bluuebunny/crossref_metadata_2025 huggingface dataset:
Defective B cell tolerance checkpoints in systemic lupus erythematosus
Authors: Yurasov Sergey , Wardemann Hedda , Hammersen Johanna , Tsuiji Makoto , Meffre Eric , Pascual Virginia , Nussenzweig Michel C.
Published: March 2005

A cardinal feature of systemic lupus erythematosus (SLE) is the development of autoantibodies. The first autoantibodies described in patients with SLE were those specific for nuclei and DNA, but subsequent work has shown that individuals with this disease produce a panoply of different autoantibodies. Thus, one of the constant features of SLE is a profound breakdown in tolerance in the antibody system. The appearance of self-reactive antibodies in SLE precedes clinical disease, but where in the B cell pathway tolerance is first broken has not been defined. In healthy humans, autoantibodies are removed from the B cell repertoire in two discrete early checkpoints in B cell development. We found these checkpoints to be defective in three adolescent patients with SLE. 25–50% of the mature naive B cells in SLE patients produce self-reactive antibodies even before they participate in immune responses as compared with 5–20% in controls. We conclude that SLE is associated with abnormal early B cell tolerance.
Consumer Culture Theory (CCT): Twenty Years of Research
Authors: Arnould Eric J. , Thompson Craig J.
Published: March 2005

This article provides a synthesizing overview of the past 20 yr. of consumer research addressing the sociocultural, experiential, symbolic, and ideological aspects of consumption. Our aim is to provide a viable disciplinary brand for this research tradition that we call consumer culture theory (CCT). We propose that CCT has fulfilled recurrent calls for developing a distinctive body of theoretical knowledge about consumption and marketplace behaviors. In developing this argument, we redress three enduring misconceptions about the nature and analytic orientation of CCT. We then assess how CCT has contributed to consumer research by illuminating the cultural dimensions of the consumption cycle and by developing novel theorizations concerning four thematic domains of research interest.
Scaling of elastic energy storage in mammalian limb tendons: do small mammals really lose out?
Authors: Bullimore Sharon R , Burn Jeremy F
Published: March 2005

It is widely believed that elastic energy storage is more important in the locomotion of larger mammals. This is based on: (a) comparison of kangaroos with the smaller kangaroo rat; and (b) calculations that predict that the capacity for elastic energy storage relative to body mass increases with size. Here we argue that: (i) data from kangaroos and kangaroo rats cannot be generalized to other mammals; (ii) the elastic energy storage capacity relative to body mass is not indicative of the importance of elastic energy to an animal; and (iii) the contribution of elastic energy to the mechanical work of locomotion will not increase as rapidly with size as the mass-specific energy storage capacity, because larger mammals must do relatively more mechanical work per stride. We predict how the ratio of elastic energy storage to mechanical work will change with size in quadrupedal mammals by combining empirical scaling relationships from the literature. The results suggest that the percentage contribution of elastic energy to the mechanical work of locomotion decreases with size, so that elastic energy is more important in the locomotion of smaller mammals. This now needs to be tested experimentally.
HFR1 is targeted by COP1 E3 ligase for post-translational proteolysis during phytochrome A signaling
Authors: Jang In-Cheol , Yang Jun-Yi , Seo Hak Soo , Chua Nam-Hai
Published: March 2005

Upon activation by far-red light, phytochrome A signals are transduced through several pathways to promote photomorphogenesis. The COP1 E3 ligase represses photomorphogenesis in part by targeting transcription activators such as LAF1 and HY5 for destruction. Another positive regulator of photomorphogenesis is HFR1, a basic helix-loop-helix (bHLH) transcription factor. Here, we show that HFR1 colocalizes with COP1 in nuclear bodies, and that the HFR1 N-terminal region (amino acids 1-131) interacts with the COP1 WD40 domain. HFR1(ΔN), an HFR1 mutant lacking the two N-terminal, COP1-interacting motifs, still localizes in nuclear bodies and retains weak affinity for COP1. Both HFR1 and HFR1(ΔN) can be ubiquitinated by COP1, although with different efficiencies. Expression of 35S-HFR1(ΔN) in wild-type plants confers greater hypersensitivity to FR than 35S-HFR1 expression, and only seedlings expressing 35S-HFR1(ΔN) display constitutive photomorphogenesis. These phenotypic differences can be attributed to the instability of HFR1 compared with HFR1(ΔN). In transgenic plants, HFR1 levels are significantly elevated upon induced expression of a dominant-negative COP1 mutant that interferes with endogenous COP1 E3 activity. Moreover, induced expression of wild-type COP1 in transgenic plants accelerates post-translational degradation of HFR1 under FR light. Taken together, our results show that HFR1 is ubiquitinated by COP1 E3 ligase and marked for post-translational degradation during photomorphogenesis.
FGF8 initiates inner ear induction in chick and mouse
Authors: Ladher Raj K. , Wright Tracy J. , Moon Anne M. , Mansour Suzanne L. , Schoenwolf Gary C.
Published: March 2005

In both chick and mouse, the otic placode, the rudiment of the inner ear, is induced by at least two signals, one from the cephalic paraxial mesoderm and the other from the neural ectoderm. In chick, the mesodermal signal, FGF19, induces neural ectoderm to express additional signals, including WNT8c and FGF3, resulting in induction of the otic placode. In mouse, mesodermalFgf10acting redundantly with neuralFgf3is required for induction of the placode. To determine how the mesodermal inducers of the otic placode are localized, we took advantage of the unique strengths of the two model organisms. We show that endoderm is necessary for otic induction in the chick and thatFgf8, expressed in the chick endoderm subjacent toFgf19, is both sufficient and necessary for the expression ofFgf19in the mesoderm. In the mouse,Fgf8is also expressed in endoderm as well as in other germ layers in the periotic placode region. We show that otic induction fails in embryos null forFgf3and hypomorphic forFgf8and expression of mesodermalFgf10is reduced. Thus,Fgf8plays a critical upstream role in an FGF signaling cascade required for otic induction in chick and mouse.
Mammalian Polycomb-mediated repression of Hox genes requires the essential spliceosomal protein Sf3b1
Authors: Isono Kyoichi , Mizutani-Koseki Yoko , Komori Toshihisa , Schmidt-Zachmann Marion S. , Koseki Haruhiko
Published: March 2005

Polycomb group (PcG) proteins are responsible for the stable repression of homeotic (Hox) genes by forming multimeric protein complexes. We show (1) physical interaction between components of the U2 small nuclear ribonucleoprotein particle (U2 snRNP), including Sf3b1 and PcG proteins Zfp144 and Rnf2; and (2) that Sf3b1 heterozygous mice exhibit skeletal transformations concomitant with ectopic Hox expressions. These alterations are enhanced by Zfp144 mutation but repressed by Mll mutation (a trithorax-group gene). Importantly, the levels of Sf3b1 in PcG complexes were decreased in Sf3b1-heterozygous embryos. These findings suggest that Sf3b1-PcG protein interaction is essential for true PcG-mediated repression of Hox genes.
Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms
Authors: Rohde Mikkel , Daugaard Mads , Jensen Mette Hartvig , Helin Kristian , Nylandsted Jesper , Jäättelä Marja
Published: March 2005

Whereas the stress-inducible heat-shock protein 70 (Hsp70) has gained plenty of attention as a putative target for tumor therapy, little is known about the role of other Hsp70 proteins in cancer. Here we present the first thorough analysis of the expression and function of the cytosolic Hsp70 proteins in human cancer cells and identify Hsp70-2, a protein essential for spermatogenesis, as an important regulator of cancer cell growth. Targeted knock-down of the individual family members by RNA interference revealed that both Hsp70 and Hsp70-2 were required for cancer cell growth, whereas the survival of tumorigenic as well as nontumorigenic cells depended on Hsc70. Cancer cells depleted for Hsp70 and Hsp70-2 displayed strikingly different morphologies (detached and round vs. flat senescent-like), cell cycle distributions (G2/M vs. G1 arrest) and gene expression profiles. Only Hsp70-2 depletion induced the expression of macrophage inhibitory cytokine-1 that was identified as a target of P53 tumor-suppressor protein and a mediator of the G1 arrest and the senescent phenotype. Importantly, concomitant depletion of Hsp70 and Hsp70-2 had a synergistic antiproliferative effect on cancer cells. Thus, highly homologous Hsp70 proteins bring about nonoverlapping functions essential for cell growth and survival.
Intergenic transcription through a Polycomb group response element counteracts silencing
Authors: Schmitt Sabine , Prestel Matthias , Paro Renato
Published: March 2005

Polycomb group response elements (PREs) mediate the mitotic inheritance of gene expression programs and thus maintain determined cell fates. By default, PREs silence associated genes via the targeting of Polycomb group (PcG) complexes. Upon an activating signal, however, PREs recruit counteracting trithorax group (trxG) proteins, which in turn maintain target genes in a transcriptionally active state. Using a transgenic reporter system, we show that the switch from the silenced to the activated state of a PRE requires noncoding transcription. Continuous transcription through the PRE induced by an actin promoter prevents the establishment of PcG-mediated silencing. The maintenance of epigenetic activation requires transcription through the PRE to proceed at least until embryogenesis is completed. At the homeotic bithorax complex of Drosophila, intergenic PRE transcripts can be detected not only during embryogenesis, but also at late larval stages, suggesting that transcription through endogenous PREs is required continuously as an anti-silencing mechanism to prevent the access of repressive PcG complexes to the chromatin. Furthermore, all other PREs outside the homeotic complex we tested were found to be transcribed in the same tissue as the mRNA of the corresponding target gene, suggesting that anti-silencing by transcription is a fundamental aspect of the cellular memory system.
Prokaryotic phylogenies inferred from protein structural domains
Authors: Deeds Eric J. , Hennessey Hooman , Shakhnovich Eugene I.
Published: March 2005

The determination of the phylogenetic relationships among microorganisms has long relied primarily on gene sequence information. Given that prokaryotic organisms often lack morphological characteristics amenable to phylogenetic analysis, prokaryotic phylogenies, in particular, are often based on sequence data. In this work, we explore a new source of phylogenetic information, the distribution of protein structural domains within fully sequenced prokaryotic genomes. The evolution of the structural domains we use has been studied extensively, allowing us to base our phylogenetic methods on testable theoretical models of structural evolution. We find that the methods that produce reasonable phylogenetic relationships are indeed the methods that are most consistent with theoretical evolutionary models. This work represents, to our knowledge, the first such theoretically motivated phylogeny, as well as the first application of structural information to phylogeny on this scale. Our results have strong implications for the phylogenetic relationships among prokaryotic organisms and for the understanding of protein evolution as a whole.
Database of mRNA gene expression profiles of multiple human organs
Authors: Son Chang Gue , Bilke Sven , Davis Sean , Greer Braden T. , Wei Jun S. , Whiteford Craig C. , Chen Qing-Rong , Cenacchi Nicola , Khan Javed
Published: March 2005

Genome-wide expression profiling of normal tissue may facilitate our understanding of the etiology of diseased organs and augment the development of new targeted therapeutics. Here, we have developed a high-density gene expression database of 18,927 unique genes for 158 normal human samples from 19 different organs of 30 different individuals using DNA microarrays. We report four main findings. First, despite very diverse sample parameters (e.g., age, ethnicity, sex, and postmortem interval), the expression profiles belonging to the same organs cluster together, demonstrating internal stability of the database. Second, the gene expression profiles reflect major organ-specific functions on the molecular level, indicating consistency of our database with known biology. Third, we demonstrate that any small (i.e., n ∼ 100), randomly selected subset of genes can approximately reproduce the hierarchical clustering of the full data set, suggesting that the observed differential expression of >90% of the probed genes is of biological origin. Fourth, we demonstrate a potential application of this database to cancer research by identifying 19 tumor-specific genes in neuroblastoma. The selected genes are relatively underexpressed in all of the organs examined and belong to therapeutically relevant pathways, making them potential novel diagnostic markers and targets for therapy. We expect this database will be of utility for developing rationally designed molecularly targeted therapeutics in diseases such as cancer, as well as for exploring the functions of genes.
Protein structure and evolutionary history determine sequence space topology
Authors: Shakhnovich Boris E. , Deeds Eric , Delisi Charles , Shakhnovich Eugene
Published: March 2005

Understanding the observed variability in the number of homologs of a gene is a very important unsolved problem that has broad implications for research into coevolution of structure and function, gene duplication, pseudogene formation, and possibly for emerging diseases. Here, we attempt to define and elucidate some possible causes behind the observed irregularity in sequence space. We present evidence that sequence variability and functional diversity of a gene or fold family is influenced by quantifiable characteristics of the protein structure. These characteristics reflect the structural potential for sequence plasticity, i.e., the ability to accept mutation without losing thermodynamic stability. We identify a structural feature of a protein domain—contact density—that serves as a determinant of entropy in sequence space, i.e., the ability of a protein to accept mutations without destroying the fold (also known as fold designability). We show that (log) of average gene family size exhibits statistical correlation (R2> 0.9.) with contact density of its three-dimensional structure. We present evidence that the size of individual gene families are influenced not only by the designability of the structure, but also by evolutionary history, e.g., the amount of time the gene family was in existence. We further show that our observed statistical correlation between gene family size and contact density of the structure is valid on many levels of evolutionary divergence, i.e., not only for closely related sequence, but also for less-related fold and superfamily levels of homology.
From genome to “venome”: Molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins
Authors: Fry Bryan G.
Published: March 2005

This study analyzed the origin and evolution of snake venom proteome by means of phylogenetic analysis of the amino acid sequences of the toxins and related nonvenom proteins. The snake toxins were shown to have arisen from recruitment events of genes from within the following protein families: acetylcholinesterase, ADAM (disintegrin/metalloproteinase), AVIT, complement C3, crotasin/β defensin, cystatin, endothelin, factor V, factor X, kallikrein, kunitz-type proteinase inhibitor, LYNX/SLUR, L-amino oxidase, lectin, natriuretic peptide, βnerve growth factor, phospholipase A2, SPla/Ryanodine, vascular endothelial growth factor, and whey acidic protein/secretory leukoproteinase inhibitor. Toxin recruitment events were found to have occurred at least 24 times in the evolution of snake venom. Two of these toxin derivations (CRISP and kallikrein toxins) appear to have been actually the result of modifications of existing salivary proteins rather than gene recruitment events. One snake toxin type, the waglerin peptides from Tropidolaemus wagleri (Wagler's Viper), did not have a match with known proteins and may be derived from a uniquely reptilian peptide. All of the snake toxin types still possess the bioactivity of the ancestral proteins in at least some of the toxin isoforms. However, this study revealed that the toxin types, where the ancestral protein was extensively cysteine cross-linked, were the ones that flourished into functionally diverse, novel toxin multigene families.
Organizations, Institutions, and the Story of Shmuel: Reflections on the 40th Anniversary of the Law and Society Association
Authors: Erlanger Howard S.
Published: March 2005

Today I would like to speak to you about Organizations, Institutions, and the Story of Shmuel.

Now, I figure everyone here knows what an organization is, and pretty much everyone at least thinks they know what an institution is. But I'm pretty sure you all are wondering, “Who's Shmuel?”
Bargaining in the Shadow of Social Institutions: Competing Discourses and Social Change in Workplace Mobilization of Civil Rights
Authors: Albiston Catherine R.
Published: March 2005

The Family and Medical Leave Act requires employers to provide job-protected leave, but little is known about how these leave rights operate in practice or how they interact with other normative systems to construct the meaning of leave. Drawing on interviews with workers who negotiated contested leaves, this study examines how social institutions influence workplace mobilization of these rights. I find that leave rights remain embedded within institutionalized conceptions of work, gender, and disability that shape workers' perceptions, preferences, and choices about mobilizing their rights. I also find, however, that workers can draw on law as a culture discourse to challenge these assumptions, to build coalitions, and to renegotiate the meaning of leave.
Dispute Resolution in a Worker Cooperative: Formal Procedures and Procedural Justice
Authors: Hoffmann Elizabeth A.
Published: March 2005

While most research on workplace grievance resolution focuses on hierarchical settings, this study examines grievance resolution in a worker cooperative, a workplace mutually owned and democratically managed. Drawing on data from in-depth interviews and observations, this research explores how workers' perceptions of procedural justice influence their anticipated grievance strategies. Despite working side by side in the same organization, both men and women had very different experiences regarding procedural justice and dispute resolution. For men, working at a cooperative meant informal dispute resolution strategies, while the women cited the cooperative identity as empowering them to use formal grievance procedures.
Challenging Medicine: Law, Resistance, and the Cultural Politics of Childbirth
Authors: Beckett Katherine , Hoffman Bruce
Published: March 2005

Whereas most sociolegal studies concerned with hegemony and resistance focus on the resistances of ordinary citizens in everyday life, this article focuses on the development of a particular social movement—the alternative birth movement—and analyzes the process by which this movement emerged and has achieved significant legislative victories. The analysis makes several contributions to the literatures on hegemony, resistance, and the law. First, by demonstrating the importance of medicine's assertion of its authority for the expansion and mobilization of the alternative birth movement, we show that the mobilization of the law by a dominant group may trigger the emergence of social movements seeking to resist hegemonic understandings and arrangements. At the same time, by examining how birth activists' organizational resources developed over time and were rendered meaningful in legislative debates, our study demonstrates the importance of avoiding dichotomous conceptions of structure and culture. In addition, by analyzing culture as a process of meaning-making rather than an independent and hierarchical set of values, the analysis shows how cultural and legal hegemony—even that of modern medicine—may be destabilized, even as it sets the terms of the effort to destabilize it and shapes the nature of the hegemony that will replace it.
Green Clubs and Voluntary Governance: ISO 14001 and Firms' Regulatory Compliance
Authors: Potoski Matthew , Prakash Aseem
Published: March 2005

Voluntary programs have become widespread tools for governments and nongovernmental actors looking to improve industry's environmental and regulatory performance. Voluntary programs can be conceptualized as club goods that provide nonrival but potentially excludable benefits to members. For firms, the value of joining a green club over taking the same actions unilaterally is to appropriate the club's positive brand reputation. Our analysis of about 3,700 U.S. facilities indicates that joining ISO 14001, an important nongovernmental voluntary program, improves facilities' compliance with government regulations. We conjecture that ISO 14001 is effective because its broad positive standing with external audiences provides a reputational benefit that helps induce facilities to take costly progressive environmental action they would not take unilaterally.
Party Government in Presidential Democracies: Extending Cartel Theory Beyond the U.S. Congress
Authors: Jones Mark P. , Hwang Wonjae
Published: March 2005

Cartel Theory (and partisan theory more generally) expertly explains the functioning of the U.S. Congress. However, as a theory originally developed to study a single legislature where the institutional context differs greatly from that found in other presidential democracies, its applicability to these democracies has been questioned. Between one extreme represented by the United States (where legislators control their own political future) and the other represented by centralized party systems (where the national party leadership controls legislators' future) exists an intermediate group of democracies where subparty bosses are the key actors, controlling the future of subsets of a party's legislative delegation. We analyze one of these intermediate democracies, Argentina, and demonstrate the general applicability of Cartel Theory to an institutional context that differs notably from that found in the United States. We highlight how the theory can be adapted to a political system where subparty bosses, not individual legislators, are the most relevant political actors.
Dynamic Responsiveness in the U.S. Senate
Authors: Fowler James
Published: March 2005

I develop a theory of dynamic responsiveness that suggests that parties that win elections choose candidates who are more extreme and parties that lose elections choose candidates who are more moderate. Moreover, the size of past victories matters. Close elections yield little change, but landslides yield larger changes in the candidates offered by both parties. I test this theory by analyzing the relationship between Republican vote share in U.S. Senate elections and the ideology of candidates offered in the subsequent election. The results show that Republican (Democratic) victories in past elections yield candidates who are more (less) conservative in subsequent elections, and the effect is proportional to the margin of victory. This suggests that parties or candidates pay attention to past election returns. One major implication is that parties may remain polarized in spite of their responsiveness to the median voter.
Intergovernmental Political Competition in American Federalism
Authors: Volden Craig
Published: March 2005

Many policies in the United States are jointly determined by federal and state actions. In the game theoretic model offered here, politicians in both the state and national governments seek credit for providing goods desired by the public and avoid blame for the taxes necessary to provide the goods. In line with Peterson's (1995) theory of functional federalism, the level of government that is better able to supply particular goods and services tends to take the lead in their provision, even to the extent of fully crowding out much less efficient governments. However, under a broad set of circumstances, both state and national politicians seek credit via public spending, and their joint provision leads to a relative “oversupply” of public goods and services, and thus to “overtaxation.” Under joint provision, states vary in their responses to changing federal spending patterns based both on the causes of the national changes and on state characteristics.
Reexamining Racial Attitudes: The Conditional Relationship Between Diversity and Socioeconomic Environment
Authors: Branton Regina P. , Jones Bradford S.
Published: March 2005

Social science research notes that racial context is related to attitudes toward social issues; however, surprisingly little research has examined how the impact of racial context on attitudes is activated. The aim of this article is to examine racial context “effects” for policy preferences, but to do so within a broader perspective. This article extends the literature on racial attitudes by considering a conditional relationship between racial and ethnic context and socioeconomic context and expanding racial context to include multiple racial and ethnic groups. The findings indicate that racial and ethnic contextual effects do emerge; however, these effects are conditional on the socioeconomic context in which an individual resides. Specifically, high socioeconomic contexts and highly diverse contexts are related to higher levels of support for racial social issues; however, contexts characterized by low socioeconomic context and high racial and ethnic diversity are associated with lower levels of support for such issues.
Do Policy Horizons Structure the Formation of Parliamentary Governments?: The Evidence from an Expert Survey
Authors: Warwick Paul V.
Published: March 2005

This article tests the hypothesis that parties in West European parliamentary systems operate under the constraint of “policy horizons,” that is, limits or bounds on the extent to which they can compromise on policy for the purpose of entering coalition governments. The test is based on a new expert survey covering thirteen West European parliamentary democracies in which respondents were asked not only to locate party positions on a number of policy dimensions, but also to estimate the parties' limits of acceptable compromise on each dimension. The survey data are first analyzed using a new computer program, Horizons 3D, to determine which parties have intersecting horizons in these systems—and hence the ability to form coalition governments under the hypothesis. These calculations are then employed to assess whether policy horizons structure the choice of governing coalition beyond any effect conveyed by the policy distances among parties. Although the potential for error in these data is considerable, the estimated horizons, with few exceptions, appear to play the role hypothesized for them.
Comparing Competing Theories on the Causes of Mandate Perceptions
Authors: Grossback Lawrence J. , Peterson David A.M. , Stimson James A.
Published: March 2005

The discussion of presidential mandates is as certain as a presidential election itself. Journalists inevitably discuss whether the president‐elect has a popular mandate. Because they see elections as too complex to allow the public to send a unitary signal, political scientists are more skeptical of mandates. Mandates, however, have received new attention by scholars asking whether perceptions of mandate arise and lead representatives to act as if voters sent a policy directive. Two explanations have emerged to account for why elected officials might react to such perceptions. One focuses on the president's strategic decision to declare a mandate, the second on how members of Congress read signals of changing preferences in the electorate from their own election results. We test these competing views to see which more accurately explains how members of Congress act in support of a perceived mandate. The results indicate that members respond more to messages about changing preferences than to the president's mandate declaration.
Women on the Sidelines: Women's Representation on Committees in Latin American Legislatures
Authors: Michelle Heath Roseanna , Schwindt‐Bayer Leslie A. , Taylor‐Robinson Michelle M.
Published: March 2005

This article explores how new groups can be marginalized after they gain representation in the legislature. We use data from six Latin American legislatures to examine the effect of institutional and political factors on how traditionally dominant male political leaders distribute scarce political resources—committee assignments—to female newcomers. In general, we find that women tend to be isolated on women's issues and social issues committees and kept off of power and economics/foreign affairs committees as the percentage of legislators who are women increases, when party leaders or chamber presidents control committee assignments, and when the structure of the committee system provides a specific committee to deal with women's issues. Thus, to achieve full incorporation into the legislative arena, newcomers must do more than just win seats. They must change the institutions that allow the traditionally dominant group to hoard scarce political resources.
Looking for Locals: Voter Information Demands and Personal Vote‐Earning Attributes of Legislators under Proportional Representation
Authors: Shugart Matthew Søberg , Valdini Melody Ellis , Suominen Kati
Published: March 2005

Proportional representation systems affect the extent to which elected legislators exhibit various attributes that allow them to earn a personal vote. The sources of variation in personal vote‐earning attributes (PVEA) lie in informational shortcuts voters use under different electoral rules. List type (closed or open) and district magnitude (the number of legislators elected from a district) affect the types of shortcuts voters employ. When lists are closed, legislators' PVEA are of decreasing usefulness to voters as magnitude (and hence the number of candidates on a list) increases. When lists are open, legislators' PVEA are increasingly useful to voters as magnitude increases, because the number of candidates from which voters must choose whom to give a preference vote increases. As predicted by the theory, the probability that a legislator will exhibit PVEA—operationalized as local birthplace or lower‐level electoral experience—declines with magnitude when lists are closed, but rises with magnitude when lists are open.
Expression patterns of S100A7 (psoriasin) and S100A9 (calgranulin‐B) in keratinocyte differentiation
Authors: Martinsson Hanna , Yhr Maria , Enerbäck Charlotta
Published: March 2005

Abstract:  S100 proteins are involved in many biological processes. S100A7 and S100A9 have been shown to be markedly upregulated both in ductal carcinoma in situ of the breast and in psoriasis. We have examined the relationship between keratinocyte differentiation and the expression of the two proteins. Using Western blot analysis and quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR), both S100A7 and S100A9 were shown to be induced in normal primary keratinocytes (HEKn), when differentiation was promoted by high extracellular calcium, loss of contact with extracellular matrix and confluent conditions, as previously reported for S100A7 in mammary epithelial cells. Differentiation was confirmed by using RT‐PCR for the differentiation marker keratin‐1. Using immunohistochemistry with monoclonal antibodies, we compared the expression of the two proteins in a spectrum of conditions of dysregulated keratinocyte differentiation. We found a strikingly similar distribution of the proteins. Their expression correlated with the degree of keratinocyte differentiation. They were both absent in undifferentiated basalioma and strongly expressed in carcinoma in situ, as well as in keratoacanthoma and differentiated squamous cell carcinoma. In normal epithelium, they were expressed in the superficial, differentiated region of the epithelium rather than in the basal region. These findings support the hypothesis that these two S100 proteins are involved in keratinocyte differentiation.
Inhibition of scratching behaviour caused by contact dermatitis in histidine decarboxylase gene knockout mice
Authors: Seike M. , Ikeda M. , Kodama H. , Terui T. , Ohtsu H.
Published: March 2005

Abstract:  A neuronal system dedicated to itch consists of primary afferent and spinothalamic projection neurons. Histamine is thought to be one of the main mediators for the transmission of itch sensation. However, there are little available information on the role of histamine in scratching behaviour and sensory transmission of atopic dermatitis and chronic eczema. In the present study, the role of histamine in scratching behaviour and neural conduction of sensation in the chronic eczema model was investigated by using l‐histidine decarboxylase (HDC) gene knockout mice lacking histamine. The chronic contact dermatitis was induced with daily application of diphenylcyclopropenone (DCP) on a hind paw of HDC (+/+) and HDC (–/–) mice for 2 months. The observation of scratching behaviour and the hot‐plate test were performed in both mice. Histological studies were performed in the skin and spinal cord tissues. Histological examination revealed that both HDC (+/+) and HDC (–/–) mice displayed the similar extent of inflammatory cell infiltration, hyperplastic epidermis and newly spreading of neuronal processes in the skin tissue. Scratching behaviour was exclusively induced in HDC (+/+) mice, whereas it was barely observed in HDC (–/–) mice. The expression of c‐Fos was specifically upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following repeated DCP application. Scratching behaviour in chronic contact dermatitis in mice was thought mainly mediated with histamine. The afferent pathway of sensation in chronic contact dermatitis model may connect with the central nervous system through lamina I of the spinal dorsal horn.
Evaluation of a sunscreen photoprotective effect by ascorbic acid assessment in human dermis using microdialysis and gas chromatography mass spectrometry
Authors: Lévêque Nathalie , Mac‐Mary Sophie , Muret Patrice , Makki Safwat , Aubin Francois , Kantelip Jean‐Pierre , Heusèle Catherine , S Schnebert , Humbert Philippe
Published: March 2005

Abstract:  Ultraviolet irradiation causes adverse effects like sunburn, photosensitivity reactions or immunologic suppression. The aim of this study was to evaluate the photo‐protective outcome of a sunscreen cream (SPF8) by the determination of erythema indexes and the assessment of ascorbic acid and its metabolites in human dermis. These substances were used as markers of oxidative effect. Eight healthy female subjects were enrolled in this study. Two abdominal areas were exposed to solar simulated irradiation with three minimal erythema dose, one with SPF8 application and the other site without SPF8 application. Two other areas were used as control, one without SPF8 application and the other site after SPF8 application. Ascorbic acid and its metabolites (dehydroascorbic acid, threonic acid, oxalic acid and xylose) were collected from human dermis by microdialysis and assessed by gas chromatography mass spectrometry. Irradiated site without sunscreen application had significantly demonstrated lower dermis ascorbic acid concentrations and a higher erythema index than the three other sites (P < 0.05). Threonic acid, oxalic acid and xylose dermis concentrations were significantly higher in site III than in the control site I (P < 0.05). The protected‐irradiated site did not show erythema formation and there was stability of ascorbic acid dermis concentrations with non‐variation in its metabolites. The assessment of ascorbic acid and its metabolites in human dermis could be an efficient tool to demonstrate the oxidative process and consequently to control the efficiency of sunscreen creams against undesirable UV effects.
Zeta‐chain‐associated protein‐70 molecule is essential for the proliferation and the final maturation of dendritic epidermal T cells
Authors: Endo Yukie , Ishikawa Osamu , Negishi Izumi
Published: March 2005

Abstract:  Adult murine epidermis contains members of the epithelial γδ T‐cell family called dendritic epidermal T cells (DETCs). Their development and maturation have been the subjects of investigations, but the details are still unclear. T‐cell receptor (TCR) zeta‐chain‐associated protein‐70 (ZAP‐70), one of the protein tyrosine kinases required for TCR signaling, plays a pivotal role in the development of αβ T cells. In mice lacking ZAP‐70, thymic development of αβ T cells was completely arrested at the immature CD4+CD8+ TCRlow stage. Here, we examined whether or not the development and maturation of DETCs were altered in ZAP‐70‐deficient mice. Immunohistochemical analyses of epidermal sheets revealed that the number of DETCs was reduced and their characteristic dendrites were lost or markedly shortened in ZAP‐70–/– mice. In flow cytometric analyses, the expression levels of γδ TCR and Thy‐1.2 on the ZAP‐70–/– DETCs were lower than those on ZAP‐70+/– DETCs. The expression of a very early activation antigen, CD69, was not detected on ZAP‐70–/– DETCs, whereas CD69 was expressed on ZAP‐70+/– DETCs. Furthermore, ZAP‐70–/– DETCs showed markedly reduced proliferation and no IL‐2 gene expression in response to anti‐CD3ε or concanavalin A stimulation. These results suggest that ZAP‐70 is essential for TCR signaling which induces the proliferation and the final maturation of DETCs in the epidermis.
In vivo and in vitro evidence for autocrine DCoH/HNF‐1α transcription of albumin in the human epidermis
Authors: Hasse S. , Kothari S. , Rokos H. , Kauser S. , Schürer N. Y. , Schallreuter K. U.
Published: March 2005

Abstract:  The presence of albumin in the human epidermis has been reported more than a decade ago, but until now, it was assumed that this protein is synthesized in the liver and transported to the avascular skin. To our knowledge, transcription of albumin in the human epidermis was never considered. In this report, we present for the first time evidence for autocrine synthesis of albumin in the human epidermis in keratinocytes in situ and in vitro. Using double immunofluorescence labelling, we identified that albumin colocalized together with its transcription factor PCD/DCoH/HNF‐1α in suprabasal keratinocytes in human full‐thickness skin sections and in keratinocytes cultured in serum‐free medium. Moreover, albumin and HNF‐1α protein expression was confirmed by Western blotting in undifferentiated and differentiated keratinocytes as well as in human epidermal suction blister roof extracts. Reverse‐transcriptase polymerase chain reaction analysis from human epidermal keratinocytes and epidermal suction blister roofs revealed the transcription of albumin. Using in vivo fluorescence excitation spectroscopy at the surface of human skin, we confirmed albumin as a major constituent yielding a λmax at 295 nm, which was assigned to the single tryptophan 214 fluorophore in this protein. This in vivo result is in agreement with albumin concentrations of 10−3 M, underlining the importance of this protein in epidermal homeostasis.
Apoptosis of the dermal papilla cells of hair follicle associated with the expression of gene HSPCO16 in vitro
Authors: Yang Wei B. , Hao Fei , Song Zhi Q. , Yang Xi C. , Ni Bing
Published: March 2005

Abstract:  The epithelial–mesenchymal interactions have an important role in the folliculomorphogenesis and mature hair follicle cycling. The dermal papilla, a dense aggregate of specialized dermis‐derived stromal cells located at the bottom of the hair follicle, is a major component of hair, which signals the follicular epithelial cells to prolong the hair growth process. However, to date, little is known about the significance of the specific gene(s) expression in the dermal papilla cells with regard to their aggregative behaviour and hair cycling. In our previous study, the differentially gene‐expressed cDNAs library had been determined by means of suppression subtractive hybridization technique between the aggregated human dermal papilla cells and control cells. Among those cDNAs library, the haematopoietic stem/progenitor cell (HSPC)‐related gene HSPC016 was found. In this study, the gene HSPC016 was confirmed to express in the human dermal papilla cells by means of in situ hybridization and reverse transcriptase‐polymerase chain reaction. In order to rudimentarily elucidate its biological function, a recombinant eucaryotic expressing plasmid pcDNA3.1(+)/HSPC016 was constructed and was transfected into the human dermal papilla cells and 3T3 fibroblast cells by means of NucleofectorTM technique (Amaxa, Cologne, Germany). Terminal deoxynucleotidyl transferase‐mediated d‐UTP nick end Labelling (TUNEL) assay showed that the expression of gene HSPCO16 resulted in the apoptosis of these cells, which suggested that the apoptosis of dermal papilla cells might be associated with the expression of gene HSPC016 in vitro.
How best to fight that nasty itch – from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches
Authors: Biró T. , Ko M. C. , Bromm B. , Wei E. T. , Bigliardi P. , Siebenhaar F. , Hashizume H. , Misery L. , Bergasa N.V. , Kamei C. , Schouenborg J. , Roostermann D. , Szabó T. , Maurer M. , Bigliardi‐Qi M. , Meingassner J. G. , Hossen M. A. , Schmelz M. , Steinhoff M.
Published: March 2005

While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic ‘itch’ on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of ‘itch’ in mind and adopts a holistic treatment approach – beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management.
The European Panel on the Appropriateness of Gastrointestinal Endoscopy guidelines colonoscopy in an open‐access endoscopy unit: a prospective study
Authors: Balaguer F. , Llach J. , Castells A. , Bordas J. M. , Ppellisé M. , Rodríguez‐Moranta F. , Mata A. , Fernández‐Esparrach G. , Ginès A. , Piqué J. M.
Published: March 2005

Background : The demand for gastrointestinal endoscopy is increasing in most developed countries, resulting in an important rise in overall costs and waiting lists for endoscopic procedures. Therefore, adherence to appropriate indications for these procedures is essential for the rational use of finite resources in an open‐access system.

Aim : To assess indications and appropriateness of colonoscopy according to the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria.

Methods : From May to June 2004, all consecutive patients referred to our Unit for open‐access colonoscopy were considered for inclusion in this prospective study. Appropriateness of each colonoscopy was established according to the EPAGE criteria. In order to evaluate whether appropriateness of use correlated with the diagnostic yield of colonoscopy, relevant endoscopic findings were also recorded.

Results : A total of 350 consecutive patients were included in the study. In 38 of them, the colonoscopy indication was not listed in the EPAGE guidelines and, consequently, they were not evaluated. In the remaining 312 patients, the indication for the procedure was considered inappropriate in 73 (23%) patients. Both referring doctor characteristics (specialty and health care setting) and patient data (age) correlated with appropriateness of endoscopy. The diagnostic yield was significantly higher for appropriate colonoscopies (42%) than in those judged inappropriate (21%) (P = 0.001).

Conclusions : A noteworthy proportion of patients referred for colonoscopy to an open‐access endoscopy unit are considered inappropriate because of their indication, with significant differences among specialties. These results suggest that implementation of validated guidelines for its appropriate use could improve this situation and, considering the correlation between appropriateness and diagnostic yield, even contribute to improve the prognosis of patients with colorectal diseases.