bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity in pathogenicity can cause outbreaks of meningococcal disease
Authors: Stollenwerk Nico , Maiden Martin C. J. , Jansen Vincent A. A.
Published: June 2004

Neisseria meningitidis, the meningococcus, is a major cause of bacterial meningitis and septicemia worldwide. Infection in most cases leads to asymptomatic carriage and only rarely to disease. Meningococcal disease often occurs in outbreaks, which are both sporadic and highly unpredictable. The occurrence of disease outbreaks in a host population in which the etiological agent is widely carried is not well understood. A potential explanation lies in the fact that meningococci are diverse with respect to disease-causing potential. We formulated a stochastic mathematical model to investigate whether diversity of the bacterial population is related to outbreaks of meningococcal disease. In the model, strains that occasionally cause the disease appear repeatedly in a population dominated by a nonpathogenic strain. When the pathogenicity, i.e., the disease-causing potential, of the pathogenic lineage was low, the model shows distinct outbreaks, the size distribution of the outbreaks follows a power law, and the ratio of the variance to the mean number of cases is high. Analysis of notification data of meningococcal disease showed that the ratio of the variance to the mean was significantly higher for meningococcal diseases than for other bacterial invasive diseases. This result lends support to the hypothesis that outbreaks of meningococcal disease are caused by diversity in the pathogenicity of meningococcal strains.
A general approach for chemical labeling and rapid, spatially controlled protein inactivation
Authors: Marks Kevin M. , Braun Patrick D. , Nolan Garry P.
Published: June 2004

Chemical labeling of proteins inside of living cells can enable studies of the location, movement, and function of proteins
in vivo
. Here we demonstrate an approach for chemical labeling of proteins that uses the high-affinity interaction between an FKBP12 mutant (F36V) and a synthetic, engineered ligand (SLF′). A fluorescein conjugate to the engineered ligand (FL-SLF′) retained binding to FKBP12(F36V) and possessed similar fluorescence properties as parental fluorescein. FL-SLF′ labeled FKBP12(F36V) fusion proteins in live mammalian cells, and was used to monitor the subcellular localization of a membrane targeted FKBP12(F36V) construct. Chemical labeling of FKBP12(F36V) fusion proteins with FL-SLF′ was readily detectable at low expression levels of the FKBP12(F36V) fusion, and the level of fluorescent staining with FL-SLF′ was proportional to the FKBP12(F36V) expression level. This FL-SLF′-FKBP12(F36V) labeling technique was tested in fluorophore assisted laser inactivation (FALI), a light-mediated technique to rapidly inactivate fluorophore-labeled target proteins. FL-SLF′ mediated FALI of a β-galactosidase-FKBP12(F36V) fusion protein, causing rapid inactivation of >90% of enzyme activity upon irradiation
in vitro
. FL-SLF′ also mediated FALI of a β-galactosidase fusion expressed in living NIH 3T3 cells, where β-galactosidase activity was reduced in 15 s. Thus, FL-SLF′ can be used to monitor proteins
in vivo
and to target rapid, spatially and temporally defined inactivation of target proteins in living cells in a process that we call FK-FALI.
Origin of the classical complement pathway: Lamprey orthologue of mammalian C1q acts as a lectin
Authors: Matsushita Misao , Matsushita Akiko , Endo Yuichi , Nakata Munehiro , Kojima Naoya , Mizuochi Tsuguo , Fujita Teizo
Published: June 2004

The lectin complement pathway in innate immunity is closely related to the classical complement pathway in adaptive immunity, with respect to the structures and functions of their components. Both pathways are initiated by complexes consisting of collagenous proteins and serine proteases of the mannose-binding lectin (MBL)-associated serine protease (MASP)/C1r/C1s family. It has been speculated that the classical pathway emerged after the lectin pathway, and that the activation mechanism of the latter was partially conserved. The classical and lectin pathways can be traced back to at least cartilaginous fish and ascidian (urochordata), respectively. To elucidate the evolution of the complement system, we isolated and characterized a GlcNAc-binding lectin from sera of lamprey (agnathans), the most primitive vertebrate that lacks the classical pathway. Lamprey GlcNAc-binding lectin was an oligomer consisting of 24-kDa subunits. cDNA and phylogenetic analyses revealed that the lamprey GlcNAc-binding lectin is an orthologue of mammalian C1q, a collagenous subcomponent of the first component involved in binding to immunoglobulins in the classical pathway. Lamprey C1q copurified with MASP-A, a serine protease of the MASP/C1r/C1s family, which exhibited proteolytic activity against lamprey C3. Surface plasmon resonance analysis showed that lamprey C1q specifically bound to GlcNAc, but not various other carbohydrates tested. These results suggest that C1q may have emerged as a lectin and may have functioned as an initial recognition molecule of the complement system in innate immunity before the establishment of adaptive immunity such as immunoglobulins in the cartilaginous fish.
Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor
Authors: Marazziti Daniela , Golini Elisabetta , Mandillo Silvia , Magrelli Armando , Witke Walter , Matteoni Rafaele , Tocchini-Valentini Glauco P.
Published: June 2004

GPR37 is an orphan G protein-coupled receptor expressed in mammalian brain, and its insoluble aggregates are found in the brain samples of juvenile Parkinson's disease patients. We have produced aGpr37knock-out mouse strain and identified several phenotypic features that are similar to those reported for mutants of genes encoding components of synaptic dopamine vesicles. Our results reveal an unanticipated role of GPR37 in regulating substantia nigra-striatum dopaminergic signaling.Gpr37-/-mice are viable, with normal brain development and anatomy, but they exhibit reduced striatal dopamine content, enhanced amphetamine sensitivity, and specific deficits in motor behavior paradigms sensitive to nigrostriatal dysfunction. These functional alterations are not associated with any substantial loss of substantia nigra neurons or degeneration of striatal dopaminergic afferences, the main histological marks of Parkinson's disease. The inactivation of GPR37, in fact, has protective effects on substantia nigra neurons, causing resistance to treatment with the Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Phosphatase inhibitors remove the run-down of γ-aminobutyric acid type A receptors in the human epileptic brain
Authors: Palma E. , Ragozzino D. A. , Di Angelantonio S. , Spinelli G. , Trettel F. , Martinez-Torres A. , Torchia G. , Arcella A. , Di Gennaro G. , Quarato P. P. , Esposito V. , Cantore G. , Miledi R. , Eusebi F.
Published: June 2004

The properties of γ-aminobutyric acid (GABA) type A receptors (GABA
A
receptors) microtransplanted from the human epileptic brain to the plasma membrane of
Xenopus
oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABA
A
receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat α1β2γ2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABA
A
receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABA
A
receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABA
A
-receptor β1, β2, β3, and γ2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABA
A
receptors. Blockage of phosphatases stabilizes the TLE GABA
A
receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy.
CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: Induction of cytokine release and cytotoxicity against tumors and dendritic cells
Authors: Sivori Simona , Falco Michela , Chiesa Mariella Della , Carlomagno Simona , Vitale Massimo , Moretta Lorenzo , Moretta Alessandro
Published: June 2004

Toll-like receptors (TLRs) are pattern-recognition receptors responible for triggering cells of innate immunity. In this study we investigated the expression and function of TLRs 3 and 9 in human natural killer (NK) cells. In the presence of IL-12, freshly isolated NK cells responded to double-stranded RNA or unmethylated CpG DNA and expressed CD69 and CD25 activation markers. Because both markers were expressed by virtually all NK cells, this would suggest that most of them can be triggered by TLRs. Remarkably, NK cell stimulation also resulted in the induction of their functional program as revealed by IFN-γ and tumor necrosis factor-α release and by up-regulation of cytolytic activity against tumor cells. IL-8 could efficiently substitute IL-12 in supporting NK cell responses to TLR-mediated stimulation. Importantly, freshly isolated NK cells acquired the ability to lyse immature dendritic cells after stimulation with double-stranded RNA and IL-12. However, responses to these stimuli were not restricted to fresh NK cells, because significant responses were also detected in polyclonal NK cells cultured in the presence of exogenous IL-2 for several weeks. The analysis of NK cell clones revealed some degree of heterogeneity in the ability to respond to TLR stimulation also among NK clones derived from a single donor. These data suggest that stimuli acting on TLR not only activate immature dendritic cells to release IL-12 but also render NK cells capable of receiving triggering signals from pathogen-associated molecules, thus exerting a regulatory control on the early steps of innate immune responses against infectious agents.
THE ETIOLOGY OF TRACHOMA
Authors: Noguchi Hideyo
Published: June 2004

Dr. Noguchi left New York on October 22, 1927, for Accra, Gold Coast, West Africa. In his absence the observations on inoculated monkeys and the further transfer of the trachomatous lesions of the monkeys were carried out, according to his plans, by his assistants. Moreover, on several occasions during his absence, the monkeys were examined by Drs. F. I. Proctor, P. Richards, A. Knapp, J. S. Friedenwald, M. Cohen, and W. C. Posey, and the results of these examinations are recorded in the individual protocols. The last examination was made on May 25, 1928.
A Criterion of Probabilistic Causation
Authors: Twardy Charles R. , Korb Kevin B.
Published: June 2004

The investigation of probabilistic causality has been plagued by a variety of misconceptions and misunderstandings. One has been the thought that the aim of the probabilistic account of causality is the reduction of causal claims to probabilistic claims. Nancy Cartwright (1979) has clearly rebutted that idea. Another ill-conceived idea continues to haunt the debate, namely the idea that contextual unanimity can do the work of objective homogeneity. It cannot. We argue that only objective homogeneity in combination with a causal interpretation of Bayesian networks can provide the desired criterion of probabilistic causality.
Realist Ennui and the Base Rate Fallacy
Authors: Magnus P. D. , Callender Craig
Published: June 2004

The no-miracles argument and the pessimistic induction are arguably the main considerations for and against scientific realism. Recently these arguments have been accused of embodying a familiar, seductive fallacy. In each case, we are tricked by a base rate fallacy, one much-discussed in the psychological literature. In this paper we consider this accusation and use it as an explanation for why the two most prominent ‘wholesale’ arguments in the literature seem irresolvable. Framed probabilistically, we can see very clearly why realists and anti-realists have been talking past one another. We then formulate a dilemma for advocates of either argument, answer potential objections to our criticism, discuss what remains (if anything) of these two major arguments, and then speculate about a future philosophy of science freed from these two arguments. In so doing, we connect the point about base rates to the wholesale/retail distinction; we believe it hints at an answer of how to distinguish profitable from unprofitable realism debates. In short, we offer a probabilistic analysis of the feeling ofennuiafflicting contemporary philosophy of science.
The Scope and Limits of Scientific Objectivity
Authors: Hanna Joseph F.
Published: June 2004

The aim of this paper is twofold: first to sketch a framework for classifying a wide range of conceptions of scientific objectivity and second to present and defend a conception of scientific objectivity that fills a neglected niche in the resulting hierarchy of viewpoints. Roughly speaking, the proposed ideal of scientific objectivity is effectiveness in the informal but technical sense of an effective method. Science progresses when “higher levels of communicative discourse” are reached by transforming subjective judgments regarding the generation and reduction of data or the testing of theories into objective decision procedures that are automatic or mechanical.
Structural Content: A Naturalistic Approach to Implicit Belief
Authors: Skokowski Paul
Published: June 2004

Various systems that learn are examined to show how content is carried in connections installed by a learning history. Agents do not explicitly use the content of such states in practical reasoning, yet the content plays an important role in explaining behavior, and the physical state carrying that content plays a role in causing behavior, given other occurrent beliefs and desires. This leads to an understanding of the environmentalreasonswhich are the determinate content of these states, and leads to a better grasp of how representational content can be carried by systems without an explicit representation.
Test Cases, Resolvability, and Group Selection: A Critical Examination of the Myxoma Case
Authors: Wilson Robert A.
Published: June 2004

The evolution of the myxoma virus in Australia has been presented for many years as a test case for the hypothesis that group selection can function effectively ‘in the wild.’ This paper critically examines the myxoma case, and argues that its failure as a test case for this hypothesis has broader implications for debates over the levels of selection.
PTGL—a web-based database application for protein topologies
Authors: May Patrick , Barthel Stefan , Koch Ina
Published: June 2004

Summary: Protein Topology Graph Library (PTGL) is a database application for the representation and retrieval of protein topologies. Protein topologies are based on a graph-theoretical protein model at secondary structure level. Different views on protein topology are given by four linear notations for their characterization. Protein topologies can be derived at different description levels considering α- and β-structures. The on-line search tool is based on an object-relational database and provides a query browser for data interrogation by string patterns, keyword queries and sequence similarity. Protein topologies are represented both as schematic diagrams and as three-dimensional images.

Availability:  http://sanaga.tfh-berlin.de/~ptgl/ptgl.html
Standardization and denoising algorithms for mass spectra to classify whole-organism bacterial specimens
Authors: Satten Glen A. , Datta Somnath , Moura Hercules , Woolfitt Adrian R. , Carvalho Maria da G. , Carlone George M. , De Barun K. , Pavlopoulos Antonis , Barr John R.
Published: June 2004

Motivation: Application of mass spectrometry in proteomics is a breakthrough in high-throughput analyses. Early applications have focused on protein expression profiles to differentiate among various types of tissue samples (e.g. normal versus tumor). Here our goal is to use mass spectra to differentiate bacterial species using whole-organism samples. The raw spectra are similar to spectra of tissue samples, raising some of the same statistical issues (e.g. non-uniform baselines and higher noise associated with higher baseline), but are substantially noisier. As a result, new preprocessing procedures are required before these spectra can be used for statistical classification.

Results: In this study, we introduce novel preprocessing steps that can be used with any mass spectra. These comprise a standardization step and a denoising step. The noise level for each spectrum is determined using only data from that spectrum. Only spectral features that exceed a threshold defined by the noise level are subsequently used for classification. Using this approach, we trained the Random Forest program to classify 240 mass spectra into four bacterial types. The method resulted in zero prediction errors in the training samples and in two test datasets having 240 and 300 spectra, respectively.

Availability: Fortran code for standardization and denoising is available at the supplementary information website.

Supplementary information:  http://www.stat.uga.edu/~datta/Massspec/supp.html
Constrained clusters of gene expression profiles with pathological features
Authors: Sese Jun , Kurokawa Yukinori , Monden Morito , Kato Kikuya , Morishita Shinichi
Published: June 2004

Motivation: Gene expression profiles should be useful in distinguishing variations in disease, since they reflect accurately the status of cells. The primary clustering of gene expression reveals the genotypes that are responsible for the proximity of members within each cluster, while further clustering elucidates the pathological features of the individual members of each cluster. However, since the first clustering process and the second classification step, in which the features are associated with clusters, are performed independently, the initial set of clusters may omit genes that are associated with pathologically meaningful features. Therefore, it is important to devise a way of identifying gene expression clusters that are associated with pathological features.

Results: We present the novel technique of ‘itemset constrained clustering’ (IC-Clustering), which computes the optimal cluster that maximizes the interclass variance of gene expression between groups, which are divided according to the restriction that only divisions that can be expressed using common features are allowed. This constraint automatically labels each cluster with a set of pathological features which characterize that cluster. When applied to liver cancer datasets, IC-Clustering revealed informative gene expression clusters, which could be annotated with various pathological features, such as ‘tumor’ and ‘man’, or ‘except tumor’ and ‘normal liver function’. In contrast, the k-means method overlooked these clusters.

Supplementary information: Our dataset is available on the following web page: http://love2.aist-nara.ac.jp/laboratory/data_download.html.
BioNetGen: software for rule-based modeling of signal transduction based on the interactions of molecular domains
Authors: Blinov Michael L. , Faeder James R. , Goldstein Byron , Hlavacek William S.
Published: June 2004

Summary: BioNetGen allows a user to create a computational model that characterizes the dynamics of a signal transduction system, and that accounts comprehensively and precisely for specified enzymatic activities, potential post-translational modifications and interactions of the domains of signaling molecules. The output defines and parameterizes the network of molecular species that can arise during signaling and provides functions that relate model variables to experimental readouts of interest. Models that can be generated are relevant for rational drug discovery, analysis of proteomic data and mechanistic studies of signal transduction.

Availability:  http://cellsignaling.lanl.gov/bionetgen
Political Learning from Rare Events: Poisson Inference, Fiscal Constraints, and the Lifetime of Bureaus
Authors: Carpenter Daniel P. , Lewis David E.
Published: June 2004

How do political actors learn about their environment when the “data” provided by political processes are characterized by rare events and highly discontinuous variation? In such learning environments, what can theory predict about how learning actors will take costly actions that are difficult to reverse (e.g., eliminating programs, approving a risky new product, revising a security policy, firing or recalling an appointed or elected official)? We develop a formal model for this problem and apply it to the termination of bureaucratic agencies. The conventional wisdom that “the older a bureau is, the less likely it is to die” (Downs 1967,Inside Bureaucracy) persists but has never been properly tested. This paper offers a learning-based stochastic optimization model of agency termination that offers two counterintuitive predictions. First, politicians terminate agencies only after learning about them, so the hazard of agencies should be nonmonotonic, contradicting Downs's prediction. Second, if terminating agencies is costly, agencies are least likely to be terminated when politicians are fiscally constrained or when the deficit is high. We assess the model by developing a battery of tests for the shape of the hazard function and estimate these and other duration models using data on U.S. federal government agencies created between 1946 and 1997. Results show that the hazard rate of agency termination is strongly nonmonotonic and that agencies are less likely to be terminated under high deficits and divided government. For the first 50 years of the agency duration distribution, the modal termination hazard occurs at five years after agencies are enabled. Methodologically, our approach ties the functional form of a hazard model tightly to theory and presents an applied “agenda” for testing the shape of an empirical hazard function. With extensions, our model and empirical framework are applicable to a range of political phenomena.
The Uncovered Set and the Limits of Legislative Action
Authors: Bianco William T. , Jeliazkov Ivan , Sened Itai
Published: June 2004

We present a simulation technique for sorting out the size, shape, and location of the uncovered set to estimate the set of enactable outcomes in “real-world” social choice situations, such as the contemporary Congress. The uncovered set is a well-known but underexploited solution concept in the literature on spatial voting games and collective choice mechanisms. We explain this solution concept in nontechnical terms, submit some theoretical observations to improve our theoretical grasp of it, and provide a simulation technique that makes it possible to estimate this set and thus enable a series of tests of its empirical relevance.
Forecasting the Vote: A Theoretical Comparison of Election Markets and Public Opinion Polls
Authors: Kou S. G. , Sobel Michael E.
Published: June 2004

The dominant methodology for short-term forecasting of electoral outcomes uses trial-heat polls, where respondents report their current electoral preferences (not their election-day predictions). Election markets, where self-selected participants trade shares of candidates at prices predictive of election-day results, provide an alternative method that often produces more accurate forecasts. Consequently, increasing attention is being paid to this methodology. However, it is poorly understood and lacks theoretical justification. Surprisingly, the rationale for forecasting using trial-heat polls has not been completely developed either. We develop the justification for using both election markets and public opinion polls to forecast electoral outcomes, giving conditions under which each method performs ideally. For the ideal case, we prove (under the reasonable assumption that market participants are aware of the poll results) that the mean square prediction error for the market forecast is smaller than that of any forecast based on one or more polls. The case in which the assumptions supporting each method fail is also considered. It is often reasonable to expect that the best case results hold approximately, in which case the market forecast should also beat any poll-based forecast. We also compare the bias and variance of market and poll-based forecasts; our results suggest the utility of using the series of market prices to study the course of campaigns.
Skills development: the missing link in increasing diversity in leadership
Authors: Kandola Binna
Published: June 2004

This article provides human resource professionals and managers with an insight into the under representation of women/ethnic minorities at senior management level in UK organisations and the issues involved in increasing diversity in leadership. It describes three leadership studies carried out by Pearn Kandola covering: barriers to the career progress of ethnic minorities; differences in perception of male and female managerial success; and changing leadership behaviour. The research was conducted via literature reviews and interviews with HR/diversity specialists, senior managers and ethnic minority employees. The findings highlight the individual and organisational barriers facing ethnic minority employees and the differences in attribution of male and female managerial success. It underlines the need for diversity policies to encompass development and progression, as well as recruitment, and for skills development. Although further quantitative research is needed, the findings raise questions about underlying stereotypes and bias and discrimination when developing and implementing appraisal systems. Practical suggestions are made regarding behaviour change and policy review.
Creating behavioural change in leaders
Authors: Whiteley Jon
Published: June 2004

Many organisations have made significant progress in developing diversity strategies and have put in place robust polices and procedures to ensure fairness and transparency. However, those organisations at the cutting edge of diversity management have now began to focus on the behaviour of their people and in particular their managers and leaders. Research has shown that those organisations with leaders modelling and demonstrating inclusive and appropriate behaviours are the same organisations who are successfully integrating diversity into the mainstream business. Jon Whiteley, head of diversity at occupational psychologists Pearn Kandola outlines the approach some organisations are taking to effect this behavioural change.
Dealing with diversity: a matter of beliefs
Authors: Gillert Arne , Chuzischvili George
Published: June 2004

This article is based on the experience of a pilot training on “dealing effectively with diversity” for branch office bank personnel in The Netherlands. We conclude that being successful in serving ethnic minority clients is a matter of beliefs, playing a more decisive role than specific “intercultural” competencies. The experience of Rabobank shows that learning to deal with diverse clients, then, will only be effective if it is part of a larger change process, and if training is just one of several interventions: impressions and lessons learned from work in progress.
Globalization and the politics of local and regional development: the question of convergenc
Authors: Cox Kevin R
Published: June 2004

Globalization, and the increased exposure to international competition that it has supposedly induced, has led to expectations of institutional convergence in, among other things, local and regional development policy and the politics surrounding it. There have been changes in the United Kingdom, but not of the decentralizing, neo‐liberalizing form anticipated. A comparison of the British with the very different, highly decentralized, American case seeks to shed light on this. Emphasis is placed on both the strongly embedded nature of institutions and on misunderstandings about the strength of the forces of globalization.
Ber‐EP4 antigen is a marker for a cell population related to the secondary hair germ
Authors: Ozawa Maki , Aiba Setsuya , Kurosawa Masahiro , Tagami Hachiro
Published: June 2004

Abstract:  Ber‐EP4 is an antibody to a cell membrane glycoprotein of unknown function. In the skin, Ber‐EP4 immunoreactivity has been reported to be localized in structures composed of basaloid epithelial cells, i.e. fetal epithelial germ cells, basal cell carcinoma, and trichoepithelioma as well as eccrine or apocrine ducts. In this study, we further characterized the follicular expression of Ber‐EP4 immunoreactivity at different stages of the hair cycle of human terminal hair follicles. In addition, to clarify the location of Ber‐EP4+ cells, we compared the Ber‐EP4 immunoreactivity with the expression of keratin 15 and keratin 19. Positive staining by Ber‐EP4 was found in the lower part of the epithelial strand of late catagen hair follicles, in the secondary hair germ of telogen hair follicles, and in the matrix of early anagen hair follicles but not in any parts of mature anagen hair follicles. In contrast, the follicular expression of keratin 15 detected by using LHK15 antibody was restricted to two distinct parts of anagen hair follicles, i.e. the outer root sheath above the hair bulb and that of the isthmus including the bulge area, and to the outer root sheath of late catagen and telogen hair follicles. The follicular expressions of keratin 19 and that of keratin 15 were apparently superimposed, whereas keratin 15 expression was more extended. The immunoreactivity of LHK15 antibody and antikeratin 19 antibody against the secondary hair germ of telogen follicles was negative or dim. Our results suggest that Ber‐EP4 reacts with the secondary hair germ and possibly a cell population related to the secondary hair germ but not with the presumptive stem cell population as revealed immunohistochemically either by the keratin 15 or keratin 19 expression.
STG does not associate with psoriasis in the Swedish population
Authors: Sánchez Fabio , Holm Sofia J. , Mallbris Lotus , O'Brien Kevin P. , Ståhle Mona
Published: June 2004

Abstract:  Psoriasis is a chronic inflammatory skin disease that is known to have a strong genetic predisposition. Several psoriasis‐susceptibility loci have been previously found through genomic scans. Of these, psoriasis‐susceptibility region 1 (PSORS1) on chromosome 6p21 remains the most consistently identified region across populations with the highest association with disease. STG is a gene that was previously isolated from rhesus monkey taste buds, and its ortholog in humans was found to be part of the cluster of genes in PSORS1, which is telomeric to HLA‐C. Upon characterization of STG, we identified several sequence variants and investigated their association with psoriasis in cases and controls from the Swedish population. None of these STG single‐nucleotide polymorphisms were found to be significantly associated with psoriasis. However, HLA‐Cw*0602 status was strongly associated with disease. STG expression was investigated in human tissues and found not to be restricted to taste buds, with signals also being detected in skin and tonsils.
Methotrexate markedly reduces the expression of vascular E‐selectin, cutaneous lymphocyte‐associated antigen and the numbers of mononuclear leucocytes in psoriatic skin
Authors: Sigmundsdottir Hekla , Johnston Andrew , Gudjonsson Johann Eli , Bjarnason Bolli , Valdimarsson Helgi
Published: June 2004

Abstract:  A positive correlation between disease severity and the frequency of cutaneous lymphocyte‐associated antigen (CLA)‐positive T cells in the blood of untreated patients with psoriasis has been previously observed. A dose‐dependent inverse relationship between disease severity and the frequency of circulating CLA+ T cells in psoriasis patients on methotrexate (MTX) treatment is reported. Circulating T cells from a patient with psoriasis were monitored for CLA expression on a daily basis for 5 weeks. A decrease in the intensity and frequency of CLA+ mononuclear leucocytes was consistently observed in the blood during the first 3–4 days after each MTX intake, but the CLA expression increased thereafter until the next weekly dose was taken. The MTX treatment of this patient was then discontinued for 16 days, and a marked subjective exacerbation was reported within 9 days, which was confirmed objectively (laser Doppler perfusion imaging) after 11 and 16 days. Biopsies taken 4 days after the last MTX intake showed only a few mononuclear leucocytes in lesional skin, but the exacerbation coincided with a marked increase in CLA expression by mononuclear blood leucocytes, followed by an increase in endothelial E‐selectin and a striking influx of CLA+ mononuclear cells into lesional skin. Conversely, a clinical improvement after the patient resumed the MTX treatment was associated with reduction in CLA expression by mononuclear cells in the blood, downregulation of endothelial E‐selectin and an approximate threefold decrease in mononuclear leucocyte infiltration of lesional skin. No MTX‐associated changes were detected in the expression of very late antigen‐4, vascular cell‐adhesion molecule‐1 nor the late activation marker CD25. It is concluded that MTX decreases the expression of CLA and E‐selectin and that this may be a major mechanism for the therapeutic effect of MTX on psoriatic skin lesions.
The progressive state, in contrast to the stable or regressive state of alopecia areata, is reflected in peripheral blood mononuclear cells
Authors: Zöller Margot , McElwee Kevin J. , Vitacolonna Mario , Hoffmann Rolf
Published: June 2004

Abstract:  Alopecia areata (AA) is a putative autoimmune disease of the skin with an inflammatory component that can be treated by the local application of contact sensitizers. Here, we explored whether responsiveness toward diphenylcyclopropenone (DPCP) is reflected by the composition and the activation state of peripheral blood mononuclear cells (PBMCs). PBMCs of 43 AA patients, 26 treated and 17 untreated, and of 31 healthy volunteers were tested. AA patients' PBMCs differed from that of healthy donors by a slight increase in CD16‐ and tumor necrosis factor‐α (TNF‐α)‐expressing cells. These features were independent of the disease state and treatment. Additional changes in the activation state of PBMCs, upregulation of the costimulatory molecules CD40 and CD80, of the accessory molecule CD154, and of interferon‐γ expression were identified only in AA patients where the disease was advancing, i.e. these changes were independent of the extent of hair loss and were not seen in patients with spontaneous or DPCP treatment‐induced, regressing AA. Thus, the progressive state of AA is accompanied by a systemic activation of T cells, and the therapeutic efficacy of treatment can be estimated by restoration of the non‐activated state. Furthermore, an increase in CD16+‐ and TNF‐α‐expressing cells may contribute to AA susceptibility.
Evaluation of the penetration of 5‐aminolevulinic acid through basal cell carcinoma: a pilot study
Authors: Ahmadi Sharareh , McCarron Paul A. , Donnelly Ryan F. , Woolfson A. David , McKenna Kevin
Published: June 2004

Abstract:  Aminolevulinic acid (ALA) is a charged, hydrophilic molecule that penetrates poorly through cellular structures. This property has been implicated in the poor clinical response of non‐superficial basal cell carcinomas (BCCs) to photodynamic therapy (PDT). Release of ALA hydrochloride from a 20% w/w formulation was found to be incomplete and that approximately 36.8% of the total dose is released during the application period of 4 h. Using scintillation spectroscopy and a precise tissue sectioning protocol, it was demonstrated that depths of penetration of at least 2 mm from the lesion surface had been reached. Using cumulative stratal ALA concentrations, it was found that 10% of the total applied dose permeated into the lesion. In spite of this, comparisons drawn with photodynamic concentrations used in tissue culture work reported elsewhere revealed that estimations of the ALA concentration at 2 mm were sufficient to elicit a possible therapeutic response. Results from this work question the reasons given for poor outcomes of PDT in nodular BCC based solely on depth as a hindering factor.
Measurement of cytokine expression and Langerhans cell migration in human skin following suction blister formation
Authors: Dearman Rebecca J. , Bhushan Monica , Cumberbatch Marie , Kimber Ian , Griffiths Christopher E. M.
Published: June 2004

Abstract:  Contact allergen‐induced migration of epidermal Langerhans cells (LCs) to draining lymph nodes is dependent upon receipt by LCs of at least two cytokine signals provided by tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β. It has been reported previously that intradermal injection of healthy human volunteers with homologous TNF‐α or IL‐1β each induces a significant reduction in LC frequency, as measured in epidermal sheets prepared from 6‐mm punch biopsies. In the current experiments, we have compared the frequency of LCs in punch biopsies with those obtained concurrently in epidermal sheets from the roofs of suction blisters isolated from the sun‐protected buttock skin of healthy adult volunteers. There was a significant, approximately 30%, reduction in CD1a+ LC numbers in suction blister roofs compared with punch biopsies. Injection of homologous recombinant IL‐1β, a stimulus that provokes measurable epidermal LC mobilization in punch biopsy sites, failed to provoke further LC migration in suction blister sites. These data suggest that the mechanical trauma to the skin caused by the creation of suction blisters provokes the degree of cutaneous inflammation necessary for LC mobilization. The responsive cells (only a proportion of resident LCs, approximately 30%) have already migrated, thus addition of an exogenous cytokine signal (IL‐1β) is without further effect. It is not possible therefore to measure the regulation of LC mobilization by exogenous cytokines in suction blister roofs. However, this technique provides an opportunity to profile induced changes in the cutaneous cytokine environment, with cytokine expression measured by a multiple cytokine array system. Using this technique, intradermal injection of IL‐1β was found to cause a marked upregulation of proinflammatory cytokines including TNF‐α, IL‐6, IL‐8, monocyte chemotactic protein‐1 (MCP‐1) and the anti‐inflammatory cytokine IL‐10 in fluid from suction blisters raised at the site of injection. In conclusion, the suction blister technique appears to be a powerful tool for measurement of induced changes in cutaneous cytokines.
Establishment of a mouse xenograft model for mycosis fungoides
Authors: Thaler Sonja , Burger Angelika M. , Schulz Thomas , Brill Boris , Bittner Alexandra , Oberholzer Patrick A. , Dummer Reinhard , Schnierle Barbara S.
Published: June 2004

Abstract:  Mycosis fungoides (MF) is the most frequent variant of cutaneous T‐cell lymphomas (CTCLs). MF primarily involves the skin initially with patches and plaques. In later stages, cutaneous tumors develop and tumor cells may spread to lymph nodes and finally to visceral sites. Here, we describe an animal model for MF in immune‐deficient nude mice, using the CTCL cell line MyLa. Subcutaneous transplantation of MyLa cells leads to the formation of cutaneous tumors in 80% of the mice (50/60 total). Spread of tumor cells to visceral sites was detected by immunohistochemistry and polymerase chain reaction (PCR)‐based detection of specific T‐cell receptor‐γ rearrangement. MyLa cells were found circulating in the blood, lymph nodes, and in blood vessels of heart, kidney, lung, and liver. In lung and liver tissue, tumor cells presented perivascular invasion, but no large secondary tumors developed. The nude mouse model described here will be a valuable test system for new therapeutic approaches for the treatment of MF and opens the unique opportunity to study the disease in vivo.
Redstart Phoenicurus phoenicurus and black redstart P. ochruros in a mosaic urban environment: neighbours or rivals?
Authors: Sedláček Ondřej , Fuchs Roman , Exnerová Alice
Published: June 2004

Redstart and black redstart inhabit different types of habitats under natural conditions. However, they come into close contact in a mosaic urban environment. Mechanisms enabling their local coexistence were looked for. We found that: 1) The two species occupied exclusive territories of different habitat compositions. 2) Territories differed in the proportion of trees and buildings. 3) Within their territories, the two species used the same foraging techniques, but with different frequencies. 4) Prey size was similar, but the proportions of taxonomic groups differed. 5) Spontaneous interspecific conflicts were observed. Interspecific aggression was confirmed in playback experiments. The black redstart was dominant in both natural and simulated encounters. We conclude that the main mechanism enabling coexistence of the two redstarts in a mosaic urban environment is different habitat selection with the proportion of trees as a key parameter. This proportion was always below 26% in black redstart territories, and above 27% in redstart territories. This is consistent with the habitat preferences these two species show in non‐urban conditions. This pattern is compared to the other cases of coexistence of congeneric bird species such as chickadees Poecile or Sylvia warblers. As the two redstart species are able to hybridise in the wild, the observed interspecific aggression may operate as a pre‐copulation barrier.
A comparison of nocturnal call counts of migrating birds and reflectivity measurements on Doppler radar
Authors: Farnsworth Andrew , Gauthreaux, Jr. Sidney A. , Blaricom Donald van
Published: June 2004

Several studies have found that the peak in bird density in the atmosphere during nocturnal migration occurs before midnight, while the peak in vocalizations from migrating birds occurs after midnight, in the hours just before dawn. In a recent study, the patterns of calling from a single species of migrating birds correlated well with the patterns of density estimates of migrating birds. We test the null hypothesis that the patterns of reflectivity measurements and number of vocalizations during nocturnal migration are not related. We sampled radar data and nocturnal flight calls during spring and fall 2000 in northwestern South Carolina and southeastern New York. We analyzed changes in the hour‐to‐hour patterns of bird density and vocalizations for 556 hours on 58 nights. We also analyzed the night‐to‐night changes in the patterns of peak hour bird density and peak hour of vocalizations on 32 nights. We found that most of the hour‐to‐hour and night‐to‐night patterns of density and vocalization counts are significantly related and reject the null hypothesis. However, despite significant relationships between reflectivity measurements and vocalization counts, a great deal of variation in vocalization counts remains unexplained. These results suggest that factors other than bird density are responsible for the variation in vocalizing by migrating birds.
Juvenile survival and recruitment of wood thrushes Hylocichla mustelina in a forest fragment
Authors: P. Brown William , R. Roth Roland
Published: June 2004

We tested if juvenile survival and recruitment (returning to breed) of wood thrushes Hylocichla mustelina into their natal population was dependent on several measures of nestling condition, growth, and site fidelity. Overall, nestling mass, wing chord, condition, and rank within the brood did not affect the probability of survival to the post‐fledging stage, independence, or recruitment. We did not identify any morphometric differences among nestlings that remained in the study area after fledging and those that did not (or those that did not survive). Time of season and the number of days nestlings were present in the study area after hatching, or site fidelity, were the only variables measured that positively influenced juvenile survival and recruitment. Based on a restricted sample, fledglings that eventually recruited did not differ in size during post‐fledging or post‐independence from fledglings that did not return to breed. Independent, immigrant hatching‐year (HY) birds are briefly described. Overall, immigrant HY birds had a higher probability of recruitment than all local fledglings. There was no difference in the probability of recruitment between immigrant HY birds and independent local fledglings (those present ≥35 days after hatching), however. Similar to local young, the number of days present in the study area increased the likelihood of recruitment for immigrant HY birds, although these effects could not be distinguished from those of emigration or survival.
Effects of long‐term implanted data loggers on macaroni penguins Eudyptes chrysolophus
Authors: Green Jonathan A. , Tanton Jane L. , Woakes Anthony J. , Boyd Ian L. , Butler Paul J.
Published: June 2004

We tested the hypothesis that implanted data loggers have no effect on the survival, breeding success and behaviour of macaroni penguins Eudyptes chrysolophus. Seventy penguins were implanted with heart rate data loggers (DLs) for periods of up to 15 months. When compared to control groups, implanted penguins showed no significant difference in over‐wintering survival rates, arrival date and mass at the beginning of the breeding season. Later in the breeding season, implanted penguins showed no significant difference in the duration of their incubation foraging trip, breeding success, fledging mass of their chicks, date of arrival to moult and mass at the beginning of the moult fast. We conclude that implanted devices had no effects on the behaviour, breeding success and survival of this species. We contrast these results to those from studies using externally attached devices, which commonly affect the behaviour of penguins. We suggest that implanted devices should be considered as an alternative to externally attached devices in order to obtain the most accurate representation of the free‐ranging behaviour, ecology and physiology of penguins.
Glacial history and colonization of Europe by the blue tit Parus caeruleus
Authors: Kvist Laura , Viiri Keijo , Dias Paula C. , Rytkönen Seppo , Orell Markku
Published: June 2004

Mitochondrial control region sequences from European populations of the blue tit Parus caeruleus were used to reveal the Pleistocene history and the post‐glacial recolonization of Europe by the species. The southern subspecies, P. c. ogliastrae was found to represent a stable population with isolation‐by‐distance structure harboring a lot of genetic variation, and the northern subspecies P. c. caeruleus a recently bottlenecked and expanded population. We suggest that after the last Ice Ages, the subspecies have colonized Europe from two different southern refuges following previously proposed general recolonization routes from the Balkans to northern and Central Europe, and from the Iberian Peninsula north‐ and eastwards. The two subspecies form a wide secondary contact zone extending from southern Spain to southern France.