bluuebunny/crossref_metadata_2025 huggingface dataset:
Julien Macho et Jean Baudoin relus par François le Moine: Étude de contenu
Authors: Puttero Giorgia
Published: December 2008

François le Moine, avocat presque méconnu de Rouen, est l’auteur d’un fablier laissé manuscrit, daté de 1656 et
intitulé Les fables d’Esope et autres fables de divers Auteurs. Les sources auxquelles Le Moine a puisé
son inspiration ont été savamment repérées par Gianni Mombello; il s’agit de Jean Baudoin, de Julien Macho, du prieur
Audin, de Mathurin Reigner.

Notre analyse se propose de comprendre comment maître Le Moine a adapté le texte de Jean Baudoin et celui plus ancien de Julien
Macho, en mettant en lumière l’emploi de certaines techniques littéraires, telles le décalque ou l’emboîtement. Les
résultats littéraires auxquels notre auteur aboutit se révèlent assez surprenants.
Les fables insérées dans Reynaerts historie (L'histoire de Renard, Flandre, XVe s.) et le Dit d'Ysopet de Marie de France
Authors: Reynaert Joris
Published: December 2008

Trois des quatre fables insérées dans Reynaerts historie sont clairement tributaires de l’Esopet flamand (XIIIème siècle), une traduction assez fidèle d’une des multiples variantes du Romulus, la version latine la plus répandue de la collection des fables ésopiques au moyen âge. Par rapport à l’Esopet, Reynaerts historie a surtout amplifié, en ajoutant des détails qui concrétisent et rendent plus vifs les aspects matériels et psychologiques des situations contées, et les implications sociales des moralisations. Sur ces points l’Historie présente non seulement une analogie de vision et de style, mais souvent aussi une ressemblance marquée avec les Fables de Marie de France et la manière dont elle aussi a amplifié le Romulus. Nous étudions de plus près les élements qui relient les deux textes entre eux, et proposons une réponse à la question de savoir quelles ont pu être les causes des analogies et des recoupements constatés. Nous pensons pouvoir conclure qu’il s’agit, entre autres, d’une relation intertextuelle directe, c.-à-d. d’une réception du texte de Marie de France en pays flamand au XVème siècle.

Pour Philippe Verelst
Gheraert Leeu as printer of fables and animal stories
Authors: Wackers Paul
Published: December 2008

This article discusses the books with animals as protagonists, published by the Dutch printer Gheraert Leeu. It shows that these books conform by and large to a common pattern but that Leeu also experimented with content and lay out during his whole career. Some of Leeu’s books were meant for the traditional reading public but he also tried to attract new readers. Many of the novelties introduced by him may be explained by this wish to accommodate and to appeal to new readers, and to people unaccustomed to reading.
Lacan and le con: Exploring the Feminine in the Roman de Renart
Authors: Weisl-Shaw Andreea
Published: December 2008

This article explores Renart’s relationship with the feminine across the various branches of the Roman de Renart. At the same time a creation of Eve (in the Enfances), and the creator of Woman’s essence, her genitalia (in Labourage/Connin), Renart obsessively circles the feminine: seeking to control it through physical power (the rape of Hersent in Renart et la love), fantasizing about it (in Le Puits) and talking about it endlessly (especially in the Confession). The enigmatic object of his desire, the con, is a dark abyss to which he returns over and over again, seeking to understand it, even to refashion it, yet he is never able to achieve true mastery of it. Using Lacanian theory and Freud’s theory of jokes, this article examines Renart’s obsession, aiming to show that the fox as trickster/jokester is less in control than he believes: he is as much controlled and defined by the feminine as he is its absolute master and the imagined key to its ultimate meaning.
Measuring mono-word termhood by rank difference via corpus comparison
Authors: Kit Chunyu , Liu Xiaoyue
Published: December 2008

Terminology as a set of concept carriers crystallizes our special knowledge about a subject. Automatic term recognition (ATR) plays a critical role in the processing and management of various kinds of information, knowledge and documents, e.g., knowledge acquisition via text mining. Measuring termhood properly is one of the core issues involved in ATR. This article presents a novel approach to termhood measurement for mono-word terms via corpus comparison, which quantifies the termhood of a term candidate as its rank difference in a domain and a background corpus. Our ATR experiments to identify legal terms in Hong Kong (HK) legal texts with the British National Corpus (BNC) as background corpus provide evidence to confirm the validity and effectiveness of this approach. Without any prior knowledge and ad hoc heuristics, it achieves a precision of 97.0% on the top 1000 candidates and a precision of 96.1% on the top 10% candidates that are most highly ranked by the termhood measure, illustrating a state-of-the-art performance on mono-word ATR in the field.
The rise of carbon neutral and compensation carbone
Authors: Dury Pascaline
Published: December 2008

This paper presents the results of a corpus-based diachronic study of the migration of vocabulary from the language of ecology into non-scientific language and vice versa. The results are extracted from a bilingual (French and English) comparable corpus compiled for the study. We show that if terms can get de-terminologized over time, words which have become widespread in the media can, in return, get terminologized over the years and move into the lexicon of ecology, as is the case in English with carbon neutral. We also show that the popularity and productivity of the prefix eco- in English does not seem to apply to éco- in French, probably because of the syntactic and semantic competition with the modifier bio. The recent emergence of compensation carbone in the French media is also discussed.
B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase
Authors: Cariappa Annaiah , Takematsu Hiromu , Liu Haoyuan , Diaz Sandra , Haider Khaleda , Boboila Cristian , Kalloo Geetika , Connole Michelle , Shi Hai Ning , Varki Nissi , Varki Ajit , Pillai Shiv
Published: December 2008

We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B cell development, signaling, and immunological tolerance. Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically removes acetyl moieties from the 9-OH position of α2–6-linked sialic acid, exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell development, and spontaneously develop antichromatin autoantibodies and glomerular immune complex deposits. The 9-O-acetylation state of sialic acid regulates the function of CD22, a Siglec that functions in vivo as an inhibitor of BCR signaling. These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage.
IL-15 trans-presentation promotes human NK cell development and differentiation in vivo
Authors: Huntington Nicholas D. , Legrand Nicolas , Alves Nuno L. , Jaron Barbara , Weijer Kees , Plet Ariane , Corcuff Erwan , Mortier Erwan , Jacques Yannick , Spits Hergen , Di Santo James P.
Published: December 2008

The in vivo requirements for human natural killer (NK) cell development and differentiation into cytotoxic effectors expressing inhibitory receptors for self–major histocompatability complex class I (MHC-I; killer Ig-like receptors [KIRs]) remain undefined. Here, we dissect the role of interleukin (IL)-15 in human NK cell development using Rag2−/−γc−/− mice transplanted with human hematopoietic stem cells. Human NK cell reconstitution was intrinsically low in this model because of the poor reactivity to mouse IL-15. Although exogenous human IL-15 (hIL-15) alone made little improvement, IL-15 coupled to IL-15 receptor α (IL-15Rα) significantly augmented human NK cells. IL-15–IL-15Rα complexes induced extensive NK cell proliferation and differentiation, resulting in accumulation of CD16+KIR+ NK cells, which was not uniquely dependent on enhanced survival or preferential responsiveness of this subset to IL-15. Human NK cell differentiation in vivo required hIL-15 and progressed in a linear fashion from CD56hiCD16−KIR− to CD56loCD16+KIR−, and finally to CD56loCD16+KIR+. These data provide the first evidence that IL-15 trans-presentation regulates human NK cell homeostasis. Use of hIL-15 receptor agonists generates a robust humanized immune system model to study human NK cells in vivo. IL-15 receptor agonists may provide therapeutic tools to improve NK cell reconstitution after bone marrow transplants, enhance graft versus leukemia effects, and increase the pool of IL-15–responsive cells during immunotherapy strategies.
INFRARED SPECTRA OF DUST AGGREGATES IN COMETARY COMAE: CALCULATION WITH OLIVINE FORMED BY EXOTHERMIC CHEMICAL REACTIONS
Authors: Kimura Hiroshi , Chigai Takeshi , Yamamoto Tetsuo
Published: December 2008

Mineralogy of cometary dust plays an important role in understanding the formation and evolution of comets, the most primitive objects in the solar system. A correct interpretation of infrared spectra observed for cometary comae is the key to success in identifying mineral constituents of cometary dust. However, the composition, size, and structure of cometary dust might have been misinterpreted in previous studies, owing to a lack of a unique solution in their analyses of infrared spectra. We present a semianalytic method to compute infrared spectra for large aggregate particles consisting of submicrometer size grains inclusive of crystalline minerals. The method is applied to calculate the absorption cross section of primordial interstellar dust that is processed in a cometary coma. The processed interstellar dust is here modeled as clusters of concentrically stratified spheres consisting of an organic refractory outer mantle, an olivine inner mantle, and an amorphous silicate core. Spectral variations in the absorption cross sections for porous aggregates with a forsterite layer exhibit noticeable features at all the wavelengths where mineral features are observed in the infrared spectra of cometary comae. In contrast, the observed infrared spectra of cometary comae show no evidence for the presence of fayalite in cometary dust. Infrared observations of cometary comae are consistent with the picture that cometary nuclei contain primordial interstellar dust as well as interstellar ices.
Electricity reform and sustainable development in China
Authors: Williams James H , Kahrl Fredrich
Published: December 2008

Reducing the environmental impact of supplying electricity is a key to China’s sustainable development, and a focus of both domestic and international concerns with greenhouse gas emissions. The environmental performance of the electricity sector is strongly affected by its institutional arrangements: regulatory frameworks, wholesale markets, pricing mechanisms, planning and coordination, and enforcement and incentive mechanisms. These arrangements are set to change as electricity reforms inaugurated in 2002, but sidetracked by several years of supply shortages, are being resumed. In this paper we examine the impact of electricity reform on environmental sustainability by analyzing case studies of four environmental initiatives in the electricity sector: retirement of inefficient generators, installation of pollution control equipment, renewable energy development, and efforts to promote energy efficiency. We find that implementation of these policies falls short of objectives for two main underlying reasons: conflicting priorities between central and provincial governments, and ineffective regulation. Sustainability will be best served not by redoubling short-term supply-oriented, market-based reforms, but by better aligning central and provincial government incentives, and by developing competent, independent regulation at the provincial level. China’s central government and sub-national governments in industrialized countries can both contribute to the latter goal.
Imitation, Language and Nation in Joachim Du Bellay's
Deffence
Authors: Keller Marcus
Published: December 2008

Du Bellay's
Deffence et illustration de la langue francoyse
(1549) not only testifies to the poet's patriotism, but also entails an intricate reflection on language and nation which complicates and raises difficult questions about their relationship. This article demonstrates how Du Bellay conceptualizes language and nation as imaginary entities shifting between culture and nature by creating a deep and broad analogy between the two. The ultimately indeterminate origin of language poses the serious quandary of the nation's lack of origin and originality. Du Bellay resolves this and other issues in part by deploying the fruit and the graft as tropes of both culture and nature. Through these metaphors he indirectly proposes the literary practice of imitation as a general cultural procedure to transform what is foreign into the national, even though the nature of imitation remains as obscure as the origin of language and nation.
Evidence of a genetic cline for Sardina pilchardus along the Northwest African coast
Authors: Chlaida M. , Laurent V. , Kifani S. , Benazzou T. , Jaziri H. , Planes S.
Published: December 2008

Chlaida, M., Laurent, V., Kifani, S., Benazzou, T., Jaziri, H., and Planes, S. 2009. Evidence of a genetic cline for Sardina pilchardus along the Northwest African coast. – ICES Journal of Marine Science, 66: 264–271. In all, 700 Sardina pilchardus from 14 locations throughout the Atlantic and Mediterranean Moroccan coastlines were screened for eight enzymatic loci that show polymorphism. Analysis of allelic frequencies showed a genetic break in the area of the Bay of Agadir, segregating two groups of samples, confirmed by analysis of molecular variance; a first consisting of Sidi Ifni (29°12′N) and southern samples down to the southern limit of the species in Mauritania (19°03′N 16°28′W), and a second starting in the Bay of Agadir (30°48′N) and consisting of northern samples that appeared homogeneous with the Mediterranean samples. Specifically, a survey of the SOD* loci demonstrated a genetic cline in allelic frequencies along the coastline. Using a clinal variation model under a state of equilibrium, we estimate a dispersal rate of 189 ± 52 km per generation between Mauritania and Ras Kebdana. This major break towards the south of the Bay of Agadir offers a new perspective on the management of sardine, which ideally ought now to be managed as two stocks along the Moroccan coast. The break is most likely induced by hydrodynamic influences that virtually isolate southern from northern populations.
Thyroid Problems in Primary Care
Authors: Lawrence Deborah
Published: December 2008

Thyroid disorders are among the most common medical problems under GP follow-up, with a prevalence rate of approximately 1 in 20. It is approximately 10 times more common in women than men.
Pituitary Problems in Primary Care
Authors: Levy Andy
Published: December 2008

Primary care is where most diagnoses of pituitary adenoma are made and pituitary adenomas are responsible for almost all pituitary problems. They typically present with a combination of symptoms of space occupation, hypopituitarism and/or inappropriate hormone secretion. As early diagnosis with optimal initial management and expert follow-up in the long-term help minimize morbidity, it could be argued that once conspicuous features of classical hormone-excess phenotypes such as acromegaly or Cushing's disease have emerged, diagnosis has been unduly delayed, even though the adenomas themselves are intrinsically benign.
Prescribing for the Elderly
Authors: Simon Chantal
Published: December 2008

We live in an ageing society. Since the early 1930s, the number of people aged over 65 has more than doubled and today, a fifth of the population is over 60 (Fig. 1). This has implications for prescribing in primary care. Prescription drug usage increases with age. One in three NHS prescriptions is issued to a patient over the age of 65 years, and 90% of these prescriptions are for repeat medications. Furthermore, adverse drug events are common reasons for hospital admission in the over-75 age group, accounting for 5–17% of admissions. Many are avoidable. This article aims to outline the principles of prescribing for older people in primary care.
Phosphate Availability Alters Lateral Root Development inArabidopsisby Modulating Auxin Sensitivity via a Mechanism Involving the TIR1 Auxin Receptor
Authors: Pérez-Torres Claudia-Anahí , López-Bucio José , Cruz-Ramírez Alfredo , Ibarra-Laclette Enrique , Dharmasiri Sunethra , Estelle Mark , Herrera-Estrella Luis
Published: December 2008

The survival of plants, as sessile organisms, depends on a series of postembryonic developmental events that determine the final architecture of plants and allow them to contend with a continuously changing environment. Modulation of cell differentiation and organ formation by environmental signals has not been studied in detail. Here, we report that alterations in the pattern of lateral root (LR) formation and emergence in response to phosphate (Pi) availability is mediated by changes in auxin sensitivity in Arabidopsis thaliana roots. These changes alter the expression of auxin-responsive genes and stimulate pericycle cells to proliferate. Modulation of auxin sensitivity by Pi was found to depend on the auxin receptor TRANSPORT INHIBITOR RESPONSE1 (TIR1) and the transcription factor AUXIN RESPONSE FACTOR19 (ARF19). We determined that Pi deprivation increases the expression of TIR1 in Arabidopsis seedlings and causes AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) auxin response repressors to be degraded. Based on our results, we propose a model in which auxin sensitivity is enhanced in Pi-deprived plants by an increased expression of TIR1, which accelerates the degradation of AUX/IAA proteins, thereby unshackling ARF transcription factors that activate/repress genes involved in LR formation and emergence.
Anthropology of Public Policy
Authors: Wedel Janine
Published: December 2008

•Anthropology and Migration Policy Elzbieta M Gozdziak
Association of Black Anthropologists
Authors: McGlotten Shaka
Published: December 2008

•Works‐in‐Progress Mentoring Session: Call for Participants Kevin Foster, Riche Barnes
Association for Political and Legal Anthropology
Authors: Krause Elizabeth , Bhan Mona
Published: December 2008

•Podcasting Political and Legal Anthropology Christine Hegel‐Cantarella, Jason Cross
General Anthropology Division
Authors: Lassiter Luke Eric
Published: December 2008

•History of Anthropology Committee Andrew Lyons
Society for Anthropology in Community Colleges
Authors: Miller Lloyd
Published: December 2008

•Laura's Top Four Reasons to Join SACC Laura Gonzalez
Society for the Anthropology of Consciousness
Authors: McBride Lawrence B
Published: December 2008

•Spring SAC Meeting Preview Mark A Schroll
Society for the Anthropology of North America
Authors: Hyatt Susan B
Published: December 2008

•SANA Book Prize Honors Local Democracy Under Siege Matt Thompson
Society for the Anthropology of Religion
Authors: Selby Jennifer
Published: December 2008

•An American Poet in Paris Kathleen Riddell
Society for East Asian Anthropology
Authors: Stevens Carolyn S , Hubbert Jennifer
Published: December 2008

•A Conversation with Aihwa Ong Shannon May
Anthropology and Environment Section
Authors: Ogden Laura
Published: December 2008

•Water‐Ecosystem Services, Drought and Environmental Justice Ted L Gragson
Archeology Division
Authors: Alexander Rani T
Published: December 2008

•International Archaeology News Janet E Levy
Association for Africanist Anthropology
Authors: Coffman Jennifer E
Published: December 2008

•AfAA Award Winners Jennifer Coffman
Association of Senior Anthropologists
Authors: Doughty Paul L
Published: December 2008

•The Amazing Ms Claflin Woodhull Alice Kehow
Council for Museum Anthropology
Authors: Herold Joyce
Published: December 2008

•Museum Anthropology Editorship Catherine S Fowler  •Notes from Museum Anthropology's New Editors Chip Colwell‐Chanthaphonh, Stephen E Nash
National Association of Student Anthropologists
Authors: Chio Jenny
Published: December 2008

•When Anthropology Meets Architecture Lindsey K Hourie
Society for Psychological Anthropology
Authors: Chapin Bambi
Published: December 2008

•What's at Stake in the Ethnography of Human Experience? Phenomenological and Psychoanalytic Perspectives Don Seeman, Sarah Willen  •New Directions in Policy‐Relevant Research on Adolescence: Perspectives from Psychological Anthropology Eileen P Anderson‐Fye, Jill E Korbin
Society for Visual Anthropology
Authors: Dickinson Wendy
Published: December 2008

•Don't Push Send: Breaking Up via New Media Ilana Gershon
The global alcohol industry: an overview
Authors: Jernigan David H.
Published: December 2008

Aims To describe the globalized sector of the alcoholic beverage industry, including its size, principal actors and activities.

Methods Market research firms and business journalism are the primary sources for information about the global alcohol industry, and are used to profile the size and membership of the three main industry sectors of beer, distilled spirits and wine.

Findings Branded alcoholic beverages are approximately 38% of recorded alcohol consumption world‐wide. Producers of these beverages tend to be large multi‐national corporations reliant on marketing for their survival. Marketing activities include traditional advertising as well as numerous other activities, such as new product development, product placement and the creation and promotion of social responsibility programs, messages and organizations.

Conclusions The global alcohol industry is highly concentrated and innovative. There is relatively little public health research evaluating the impact of its many marketing activities.
An investigation of seawater and sediment depth using a prototype airborne electromagnetic instrumentation system – a case study in Broken Bay, Australia
Authors: Vrbancich Julian
Published: December 2008

Previous studies using commercial airborne electromagnetic equipment that is not optimized for marine surveying have demonstrated the use of airborne electromagnetic methods for measuring water depth and estimating sediment thickness. A new prototype helicopter time‐domain airborne electromagnetic system, SeaTEM(0), is now under development for bathymetric surveying. The first sea trial of the SeaTEM(0) system took place over Broken Bay, New South Wales, Australia, in shallow water up to ∼30 m in depth. Broken Bay was chosen because the separate paleodrainage systems for the Hawkesbury River, Brisbane Water and Pittwater, which join in Broken Bay give rise to paleovalleys infilled with unconsolidated sediments, ranging in thickness between 0 m (bedrock outcrop) and ∼200 m. The survey area also included a tombolo with a beach either side, which provided the opportunity to measure water depth through a surf zone. Sediment thickness and water depth is predicted from stitched layered‐earth inversion of data based on a simplified two‐layer model that represents seawater and sediment overlying a resistive half‐space basement (bedrock). The resulting bathymetric profiles show agreement typically to within ∼±1 m and ∼±0.5 m with known water depths in areas less than 20 and 6 m deep respectively. The inverted depth profile of the second (sediment) layer is noisy; however, the profiles reveal coarse topographic features of paleovalleys to depth limits of ∼60 to 80 m below sea level in 20 to 30 m water depth, as well as resolving bedrock ridges and exposed reefs in shallow waters.
Cytolytic mechanisms and T‐cell receptor Vβ usage by ex vivo generated Epstein–Barr virus‐specific cytotoxic T lymphocytes
Authors: Vanhoutte Victoria J. , McAulay Karen A. , McCarrell Erin , Turner Marc , Crawford Dorothy H. , Haque Tanzina
Published: December 2008

Ex‐vivo‐generated Epstein–Barr virus (EBV)‐specific cytotoxic T lymphocytes (CTL) have been used for cellular adoptive immunotherapy of EBV‐associated lymphomas. Here we investigated the phenotypes, cytolytic mechanisms, polyfunctionality and T‐cell receptor (TCR) usage in growing and established CTL, generated by weekly stimulation with an EBV‐transformed autologous lymphoblastoid cell line (LCL). Our results showed that phenotypically mature CTL developed within the first 4 weeks of culture, with an increase in CD45RO and CD69, and a decrease in CD45RA, CD62L, CD27 and CD28 expression. Spectratyping analysis of the variable β‐chain of the TCR revealed that TCR repertoire remained diverse during the course of culture. Cytotoxicity of CTL was significantly inhibited by concanamycin A (P < 0·0001) and ethylene glycol‐bis tetraacetic acid (P < 0·0001), indicating that a calcium and perforin‐mediated exocytosis pathway with the release of granzyme B was the principal cytotoxic mechanism. The CTL mainly produced interferon‐γ (IFN‐γ) or tumour necrosis factor‐α (TNF‐α) upon restimulation with autologous LCL, although there were some polyfunctional cells producing IFN‐γ and TNF‐α. Granzyme B, perforin and Fas ligand were detected in CD8+ and CD4+ cells in all CTL; however, a greater proportion of CD8+ than CD4+ T cells expressed granzyme B (P < 0·0001) and more granzyme B was detected in CD8+ T cells than in CD4+ T cells (P = 0·001). This difference was not observed with Fas ligand or perforin expression. Our results provide insight into the basic characteristics of ex‐vivo‐generated CTL.
Do all stoneflies nymphs have respiratory proteins? Further data on the presence of hemocyanin in the larval stages of plecoptera species
Authors: Amore V. , Belardinelli M. , Guerra L. , Buonocore F. , Fausto A. M. , Ubero‐Pascal N. , Fochetti R.
Published: December 2008

Contrary to what was assumed regarding the presence of respiratory proteins in insects, a functional hemocyanin was recently found in larvae and adults of the stoneflies species Perla marginata, whereas in the close species Perla grandis, hemocyanin functionality was deduced from sequence data. In order to verify if the presence of this ancient trait is widespread within the order and to investigate why stoneflies have maintained it, we have extended the search for hemocyanin to species of other Plecoptera families. In particular, we assessed the presence of hemocyanin in the larval stage of nine Plecoptera species, belonging to six of the seven families of the European stonefly‐fauna, and analyzed its potential functionality as deduced by sequence data. We cloned and sequenced the corresponding cDNAs and studied their expression with RT‐PCR technique. Moreover, we performed homology studies using the deduced amino acid sequences. On the basis of our analysis, we hypothesized a functional role of the hemocyanin only for two species: Dinocras cephalotes and Isoperla grammatica (Perloidea). In all the investigated Nemouroidea and in Siphonoperla torrentium (Perloidea), this protein may have been lost. Larval size, life‐cycle length, trophic role and environmental induction are discussed as possible explanations of these different physiological requirements.
Surviving glacial ages within the Biotic Gap: phylogeography of the New Zealand cicada Maoricicada campbelli
Authors: Hill Kathy B. R. , Simon Chris , Marshall David C. , Chambers Geoffrey K.
Published: December 2008

Aim  New Zealand is an ideal location in which to investigate the roles of landscape and climate change on speciation and biogeography. An earlier study of the widespread endemic cicada Maoricicada campbelli (Myers) found two phylogeographically distinguishable major clades – northern South Island plus North Island (northern‐SI + NI) and Otago. These two clades appeared to have diverged on either side of an area of the South Island known as the Biotic Gap. We sampled more intensively to test competing theories for this divergence. We aimed to discover if M. campbelli had survived within the Biotic Gap during recent glacial maxima, and if predicted areas of secondary contact between the two major clades existed.

Location  New Zealand.

Methods  We analysed mitochondrial DNA sequences (1520 bp; 212 individuals; 91 populations) using phylogenetic (maximum likelihood, Bayesian), population genetic (analysis of molecular variance) and molecular dating methods (Bayesian relaxed clock with improved priors).

Results  We found strong geographical structuring of genetic variation. Our dating analyses suggest that M. campbelli originated 1.83–2.58 Ma, and split into the two major clades 1.45–2.09 Ma. The main subclades in the northern‐SI + NI clade arose almost simultaneously at 0.69–1.03 Ma. Most subclades are supported by long internal branches and began to diversify 0.40–0.78 Ma. We found four narrow areas of secondary contact between the two major clades. We also found a difference between calling songs of the Otago vs. northern‐SI + NI clades.

Main conclusions  Phylogeographical patterns within M. campbelli indicate an early Pleistocene split into two major clades, followed by late Pleistocene range expansion and in situ population differentiation of subclades. The northern‐SI + NI clade diversified so rapidly that the main subclade relationships cannot be resolved, and we now have little evidence for a disjunction across the Biotic Gap. Structure within the main subclades indicates rapid divergence after a common bottlenecking event, perhaps attributable to an extremely cold glacial maximum at c. 0.43 Ma. Clade structure and dating analyses indicate that M. campbelli survived in many refugia during recent glacial maxima, including within the Biotic Gap. The narrow overlap between the two major clades is attributed to recent contact during the current interglacial and slow gene diffusion. The two major clades appear to be in the early stages of speciation based on genetic and behavioural differences.
Clusterings should not be compared by visual inspection: response to Gagné & Proulx
Authors: Heikinheimo H. , Fortelius M. , Eronen J. , Mannila H.
Published: December 2008

In Heikinheimo et al. (Journal of Biogeography, 2007, 34, 1053–1064) we used clustering to analyse European land mammal fauna. Gagné & Proulx criticized our choice of the Euclidean distance measure in the analysis, and advocated the use of the Hellinger distance measure, claiming that this leads to very different clustering results. The criticism fails to take into account the probabilistic nature of the methods used and the fact that in this case the similarity measures correlate strongly. Gagné & Proulx used subjective inspection as the criterion of similarity between clusterings. We show that this is insufficient and misleading. Namely, owing to the local minimum problem, two clustering runs rarely give identical results. In the case of our study, the measured similarity (using the kappa statistic) between the Euclidean‐ and Hellinger‐based clusterings is roughly equal to the similarity between two clusterings that both use the Hellinger distance but different random initialization points.
Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta‐analysis of randomized controlled trials
Authors: Pandor A. , Ara R. M. , Tumur I. , Wilkinson A. J. , Paisley S. , Duenas A. , Durrington P. N. , Chilcott J.
Published: December 2008

Objectives.  To study the evidence on the efficacy and safety of ezetimibe monotherapy for the treatment of primary (heterozygous familial and non‐familial) hypercholesterolaemia.

Design.  Systematic review and meta‐analysis of randomized controlled trials (RCTs).

Methods.  Eleven electronic bibliographic databases covering the biomedical, scientific and grey literature were searched from inception and supplemented by contact with experts in the field. Two reviewers independently determined the eligibility of RCTs, with a minimum treatment duration of 12 weeks, which compared ezetimibe monotherapy (10 mg per day) with placebo.

Results.  In the absence of data from clinical outcome trials, surrogate endpoints such as changes in lipid concentrations were used as indicators of clinical outcomes. A meta‐analysis of eight randomized, double‐blind, placebo‐controlled trials (all 12 weeks) showed that ezetimibe monotherapy was associated with a statistically significant mean reduction in LDL cholesterol (from baseline to endpoint) of −18.58%, (95% CI: −19.67 to −17.48, P < 0.00001) compared with placebo. Significant (P < 0.00001) changes were also found in total cholesterol (−13.46%, 95% CI: −14.22 to −12.70), HDL cholesterol (3.00%, 95% CI: 2.06–3.94) and triglyceride levels (−8.06%, 95% CI: −10.92 to −5.20). Ezetimibe monotherapy appeared to be well tolerated with a safety profile similar to placebo.

Conclusions.  In a meta‐analysis restricted to short‐term trials in hypercholesterolaemia, significant potentially favourable changes in lipid and lipoprotein levels relative to baseline occurred with ezetimibe monotherapy. Further long‐term studies with cardiovascular and other clinical outcome data are needed to assess the efficacy and safety of ezetimibe more fully.
Genetic diversity and differentiation processes in the ploidy series of Olea europaea L.: a multiscale approach from subspecies to insular populations
Authors: GARCÍA‐VERDUGO C. , FAY M. F. , GRANADO‐YELA C. , DE CASAS R. RUBIO , BALAGUER L. , BESNARD G. , VARGAS P.
Published: December 2008

Geographical isolation and polyploidization are central concepts in plant evolution. The hierarchical organization of archipelagos in this study provides a framework for testing the evolutionary consequences for polyploid taxa and populations occurring in isolation. Using amplified fragment length polymorphism and simple sequence repeat markers, we determined the genetic diversity and differentiation patterns at three levels of geographical isolation in Olea europaea: mainland‐archipelagos, islands within an archipelago, and populations within an island. At the subspecies scale, the hexaploid ssp. maroccana (southwest Morocco) exhibited higher genetic diversity than the insular counterparts. In contrast, the tetraploid ssp. cerasiformis (Madeira) displayed values similar to those obtained for the diploid ssp. guanchica (Canary Islands). Geographical isolation was associated with a high genetic differentiation at this scale. In the Canarian archipelago, the stepping‐stone model of differentiation suggested in a previous study was partially supported. Within the western lineage, an east‐to‐west differentiation pattern was confirmed. Conversely, the easternmost populations were more related to the mainland ssp. europaea than to the western guanchica lineage. Genetic diversity across the Canarian archipelago was significantly correlated with the date of the last volcanic activity in the area/island where each population occurs. At the island scale, this pattern was not confirmed in older islands (Tenerife and Madeira), where populations were genetically homogeneous. In contrast, founder effects resulted in low genetic diversity and marked genetic differentiation among populations of the youngest island, La Palma.
Parts exchange: tuning the flagellar motor to fit the conditions
Authors: Delalez Nicolas , Armitage Judith P.
Published: December 2008

Many cellular activities are driven by complex protein machines. By measuring the behaviour of fluorescent protein fusions in real time in living cells it has become apparent that many of these complexes are not fixed, but are dynamic. To some extent this might be expected, for example, for cell division complexes, as defining mid‐cell is linked to growth and cell cycle, but perhaps comes as more of a surprise with a complex anchored machine like the bacterial flagellar motor. The assumption has been that once made it remains intact. However, the dynamics of this structure is strongly supported in two manuscripts in this issue of Molecular Microbiology. The stator units which form a peptioglycan anchored ring around the rotor, generating torque in response to the ion motive force, clearly disengage when conditions change. The driving ion is shown to be important in both engagement of the stator to the rotor and the selection of the type of stator unit. These new results provide an insight into the mechanisms underlying motor function, which might rely on dynamic processes, and clearly illustrate the need to move away from a static view of cellular structures.
Production, characterization and determination of the real catalytic properties of the putative ‘succinate dehydrogenase’ from Wolinella succinogenes
Authors: Juhnke Hanno D. , Hiltscher Heiko , Nasiri Hamid R. , Schwalbe Harald , Lancaster C. Roy D.
Published: December 2008

Both the genomes of the epsilonproteobacteria Wolinella succinogenes and Campylobacter jejuni contain operons (sdhABE) that encode for so far uncharacterized enzyme complexes annotated as ‘non‐classical’ succinate:quinone reductases (SQRs). However, the role of such an enzyme ostensibly involved in aerobic respiration in an anaerobic organism such as W. succinogenes has hitherto been unknown. We have established the first genetic system for the manipulation and production of a member of the non‐classical succinate:quinone oxidoreductase family. Biochemical characterization of the W. succinogenes enzyme reveals that the putative SQR is in fact a novel methylmenaquinol:fumarate reductase (MFR) with no detectable succinate oxidation activity, clearly indicative of its involvement in anaerobic metabolism. We demonstrate that the hydrophilic subunits of the MFR complex are, in contrast to all other previously characterized members of the superfamily, exported into the periplasm via the twin‐arginine translocation (tat)‐pathway. Furthermore we show that a single amino acid exchange (Ala86→His) in the flavoprotein of that enzyme complex is the only additional requirement for the covalent binding of the otherwise non‐covalently bound FAD. Our results provide an explanation for the previously published puzzling observation that the C. jejuni sdhABE operon is upregulated in an oxygen‐limited environment as compared with microaerophilic laboratory conditions.
Nesting sub‐studies and randomised controlled trials within birth cohort studies
Authors: Golding Jean
Published: December 2008

Although birth cohort studies can stand on their own, there are a number of different types of sub‐studies that can add value to the overall project. These can be summarised within four main categories: (A) more detailed observations of relatively small subgroups aimed at describing mechanisms and processes; (B) nested case–control studies; (C) use of detailed observations to validate data collection by questionnaire or interview; (D) randomised controlled trials. For each category we give examples of ways in which they have been employed in current pregnancy birth cohort studies.
Highly Arthritis‐susceptible DA Rats Express IL‐1β in Articular Cartilage
Authors: Weiss R. J. , Erlandsson Harris H. , Palmblad K.
Published: December 2008

There are genetically determined differences in susceptibility to arthritis among inbred rat strains. The aim of the present study was to elucidate phenotypical differences, by determining expression of TNF and IL‐1β, two pivotal mediators of arthritis, in the highly arthritis‐prone Dark Agouti (DA) rat compared to that of two arthritis‐resistant rat strains, the major histocompatibility complex‐homologous Piebald‐Viral‐Glaxo (PVG.1AV1) rat and the Brown Norway (BN) rat, assessed by immunohistochemistry. We demonstrate a distinct difference in articular cartilage, with chondrocytes expressing IL‐1β, not TNF, in the highly arthritis‐prone DA rat as opposed to the two arthritis‐resistant BN or PVG.1AV1 rat strains, where no cytokine expression was documented. The results were otherwise congruent among the rat strains. We observed TNF‐ and IL‐1β‐expressing cells within the synovial lining layer in all rat strains. Other tissues studied, auricular cartilage as well as muscle, lung, thyroid gland and kidney tissue, were devoid of cytokine expression. Constitutional expression of IL‐1β in chondrocytes might facilitate initiation and perpetuation of inflammation. This may offer one explanation of why erosive arthritides are so easily induced in the DA rat and also support the hypothesis that articular chondrocytes may themselves play a major role in cartilage matrix degradation.
Relationship between Circulating Levels of IFN‐γ, IL‐10, CXCL9 and CCL2 in Pulmonary and Extrapulmonary Tuberculosis is Dependent on Disease Severity
Authors: Hasan Z. , Jamil B. , Khan J. , Ali R. , Khan M. A. , Nasir N. , Yusuf M. S. , Jamil S. , Irfan M. , Hussain R.
Published: December 2008

Protection against Mycobacterium tuberculosis infection is dependent on T cell and macrophage activation regulated by cytokines. Cytokines and chemokines produced at disease sites may be released into circulation. Data available on circulating cytokines in tuberculosis (TB) is mostly on pulmonary TB (PTB) with limited information on extrapulmonary disease (EPul‐TB). We measured interferon‐gamma (IFN‐γ), interkeukin‐10 (IL‐10), CXCL9 and CCL2 in sera of patients (n = 80) including; PTB (n = 42), EPul‐TB (n = 38) and BCG vaccinated healthy endemic controls (EC, n = 42). EPul‐TB patients comprised those with less severe (LNTB) or severe (SevTB) disease. Serum IFN‐γ, IL‐10 and CXCL9 levels were significantly greater while CCL2 was reduced in TB patients as compared with EC. IFN‐γ was significantly greater in PTB as compared with LNTB (P = 0.002) and SevTB (P = 0.029). CXCL9 was greater in PTB as compared with LNTB (P = 0.009). In contrast, CCL2 levels were reduced in PTB as compared with LNTB (P = 0.021) and SevTB (P = 0.024). A Spearman’s rank correlation analysis determined a positive association between IFN‐γ and IL‐10 (rho = 0.473, P = 0.002) and IFN‐γ and CXCL9 (rho = 0.403, P = 0.008) in the PTB group. However, in SevTB, only IFN‐γ and CXCL9 were positively associated (rho = 0.529, P = 0.016). Systemic levels of cytokines are reflective of local responses at disease sites. Therefore, our data suggests that in PTB increased IFN‐γ and CXCL9 balanced by IL‐10 may result in a more effective cell mediated response in the host. However, elevated inflammatory chemokines CXCL9 and CCL2 in severe EPul‐TB without concomitant down modulatory cytokines may exacerbate disease related pathology and hamper restriction of M. tuberculosis infection.
Effect of an Extract Based on the Medicinal Mushroom Agaricus blazei Murill on Release of Cytokines, Chemokines and Leukocyte Growth Factors in Human Blood Ex Vivo and In Vivo
Authors: Johnson E. , Førland D. T. , Sætre L. , Bernardshaw S. V. , Lyberg T. , Hetland G.
Published: December 2008

An immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM) has been shown to stimulate mononuclear phagocytes in vitro to produce pro‐inflammatory cytokines, and to protect against lethal peritonitis in mice. The present aim was to study the effect of AbM on release of several cytokines in human whole blood both after stimulation ex vivo and in vivo after oral intake over several days in healthy volunteers. The 17 signal substances examined were; T helper 1 (Th1) cytokines [interleukin (IL)‐2, interferon (IFN)‐γ and IL‐12], T helper 2 cytokines (IL‐4, IL‐5 and IL‐13), pleiotropic (IL‐7, IL‐17), pro‐inflammatory [IL‐1β, IL‐6, tumour necrosis factor (TNF)‐α (mainly produced by Th1 cells)] – and anti‐inflammatory (IL‐10) cytokines, chemokines [IL‐8, macrophage inhibitory protein (MIP)‐1β and monocyte chemoattractant protein (MCP)‐1] and leukocyte growth factors [granulocyte colony‐stimulating factor (G‐CSF), granulocyte/macrophage colony stimulating factor]. After stimulation of whole blood ex vivo with 0.5–5.0% of a mushroom extract, AndoSan™ mainly containing AbM, there was a dose‐dependent increase in all the cytokines studied, ranging from two to 399‐fold (TNF‐α). However, in vivo in the eight volunteers who completed the daily intake (60 ml) of this AbM extract for 12 days, a significant reduction was observed in levels of IL‐1β (97%), TNF‐α (84%), IL‐17 (50%) and IL‐2 (46%). Although not significant, there was a trend towards reduced levels for IL‐8, IFN‐γ and G‐CSF, whilst those of the remaining nine cytokines tested, were unaltered. The discrepant results on cytokine release ex vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited absorption of its large, complex and bioactive β‐glucans across the intestinal mucosa to the reticuloendothelial system and blood.
Natural Immunity has Significant Impact on Immune Responses Against Cancer
Authors: Rubin B.
Published: December 2008

The immune system defends the host against pathogenic attacks by micro‐organisms and their products. It does not react against self‐components due to the relatively efficient negative selection of developing T lymphocytes in the thymus. This process does permit T cells with low avidity against self to be present in the T cell repertoire. Such cells play an important physiological role as the host needs so‐called autoimmune reactions in order to eliminate dying cells or transformed tumour cells. One of the mysteries in immunology is how the host maintains beneficial autoimmune reactions and avoids pathogenic autoimmune reactions. Activation of the adaptive T lymphocytes is mediated by the low avidity interaction between T‐cell antigen receptors and antigenic peptides associated with major histocompatibility complex class I or class II molecules. This interaction is strengthened by T‐cell co‐receptors such as CD2, CD4, CD8, CD28 and CD154, which react with ligands expressed by cells of the innate immune system. In recent years, the importance of pre‐activation of the innate immune system for initiation of adaptive T‐cell immune responses has been appreciated. In the present review, I will summarize our work on how natural immunity plays an important role in determining the level of beneficial autoimmune reactions against cancer.
Dendritic Cells Engineered to Express Defined Allo‐HLA Peptide Complexes Induce Antigen‐specific Cytotoxic T Cells Efficiently Killing Tumour Cells
Authors: Stronen E. , Abrahamsen I. W. , Gaudernack G. , Wälchli S. , Munthe E. , Buus S. , Johansen F.‐E. , Lund‐Johansen F. , Olweus J.
Published: December 2008

Most tumour‐associated antigens (TAA) are non‐mutated self‐antigens. The peripheral T cell repertoire is devoid of high‐avidity TAA‐specific cytotoxic T lymphocytes (CTL) due to self‐tolerance. As tolerance is major histocompatibility complex‐restricted, T cells may be immunized against TAA presented by a non‐self human leucocyte antigen (HLA) molecule and transferred to cancer patients expressing that HLA molecule. Obtaining allo‐restricted CTL of high‐avidity and low cross‐reactivity has, however, proven difficult. Here, we show that dendritic cells transfected with mRNA encoding HLA‐A*0201, efficiently present externally loaded peptides from the antigen, Melan‐A/MART‐1 to T cells from HLA‐A*0201‐negative donors. CD8+ T cells binding HLA‐A*0201/MART‐1 pentamers were detected already after 12 days of co‐culture in 11/11 donors. The majority of cells from pentamer+ cell lines were CTL and efficiently killed HLA‐A*0201+ melanoma cells, whilst sparing HLA‐A*0201+ B‐cells. Allo‐restricted CTL specific for peptides from the leukaemia‐associated antigens CD33 and CD19 were obtained with comparable efficiency. Collectively, the results show that dendritic cells engineered to express defined allo‐HLA peptide complexes are highly efficient in generating CTL specifically reacting with tumour‐associated antigens.