bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional specificity of Candida albicans Als3p proteins and clade specificity of ALS3 alleles discriminated by the number of copies of the tandem repeat sequence in the central domain
Authors: Oh Soon-Hwan , Cheng Georgina , Nuessen Jennifer A. , Jajko Robert , Yeater Kathleen M. , Zhao Xiaomin , Pujol Claude , Soll David R. , Hoyer Lois L.
Published: March 2005

Candida albicansstrain SC5314 contains twoALS3alleles, which differ in sequence with respect to the number of copies of the 108 bp tandem repeat sequence within the central domain of the coding region. One allele (ALS3(12)) has 12 tandem repeat copies while the other (ALS3(9)) has 9 copies. Wild-typeC. albicans(ALS3(12)/ALS3(9)) and those containing variousALS3alleles (ALS3(12)/als3Δ(9),als3Δ(12)/ALS3(9) andals3Δ(12)/als3Δ(9)) were assayed for adhesion to monolayers of cultured vascular endothelial and pharyngeal epithelial cells. These assays showed obvious adhesive function for the larger Als3p protein, compared to a minor contribution to adhesion from the smaller protein. These functional differences in strain SC5314 prompted examination ofALS3allelic diversity across the five major genetic clades ofC. albicans. This analysis focused on the number of copies of the tandem repeat sequence within the central domain of the coding region and showed a range of alleles encoding from 6 to 19 tandem repeat copies. Clades differed with respect to prevalentALS3alleles and allele distribution, but were similar for the mean number of tandem repeat copies perALS3allele. Analysis of allelic pairing showed clade differences and the tendency forC. albicansstrains to encode one longer and one shorterALS3allele. The allelic variability observed forALS3and its functional consequences observed in strain SC5314 highlight the importance of understanding ALS allelic diversity in order to draw accurate conclusions about Als protein function.
Statistical assessment of a laboratory method for growing biofilms
Authors: Goeres Darla M. , Loetterle Linda R. , Hamilton Martin A. , Murga Ricardo , Kirby Douglas W. , Donlan Rodney M.
Published: March 2005

Microbial biofilms have been grown in laboratories using a variety of different approaches. A laboratory biofilm reactor system, called the CDC biofilm reactor (CBR) system, has been devised for growing biofilms under moderate to high fluid shear stress. The reactor incorporates 24 removable biofilm growth surfaces (coupons) for sampling and analysing the biofilm. Following preliminary experiments to verify the utility of the CBR system for growing biofilms of several clinically relevant organisms, a standard operating procedure for growing a Pseudomonas aeruginosa biofilm was created. This paper presents the results of a rigorous, intra-laboratory, statistical evaluation of the repeatability and ruggedness of that procedure as well as the results of the experiments with clinically relevant organisms. For the statistical evaluations, the outcome of interest was the density (c.f.u. cm−2) of viable P. aeruginosa. Replicate experiments were conducted to assess the repeatability of the log density outcome. The mean P. aeruginosa log10 density was 7·1, independent of the coupon position within the reactor. The repeatability standard deviation of the log density based on one coupon per experiment was 0·59. Analysis of variance showed that the variability of the log density was 53 % attributable to within-experiment sources and 47 % attributable to between-experiments sources. The ruggedness evaluation applied response-surface design and regression analysis techniques, similar to those often used for sensitivity analyses in other fields of science and engineering. This approach provided a quantitative description of ruggedness; specifically, the amount the log density was altered by small adjustments to four key operational factors – time allowed for initial surface colonization, temperature, nutrient concentration, and fluid shear stress on the biofilm. The small size of the regression coefficient associated with each operational factor showed that the method was rugged; that is, relatively insensitive to minor perturbations of the four factors. These results demonstrate that the CBR system is a reliable experimental tool for growing a standard biofilm in the laboratory and that it can be adapted to study several different micro-organisms.
Long‐term habituation of the speech‐elicited mismatch negativity
Authors: McGee T.J. , King C. , Tremblay K. , Nicol T.G. , Cunningham J. , Kraus N.
Published: March 2005

A significant issue in the use of the mismatch negativity evoked potential (MMN) concerns its low signal‐to‐noise ratio (SNR). One can improve the noise level by increasing the number of samples included in the averaged response. However, improvement achieved in this way assumes that the signal, the MMN, remains stable for extended test times, an assumption which has not been tested. If the MMN is not stable, or exhibits habituation over the test session, then SNR would be adversely affected. MMN response magnitude was measured in 5‐min intervals over the course of a test session in response to various speech syllable contrasts. Significant long‐term habituation of MMN was observed for all three subject populations tested: young adults, school‐age children, and guinea pigs. The time course of the habituation and the stimulus conditions under which it occurs have important implications for research and clinical applications of the MMN. Recording procedures that minimize habituation effects may be used to advantage to improve the signal‐to‐noise ratio of the MMN.
Intraindividual analysis of instantaneous heart rate variability
Authors: Kettunen Joni , Keltikangas‐Järvinen Liisa
Published: March 2005

We examined the use and potential of quantifying instantaneous heart rate variability (HRV) using a joint time‐frequency and time‐domain methods. These new techniques are promising, because they provide tools to quantify nonstationary, beat‐by‐beat changes in HRV components, and are therefore flexible with respect to the design of experimental protocols. A smoothed pseudo‐Wigner–Ville distribution (SPWVD) and a time‐domain index using polynomial filtering produced fairly coherent estimates of band‐specific HRV amplitudes, whereas SPWVD yielded additional information on the frequency characteristics of HRV. Instantaneous HRV appeared to have a complex and a frequency‐specific relationship to cardiac activity and electrodermal activity. It is concluded that the time‐frequency analysis of HRV is a very promising method for mapping transient changes in the frequency and amplitude characteristics of cardiac dynamics.
Is there pre‐attentive memory‐based comparison of pitch?
Authors: Jacobsen Thomas , Schröger Erich
Published: March 2005

The brain's responsiveness to changes in sound frequency has been demonstrated by an overwhelming number of studies. Change detection occurs unintentionally and automatically. It is generally assumed that this brain response, the so‐called mismatch negativity (MMN) of the event‐related brain potential or evoked magnetic field, is based on the outcome of a memory‐comparison mechanism rather than being due to a differential state of refractoriness of tonotopically organized cortical neurons. To the authors' knowledge, however, there is no entirely compelling evidence for this belief. An experimental protocol controlling for refractoriness effects was developed and a true memory‐comparison‐based brain response to pitch change was demonstrated.
Changes in life‐history traits in an expanding moss species: phenotypic plasticity or genetic differentiation? A reciprocal transplantation experiment withPogonatum dentatum
Authors: Hassel Kristian , Pedersen Bård , Söderström Lars
Published: March 2005

A transplant experiment was performed to investigate whether differences in life‐history traits of the bryophytePogonatum dentatumthat recently expanded its distribution range, were genetically or environmentally determined, or a combination of both. Plants were transplanted reciprocally between the original mountain area and a recently colonised lowland area. Vegetative biomass of annual segments and branches tended to be higher in the mountain area than in the lowland area. Reproductive investment was higher for plants transplanted to the lowland area, and lowland shoots tended to produce larger sporophytes than mountain shoots when placed in the same environment. Age of reproducing shoots showed no consistent pattern.  Native shoots were often outperformed by non‐native shoots transplanted into the same site. Non‐native shoots grew larger and produced larger sporophytes than native shoots. Much of the observed variation was at the site level instead of between mountain and lowland areas, with both genetic origin and environmental effects contributing together. Range expansion ofP. dentatummay have taken place by dispersal from populations with shoots whose growth is plastic. Such shoots grow larger and potentially produce more spores for dispersal.
Corticolous arthropods under climatic fluctuations: compensation is more important than migration
Authors: Prinzing Andreas
Published: March 2005

Animals can cope with fluctuating climates by physiological tolerance, tracking of climatic fluctuations (migration) and compensatory redistribution among (micro)habitats (compensation). Compensation is less demanding and thus more important than migration at large geographic scales. It is not clear however which strategy is more important at the small scale of a microhabitat landscape. I investigated how six arthropod species (Collembola, Oribatei, Psocoptera, Isopoda) respond to microclimatic fluctuations at the surface of exposed tree trunks. Across a nine‐month period I characterized the microclimatic zonation of 299 trunks, and focally sampled the arthropods from different microhabitat types (different cryptogam species and bark crevices) within different microclimatic zones. I found that compensatory microhabitat‐use was a general phenomenon. The distribution of all species across microhabitats was influenced significantly by ambient microclimate. Also, the arthropods’ microhabitat use changed throughout their ontogeny, and microhabitats were used even if they were rare. Most interestingly, the arthropods responded to microclimatic fluctuations primarily by redistribution among microhabitats and less by fluctuations of overall abundances across all microhabitats. Hence compensation was more important than migration. The animals moved for centimeters to decimeters rather than for decimeters to meters; they perceived and utilized their environment primarily at the finest, but also most complex scale. This has implications for the resilience of arthropod populations, their interactions with cryptogams and the turnover of species between macrohabitats.
Effect of land‐use heterogeneity on carabid communities at the landscape scale
Authors: Vanbergen Adam J. , Woodcock Ben A. , Watt Allan D. , Niemelä Jari
Published: March 2005

Carabid beetle assemblages were studied to assess how diversity and community structure varied along a gradient of land‐use. This gradient was composed of six 1 km2quadrats with an increasing proportion of agricultural land reflecting the anthropogenic fragmentation and intensification of landscapes. Carabid species richness and abundance was predicted to peak in the most heterogeneous landscape, in accord with the intermediate disturbance hypothesis (IDH), and then decline as agricultural intensification increased. It was also predicted that the different landscapes would support beetle communities distinct from each other. The IDH was unsupported‐in both years of this study carabid species richness and abundance was greatest in the most intensively managed, agricultural sites. Detrended correspondence analysis revealed a clear separation in beetle community structure between forested and open habitats and between different forest types. Canonical correspondence analysis revealed a significant correlation between beetle community structure and the environment, showing distinct beetle assemblages to be significantly associated with specific edaphic and botanical features of the land‐use gradient. This study adds to increasing evidence that landscape‐scale patterns in land‐use significantly affect beetle community structure producing distinct assemblages.
From null community to non‐randomly structured actual plant assemblages: parsimony analysis of species co‐occurrences
Authors: Ribichich Alejandra M.
Published: March 2005

Null community is a spatio‐temporal abstraction of an initial regional species pool from which local species pools and actual community assemblages are organized. Any process that causes joint responses of species with similar susceptibilities affects community assembly. Through time, sequential assembly processes change the composition of a species pool in a way analogous to the one in which evolutionary processes promote character changes from an ancestor to current species. The segregation of species occurrences in an actual community suggests that assembly processes non‐randomly structured the observed community assemblages. However, going backwards to imply the causes of a particular arrangement of species is a non‐trivial challenge. I merge these premises with the philosophical and methodological foundations of cladistics. I propound parsimony analysis of species co‐occurrences as an outstanding means of devising operational hypotheses about the assembly of any non‐randomly structured set of actual community assemblages related to a common species pool. To explore this approach, I used field data gathered in a suite of 10 wetland assemblages. First, I tested independence of 101 plant species occurrences by a null model. As significant non‐random species co‐occurrence was detected, I applied a parsimony analysis taking the species occurrences as attributes, the assemblages as terminal units, and a putative null community constituted by all the present local species as the root of the assembly suite. The analysis produced four most parsimonious trees of assembly relationships. These trees maximize the number of similarities among community assemblages that can be explained by the sole fact of sharing a common regional species pool. One most parsimonious spatio‐temporal arrangement of species occurrence changes was reconstructed on one of the trees. I interpret this reconstruction in terms of assembly events, species exclusions and recruitments, showing the potentialities of this analysis to formulate operational hypotheses about community organization.
Foraging flight distances as a measure of parental effort in blue tits Parus caeruleus differ with environmental conditions
Authors: Stauss Michael J. , Burkhardt Joachim F. , Tomiuk Jürgen
Published: March 2005

Life‐history theory predicts that parental effort in nestling provisioning is optimised in relation to the quality of individuals and/or their habitat. We studied the investment of breeding pairs of blue tits Parus caeruleus for their reproduction during three breeding seasons in deciduous (high quality) vs. mixed (low quality) habitats in order to quantify to what extent habitat quality affects parental effort. Parental effort (costs) was related to their feeding rates and flight distances during foraging. In the deciduous habitat flight distances between nest and foraging patch were shorter than in the mixed habitat (22 m and 40 m, respectively), but the feeding rates did not differ between the habitats. The total flight distance per breeding pair from the first day after hatching until the 17th day of the nestling period was about half of the distance observed in the mixed habitat (375 km and 674 km, respectively). As the quality of fledglings did not differ between habitats, the higher number of fledglings per brood reflects better rewards per foraging trip in the deciduous than in the mixed habitat. Considering the parental foraging effort (costs) and, the quality and number of offspring (benefits), the benefit‐cost‐ratio was 2–3 times higher in the deciduous than in the mixed woodland.
Successful pregnancy, achieved by ovulation induction using a human menopausal gonadotropin low‐dose step‐up protocol in an infertile patient with Kallmann's syndrome
Authors: Nakagawa Koji , Iwasaki Wakako , Sato Mami , Ito Megumu , Kawachiya Satoshi , Murashima Atsuko , Kitagawa Michihiko , Natori Michiya , Saito Hidekazu
Published: March 2005

A 25‐year‐old woman, diagnosed with Kallmann's syndrome and wanting to become pregnant, visited our hospital. Because her serum gonadotropin levels indicated hypogonadotropic hypogonadism, a main symptom of Kallmann's syndrome, we attempted to induce ovulation using a low‐dose human menopausal gonadotropin (hMG) step‐up protocol. In this protocol, 75 IU of hMG was used as an initial dose and this was continued for the first 14 days because adequate follicular development was not achieved. The dose of hMG was subsequently increased to 150 IU for the next 7 days. After 22 days from the start of stimulation, two follicles had developed, and were ovulated using an injection of human chorionic gonadotropin. She became pregnant, and her pregnancy was uneventful during the first trimester; however, in the second trimester both uterine contractions and blood pressure could not be controlled, and at 27 weeks’ gestation she delivered a male infant weighing 830 g by cesarean section.
Clear‐cutting of a Norway spruce stand: implications for controls on the dynamics of dissolved organic matter in the forest floor
Authors: Kalbitz K. , Glaser B. , Bol R.
Published: March 2005

Clear‐cutting of forest provides a unique opportunity to study the response of dynamic controls on dissolved organic matter. We examined differences in concentrations, fluxes and properties of dissolved organic matter from a control and a clear‐cut stand to reveal controlling factors on its dynamics. We measured dissolved organic C and N concentrations and fluxes in the Oi, Oe and Oa horizons of a Norway spruce stand and an adjacent clear‐cutting over 3 years. Aromaticity and complexity of organic molecules were determined by UV and fluorescence spectroscopy, and we measured δ13C ratios over 1 year.

Annual fluxes of dissolved organic C and N remained unchanged in the thin Oi horizon (∼ 260 kg C ha−1, ∼ 8.5 kg N ha−1), despite the large reduction in fresh organic matter inputs after clear‐cutting. We conclude that production of dissolved organic matter is not limited by lack of resource. Gross fluxes of dissolved organic C and N increased by about 60% in the Oe and 40% in the Oa horizon upon clear‐cutting. Increasing organic C and N concentrations and increasing water fluxes resulted in 380 kg C ha−1 year−1 and 10.5 kg N ha−1 year−1 entering the mineral soil of the clear‐cut plots. We found numerous indications that the greater microbial activity induced by an increased temperature of 1.5°C in the forest floor is the major factor controlling the enhanced production of dissolved organic matter. Increasing aromaticity and complexity of organic molecules and depletion of 13C pointed to an accelerated processing of more strongly decomposed parts of the forest floor resulting in increased release of lignin‐derived molecules after clear‐cutting. The largest net fluxes of dissolved organic C and N were in the Oi horizon, yet dissolved organic matter sampled in the Oa horizon did not originate mainly from the Oi horizon. Largest gross fluxes in the Oa horizon (control 282 kg C ha−1) and increased aromaticity and complexity of the molecules with increasing depth suggested that dissolved organic matter was derived mainly from decomposition, transformation and leaching of more decomposed material of the forest floor. Our results imply that clear‐cutting releases additional dissolved organic matter which is sequestered in the mineral soil where it has greater resistance to microbial decay.
Clinical experience of patients undergoing photodynamic therapy for Barrett's dysplasia or cancer
Authors: Wolfsen H. C. , Hemminger L. L. , Wallace M. B. , DeVault K. R.
Published: March 2005

Introduction : Barrett's oesophagus is the most important risk factor in the increase in incidence of oesophageal adenocarcinoma. Photodynamic therapy using porfimer sodium is the only approved endoscopic treatment for use in patients with Barrett's high‐grade dysplasia.

Aim : To determine clinical characteristics, endoscopic findings and treatment complications in Barrett's high‐grade dysplasia patients undergoing photodynamic therapy.

Methods : We reviewed our experience using porfimer sodium photodynamic therapy to treat patients with Barrett's oesophagus and high‐grade dysplasia or mucosal carcinoma. Data collected included patients characteristics, presentation symptoms, endoscopic findings, subsequent use of surveillance endoscopy and outcome after photodynamic therapy.

Results : Since 1997, 102 patients with Barrett's high‐grade dysplasia (69 patients) or mucosal adenocarcinoma (33 patients) have been treated with photodynamic therapy using porfimer sodium as an alternative to oesophagectomy (median series follow‐up time = 1.6 years). Almost half (46%) of patients had high‐grade dysplasia or carcinoma detected on their first endoscopy and the remainder (54%) were found during surveillance of known Barrett's oesophagus. Symptoms typically associated with oesophageal disease were only found in 29 of 47 (62%) patients in whom dysplasia/carcinoma was detected on the initial endoscopy – chest pain in 13 patients, dysphagia in nine patients and chronic gastro‐oesophageal disease in seven patients. Comparison of endoscopic characteristics found the median Barrett's glandular segment length was significantly shorter in adenocarcinoma patients (median 3 cm; range: 1–12) vs. Barrett's high‐grade dysplasia patients (median 5 cm; range: 1–16, P < 0.001). Overall treatment results found complete ablation of glandular epithelium with one course of photodynamic therapy in most patients (56%). Stricture requiring dilation occurred in 20 patients (20%) was the most common serious adverse event. Photodynamic therapy failed to ablate dysplasia or carcinoma in four patients and subsequent oesophagectomy was curative in three of these patients.

Conclusions : Approximately 40% of newly diagnosed patients with Barrett's associated dysplasia or carcinoma had no oesophageal symptoms and had carcinoma associated with short segment (3 cm or less). Photodynamic therapy is a highly effective, safe and minimally invasive first‐line treatment for patients with Barrett's dysplasia and mucosal adenocarcinoma.
Changes in surface reactivity and organic matter composition of clay subfractions with duration of fertilizer deprivation
Authors: Kleber M. , Mertz C. , Zikeli S. , Knicker H. , Jahn R.
Published: March 2005

Preservation of organic matter in soils depends on the chemical structure of organic compounds and on the surface properties of the mineral matrix. We tested the effect of mineral surface reactivity on organic matter decomposition by (i) investigating changes of organic matter composition in clay subfractions of an illitic Haplic Chernozem along a time series of fertilizer deprivation and (ii) simultaneously characterizing the reactivity of mineral surfaces. The soil was subjected to fertilizer deprivation for 18, 44 and 98 years, respectively. Mineral surface properties were characterized by selective dissolution of pedogenic oxides. The number of hydroxyls released after exposure to sodium fluoride was taken as an index for mineral surface reactivity. Organic soil constituents were determined by 13C cross‐polarization magic‐angle spinning nuclear magnetic resonance (13C CPMAS NMR).

Clay subfractions had different mineral surface properties. The coarse fractions have more reactive surfaces and contain more organic carbon than the fine clay fractions. Mineral surface properties are constant over time and are not affected by fertilizer deprivation. Surface reactivity is a function of iron oxide density and controls carbon concentrations in the clay subfractions. Within the time frame of our investigation, alkyl C and aromatic C responded to the duration of fertilizer deprivation, but were indifferent to mineral surface reactivity. O–alkyl C seems to be protected by interactions with pedogenic oxides.
Traumatic brain injury results in mast cell increase and changes in regulation of central histamine receptors
Authors: Lozada A. , Maegele M. , Stark H. , Neugebauer E. M. A. , Panula P.
Published: March 2005

Experimental fluid‐percussion models produce brain injury by rapidly injecting saline into the closed cranium of rats. In this study our purpose was to determine how the central histaminergic system, which controls excitability and neurotransmitter release through G‐protein coupled receptors, is affected by the pathophysiology of traumatic brain injury. We found that mast cell infiltration, as a result of the trauma, occurred primarily in the injured cortex and did not proceed beyond the fimbria of the hippocampus. In comparing injured animals with controls we found that H3 receptor binding densities are significantly decreased bilaterally in the cortex but are significantly increased bilaterally in the thalamus. H3 receptor binding densities may well be affected by mast cell secretion of mediators (i.e. histamine, heparin, leukotrienes), evidenced by detection of a cosecreted enzyme (mast cell tryptase) in the extracellular region. Moreover, we detected significant decreases in H1 and H3 receptor mRNA as well as Cu/Zn‐dependent superoxide dismutase (SOD) mRNA in the thalamic region closest to the trauma. These significant decreases delineate the extent of cellular damage because of trauma and may underlie sustained cognitive and motor deficits displayed by these animals.
Determination of soil depth inhabited by Frankliniella occidentalis (Pergande) and Thrips tabaci Lindeman (Thysan., Thripidae) under greenhouse cultivation
Authors: Deligeorgidis P. N. , Ipsilandis C. G.
Published: March 2005

The objectives of this study were to determine the depth of penetration into the soil by Frankliniella occidentalis (Pergande) and Thrips tabaci Lindeman (Thysan., Thripidae) in cucumber and tomato crops in greenhouses. A metal sampling apparatus sampled for the two species of thrips at five levels of soil depth (0–10 cm), over seven dates of sampling, each in eight replications. In general, thrips were found to be in greater numbers in the first 2 cm of soil, with the number of insects decreasing with depth increasing. In the depth of 8–10 cm, no insects were found. Number of thrips found in the soil under cucumber plants was greater in comparison with the tomato samplings. Frankliniella occidentalis was found in greater numbers in comparison with T. tabaci. The date of sampling showed a significant interaction with soil depth, with the number of insects found increasing from the first to the last date of sampling.
Comparing professions through actor‐centred governance: community nursing in Britain and Germany
Authors: Burau Viola
Published: March 2005

Abstract  Professions are increasingly studied from an international perspective, and understanding context is key to cross‐national comparison of professions. This paper builds on studies of health service work in different countries and introduces actor‐centred governance as a framework for comparing professions. The framework conceptualises context as institutions and, as such, offers a more systematic analysis of context and the interplay between context and actors. The framework is applied to a comparative study of community nursing in Britain and Germany, which includes a local case study of the governance of internal boundaries. Actor‐centred governance helps to map out different actors and the interplay among them, to identify different types of institutions, and to trace how institutions relate to actors and vice versa. As such, actor‐centred governance allows for a more systematic analysis of similarities and differences, and facilitates comparisons across different countries.
The control of leaf development
Authors: Fleming Andrew J.
Published: March 2005

The formation of a leaf is a basic aspect of plant development. This review provides an overview of our present understanding of the process from initiation to the final form of the leaf. Molecular genetic and cell biology approaches have yielded significant advances in this area, adding not only to our knowledge of leaf development but also to fundamental principles in plant biology. These principles will be highlighted, as well as areas where our understanding is still incomplete, in particular the problem of coordinating the multifaceted steps involved in the generation of the leaf structure.

Contents

Summary
9

I.
Introduction
9

II.
The shoot apical meristem: the creation of a field of cells from which leaves can be formed
10

III.
Patterning: the selection of leaf initiation site
10

IV.
Morphogenesis: the initial stages of leaf formation
12

V.
Differentiation and determination: transcriptional networks controlling determinancy
14

VI.
The elaboration of leaf form
14

VII.
Early steps in leaf histogenesis
15

VIII.
Later steps in leaf differentiation: epidermal cell fate
16

IX.
Compound and simple leaves: variation on a theme?
17

X.
Changes in leaf form: developmental and environmental influences
17

XI.
A model of leaf formation
17

Acknowledgements
18

References
18
Constraints on the evolution of adaptive phenotypic plasticity in plants
Authors: Van Kleunen Mark , Fischer Markus
Published: March 2005

The high potential fitness benefit of phenotypic plasticity tempts us to expect phenotypic plasticity as a frequent adaptation to environmental heterogeneity. Examples of proven adaptive plasticity in plants, however, are scarce and most plastic responses actually may be ‘passive’ rather than adaptive. This suggests that frequently requirements for the evolution of adaptive plasticity are not met or that such evolution is impeded by constraints. Here we outline requirements and potential constraints for the evolution of adaptive phenotypic plasticity, identify open questions, and propose new research approaches. Important open questions concern the genetic background of plasticity, genetic variation in plasticity, selection for plasticity in natural habitats, and the nature and occurrence of costs and limits of plasticity. Especially promising tools to address these questions are selection gradient analysis, meta‐analysis of studies on genotype‐by‐environment interactions, QTL analysis, cDNA‐microarray scanning and quantitative PCR to quantify gene expression, and two‐dimensional gel electrophoresis to quantify protein expression. Studying plasticity along the pathway from gene expression to the phenotype and its relationship with fitness will help us to better understand why adaptive plasticity is not more universal, and to more realistically predict the evolution of plastic responses to environmental change.
A modular concept of phenotypic plasticity in plants
Authors: De Kroon Hans , Huber Heidrun , Stuefer Josef F. , Van Groenendael Jan M.
Published: March 2005

Based on empirical evidence from the literature we propose that, in nature, phenotypic plasticity in plants is usually expressed at a subindividual level. While reaction norms (i.e. the type and the degree of plant responses to environmental variation) are a property of genotypes, they are expressed at the level of modular subunits in most plants. We thus contend that phenotypic plasticity is not a whole‐plant response, but a property of individual meristems, leaves, branches and roots, triggered by local environmental conditions. Communication and behavioural integration of interconnected modules can change the local responses in different ways: it may enhance or diminish local plastic effects, thereby increasing or decreasing the differences between integrated modules exposed to different conditions. Modular integration can also induce qualitatively different responses, which are not expressed if all modules experience the same conditions. We propose that the response of a plant to its environment is the sum of all modular responses to their local conditions plus all interaction effects that are due to integration. The local response rules to environmental variation, and the modular interaction rules may be seen as evolving traits targeted by natural selection. Following this notion, whole‐plant reaction norms are an integrative by‐product of modular plasticity, which has far‐reaching methodological, ecological and evolutionary implications.
Thromboelastography: a tool for measuring hypercoagulability, hypocoagulability, and fibrinolysis
Authors: Donahue Suzanne M. , Otto Cynthia M.
Published: March 2005

Objective: To describe the technique of thromboelastography (TEG) and review the applications of this coagulation test in humans and small animals.

Data sources: Data sources included scientific reviews and original research publications.

Human data synthesis: TEG in humans has been used for documentation of hypercoagulable and hypocoagulable states and has been shown to be beneficial in patient management.

Veterinary data synthesis: Clinical evaluation of TEG in veterinary medicine is limited; however, recent reports have documented evidence of hypercoagulability in dogs with parvovirus and protein‐losing nephropathy. Additionally, many of the research models may be relevant to veterinary patients.

Conclusions: TEG provides information about coagulation that is not available through routine coagulation tests. The application of TEG monitoring to veterinary patients shows promise; however, prospective clinical studies are needed.
Efficacy of Cranberry Juice on Helicobacter pylori Infection: a Double‐Blind, Randomized Placebo‐Controlled Trial
Authors: Zhang Lian , Ma Junling , Pan Kaifeng , Go Vay Liang W. , Chen Junshi , You Wei‐cheng
Published: March 2005

Background.  Helicobacter pylori infection is a major cause of peptic ulcer disease and gastric cancer. This study postulated that cranberry juice would be effective in the suppression of H. pylori in an endemically infected population at high risk for gastric cancer.

Materials and methods.  A prospective, randomized, double‐blind, placebo‐controlled trial was conducted in Linqu County of Shandong Province, China, where 189 adults aged 48.9 ± 11.2 years (mean ± SD) with H. pylori infection were randomly divided into two groups: cranberry juice (n = 97) and placebo (n = 92). Participants were assigned to orally receive two 250‐ml juice boxes of cranberry juice or matching placebo beverage daily for 90 days. The degree of H. pylori infection was determined using the 13C‐urea breath test before randomization at 35 and 90 days of intervention to assess the efficacy of cranberry juice in alleviating infection.

Results.  A total of 189 subjects with positive 13C‐urea breath test results prior to randomization completed the study. At day 35 of intervention, 14 of the 97 (14.43%) from the the cranberry juice treatment group and 5 of the 92 (5.44%) of the placebo recipients had negative 13C‐urea breath test results. After 90 days, the study concluded that 14 of the 97 subjects in the cranberry juice treatment group versus 5 of the 92 in the placebo group yielded negative test results. Eleven individuals from the cranberry juice treatment group and only two from the placebo group were negative at 35 and 90 days of experiment. These results are significant (p < .05).

Conclusions.  Regular consumption of cranberry juice can suppress H. pylori infection in endemically afflicted populations.
Geographic Pathology of Helicobacter pylori Gastritis
Authors: Liu Yi , Ponsioen Cyriel I. J. , Xiao Shu‐dong , Tytgat Guido N. J. , Ten Kate Fiebo J. W.
Published: March 2005

Background and aim.  Helicobacter pylori is etiologically associated with gastritis and gastric cancer. There are significant geographical differences between the clinical manifestation of H. pylori infections. The aim of this study was to compare gastric mucosal histology in relation to age among H. pylori‐infected patients from different geographical areas using the same grading system. The prevalence of atrophy and intestinal metaplasia were also compared with the respective gastric cancer incidence in the different countries.

Methods.  A total of 1906 patients infected with H. pylori from seven countries were evaluated. Entry criteria included H. pylori positive cases with antral and corpus biopsies between the ages of 18 and 75 years. The minimum number of cases required from a country was 100. Hematoxylin‐eosin stained biopsies from antrum and corpus were scored semiquantitatively using the parameters suggested by the Sydney Classification System. Statistical evaluation was performed using Krusakal‐Wallis test and Spearman's rank correlation test.

Results.  The severity of gastric atrophy varied among the different groups with the highest scores being present in Japan. The lowest scores were found in four European countries and in Thailand. The scores for intestinal metaplasia were low in general except for Xi‐an, Japan, and Shanghai. For all the countries, the presence of atrophy in the antrum correlated well (r = 0.891) with the incidence of gastric cancer.

Conclusion.  Using a standardized grading system in a large study of H. pylori‐related geographic pathology, we found major differences in the overall prevalence and severity of H. pylori gastritis in relation to age. These differences mirrored the respective incidences of gastric cancer in those geographical areas.
Molecular regulation of the VEGF family – inducers of angiogenesis and lymphangiogenesis
Authors: McCOLL BRADLEY K. , STACKER STEVEN A. , ACHEN MARC G.
Published: March 2005

The vascular endothelial growth factor (VEGF) family of secreted glycoproteins are critical inducers of angiogenesis (growth of blood vessels) and lymphangiogenesis (growth of lymphatic vessels). These proteins are attractive therapeutic targets for blocking growth of blood vessels and lymphatics in tumors and thereby inhibiting the growth and spread of cancer – in fact, the first VEGF inhibitor has recently entered the clinic for treatment of cancer. In addition, the VEGFs are being considered for stimulation of angiogenesis in the context of ischemic disease and lymphangiogenesis for treatment of lymphedema. These therapeutic possibilities have focused great interest on the molecular regulation of VEGF family members. Much has been learned in the past five years about the mechanisms controlling the action of the VEGFs, including the importance of hypoxia, proteolysis, transcription factors and RNA splicing. An understanding of these mechanisms offers broader opportunities to manipulate expression and activity of the VEGFs for treatment of disease.
Endogenous angiogenesis inhibitors
Authors: FOLKMAN JUDAH
Published: March 2005

When the FDA commissioner announced in February 2004 the approval of Avastin for the treatment of patients with colon cancer, he called angiogenesis inhibitors a fourth modality of anti‐cancer therapy. Because angiogenesis inhibitors are relatively less toxic than conventional chemotherapy and have a lower risk of drug resistance, they may also represent a new class of anti‐cancer agents, some of which have sufficiently reduced toxicity that they may be safely used long term. These include immunotherapy, vaccines, telomerase inhibitors, apoptosis inducers, low dose metronomic chemotherapy, novel hormonal therapies, gene therapy and others. However, at least 16 endogenous angiogenesis inhibitors have been discovered in the circulation, and/or in the extracellular matrix. These may become the safest and least toxic of anti‐cancer therapies. Four are already being administered by injection in clinical trials for cancer. Recently, it has been reported that at least two endogenous angiogenesis inhibitors can be significantly increased in humans (endostatin), and in mice (thrombospondin), by oral administration of small molecules which themselves are already FDA approved for other uses. This finding suggests several new clinical applications for the future, including the possibility of guiding the use of angiogenesis inhibitors by blood or urinary biomarkers, currently being developed, that may detect the presence of cancer before it is symptomatic, or before it can be located by conventional methods.
Vasculogenic mimicry
Authors: FOLBERG ROBERT , MANIOTIS ANDREW J.
Published: March 2005

The term vasculogenic mimicry describes the formation of fluid‐conducting channels by highly invasive and genetically dysregulated tumor cells. Two distinctive types of vasculogenic mimicry have been described. Vasculogenic mimicry of the tubular type may be confused morphologically with endothelial cell‐lined blood vessels. Vasculogenic mimicry of the patterned matrix type in no way resembles blood vessels morphologically or topologically. Matrix proteins such as laminin, heparan sulfate proteoglycan, and collagens IV and VI have been identified in these patterns. The patterned matrix anastomoses with blood vessels, and systemically injected tracers co‐localize to these patterns. Vasculogenic mimicry of the patterned matrix type has been identified in uveal, cutaneous and mucous membrane melanomas, inflammatory and ductal breast carcinoma, ovarian and prostatic carcinoma, and soft tissue sarcomas, including synovial sarcoma rhabdomyosarcoma, osteosarcoma, and pheochromocytoma. Because the microcirculation of many tumors may be heterogeneous – including incorporated or co‐opted vessels, angiogenic vessels, mosaic vessels, and vasculogenic mimicry of the tubular and patterned matrix types – therapeutic regimens that target angiogenesis alone may be ineffective against highly invasive tumors that contain patterned matrices. Vasculogenic mimicry provides an opportunity to investigate the interrelationships between the genetically dysregulated invasive tumor cell, the microenvironment, and the malignant switch.
Principal expression of two mRNA isoforms (ABCB  5α and ABCB  5β ) of the ATP‐binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes
Authors: Chen Kevin G. , Szakács Gergely , Annereau Jean‐Philippe , Rouzaud Francois , Liang Xing‐Jie , Valencia Julio C. , Nagineni Chandrasekharam N. , Hooks John J. , Hearing Vincent J. , Gottesman Michael M.
Published: March 2005

ATP‐binding cassette (ABC) transporters play a pivotal role in physiology and pathology. We identified and cloned two novel mRNA isoforms (ABCB 5α and ABCB 5β) of the ABC transporter ABCB 5 in human melanoma cells. The deduced ABCB 5α protein appears to be an altered splice variant containing only a putative ABC, whereas the ABCB 5β isoform shares approximately 70% similarity with ABCB1 (MDR1) and has a deduced topological arrangement similar to that of the whole carboxyl terminal half of the ABCB1 gene product, P‐glycoprotein, including an intact ABC. Northern blot, real‐time PCR, and conventional RT‐PCR were used to verify the expression profiles of ABCB 5α/β. We found that the melanomas included among the NCI‐60 panel of cell lines preferentially expressed both ABCB 5α and ABCB 5β. However, ABCB 5α/β expression was undetectable in two amelanotic melanomas (M14 and LOX‐IMVI). The expression profile of ABCB 5α/β in all of the other melanomas of the panel was confirmed both by RT‐PCR and by sequencing. Neither ABCB 5α nor ABCB 5β expression was found in normal tissues such as liver, spleen, thymus, kidney, lung, colon, small intestines or placenta. ABCB 5α/β mRNAs were also expressed in normal melanocytes and in retinal pigment epithelial cells, suggesting that ABCB 5α/β expression is pigment cell‐specific and might be involved in melanogenesis. Our findings indicate that expression of ABCB 5α/β might possibly provide two novel molecular markers for differential diagnosis of melanomas and constitute potential molecular targets for therapy of melanomas.
The Impact of Dydrogesterone Supplementation on Hormonal Profile and Progesterone‐induced Blocking Factor Concentrations in Women with Threatened Abortion
Authors: Kalinka Jarosław , Szekeres‐Bartho Julia
Published: March 2005

Problem:  The therapeutic value of progestogens in threatened abortion is still under debate. In the presence of sufficient progesterone levels during pregnancy, lymphocytes synthesize a mediator [progesterone‐induced blocking factor (PIBF)] that is anti‐abortive in mice. The aim of this study was to evaluate the effect of dydrogesterone on pregnancy outcome of threatened aborters.

Method of Study:  Twenty‐seven threatened aborters were treated for 10 days with dydrogesterone (30–40 mg/day). Sixteen healthy pregnant controls received no treatment. Serum progesterone and estradiol concentrations as well as urine PIBF concentrations were measured by enzyme‐linked immunosorbent assay (ELISA).

Results:  Pregnancy outcomes in dydrogesterone‐treated threatened aborters did not statistically differ from those in healthy controls. Serum progesterone concentrations in control patients, but not those in threatened aborters increased as pregnancy progressed. Following dydrogesterone treatment, initially low PIBF concentrations of threatened aborters significantly increased (P = 0.001) to reach the PIBF level found in healthy controls.

Conclusions:  These data suggest that by inducing PIBF production, dydrogesterone might improve pregnancy success rates in threatened aborters.
Homing in on the Cellular Immune Response to HSV‐2 in Humans*
Authors: Koelle David M. , Gonzalez Julio C. , Johnson Andrew S.
Published: March 2005

Problem:  Genital herpes simplex infections are generally limited to epithelia and neurons. Vaccines have had activity in herpes simplex virus (HSV)‐seronegative women only. Understanding how HSV‐specific T cells traffic to infected sites may assist in vaccine design.

Method of Study:  Herpes simplex virus epitopes recognized by HSV‐specific CD8 T cells were identified and used to make fluorescent human leukocyte antigen (HLA)‐peptide tetramers. Molecules related to lymphocyte rolling adhesion were studied by flow cytometry and cell binding. HSV‐specific CD4 T cells identified ex vivo by cytokine accumulation or activation marker expression, or detected in vitro by 5‐(and‐6)‐carboxyfluorescein diacetate, succinimidyl ester (CFSE) dilution, were similarly investigated.

Results:  Herpes simplex virus‐specific T cells are 10‐ to 100‐fold more prevalent in lesional skin compared with blood and greatly enriched in lesions compared with normal skin. Diverse viral antigens are recognized by HSV‐specific T cells. Functionally active E‐selectin ligand, and cutaneous lymphocyte antigen (CLA), are expressed by circulating HSV‐2‐specific CD8 cells. CD4 cells display lower levels of CLA that are dramatically up‐regulated upon re‐stimulation with antigen.

Conclusions:  Herpes simplex virus‐2‐specific CD8 and CD4 T cells differ in constitutive expression of skin homing molecules. Vaccines designed to induce proper homing are postulated to have increased efficacy.