCV), which likely contributes to immune escape, is most pronounced in hypervariable region 1 (HVR1) of viral envelope protein 2. This domain is the target for neutralizing antibodies, and its deletion attenuates replicationin vivo. Here we characterized the relevance of HVR1 for virus replicationin vitrousing cell culture-derived HCV. We show that HVR1 is dispensable for RNA replication. However, viruses lacking HVR1 (ΔHVR1) are less infectious, and separation by density gradients revealed that the population of ΔHVR1 virions comprises fewer particles with low density. Strikingly, ΔHVR1 particles with intermediate density (1.12 g/ml) are as infectious as wild-type virions, while those with low density (1.02 to 1.08 g/ml) are poorly infectious, despite quantities of RNA and core similar to those in wild-type particles. Moreover, ΔHVR1 particles exhibited impaired fusion, a defect that was partially restored by an E1 mutation (I347L), which also rescues infectivity and which was selected during long-term culture. Finally, ΔHVR1 particles were no longer neutralized by SR-B1-specific immunoglobulins but were more prone to neutralization and precipitation by soluble CD81, E2-specific monoclonal antibodies, and patient sera. These results suggest that HVR1 influences the biophysical properties of released viruses and that this domain is particularly important for infectivity of low-density particles. Moreover, they indicate that HVR1 obstructs the viral CD81 binding site and conserved neutralizing epitopes. These functions likely optimize virus replication, facilitate immune escape, and thus foster establishment and maintenance of a chronic infection.
p62/Sequestosome-1 Associates with and Sustains the Expression of Retroviral Restriction Factor TRIM5α
Authors: O'Connor Christopher , Pertel Thomas , Gray Seth , Robia Seth L. , Bakowska Joanna C. , Luban Jeremy , Campbell Edward M.
Published: April 2010

TRIM5 proteins mediate a potent block to the cross-species transmission of retroviruses, the most well known being the TRIM5α protein from rhesus macaques, which potently inhibits human immunodeficiency virus type 1 (HIV-1) infection. This restriction occurs at an early stage in the replication cycle and is mediated by the binding of TRIM5 proteins to determinants present in the retroviral capsid. TRIM5α, as well as other TRIM family proteins, has been shown to be regulated by interferons (IFN). Here we show that TRIM5α associates with another IFN-induced gene, sequestosome-1/p62 (p62). p62 plays a role in several signal transduction cascades that are important for maintaining the antiviral state of cells. Here we demonstrate that p62 localizes to both human and rhesus macaque TRIM5α cytoplasmic bodies, and fluorescence resonance energy transfer (FRET) analysis demonstrates that these proteins closely associate in these structures. When p62 expression was knocked down via small interfering RNA (siRNA), the number of TRIM5α cytoplasmic bodies and the level of TRIM5α protein expression were reduced in cell lines stably expressing epitope-tagged versions of TRIM5α. In accordance with these data, p62 knockdown resulted in reduced TRIM5α-mediated retroviral restriction in cells expressing epitope-tagged TRIM5α or expressing endogenously expressed human TRIM5α. p62 may therefore operate to enhance TRIM5α-mediated retroviral restriction, contributing to the antiviral state of cells following IFN treatment.
Route of Adenovirus-Based HIV-1 Vaccine Delivery Impacts the Phenotype and Trafficking of Vaccine-Elicited CD8
+
T Lymphocytes
Authors: Kaufman David R. , Bivas-Benita Maytal , Simmons Nathaniel L. , Miller Darby , Barouch Dan H.
Published: April 2010

Candidate HIV-1 vaccine regimens utilizing intramuscularly (i.m.) administered recombinant adenovirus (rAd)-based vectors can induce potent mucosal cellular immunity. However, the degree to which mucosal rAd vaccine routing might alter the quality and anatomic distribution of vaccine-elicited CD8
+
T lymphocytes remains unclear. We show that the route of vaccination critically impacts not only the magnitude but also the phenotype and trafficking of antigen-specific CD8
+
T lymphocytes in mice. I.m. rAd immunization induced robust local transgene expression and elicited high-frequency, polyfunctional CD8
+
T lymphocytes that trafficked broadly to both systemic and mucosal compartments. In contrast, intranasal (i.n.) rAd immunization led to similarly robust local transgene expression but generated low-frequency, monofunctional CD8
+
T lymphocytes with restricted anatomic trafficking patterns. Respiratory rAd immunization elicited systemic and mucosal CD8
+
T lymphocytes with phenotypes and trafficking properties distinct from those elicited by i.m. or i.n. rAd immunization. Our findings indicate that the anatomic microenvironment of antigen expression critically impacts the phenotype and trafficking of antigen-specific CD8
+
T lymphocytes.
Coinfection of Hepatic Cell Lines with Human Immunodeficiency Virus and Hepatitis B Virus Leads to an Increase in Intracellular Hepatitis B Surface Antigen
Authors: Iser David M. , Warner Nadia , Revill Peter A. , Solomon Ajantha , Wightman Fiona , Saleh Suha , Crane Megan , Cameron Paul U. , Bowden Scott , Nguyen Tin , Pereira Cândida F. , Desmond Paul V. , Locarnini Stephen A. , Lewin Sharon R.
Published: April 2010

Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV) coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a vesicular stomatitis virus (VSV)-pseudotyped HIV expressing enhanced green fluorescent protein (EGFP). Following HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8 infection of AD38 cells was inhibited by maraviroc and NL4-3 was inhibited by AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV. Coinfection of the AD38 cell line with HIV did not alter the HBV DNA amount or species as determined by Southern blotting or nucleic acid signal amplification. However, coinfection with HIV was associated with a significant increase in intracellular HBsAg when measured by Western blotting, quantitative HBsAg, and fluorescence microscopy. We conclude that HIV infection of HBV-infected hepatic cell lines significantly increased intracellular HBsAg but not HBV DNA synthesis and that increased intrahepatic HBsAg secondary to direct infection by HIV may contribute to accelerated liver disease in HIV-HBV-coinfected individuals.
Autologous Neutralizing Antibodies to the Transmitted/Founder Viruses Emerge Late after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys
Authors: Yeh Wendy W. , Rahman Ishita , Hraber Peter , Coffey Rory T. , Nevidomskyte Daiva , Giri Ayush , Asmal Mohammed , Miljkovic Svetlana , Daniels Marcus , Whitney James B. , Keele Brandon F. , Hahn Beatrice H. , Korber Bette T. , Shaw George M. , Seaman Michael S. , Letvin Norman L.
Published: April 2010

While the simian immunodeficiency virus (SIV)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (HIV-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. In HIV-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. However, the ontogeny of the SIV-specific neutralizing antibody response in mucosally infected animals has not been defined. We characterized the kinetics of the autologous neutralizing antibody response to the transmitted/founder SIVmac251 using a pseudovirion-based TZM-bl cell assay and monitored
env
sequence evolution using single-genome amplification in four rhesus animals that were infected via intrarectal inoculations. We show that the SIVmac251 founder viruses induced neutralizing antibodies at 5 to 8 months after infection. Despite their slow emergence and low titers, these neutralizing antibodies selected for escape mutants that harbored substitutions and deletions in variable region 1 (V1), V2, and V4 of Env. The neutralizing antibody response was initially focused on V4 at 5 to 8 months after infection and then targeted V1/V2 and V4 by 16 months. These findings reveal a striking delay in the development of neutralizing antibodies in SIVmac-infected animals, thus raising questions concerning the suitability of SIVmac251 as a challenge strain to screen AIDS vaccines that elicit neutralizing antibodies as a means to prevent virus acquisition. They also illustrate the capacity of the SIVmac quasispecies to modify antigenic determinants in response to very modest titers of neutralizing antibodies.
High resolution manometry and multichannel intraluminal impedance oesophageal manometry in clinical practice
Authors: Mainie Inder
Published: April 2010

The past decade has seen new technological advances in the investigation of oesophageal motility disorders. Multichannel intraluminal impedance monitoring has been used as an adjunct to conventional manometry in the assessment of oesophageal function, independent of radiography. High resolution manometry provides additional information over conventional manometry, and its topographic analysis makes interpretation of studies easier. Both utilities in non-obstructive dysphagia have been used ultimately in research; however, more studies are addressing their clinical application.
Postmenopausal breast cancer and occupational exposures
Authors: Labrèche France , Goldberg Mark S , Valois Marie-France , Nadon Louise
Published: April 2010

Objective

To determine whether exposures in the workplace to organic solvents and to other agents, such as polycyclic aromatic hydrocarbons, are associated with increased risks of developing postmenopausal breast cancer.

Methods

Between 1996 and 1997 a case–control study was conducted in Montreal, Quebec. Cases comprised 556 women, aged 50–75 years, with incident malignant breast cancer, and their controls were 613 women with other cancers, frequency matched for age, date of diagnosis and hospital. An expert team of chemists and industrial hygienists translated their job histories into exposure to about 300 agents.

Results

Odds ratios (ORs) were increased for the usual risk factors for breast cancer and, adjusting for these, risks increased with occupational exposure to several agents, and were highest for exposures occurring before age 36 years. Increased ORs were found for each 10-year increment in duration of exposure, before age 36 years (OR<36), to acrylic fibres (OR<36=7.69) and to nylon fibres (OR<36=1.99). For oestrogen-positive and progesterone-negative tumours, the OR doubled or more for each 10-year increase in exposure to monoaromatic hydrocarbons, and to acrylic and rayon fibres. The OR<36also doubled for exposure to organic solvents that metabolise into reactive oxygen species, and to acrylic fibres. A threefold increase was found for oestrogen- and progesterone-positive tumours, with exposure to polycyclic aromatic hydrocarbons from petroleum sources.

Conclusion

Certain occupational exposures appear to increase the risk of developing postmenopausal breast cancer, although some findings might be due to chance or to undetected bias. Our findings are consistent with the hypothesis that breast tissue is more sensitive to adverse effects if exposure occurs when breast cells are still proliferating. More refined analyses, adjusting for hormonal receptor subtypes and studies focusing on certain chemical exposures are required to further our understanding of the role of chemicals in the development of breast cancer.