bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectrum of genetic diversity and networks of clonal organisms
Authors: Rozenfeld Alejandro F , Arnaud-Haond Sophie , Hernández-García Emilio , Eguíluz Víctor M , Matías Manuel A , Serrão Ester , Duarte Carlos M
Published: May 2007

Clonal reproduction characterizes a wide range of species including clonal plants in terrestrial and aquatic ecosystems, and clonal microbes such as bacteria and parasitic protozoa, with a key role in human health and ecosystem processes. Clonal organisms present a particular challenge in population genetics because, in addition to the possible existence of replicates of the same genotype in a given sample, some of the hypotheses and concepts underlying classical population genetics models are irreconcilable with clonality. The genetic structure and diversity of clonal populations were examined using a combination of new tools to analyse microsatellite data in the marine angiospermPosidonia oceanica. These tools were based on examination of the frequency distribution of the genetic distance among ramets, termed the spectrum of genetic diversity (GDS), and of networks built on the basis of pairwise genetic distances among genets. Clonal growth and outcrossing are apparently dominant processes, whereas selfing and somatic mutations appear to be marginal, and the contribution of immigration seems to play a small role in adding genetic diversity to populations. The properties and topology of networks based on genetic distances showed a ‘small-world’ topology, characterized by a high degree of connectivity among nodes, and a substantial amount of substructure, revealing organization in subfamilies of closely related individuals. The combination of GDS and network tools proposed here helped in dissecting the influence of various evolutionary processes in shaping the intra-population genetic structure of the clonal organism investigated; these therefore represent promising analytical tools in population genetics.
Experimental characterization and computational modelling of two-dimensional cell spreading for skeletal regeneration
Authors: Sengers Bram G , Please Colin P , Oreffo Richard O.C
Published: May 2007

Limited cell ingrowth is a major problem for tissue engineering and the clinical application of porous biomaterials as bone substitutes. As a first step, migration and proliferation of an interacting cell population can be studied in two-dimensional culture. Mathematical modelling is essential to generalize the results of these experiments and to derive the intrinsic parameters that can be used for predictions. However, a more thorough evaluation of theoretical models is hampered by limited experimental observations. In this study, experiments and image analysis methods were developed to provide a detailed spatial and temporal picture of how cell distributions evolve. These methods were used to quantify the migration and proliferation of skeletal cell types including MG63 and human bone marrow stromal cells (HBMSCs). The high level of detail with which the cell distributions were mapped enabled a precise assessment of the correspondence between experimental results and theoretical model predictions. This analysis revealed that the standard Fisher equation is appropriate for describing the migration behaviour of the HBMSC population, while for the MG63 cells a sharp front model is more appropriate. In combination with experiments, this type of mathematical model will prove useful in predicting cell ingrowth and improving strategies and control of skeletal tissue regeneration.
DNA barcoding cannot reliably identify species of the blowfly genusProtocalliphora(Diptera: Calliphoridae)
Authors: Whitworth T.L , Dawson R.D , Magalon H , Baudry E
Published: May 2007

In DNA barcoding, a short standardized DNA sequence is used to assign unknown individuals to species and aid in the discovery of new species. A fragment of the mitochondrial gene cytochromecoxidase subunit 1 is emerging as the standard barcode region for animals. However, patterns of mitochondrial variability can be confounded by the spread of maternally transmitted bacteria that cosegregate with mitochondria. Here, we investigated the performance of barcoding in a sample comprising 12 species of the blow fly genusProtocalliphora, known to be infected with the endosymbiotic bacteriaWolbachia. We found that the barcoding approach showed very limited success: assignment of unknown individuals to species is impossible for 60% of the species, while using the technique to identify new species would underestimate the species number in the genus by 75%. This very low success of the barcoding approach is due to the non-monophyly of many of the species at the mitochondrial level. We even observed individuals from four different species with identical barcodes, which is, to our knowledge, the most extensive case of mtDNA haplotype sharing yet described. The pattern ofWolbachiainfection strongly suggests that the lack of within-species monophyly results from introgressive hybridization associated withWolbachiainfection. Given thatWolbachiais known to infect between 15 and 75% of insect species, we conclude that identification at the species level based on mitochondrial sequence might not be possible for many insects. However, given thatWolbachia-associated mtDNA introgression is probably limited to very closely related species, identification at the genus level should remain possible.
The concept of correlated progression as the basis of a model for the evolutionary origin of major new taxa
Authors: Kemp T.S
Published: May 2007

Understanding the evolutionary processes responsible for the long treks through morphospace associated with the origin of new higher taxa is hampered by the lack of a realistic and usable model that accounts for long-term phenotypic evolvability. The systems-related concept of correlated progression, in which all the traits are functionally linked and so constrained to evolve by small increments at a time in parallel with each other, provides the basis for such a model. Implications for the process of evolution at high taxonomic level are that: the evolving traits must be considered together as a system, and the exact sequence of incremental changes in characters is indeterminable; there are no identifiable key innovations; selection acts on the phenotype as a whole rather than on individual traits; and the selection force is therefore multidimensional. Application of the model to the pattern of evolution of traits and trait states as revealed by the fossil record of the stem groups of such taxa as mammals, turtles and tetrapods generates realistic testable hypotheses about how such groups evolved.
Drd4
gene polymorphisms are associated with personality variation in a passerine bird
Authors: Fidler Andrew E , van Oers Kees , Drent Piet J , Kuhn Sylvia , Mueller Jakob C , Kempenaers Bart
Published: May 2007

Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (
Drd4
) variants and novelty-seeking behaviour. However, genetic epistasis, genotype–environment interactions and confounding environmental factors all act to obscure genotype–personality relationships. Such problems can be addressed by measuring personality under standardized conditions and by selection experiments, with both approaches only feasible with non-human animals. Looking for similar
Drd4
genotype–personality associations in a free-living bird, the great tit (
Parus major
), we detected 73 polymorphisms (66 SNPs, 7 indels) in the
P. major Drd4
orthologue. Two of the
P. major Drd4
gene polymorphisms were investigated for evidence of association with novelty-seeking behaviour: a coding region synonymous single nucleotide polymorphism (SNP830) and a 15 bp indel (ID15) located 5′ to the putative transcription initiation site. Frequencies of the three
Drd4
SNP830 genotypes, but not the ID15 genotypes, differed significantly between two
P. major
lines selected over four generations for divergent levels of ‘early exploratory behaviour’ (EEB). Strong corroborating evidence for the significance of this finding comes from the analysis of free-living, unselected birds where we found a significant association between SNP830 genotypes and differing mean EEB levels. These findings suggest that an association between
Drd4
gene polymorphisms and animal personality variation predates the divergence of the avian and mammalian lineages. Furthermore, this work heralds the possibility of following microevolutionary changes in frequencies of behaviourally relevant
Drd4
polymorphisms within populations where natural selection acts differentially on different personality types.
A generative bias towards average complexity in artificial cell lineages
Authors: Lohaus Rolf , Geard Nicholas L , Wiles Janet , Azevedo Ricardo B.R
Published: May 2007

The evolution of life on earth has been characterized by generalized long-term increases in phenotypic complexity. Although natural selection is a plausible cause for these trends, one alternative hypothesis—generative bias—has been proposed repeatedly based on theoretical considerations. Here, we introduce a computational model of a developmental system and use it to test the hypothesis that long-term increasing trends in phenotypic complexity are caused by a generative bias towards greater complexity. We use our model to generate random organisms with different levels of phenotypic complexity and analyse the distributions of mutational effects on complexity. We show that highly complex organisms are easy to generate but there are trade-offs between different measures of complexity. We also find that only the simplest possible phenotypes show a generative bias towards higher complexity, whereas phenotypes with high complexity display a generative bias towardslowercomplexity. These results suggest that generative biases alone are not sufficient to explain long-term evolutionary increases in phenotypic complexity. Rather, our finding of a generative bias towards average complexity argues for a critical role of selective biases in driving increases in phenotypic complexity and in maintaining high complexity once it has evolved.
Emergence of protocellular growth laws
Authors: Rocheleau Tristan , Rasmussen Steen , Nielsen Peter E , Jacobi Martin N , Ziock Hans
Published: May 2007

Template-directed replication is known to obey a parabolic growth law due to product inhibition (Sievers & Von Kiedrowski 1994
Nature
369
, 221; Lee
et al
. 1996
Nature
382
, 525; Varga & Szathmáry 1997
Bull. Math. Biol
.
59
, 1145). We investigate a template-directed replication with a coupled template catalysed lipid aggregate production as a model of a minimal protocell and show analytically that the autocatalytic template–container feedback ensures balanced exponential replication kinetics; both the genes and the container grow exponentially with the same exponent. The parabolic gene replication does not limit the protocellular growth, and a detailed stoichiometric control of the individual protocell components is not necessary to ensure a balanced gene–container growth as conjectured by various authors (Gánti 2004
Chemoton theory
). Our analysis also suggests that the exponential growth of most modern biological systems emerges from the inherent spatial quality of the container replication process as we show analytically how the internal gene and metabolic kinetics determine the cell population's generation time and not the growth law (Burdett & Kirkwood 1983
J. Theor. Biol
.
103
, 11–20; Novak
et al
. 1998
Biophys. Chem
.
72
, 185–200; Tyson
et al
. 2003
Curr. Opin. Cell Biol
.
15
, 221–231). Previous extensive replication reaction kinetic studies have mainly focused on template replication and have not included a coupling to metabolic container dynamics (Stadler
et al
. 2000
Bull. Math. Biol
.
62
, 1061–1086; Stadler & Stadler 2003
Adv. Comp. Syst
.
6
, 47). The reported results extend these investigations. Finally, the coordinated exponential gene–container growth law stemming from catalysis is an encouraging circumstance for the many experimental groups currently engaged in assembling self-replicating minimal artificial cells (Szostak 2001
et al
.
Nature
409
, 387–390; Pohorille & Deamer 2002
Trends Biotech
.
20
123–128; Rasmussen
et al
. 2004
Science
303
, 963–965; Szathmáry 2005
Nature
433
, 469–470; Luisi
et al
. 2006
Naturwissenschaften
93
, 1–13).
1
Environmental constraints upon locomotion and predator–prey interactions in aquatic organisms: an introduction
Authors: Domenici P , Claireaux G , McKenzie D.J
Published: May 2007

Environmental constraints in aquatic habitats have become topics of concern to both the scientific community and the public at large. In particular, coastal and freshwater habitats are subject to dramatic variability in various environmental factors, as a result of both natural and anthropogenic processes. The protection and sustainable management of all aquatic habitats requires greater understanding of how environmental constraints influence aquatic organisms. Locomotion and predator–prey interactions are intimately linked and fundamental to the survival of mobile aquatic organisms. This paper summarizes the main points from the review and research articles which comprise the theme issue ‘Environmental constraints upon locomotion and predator–prey interactions in aquatic organisms’. The articles explore how natural and anthropogenic factors can constrain these two fundamental activities in a diverse range of organisms from phytoplankton to marine mammals. Some major environmental constraints derive from the intrinsic properties of the fluid and are mechanical in nature, such as viscosity and flow regime. Other constraints derive from direct effects of factors, such as temperature, oxygen content of the water or turbidity, upon the mechanisms underlying the performance of locomotion and predator–prey interactions. The effect of these factors on performance at the tissue and organ level is reflected in constraints upon performance of the whole organism. All these constraints can influence behaviour. Ultimately, they can have an impact on ecological performance. One issue that requires particular attention is how factors such as temperature and oxygen can exert different constraints on the physiology and behaviour of different taxa and the ecological implications of this. Given the multiplicity of constraints, the complexity of their interactions, and the variety of biological levels at which they can act, there is a clear need for integration between the fields of physiology, biomechanics, behaviour, ecology, biological modelling and evolution in both laboratory and field studies. For studies on animals in their natural environment, further technological advances are required to allow investigation of how the prevailing physico-chemical conditions influence basic physiological processes and behaviour.
Complex physiological traits as biomarkers of the sub-lethal toxicological effects of pollutant exposure in fishes
Authors: McKenzie D.J , Garofalo E , Winter M.J , Ceradini S , Verweij F , Day N , Hayes R , van der Oost R , Butler P.J , Chipman J.K , Taylor E.W
Published: May 2007

Complex physiological traits, such as routine aerobic metabolic rate or exercise performance, are indicators of the functional integrity of fish that can reveal sub-lethal toxicological effects of aquatic pollutants. These traits have proved valuable in laboratory investigations of the sub-lethal effects of heavy metals, ammonia and various xenobiotics. It is not known, however, whether they can also function as biomarkers of the complex potential range of effects upon overall functional integrity caused by exposure to mixtures of chemicals in polluted natural environments. The current study used portable swimming respirometers to compare exercise performance and respiratory metabolism of fish exposed in cages for three weeks to either clean or polluted sites on three urban European river systems: the river Lambro, Milan, Italy; the rivers Blythe, Cole and Tame, Birmingham, UK; and the river Amstel, Amsterdam, The Netherlands. The UK and Italian rivers were variously polluted with high levels of both bioavailable heavy metals and organics, and the Amstel by mixtures of bioavailable organics at high concentrations. In both the UK and Italy, indigenous chub (Leuciscus cephalus) exposed to clean or polluted sites swam equally well in an initial performance test, but the chub from polluted sites could not repeat this performance after a brief recovery interval. These animals were unable to raise the metabolic rate and allocate oxygen towards exercise in the second trial, an effect confirmed in successive campaigns in Italy. Swimming performance was therefore a biomarker indicator of pollutant exposure in chub exposed at these sites. Exposure to polluted sites on the river Amstel did not affect the repeat swimming performance of cultured cloned carp (Cyprinus carpio), indicating either a species-specific tolerance or relative absence of heavy metals. However, measurements of oxygen uptake during swimming revealed increased rates of routine aerobic metabolism in both chub and carp at polluted sites in all of the rivers studied, indicating a sub-lethal metabolic loading effect. Therefore, the physiological traits of exercise performance and metabolic rate have potential as biomarkers of the overall sub-lethal toxic effects of exposure to complex mixtures of pollutants in rivers, and may also provide insight into why fish do not colonize some polluted environments.
Predator–prey interactions and changing environments: who benefits?
Authors: Abrahams Mark V , Mangel Marc , Hedges Kevin
Published: May 2007

While aquatic environments have long been thought to be more moderate environments than their terrestrial cousins, environmental data demonstrate that for some systems this is not so. Numerous important environmental parameters can fluctuate dramatically, notably dissolved oxygen, turbidity and temperature. The roles of dissolved oxygen and turbidity on predator–prey interactions have been discussed in detail elsewhere within this issue and will be considered only briefly here. Here, we will focus primarily on the role of temperature and its potential impact upon predator–prey interactions. Two key properties are of particular note. For temperate aquatic ecosystems, all piscine and invertebrate piscivores and their prey are ectothermic. They will therefore be subject to energetic demands that are significantly affected by environmental temperature. Furthermore, the physical properties of water, particularly its high thermal conductivity, mean that thermal microenvironments will not exist so that fine-scale habitat movements will not be an option for dealing with changing water temperature in lentic environments. Unfortunately, there has been little experimental analysis of the role of temperature on such predator–prey interactions, so we will instead focus on theoretical work, indicating that potential implications associated with thermal change are unlikely to be straightforward and may present a greater threat to predators than to their prey. Specifically, we demonstrate that changes in the thermal environment can result in a net benefit to cold-adapted species through the mechanism of predator–prey interactions.
Locomotion in diving elephant seals: physical and physiological constraints
Authors: Davis Randall W , Weihs Daniel
Published: May 2007

To better understand how elephant seals (Mirounga angustirostris) use negative buoyancy to reduce energy metabolism and prolong dive duration, we modelled the energetic cost of transit and deep foraging dives in an elephant seal. A numerical integration technique was used to model the effects of swim speed, descent and ascent angles, and modes of locomotion (i.e. stroking and gliding) on diving metabolic rate, aerobic dive limit, vertical displacement (maximum dive depth) and horizontal displacement (maximum horizontal distance along a straight line between the beginning and end locations of the dive) for aerobic transit and foraging dives. Realistic values of the various parameters were taken from previous experimental data. Our results indicate that there is little energetic advantage to transit dives with gliding descent compared with horizontal swimming beneath the surface. Other factors such as feeding and predator avoidance may favour diving to depth during migration. Gliding descent showed variable energy savings for foraging dives. Deep mid-water foraging dives showed the greatest energy savings (approx. 18%) as a result of gliding during descent. In contrast, flat-bottom foraging dives with horizontal swimming at a depth of 400 m showed less of an energetic advantage with gliding descent, primarily because more of the dive involved stroking. Additional data are needed before the advantages of gliding descent can be fully understood for male and female elephant seals of different age and body composition. This type of data will require animal-borne instruments that can record the behaviour, three-dimensional movements and locomotory performance of free-ranging animals at depth.
Successful foraging zones of southern elephant seals from the Kerguelen Islands in relation to oceanographic conditions
Authors: Bailleul Frédéric , Charrassin Jean-Benoît , Monestiez Pascal , Roquet Fabien , Biuw Martin , Guinet Christophe
Published: May 2007

Southern elephant seals,Mirounga leonina, undertake large-scale oceanic movements to access favourable foraging areas. Successful foraging areas of elephant seals from the Kerguelen Islands are investigated here in relation to oceanographic parameters. Movements and diving activity of the seals as well as oceanographic data were collected through a new generation of satellite relayed devices measuring and transmitting locations, pressure, temperature and salinity. For the first time, we have associated foraging behaviour, determined by high increased sinuosity in tracks, and dive density (i.e. number of dives performed per kilometre covered), and changes in body condition, determined by variations in drift rate obtained from drift dives, to identify the oceanographic conditions of successful foraging zones for this species. Two main sectors, one close to the Antarctic continent and the other along the Polar Front (PF), where both foraging activity and body condition increase, seem to be of particular interest for the seals. Within these regions, some seals tended to focus their foraging activity on zones with particular temperature signatures. Along the Antarctic continent, some seals targeted colder waters on the sea bottom during benthic dives, while at the PF the favourable zones tended to be warmer. The possible negative effect of colder waters in Antarctic on the swimming performances of potential fish or squid prey could explain the behaviour of elephant seals in these zones, while warmer waters within the PF could correspond to the optimal conditions for potential myctophid prey of elephant seals.
Is Financial Globalization Beneficial?
Authors: MISHKIN FREDERIC S.
Published: May 2007

This lecture examines whether financial globalization is beneficial to developing countries by first examining the evidence on financial development and economic growth and concludes that financial development is indeed a key element in promoting economic growth. It then asks why if financial development is so beneficial, it often does not occur. It then goes on to examine whether globalization, particularly of the financial kind, can help encourage financial and economic development and argues that it can. However, financial globalization does not always work to encourage economic development because it often leads to devastating financial crises. The issue is thus not whether financial globalization is inherently good or bad, but whether it can be done right.
Competition from Large, Multimarket Firms and the Performance of Small, Single‐Market Firms: Evidence from the Banking Industry
Authors: BERGER ALLEN N. , DICK ASTRID A. , GOLDBERG LAWRENCE G. , WHITE LAWRENCE J.
Published: May 2007

We offer and test two competing hypotheses for the consolidation trend in banking using U.S. banking industry data over the period 1982–2000. Under the efficiency hypothesis, technological progress improved the performance of large, multimarket firms relative to small, single‐market firms, whereas under the hubris hypothesis, consolidation was largely driven by corporate hubris. Our results are consistent with an empirical dominance of the efficiency hypothesis over the hubris hypothesis—on net, technological progress allowed large, multimarket banks to compete more effectively against small, single‐market banks in the 1990s than in the 1980s. We also isolate the extent to which technological progress occurred through scale versus geographic effects and how they affected the performance of small, single‐market banks through revenues versus costs. The results may shed light as well on some of the research and policy issues related to community banking.
Temporal Patterns in Foreign Exchange Returns and Options
Authors: CHARLEBOIS MAXIME , SAPP STEPHEN
Published: May 2007

Although the foreign exchange market is believed to be one of the most efficient financial markets in the world, there is significant evidence that technical analysis is profitable in this market. In this study we investigate the ability of information from the options market to supplement the commonly used information on past prices to predict temporal patterns in foreign exchange returns. We find that strategies using information from at‐the‐money options were more consistently profitable than the commonly used strategies based on only historical spot exchange rates (past prices). Consequently, options appear to contain information regarding future spot exchange rate movements.
A Long‐Run Non‐Linear Approach to the Fisher Effect
Authors: CHRISTOPOULOS DIMITRIS K. , LEÓN‐LEDESMA MIGUEL A.
Published: May 2007

We argue that the empirical failure of the Fisher effect found in the literature may be due to the existence of non‐linearities in the long‐run relationship between interest rates and inflation. We present evidence that, for the U.S. during the 1960–2004 period, the Fisher relation presents important non‐linearities. We model the long‐run non‐linear relationship and find that an ESTR model for the pre‐Volcker era and an LSTR model for the post‐Volcker era are able to control for non‐linearities and constitute long‐run co‐integration vectors. Monte Carlo evidence produces support for the hypothesis that non‐linearities may also be responsible for the less than proportional coefficients of inflation usually found in the linear specifications.
Quantifying the Risk of Deflation
Authors: KILIAN LUTZ , MANGANELLI SIMONE
Published: May 2007

We propose formal and quantitative measures of the risk that future inflation will be excessively high or low relative to the range preferred by a private sector agent. Unlike alternative measures of risk, our measures are designed to make explicit the dependence of risk measures on the private sector agent's preferences with respect to inflation. We illustrate our methodology by estimating the risks of deflation for the United States, Germany, and Japan for horizons of up to 2 years. The question of how large these risks are has been subject to considerable public debate. We find that, as of September 2002 when this question first arose, there was no evidence of substantial deflation risks for the United States and for Germany, contrary to some conjectures at the time. In contrast, there was evidence of substantial deflation risks in Japan.
The Slow Adjustment of Aggregate Consumption to Permanent Income
Authors: MORLEY JAMES C.
Published: May 2007

This paper investigates the relationship between aggregate consumption and permanent income using a new approach to the estimation of cointegrated systems that builds on Stock and Watson's common stochastic trends representation. The permanent and transitory movements in aggregate income and consumption are estimated directly using the Kalman filter and are allowed to be correlated. This approach avoids any implicit restriction that permanent income be as smooth as consumption. Instead, permanent income appears to be relatively volatile, with consumption adjusting toward it only slowly over time. These results provide a clear rejection of the standard version of the permanent income hypothesis and are suggestive of alternative theories of consumption behavior such as habit formation or precautionary savings.
Does Monetary Policy Have Asymmetric Effects on Stock Returns?
Authors: CHEN SHIU‐SHENG
Published: May 2007

This paper investigates whether monetary policy has asymmetric effects on stock returns using Markov‐switching models. Different measures of a monetary policy stance are adopted. Empirical evidence from monthly returns on the Standard & Poor's 500 price index suggests that monetary policy has larger effects on stock returns in bear markets. Furthermore, it is shown that a contractionary monetary policy leads to a higher probability of switching to the bear‐market regime.
Evidence on the Extent and Potential Sources of Long Memory in U.S. Treasury Security Returns and Yields
Authors: CONNOLLY ROBERT A. , GÜNER Z. NURAY , HIGHTOWER KENNETH N.
Published: May 2007

Unlike equity returns, many fixed‐income return measures appear to display long memory. We show that the extent of long memory differs strongly for gross and excess holding period returns on U.S. Treasury securities. Granger and others have argued that long memory may only reflect infrequent structural breaks. We explore the impact of structural instability on tests for long memory and find only weak indications that it lies behind the long memory in our return series. The evidence of long memory remains strong for yield and term premia series even after accounting for a series of potential underlying structural changes.
Arterial Hypertension and Cognitive Dysfunction in Physiologic and Pathologic Aging of the Brain
Authors: Lanari Alessia , Silvestrelli Giorgio , Dominicis Pierangelo De , Tomassoni Daniele , Amenta Francesco , Parnetti Lucilla
Published: May 2007

Arterial hypertension is the most important modifiable cerebrovascular risk factor; its relationship with cerebrovascular disease is continuous, consistent, and independent. Different and probably converging pathophysiologic mechanisms explain the role of arterial hypertension in causing cognitive dysfunction in pathologic aging of the brain, specifically, vascular dementia and Alzheimer's disease.
Involvement of CD147 in regulation of multidrug resistance to P‐gp substrate drugs andin vitroinvasion in breast cancer cells
Authors: Li Qing‐Quan , Wang Wen‐Juan , XU Jing‐Da , Cao Xi‐Xi , Chen Qi , Yang Jin‐Ming , Xu Zu‐De
Published: May 2007

Multidrug resistant (MDR) cancer cells overexpressing P‐glycoprotein (P‐gp) display variations in invasive and metastatic behavior. We aimed to clarify the mechanism(s) underlying this observation and transfected vectors carrying CD147, a glycoprotein enriched on the surface of tumor cells that stimulates the production of matrix metalloproteinases (MMPs), and specific shCD147 into MCF7 and MCF7/Adr cells, respectively. Using quantitative real‐time polymerase chain reaction and Western blot, we found that overexpression of CD147 in MCF7 cells up‐regulated MDR1, MMP2, and MMP9 on both transcription and expression levels, which promoted tumor cells metastasis and conferred them multidrug resistance to P‐gp substrate drugs, as determined byin vitroinvasion assay and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. On the other hand, silencing of CD147 in MCF7/Adr cells led to the opposite effect. Moreover, Erk1/2 in CD147‐overexpressing clones were observed to be highly activate and after treatment with U0126, an Erk1/2‐specific inhibitor, the expression of MDR1, MMP2 and MMP9 were decreased significantly. Thus, CD147 may assume a dual role, since it had intrinsic stimulative effects on tumor invasionin vitroas well as increasing resistance to P‐gp substrate drugs. (Cancer Sci2007; 98: 1064–1069)
Fire‐tolerance mechanisms of common woody plant species in a semiarid savanna in south‐western Zimbabwe
Authors: Nefabas Lulu L. , Gambiza James
Published: May 2007

The frequency of fire has increased in savannas yet few studies have assessed how plants persist when subjected to long‐term disturbance by fire. We investigated the contributions of bark thickness and resprouting to the persistence of woody plants in two fire trials that were started in 1948 and 1949. The number of resprouts per individual, bark thickness, basal diameter and height of woody plants were measured in unburnt plots and those burnt annually, triennially and quinquennially during the late dry season. Changes in tree density, number of resprouts and individuals in different height classes between 1963 and 2002 were assessed. Bark thickness varied among species and also increased with increases in basal diameter. Generally, plants with thick bark survived fire more than those with thin bark. Resprouting was the major fire survival strategy for most species. The number of resprouts produced per plant ranged from 4 ± 3 (Acacia rehmanniana) to 14 ± 9 (Pseudolachnostylis maprouneifolia). Fire reduced species richness in plots burnt annually and triennially by 47% and 6% respectively. Species richness increased in unburnt plots (5%) and those burnt quinquennially (16%). Most woody species survived fire through a combination of traits.
Safety and efficacy of bortezomib in high‐risk and elderly patients with relapsed multiple myeloma
Authors: Richardson Paul G. , Sonneveld Pieter , Schuster Michael W. , Irwin David , Stadtmauer Edward A. , Facon Thierry , Harousseau Jean‐Luc , Ben‐Yehuda Dina , Lonial Sagar , San Miguel Jesús‐F. , Cavenagh Jamie D. , Anderson Kenneth C.
Published: May 2007

Adverse prognostic factors in multiple myeloma include advanced age, number of prior therapies, and higher International Staging System (ISS) disease stage. In the international, randomised, phase‐3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study, bortezomib demonstrated significantly longer time to progression (TTP), higher response rates and improved survival compared with high‐dose dexamethasone in patients with relapsed multiple myeloma following one to three prior therapies. In this APEX subgroup analysis, efficacy of bortezomib and dexamethasone was compared in elderly (age ≥65 years) and high‐risk (>1 prior line of therapy; ISS stage II/III; refractory to prior therapy) patients. Bortezomib demonstrated substantial clinical activity in these patients. Response rate (34–40% vs. 13–19%), including complete response rate (5–8% vs. 0–1%), was significantly higher with bortezomib versus dexamethasone in all four subgroups. Similarly, median TTP was significantly longer with bortezomib versus dexamethasone, and 1‐year survival probability was significantly higher in all subgroups. As in the total APEX population, rates of grade 3/4 adverse events were higher in bortezomib‐ versus dexamethasone‐treated patients aged ≥65 years and with >1 prior line, while rates of serious adverse events were similar; toxicities generally proved manageable. Bortezomib should be considered an appropriate treatment for elderly and high‐risk patients with relapsed multiple myeloma.
Graft‐versus‐leukaemia effect after non‐myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP‐70 in refractory chronic lymphocytic leukaemia
Authors: Khouri Issa F. , Saliba Rima M. , Admirand Joan , O'Brien Susan , Lee Ming‐S. , Korbling Martin , Samuels Barry I. , Giralt Sergio , Lima De Marcos , Keating Michael J. , Champlin Richard E. , Bueso‐Ramos Carlos
Published: May 2007

ZAP‐70 (zeta‐chain‐associated protein 70 kDa) expression is associated with poor prognosis in patients with chronic lymphocytic leukaemia (CLL). This study evaluated the efficacy of non‐myeloablative allogeneic stem cell transplantation in patients with advanced CLL and assessed the impact of ZAP‐70 expression on the outcome. Thirty‐nine sequential patients were included. All had previously been treated with fludarabine. All patients received a preparative regimen of fludarabine (30 mg/m2/d for 3 d), intravenous cyclophosphamide (750 mg/m2/d for 3 d), and high‐dose rituximab. Immunohistochemical techniques on marrow biopsy samples were used to determine that ZAP‐70 was expressed in 25 patients, whereas 13 other patients were ZAP‐70 negative, and one was of indeterminate status. With a median follow‐up time of 27 months, the estimated overall survival and current progression‐free survival (CPFS) rates at 4 years were 48% and 44% respectively. Patients who were ZAP‐70 positive had 56% survival, and their CPFS rate increased from 30% to 53% after a donor lymphocyte infusion. Multivariate analysis indicated that chemorefractory disease and mixed T cell chimerism at day 90, but not ZAP‐70 positivity, were associated with the risk of disease progression after transplantation. These results demonstrate a potent graft‐versus‐leukaemia effect that can overcome the adverse prognostic effect of ZAP‐70 expression.
Habitat utilization and vertical movements of white marlin (Tetrapturus albidus) released from commercial and recreational fishing gears in the western North Atlantic Ocean: inferences from short duration pop‐up archival satellite tags
Authors: HORODYSKY ANDRIJ Z. , KERSTETTER DAVID W. , LATOUR ROBERT J. , GRAVES JOHN E.
Published: May 2007

Researchers have applied numerous techniques to improve billfish stock assessments, including habitat‐based models that incorporate behavioral and oceanographic parameters to standardize historical catch‐per‐unit‐effort time‐series data. These methods have allowed researchers to account for significant changes in the depths of pelagic longline (PLL) gear deployments over time. This study presents habitat‐use data recovered from high‐resolution 5‐ and 10‐day pop‐up satellite archival tags (PSATs) attached to 47 surviving white marlin released from commercial and recreational fishing gears offshore of the U.S. East Coast, the northern Caribbean, and Venezuela between 2002 and 2004. Data recovered from transmitting tags indicated that white marlin spent nearly half of their time associated with warm, near‐surface waters (<10 m). All fish displayed frequent short duration (mean: 39.8 min) vertical excursions from surface waters to depths averaging 51 m. Qualitative and multivariate classifications of data from completely transmitted movements of surviving white marlin revealed two major types of descents: one pattern was characterized by deep ‘V’‐shaped excursions of relatively short duration (mean: 23.4 min) while the other featured descents that were more broadly ‘U’‐shaped and confined to a specific depth range for an extended period of time (mean: 75.8 min). Based on the frequency, persistence, and patterns of these vertical movements, white marlin appear to direct a considerable proportion of foraging effort well below surface waters, a behavior that may account for relatively high catch rates of white marlin on some deep‐set PLL deployments.
Evidence of Morocco dentex (Dentex maroccanus) distribution in the NE Mediterranean and relationships with environmental factors determined by Generalized Additive Modelling
Authors: MARAVELIAS CHRISTOS D. , TSITSIKA EFTHYMIA V. , PAPACONSTANTINOU COSTAS
Published: May 2007

The seasonal distribution of Morocco dentex (Dentex maroccanus) was investigated in relation to ocean environmental conditions in the NE Mediterranean Sea. Data were collected during a 2‐yr period (1996–1997) of quasi‐synoptic seasonal sampling using demersal trawl surveys. The study revealed evidence for the existence of environmental relationships and temporal habitat associations of Morocco dentex. The sea‐bottom salinity, the water depth (through its interaction with bottom salinity) and the spatial location appeared to be key determinants of distribution. There was a strong consistency in the pattern and significance of the observed relationships across all seasons. The present results provided direct support for a preferential seasonal aggregation of Morocco dentex in specific geographic and bathymetric regions of the study area. In all four seasons, these favourable regions were found to be relatively stable and distinct, had the highest catch‐per‐unit‐effort index, and were located over shallower grounds (50–70 m) having bottom salinity around 39.1. The current findings also indicated that, throughout the year, the species was confined below the thermocline and avoided the deeper waters (>80 m). Morocco dentex ecological preferences for certain sea‐bottom salinities, water depth zones and hydrographic regimes were suggested to contribute to the processes governing differential settlement to preferred grounds.
Egg and larval distributions of seven fish species in north‐east Atlantic waters
Authors: IBAIBARRIAGA L. , IRIGOIEN X. , SANTOS M. , MOTOS L. , FIVES J. M. , FRANCO C. , LAGO DE LANZÓS A. , ACEVEDO S. , BERNAL M. , BEZ N. , ELTINK G. , FARINHA A. , HAMMER C. , IVERSEN S. A. , MILLIGAN S. P. , REID D. G.
Published: May 2007

The distribution of egg and larvae of mackerel, horse mackerel, sardine, hake, megrim, blue whiting and anchovy along the European Atlantic waters (south Portugal to Scotland) during 1998 is described. Time of the year, sea surface temperature and bottom depth are used to define the spawning habitat of the different species. Mackerel, horse mackerel, and sardine eggs and larvae presented the widest distribution, whereas megrim and anchovy showed a limited distribution, restricted to the Celtic Sea and the Bay of Biscay respectively. Correspondingly mackerel, horse mackerel and sardine showed the highest aggregation indices. Blue whiting larvae were found at the lowest temperatures, whereas anchovy eggs and larvae were found in the warmest waters. The analysis is a basis for evaluation of ongoing changes in the pelagic ecosystem of the north‐east Atlantic.
Case study research methods in end‐of‐life care: reflections on three studies
Authors: Payne Sheila , Field David , Rolls Liz , Hawker Sheila , Kerr Chris
Published: May 2007

Title. Case study research methods in end‐of‐life care: reflections on three studies

Aim.  This paper is an evaluation of the use of case study methods, drawing on three research studies conducted by the authors in end‐of‐life care and bereavement.

Background.  Case study methods have their origins in social anthropology and draw on the principles of naturalistic inquiry. They have been used in a number of disciplines, including qualitative sociology, management science, education and organizational psychology for the understanding and evaluation of complex social systems. They are an appropriate research design for examining processes and outcomes in dynamic healthcare organizations, where it is important to obtain multiple perspectives.

Method.  We explore issues in case study research design, recruitment and data collection drawing on three studies conducted between 2000 and 2005 in six community hospitals, five adult hospice bereavement services and eight childhood bereavement services in the United Kingdom. Quantitative and qualitative data were collected using interviews, focus groups, observations, documentary analysis, standardized measures and questionnaires.

Discussion.  The process of case study design is described, including building upon a clear rationale for the selection of cases, collection of data, preparation of single case reports, cross‐case analysis and interpretation. In a critical discussion of recruitment, we recommend identification of a key contact person at each site to facilitate access and minimize misunderstanding, disruption to clinical services and ‘gate‐keeping’. Three principal methods of data collection: interviews, observation and documentary data analysis form the foundation of the rich data set necessary to explore cases in their situational contexts.

Conclusion.  Case study methods may be empowering for participants because they value their experiences and reveal how their work contributes to teamwork within organizations. They can therefore be both affirming and challenging, as they may expose both conflicts and tensions.
A socially inclusive approach to user participation in higher education
Authors: Simons Lucy , Tee Steve , Lathlean Judith , Burgess Abigail , Herbert Lesley , Gibson Colin
Published: May 2007

Title. A socially inclusive approach to user participation in higher education

Aim.  This paper is a report of a study to evaluate the development of an innovative Service User Academic post in mental health nursing in relation to student learning and good employment practice in terms of social inclusion.

Background.  Institutions providing professional mental health education are usually expected to demonstrate user involvement in the design, delivery and evaluation of their educational programmes to ensure that user voices are central to the development of clinical practice. Involvement can take many forms but not everyone values user knowledge as equal to other sources of knowledge. This can lead to users feeling exploited, rather than fully integrated in healthcare professional education processes. Development of the post discussed in this paper was stimulated and informed by an innovative example from Australia.

Method.  An observational case study of the development and practice of a Service User Academic post was undertaken in 2005. Participants were purposively sampled and included the User Academic, six members of a user and carer reference group, 10 educators and 35 students. Data were collected by group discussions and interviews. Data analysis was based on the framework approach.

Findings.  The evaluation revealed tangible benefits for the students and the wider academic community. Most important was the powerful role model the Service User Academic provided for students. The post proved an effective method to promote service user participation and began to integrate service user perspectives within the educational process. However, the attempts to achieve socially inclusive practices were inhibited by organizational factors. The expectations of the role and unintended discriminatory behaviours had an impact on achieving full integration of the role. Furthermore, shortcomings in the support arrangements were revealed.

Conclusions.  The search for an optimum model of involvement may prove elusive, but the need to research and debate different strategies, to avoid tokenism and exploitation, remains.