bluuebunny/crossref_metadata_2025 huggingface dataset:
Multisensory Processing in “Unimodal” Neurons: Cross-Modal Subthreshold Auditory Effects in Cat Extrastriate Visual Cortex
Authors: Allman Brian L. , Meredith M. Alex
Published: May 2007

Historically, the study of multisensory processing has examined the function of the definitive neuron type, the bimodal neuron. These neurons are excited by inputs from more than one sensory modality, and when multisensory stimuli are present, they can integrate their responses in a predictable manner. However, recent studies have revealed that multisensory processing in the cortex is not restricted to bimodal neurons. The present investigation sought to examine the potential for multisensory processing in nonbimodal (unimodal) neurons in the retinotopically organized posterolateral lateral suprasylvian (PLLS) area of the cat. Standard extracellular recordings were used to measure responses of all neurons encountered to both separate- and combined-modality stimulation. Whereas bimodal neurons behaved as predicted, the surprising result was that 16% of unimodal visual neurons encountered were significantly facilitated by auditory stimuli. Because these unimodal visual neurons did not respond to an auditory stimulus presented alone but had their visual responses modulated by concurrent auditory stimulation, they represent a new form of multisensory neuron: the subthreshold multisensory neuron. These data also demonstrate that bimodal neurons can no longer be regarded as the exclusive basis for multisensory processing.
Games of Pain: Pain as Haptic Stimulation in Computer-Game—Based Media Art
Authors: Laso Pau Waelder
Published: May 2007

The text describes several media-art projects that introduce pain as a form of interaction within the context of a two-player game: PainStation (2001–2003) and LegShocker (2002) by Tilman Reiff and Volker Morawe, Tekken Torture (2001) by C-Level and Tazer Tag (2005) by Randy Sarafan. By presenting these examples and briefly analyzing the nature of pain and games, this text offers an overview of the implications of incorporating pain into a computer game and presents an approach to the motivations that lead players to perceive a painful experience as fun and addictive.
Fractal Reactor: Re-Creating the Sun
Authors: Siler Todd
Published: May 2007

The author recounts his quest to design an alternative plasma fusion device that could generate limitless energy through nuclear fusion. The proposed Fractal Reactor is based on fractal geometry rather than the Euclidean geometry used in the designs for the containment systems of plasma fusion devices. Fusion energy systems might become more effective if they more closely embody the geometry and physics of stars, nature's “fractal reactors.” The author aims to work with nature and not against it in controlling the forces that govern burning plasmas. Instead of jamming the square peg of Euclidean geometry into the round hole of fractal geometry, the author considers exerting intense forces on plasmas that approximate the gravitational forces in a star.
The Nature and Functions of Synesthesia in Music
Authors: Galeyev B.M.
Published: May 2007

The author considers the phenomenon of synesthesia, defining it as intersensory association formed by similarity or “contiguity” of heteromodal perceptions. The results of this associative process (occurring mainly at the subconscious level), when coming to the light of consciousness, may be fixed either in verbal form or directly in the sensuous material of the nonverbal arts (most significantly music). Synesthesia calls forth such notions as “melody line,” “the hearing space” and “tone color,” and makes it possible to perceive sounds and chords as “sharp,” “dull” or “high.” Synesthesia (and the particular case of “color hearing”) is the essential component of musical thinking, first of all, in music intended to evoke images.
Rectangular Structure in My Montage Paintings
Authors: Bearden Romare
Published: May 2007

The author describes his change from being a student of mathematics to that of being a painter, after studying with George Grosz. Through Grosz, the author was led to study Brueghel, and the Dutch masters and their art, together with Byzantine mosaics and African sculpture, have remained a major influence in his work.

A study of the paintings of De Hooch and Vermeer was also helpful from the point of view of the way those artists were able to control their large shapes, even when disparate elements were included within these shapes. Also, the author describes the influence upon him of examples of Chinese paintings and his method of working with mounted layers of torn papers.

Both the similarities as well as the differences to Cubism in his style are described in detail, with the hope that the structural content of his work will be understood and even more valued than its social message.
Themed article: Sexed up intelligence or irresponsible reporting? The interplay of virtual communication and emotion in dispute sensemaking
Authors: Myers Piers
Published: May 2007

In the context of an exploratory case study of an interorganizational dispute between the BBC and the UK Government, this article develops a conceptual framework through which the interplay of emotion, sensemaking and virtuality in disputes can be better understood. One contribution of the article is reconsideration of the general relationship between emotion and sensemaking. It is suggested that emotions as temporary social roles complement sensemaking itself, enabling plausible accounts to be constructed when there would otherwise be no socially acceptable bridge between beliefs and behaviour. A second contribution is appreciation of the difficulties for virtual communication arising from the capabilities for review and replication of messages which it affords, so that discourse is explicit, irrevocable and potentially public. When, particularly across the lines of a dispute, communications are contentious this can lead to sensemaking through behavioural commitment and the evocation of justifying beliefs; or it can lead to emotional dynamics justifying communication as passion or obviating the need to attend to other's responses. The ar ticle reflects on implications for the development, escalation and resolution of disputes.
Psychological Mechanisms Underlying the Köhler Motivation Gain
Authors: Kerr Norbert L. , Messé Lawrence A. , Seok Dong-Heon , Sambolec Eric J. , Lount Robert B. , Park Ernest S.
Published: May 2007

Sometimes group work conditions lead to motivation gains rather than to social loafing. Two theoretical explanations for the Köhler motivation gain effect are identified, one stressing social comparison and a second stressing the indispensability of one's effort to the group. The results of three new experiments are reported. Experiment 1 suggested that both explanations are valid and contribute to the Köhler effect. Prior studies suggested that there might be gender differences in the relative importance of these two explanatory processes. Experiment 2 confirmed this suggestion. In Experiment 3, the gender difference was eliminated by priming women with a goal (viz., competition) presumed to be chronically more important to men. It is argued that the relative importance of these two motivational processes will depend on the immediate and chronic importance attached to more personal (viz., to achieve a favorable social comparison) versus collective (viz., to contribute to one's group) goals.
Difficult Children and Difficult Parents
Authors: Owens Erica , Ring Gail
Published: May 2007

As more mothers of young children work, concerns about child care have gained prominence. Analyses of this topic typically address availability, safety, and costs of care, or the impact of care on children's “outcomes.” When providers' input is included, it is generally used as an assessment tool to reinforce the researcher's conceptual framework. This study addresses the issue of nonparental child care by allowing the providers to tell their story of caregiving. We have conducted a series of hour-long interviews with 12 in-home child care providers. Their narratives show patterned perceptions of both the children and children's parents. Our analysis focuses on providers' constructions of difficult children and parents. Greater understanding of this aspect of care work may help to improve the quality of the work experience for providers, which may in turn contribute to a more positive care environment experienced by children.
Shift Work, Parenting Behaviors, and Children's Socioemotional Well-Being
Authors: Barnett Rosalind Chait , Gareis Karen C.
Published: May 2007

Many U.S. employees with children work nonstandard hours, yet we know little about the linkages among maternal shift schedules, mothers' and fathers' parenting behaviors, and children's socioemotional outcomes. In a sample of 55 dual-earner families with children age 8 to 14 years and mothers working day versus evening shifts, the authors found that mothers' work schedules are unrelated to their parenting behaviors. However, fathers whose wives work evenings (vs. days) spend more time with children, know more about children's activities, receive more disclosures from children, and have better parenting skills, variables that are inversely associated with children's internalizing, externalizing, and risk-taking behaviors.
Sport and Commodification
Authors: Moor Liz
Published: May 2007

Studies of the impact of structural changes in sports organizations on the nature of fan cultures have been an important part of the sociology of sport in recent years, and such studies have come to rely on the concepts of class, commodification, and consumption. This paper suggests that although such concepts are indeed important, their contentiousness and complexity are not always acknowledged, and that the concepts may therefore acquire an overgeneralized and taken-for-granted set of meanings. The paper uses examples from studies of football fan cultures in Britain to highlight some of the potential problems with this, before going on to outline some additional and alternative approaches to these terms, and to make suggestions as to how these might be incorporated into future research.
Learning braille and print together — the mainstream issues
Authors: Rogers Sue
Published: May 2007

This article reports on a national survey and follow-up interviews with vision-support teachers. The study related to pupils in mainstream schools who are identified as able to read large print but also need to learn braille to increase access to the curriculum. The aim of the survey was to elicit information about the diversity of the group and the major issues that vision-support teachers identified as impacting on these children. Factors that enhance success are identified and discussed with reference to mainstream settings. Areas requiring further research are also identified. A case study within a local school describing the context of a child learning braille and print together was also undertaken as part of the research but is not covered in this article.
Myths, stereotypes and self-perception: the impact of albinism on self-esteem
Authors: Palmer Carolyn
Published: May 2007

Albinism has the potential to affect young people both emotionally and psychologically. Their condition is unique and is surrounded by myths and stereotypes. The unusual appearance of children with oculocutaneous albinism draws attention to them and their vision impairment can impact on their development of social skills and peer relationships. In addition social attitudes can affect how they perceive themselves and evidence from the research literature suggests that for a child to be socially competent he or she needs to have a positive self-concept and demonstrate socially acceptable behaviours. Self-esteem influences a child's interaction with peers, and this influence can be either positive or negative. Measures of self-esteem allow normative data to be gathered providing another perspective on the development of peer relationships of young people with albinism. This article investigates the self-esteem of a small group of students with albinism. Data were collected using a widely recognized psychological instrument: the Coopersmith Self-Esteem Inventories (SEI). The findings indicated that the self-esteem of the participants in this study was generally high.
Structure of the second language mental lexicon: how does it compare to native speakers' lexical organization?
Authors: Zareva Alla
Published: May 2007

One of the questions frequently asked in second language (L2) lexical research is how L2 learners' patterns of lexical organization compare to those of native speakers (NSs). A growing body of research addresses this question by using word association (WA) tests. However, little research has been done on the role of language proficiency in the associative patterning of L2 learners' lexical knowledge, especially the way it affects the quantitative and the qualitative patterns of meaning connections. Similarly, no research attention has been devoted to the strength of the relationship between these patterns, although the general assumption seems to be that they are interrelated. To address these issues, first some traditional distinctions that first language (L1) WA researchers make between the qualitative and quantitative features of WA domains are discussed. Next, the application of WA tests in L2 studies and some of the most significant findings concerning L2 learners' vocabulary structure are briefly reviewed. Finally, a study involving native speakers ( n = 29), L2 advanced ( n = 29) and L2 intermediate learners of English ( n = 29) is presented. Results suggest that differences in the organization of lexical knowledge between L2 speakers and NSs are quantitative rather than qualitative.
Acceptable ungrammaticality in sentence matching
Authors: Duffield Nigel , Matsuo Ayumi , Roberts Leah
Published: May 2007

This article presents a new set of experiments using the sentence-matching paradigm (Forster, 1979; Freedman and Forster, 1985; see also Bley-Vroman and Masterson, 1989), investigating native speakers' and second language (L2) learners' knowledge of constraints on clitic placement in French. Our purpose is three-fold:

• to shed more light on the contrasts between native speakers and L2 learners observed in previous experiments, especially Duffield and White (1999), and Duffield et al . (2002);

• to address some of the specific criticisms of the sentence-matching paradigm levelled by Gass (2001); and

• to provide a firm empirical basis for follow-up experiments with L2 learners.

The results reported here provide some confirmation of the validity of Duffield et al.'s earlier work, and help to adjudicate among competing interpretations of the previous effects.
A Comparison of Rapists and Sexual Murderers on Demographic and Selected Psychometric Measures
Authors: Oliver Caroline J. , Beech Anthony R. , Fisher Dawn , Beckett Richard
Published: May 2007

This study compared 58 sexual murderers and 112 rapists who were about to undergo treatment in prison for their sexual offending behavior. The two groups were compared on background, personality, offense, and victim characteristics. The sexual murderer group were less likely to have been involved in a relationship at the time of their index offense, generally attacked older victims, and had higher self-esteem. The rapist sample were found to have more violent previous convictions and scored higher on measures of historical deviance (nonsexual), paranoid suspicion, and resentment. No differences were found on the personality or clinical syndrome scales of the Millon Clinical Multiaxial Inventory—III. However, the rapist sample had significantly higher mean scores on the Paranoid Suspicion, Resentment, and Self-Esteem subscales of the Antisocial Personality Questionnaire. Future research should compare the two groups on dynamic or changeable factors to determine differential treatment needs.
Male Batterers With and Without Psychopathy
Authors: Echeburúa Enrique , Fernández-Montalvo Javier
Published: May 2007

The aim of this study was to analyze the differential profile of male batterers in prison with and without psychopathy. The sample consisted of 162 perpetrators sentenced for a serious offence against their intimate partner. The prevalence of psychopathy or psychopathic traits, established according to the Psychopathy Checklist—Revised, was about 12%. The psychopathic batterers were younger, more impulsive, more suspicious, and less empathetic and had lower self-esteem than nonpsychopathic batterers. However, the psychopathic batterers were not engaged in intimate femicide more often than were the nonpsychopathic batterers. The severity of the crime was similar in both groups, so it may be attributed to other variables (e.g., substance abuse, intoxication at the time of the offence, violence history, jealousy, etc.). Implications of these results for further research and clinical practice are discussed.
Diagnostic and Risk Profiles Among Civilly Committed Sex Offenders in Washington State
Authors: Jackson Rebecca L. , Richards Henry J.
Published: May 2007

Since 1990, 17 states have passed legislation allowing for the civil commitment of a small number of sex offenders who are deemed at a particularly high risk for reoffense. Despite the very public and controversial nature of these laws, little is known about the individuals who are detained pursuant to them. The current article presents data on 190 civilly committed and detained sexually violent predators in Washington State. These sexual offenders suffer from a variety of mental illnesses. The modal offender is diagnosed with both an Axis I and an Axis II disorder. Furthermore, these offenders are at moderate to high risk for reoffense and present with a significant degree of psychopathy.
Assays for Endogenous Components of Human Milk
Authors: Hines Erin P. , Rayner Jennifer L. , Barbee Randy , Moreland Rae Ann , Valcour Andre , Schmid Judith E. , Fenton Suzanne E.
Published: May 2007

Breast milk is a primary source of nutrition that contains many endogenous compounds that may affect infant development. The goals of this study were to develop reliable assays for selected endogenous breast milk components and to compare levels of those in milk and serum collected from the same mother twice during lactation (2-7 weeks and 3-4 months). Reliable assays were developed for glucose, secretory IgA, interleukin-6, tumor necrosis factor-a, triglycerides, prolactin, and estradiol from participants in a US EPA study called Methods Advancement in Milk Analysis (MAMA). Fresh and frozen (—20°C) milk samples were assayed to determine effects of storage on endogenous analytes. The source effect (serum vs milk) seen in all 7 analytes indicates that serum should not be used as a surrogate for milk in children's health studies. The authors propose to use these assays in studies to examine relationships between the levels of milk components and children's health. J Hum Lact. 23(2):144-156.
Concentrations of Methadone in Breast Milk and Plasma in the Immediate Perinatal Period
Authors: Jansson Lauren M. , Choo Robin E. , Harrow Cheryl , Velez Martha , Schroeder Jennifer R. , Lowe Ross , Huestis Marilyn A.
Published: May 2007

This study evaluates concentrations of methadone in breast milk and plasma among a sample of methadone-maintained women in the immediate perinatal period. Twelve methadone-maintained, lactating women provided blood and breast milk specimens 1, 2, 3, and 4 days after delivery. Specimens were collected at the time of trough (just before methadone dose) and peak (3 hours after dosing) maternal methadone levels. Paired specimens of foremilk (prefeed) and hindmilk (postfeed) were obtained at each sampling time. Although there was a significant increase in methadone concentration in breast milk over time for the peak postfeed sampling time, t (22) = 2.40, P = .0255, methadone concentrations in breast milk were small, ranging from 21 to 314 ng/mL, and were unrelated to maternal methadone dose. Results obtained from this study contribute to the recommendation of breastfeeding for methadone-maintained women regardless of methadone dose. J Hum Lact. 23(2):184-190.
A Theory of Nonphysical Suffering and Trust in Hospice Patients
Authors: Sacks Jodi L. , Nelson Jenenne P.
Published: May 2007

Suffering is a complex, dynamic experience that overarches life experiences and includes physical, social, spiritual, and emotional domains. The purpose of this grounded theory study was to uncover participants' experiences of nonphysical suffering and what was helpful during this time. Eighteen patients who were chronically ill participated in this grounded theory study. Trust was uncovered as a central issue within nonphysical suffering, whereas meaning was the vehicle that enabled the individual to move within the suffering. Participants acknowledged suffering through the identification of various meanings of a situation within their constructed reality and belief system. During individuals' suffering, time was altered and the experience occurred within an expanded present. The individual created an emotional space apart from the meaning of loss within suffering. Trust included the categories of dynamic experience, losing trust, and dealing to regain trust. Participants identified nurse trustworthiness as important for decreasing energy expenditures associated with suffering.
Cancer Patients' Negotiation of Therapeutic Options in Pakistan
Authors: Tovey Philip , Broom Alex
Published: May 2007

Cancer is the second leading cause of death in Pakistan. There is increasing evidence that patients are using a range of (biomedical and nonbiomedical) therapeutic options for cancer treatment. To date there has been no sociologically informed research into the engagement of cancer patients in Pakistan with available modalities. In this article, the authors present findings from the first such study. They purposively sampled 46 cancer patients from four hospitals in Lahore and conducted semistructured interviews with them. They argue that individuals are actively mediating therapeutic possibilities by drawing on, and at times being constrained by, personal, social, and cultural resources. It is the authors' contention that this can be conceptualized by an appreciation of individuals' active engagement with three temporally and spatially specific dimensions: structural and practical constraint; pragmatic experimentation; and cultural and religious affiliation. The negotiation (and varying power) of these dimensions is crucial to the process.
The 2005 Reauthorization of the Violence Against Women Act
Authors: Conyers John
Published: May 2007

The author provides an overview of the history of congressional involvement with the Violence Against Women Act's (VAWA) provisions to protect immigrant victims of domestic violence and other forms of violence against women. He also outlines the reasoning behind, and purpose of, the most recent enhancements in legal protections for immigrant victims of domestic violence, sexual assault, trafficking, and foreign fiancés and spouses that were included in the recently reauthorized VAWA 2005, also describing the bipartisan work that resulted in this newest piece of legislation.
Batterer Intervention Program Enrollment and Completion Among Immigrant Men in Massachusetts
Authors: Rothman Emily F. , Gupta Jhumka , Pavlos Carlene , Dang Quynh , Coutinho Paula
Published: May 2007

This study describes immigrant clients enrolled in Massachusetts batterer intervention (BI) programs from 2002 to 2004 ( N = 480). Our study sought to (a) describe the immigrant men enrolled in Massachusetts BI programs, (b) investigate whether immigrants were more or less likely to complete BI programs than were nonimmigrants, and (c) investigate whether immigrants in non-English, culturally specific groups were more or less likely to complete BI programs than were immigrants in mainstream groups. Of BI program clients, 14% were immigrants. Of these, 73% were not U.S. citizens. Immigrants were more likely to complete the programs than were nonimmigrants (54% vs. 38%). Although a greater proportion of immigrants who attended non-English groups completed the programs than did immigrants who attended mainstream groups (66% and 46%), neither the bivariate nor the adjusted odds ratio was statistically significant. Possible reasons for differences between immigrant and nonimmigrant characteristics and program completion rates are discussed.
On Making Them All One: Unity, Transcendence and the Anglican Church
Authors: Baker Anthony D.
Published: May 2007

The question of unity looms large in current vocabulary of the Anglican Communion. This article suggests, first of all, that the term is a rich theological one that ought to come under rigorous theological scrutiny and, secondly, that such scrutiny could in fact alter the way Anglicans understand themselves as an ecclesial body. While the works of Rowan Williams and Ephraim Radner have issued important and necessary calls for a return to ecclesiology, both, it is here suggested, do not illuminate fully the implications of the New Testament call to ‘be one’. Making substantial reference to Hooker's theology of the church, which is properly seen as an extension of his Christology, it is here suggested that unity is both a gift that transcends the church in its descent in the Spirit, and a craft that takes shape as the church struggles to make and remake itself in the image of Christ, whose prayer that his followers would all be one as ‘you and I’ is one that has consistently supplied the framework for the tradition of Christian ecclesiology.
The Stained Body
Authors: Minge Jeanine Marie
Published: May 2007

This fusion of embodied art combines painting, autoethnographic narrative, and poetry to understand the way the body stores the memory of rape and love. The author defines the fusion of embodied art as the process of inquiry that adds depth of emotion, perception, sensory detail, meaning, and creation of meaning to both the lived and the recreated experience through the blending of various art forms. Through the exploration of life-crushing moments, the author hopes to both define and transform the body as a site of knowledge, a source of desire and confinement.
Reintroduction of C/EBPα in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis
Authors: Schepers Hein , Wierenga Albertus T. J. , van Gosliga Djoke , Eggen Bart J. L. , Vellenga Edo , Schuringa Jan Jacob
Published: May 2007

The CCAAT/enhancer binding protein (C/EBP) α transcription factor is indispensable for myeloid differentiation. In various myeloid leukemias, C/EBPα is mutated or functionally impaired due to decreased C/EBPα expression or phosphorylation. In order to investigate the functional consequences of decreased C/EBPα function in AML, we reintroduced C/EBPα in primary CD34+ sorted acute myeloid leukemia (AML) cells using a lentiviral approach. Self-renewal and differentiation of primary AML stem cells were studied on long-term MS5 cocultures. Activation of C/EBPα immediately led to a growth arrest in all AML cultures (N = 7), resulting in severely reduced expansion compared with control cultures. This growth arrest corresponded with enhanced myeloid differentiation as assessed by fluorescence-activated cell sorter (FACS) analysis for CD14, CD15, and CD11b. Myeloid differentiation was further confirmed by the up-regulation of neutrophil elastase and granulocyte colony-stimulating factor (G-CSF) receptor in C/EBPα transduced cells. C/EBPα-expressing AML CD34+ cells failed to generate second and third leukemic cobblestone areas (L-CAs) in serial replating experiments, while control cultures could be sequentially passaged for more than 4 times, indicating that reintroduction of C/EBPα impaired the self-renewal capacity of the leukemic CD34+ compartment. Together, our data indicate that low C/EBPα levels are necessary to maintain self-renewal and the immature character of AML stem cells.
Immunologic evidence for lack of heterologous protection following resolution of HCV in patients with non–genotype 1 infection
Authors: Schulze zur Wiesch Julian , Lauer Georg M. , Timm Joerg , Kuntzen Thomas , Neukamm Martin , Berical Andrew , Jones Andrea M. , Nolan Brian E. , Longworth Steve A. , Kasprowicz Victoria , McMahon Cory , Wurcel Alysse , Lohse Ansgar W. , Lewis-Ximenez Lia L. , Chung Raymond T. , Kim Arthur Y. , Allen Todd M. , Walker Bruce D.
Published: May 2007

Chronic hepatitis C virus (HCV) infection is typically characterized by a lack of virus-specific CD4+ T-cell–proliferative responses, but strong responses have been described in a subset of persons with persistent viremia. One possible explanation for these responses is that they were primed by an earlier resolved infection and do not recognize the current circulating virus. We defined all targeted epitopes using overlapping peptides corresponding to a genotype 1a strain in 44 patients chronically infected with different HCV genotypes (GT). Surprisingly, more HCV-specific CD4+ T-cell responses were detected in patients with chronic non-GT1 infection compared with patients with chronic GT1 infection (P = .017). Notably, we found serologic evidence of a previous exposure to GT1 in 4 patients with non-GT1 infection, and these persons also demonstrated significantly more responses than non-GT1 patients in whom genotype and HCV serotype were identical (P < .001). Comparison of recognition of GT1-specific peptides to peptides representing autologous virus revealed the absence of cross-recognition of the autologous circulating virus. These data indicate that persisent HCV infection can occur in the presence of an HCV-specific T-cell response primed against a heterologous HCV strain, and suggest that clearance of 1 GT does not necessarily protect against subsequent exposure to a second GT.
Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and postsynaptic defects in function
Authors: Voskoboinik Ilia , Sutton Vivien R. , Ciccone Annette , House Colin M. , Chia Jenny , Darcy Phillip K. , Yagita Hideo , Trapani Joseph A.
Published: May 2007

Perforin (PRF), a pore-forming protein expressed in cytotoxic lymphocytes, plays a key role in immune surveillance and immune homeostasis. The A91V substitution has a prevalence of 8% to 9% in population studies. While this variant has been suspected of predisposing to various disorders of immune homeostasis, its effect on perforin's function has not been elucidated. Here we complemented, for the first time, the cytotoxic function of perforin-deficient primary cytotoxic T lymphocytes (CTLs) with wild-type (hPRF-WT) and A91V mutant (hPRF-A91V) perforin. The cytotoxicity of hPRF-A91V–expressing cells was about half that of hPRF-WT–expressing counterparts and coincided with a moderate reduction in hPRF-A91V expression. By contrast, the reduction in cytotoxic function was far more pronounced (more than 10-fold) when purified proteins were tested directly on target cells. The A91V substitution can therefore be manifested by abnormalities at both the lymphocyte (presynaptic) and target cell (postsynaptic) levels. However, the severe intrinsic defect in activity can be partly rescued by expression in the physiological setting of an intact CTL. These findings provide the first direct evidence that hPRF-A91V is functionally abnormal and provides a rationale for why it may be responsible for disordered immune homeostasis if inherited with another dysfunctional perforin allele.
Mutation screen and association studies in the Diacylglycerol O-acyltransferase homolog 2 gene (DGAT2), a positional candidate gene for early onset obesity on chromosome 11q13
Authors: Friedel Susann , Reichwald Kathrin , Scherag André , Brumm Harald , Wermter Anne-Kathrin , Fries Hans-Rudolf , Koberwitz Kerstin , Wabitsch Martin , Meitinger Thomas , Platzer Matthias , Biebermann Heike , Hinney Anke , Hebebrand Johannes
Published: May 2007

Background

DGAT2 is a promising candidate gene for obesity because of its function as a key enzyme in fat metabolism and because of its localization on chromosome 11q13, a linkage region for extreme early onset obesity detected in our sample.

We performed a mutation screen in 93 extremely obese children and adolescents and 94 healthy underweight controls. Association studies were performed in samples of up to 361 extremely obese children and adolescents and 445 healthy underweight and normal weight controls. Additionally, we tested for linkage and performed family based association studies at four common variants in the 165 families of our initial genome scan.

Results

The mutation screen revealed 15 DNA variants, four of which were coding non-synonymous exchanges: p.Val82Ala, p.Arg297Gln, p.Gly318Ser and p.Leu385Val. Ten variants were synonymous: c.-9447A > G, c.-584C > G, c.-140C > T, c.-30C > T, IVS2-3C > G, c.812A > G, c.920T > C, IVS7+23C > T, IVS7+73C > T and *22C > T. Additionally, the small biallelic trinucleotide repeat rs3841596 was identified. None of the case control and family based association studies showed an association of investigated variants or haplotypes in the genomic region of DGAT2.

Conclusion

In conclusion, our results do not support the hypothesis of an important role of common genetic variation in DGAT2 for the development of obesity in our sample. Anyhow, if there is an influence of genetic variation in DGAT2 on body weight regulation, it might either be conferred by the less common variants (MAF < 0.1) or the detected, rare non-synonymous variants.
Neuronal expression of muskelin in the rodent central nervous system
Authors: Tagnaouti Nadia , Loebrich Sven , Heisler Frank , Pechmann Yvonne , Fehr Susanne , De Arcangelis Adèle , Georges-Labouesse Elisabeth , Adams Josephine C , Kneussel Matthias
Published: May 2007

Background

The kelch repeat protein muskelin mediates cytoskeletal responses to the extracellular matrix protein thrombospondin 1, (TSP1), that is known to promote synaptogenesis in the central nervous system (CNS). Muskelin displays intracellular localization and affects cytoskeletal organization in adherent cells. Muskelin is expressed in adult brain and has been reported to bind the Cdk5 activator p39, which also facilitates the formation of functional synapses. Since little is known about muskelin in neuronal tissues, we here analysed the tissue distribution of muskelin in rodent brain and analysed its subcellular localization using cultured neurons from multiple life stages.

Results

Our data show that muskelin transcripts and polypeptides are expressed throughout the central nervous system with significantly high levels in hippocampus and cerebellum, a finding that resembles the tissue distribution of p39. At the subcellular level, muskelin is found in the soma, in neurite projections and the nucleus with a punctate distribution in both axons and dendrites. Immunostaining and synaptosome preparations identify partial localization of muskelin at synaptic sites. Differential centrifugation further reveals muskelin in membrane-enriched, rather than cytosolic fractions.

Conclusion

Our results suggest that muskelin represents a multifunctional protein associated with membranes and/or large protein complexes in most neurons of the central nervous system. These data are in conclusion with distinct roles of muskelin's functional interaction partners.
Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface binding
Authors: Bateman David A , McLaurin JoAnne , Chakrabartty Avijit
Published: May 2007

Background

Aggregation of the amyloid peptides, Aβ40 and Aβ42, is known to be involved in the pathology of Alzheimer's disease (AD). Here we investigate the relationship between peptide aggregation and cell surface binding of three forms of Aβ (Aβ40, Aβ42, and an Aβ mutant).

Results

Using confocal microscopy and flow cytometry with fluorescently labelled Aβ, we demonstrate a correlation between the aggregation propensity of the Alzheimer amyloid peptides and their neuronal cell surface association. We find that the highly aggregation prone Aβ42 associates with the surface of neuronal cells within one hour, while the less aggregation prone Aβ40 associates over 24 hours. We show that a double mutation in Aβ42 that reduces its aggregation propensity also reduces its association with the cell surface. Furthermore, we find that a cell line that is resistant to Aβ cytotoxicity, the non-neuronal human lymphoma cell line U937, does not bind either Aβ40 or Aβ42.

Conclusion

Taken together, our findings reveal that amyloid peptide aggregation propensity is an essential determinant of neuronal cell surface association. We anticipate that our approach, involving Aβ imaging in live cells, will be highly useful for evaluating the efficacy of therapeutic drugs that prevent toxic Aβ association with neuronal cells.
Hypoxia-inducible factor-1 (HIF-1) is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and MCP-5 (Ccl12) in astrocytes
Authors: Mojsilovic-Petrovic Jelena , Callaghan Debbie , Cui Hong , Dean Clare , Stanimirovic Danica B , Zhang Wandong
Published: May 2007

Background

Neuroinflammation has been implicated in various brain pathologies characterized by hypoxia and ischemia. Astroglia play an important role in the initiation and propagation of hypoxia/ischemia-induced inflammation by secreting inflammatory chemokines that attract neutrophils and monocytes into the brain. However, triggers of chemokine up-regulation by hypoxia/ischemia in these cells are poorly understood. Hypoxia-inducible factor-1 (HIF-1) is a dimeric transcriptional factor consisting of HIF-1α and HIF-1β subunits. HIF-1 binds to HIF-1-binding sites in the target genes and activates their transcription. We have recently shown that hypoxia-induced expression of IL-1β in astrocytes is mediated by HIF-1α. In this study, we demonstrate the role of HIF-1α in hypoxia-induced up-regulation of inflammatory chemokines, human monocyte chemoattractant protein-1 (MCP-1/CCL2) and mouse MCP-5 (Ccl12), in human and mouse astrocytes, respectively.

Methods

Primary fetal human astrocytes or mouse astrocytes generated from HIF-1α+/+and HIF-1α+/-mice were subjected to hypoxia (<2% oxygen) or 125 μM CoCl2for 4 h and 6 h, respectively. The expression of HIF-1α, MCP-1 and MCP-5 was determined by semi-quantitative RT-PCR, western blot or ELISA. The interaction of HIF-1α with a HIF-1-binding DNA sequence was examined by EMSA and supershift assay. HIF-1-binding sequence in the promoter of MCP-1 gene was cloned and transcriptional activation of MCP-1 by HIF-1α was analyzed by reporter gene assay.

Results

Sequence analyses identified HIF-1-binding sites in the promoters of MCP-1 and MCP-5 genes. Both hypoxia and HIF-1α inducer, CoCl2, strongly up-regulated HIF-1α expression in astrocytes. Mouse HIF-1α+/-astrocytes had lower basal levels of HIF-1α and MCP-5 expression. The up-regulation of MCP-5 by hypoxia or CoCl2in HIF-1α+/+and HIF-1α+/-astrocytes was correlated with the levels of HIF-1α in cells. Both hypoxia and CoCl2also up-regulated HIF-1α and MCP-1 expression in human astrocytes. EMSA assay demonstrated that HIF-1 activated by either hypoxia or CoCl2binds to wild-type HIF-1-binding DNA sequence, but not the mutant sequence. Furthermore, reporter gene assay demonstrated that hypoxia markedly activated MCP-1 transcription but not the mutated MCP-1 promoter in transfected astrocytes.

Conclusion

These findings suggest that both MCP-1 and MCP-5 are HIF-1 target genes and that HIF-1α is involved in transcriptional induction of these two chemokines in astrocytes by hypoxia.
Liquid versus gel handrub formulation: a prospective intervention study
Authors: Traore Ousmane , Hugonnet Stéphane , Lübbe Jann , Griffiths William , Pittet Didier
Published: May 2007

Introduction

Hand hygiene is one of the cornerstones of the prevention of health care-associated infection, but health care worker (HCW) compliance with good practices remains low. Alcohol-based handrub is the new standard for hand hygiene action worldwide and usually requires a system change for its successful introduction in routine care. Product acceptability by HCWs is a crucial step in this process.

Methods

We conducted a prospective intervention study to compare the impact on HCW compliance of a liquid (study phase I) versus a gel (phase II) handrub formulation of the same product during daily patient care. All staff (102 HCWs) of the medical intensive care unit participated. Compliance with hand hygiene was monitored by a single observer. Skin tolerance and product acceptability were assessed using subjective and objective scoring systems, self-report questionnaires, and biometric measurements. Logistic regression was used to estimate the association between predictors and compliance with the handrub formulation as the main explanatory variable and to adjust for potential risk factors.

Results

Overall compliance (phases I and II) with hand hygiene practices among nurses, physicians, nursing assistants, and other HCWs was 39.1%, 27.1%, 31.1%, and 13.9%, respectively (p = 0.027). Easy access to handrub improved compliance (35.3% versus 50.6%, p = 0.035). Nurse status, working on morning shifts, use of the gel formulation, and availability of the alcohol-based handrub in the HCW's pocket were independently associated with higher compliance. Immediate accessibility was the strongest predictor. Based on self-assessment, observer assessment, and the measurement of epidermal water content, the gel performed significantly better than the liquid formulation.

Conclusion

Facilitated access to an alcohol-based gel formulation leads to improved compliance with hand hygiene and better skin condition in HCWs.
Global transcriptional responses of fission and budding yeast to changes in copper and iron levels: a comparative study
Authors: Rustici Gabriella , van Bakel Harm , Lackner Daniel H , Holstege Frank C , Wijmenga Cisca , Bähler Jürg , Brazma Alvis
Published: May 2007

Background

Recent studies in comparative genomics demonstrate that interspecies comparison represents a powerful tool for identifying both conserved and specialized biologic processes across large evolutionary distances. All cells must adjust to environmental fluctuations in metal levels, because levels that are too low or too high can be detrimental. Here we explore the conservation of metal homoeostasis in two distantly related yeasts.

Results

We examined genome-wide gene expression responses to changing copper and iron levels in budding and fission yeast using DNA microarrays. The comparison reveals conservation of only a small core set of genes, defining the copper and iron regulons, with a larger number of additional genes being specific for each species. Novel regulatory targets were identified in Schizosaccharomyces pombe for Cuf1p (pex7 and SPAC3G6.05) and Fep1p (srx1, sib1, sib2, rds1, isu1, SPBC27B12.03c, SPAC1F8.02c, and SPBC947.05c). We also present evidence refuting a direct role of Cuf1p in the repression of genes involved in iron uptake. Remarkable differences were detected in responses of the two yeasts to excess copper, probably reflecting evolutionary adaptation to different environments.

Conclusion

The considerable evolutionary distance between budding and fission yeast resulted in substantial diversion in the regulation of copper and iron homeostasis. Despite these differences, the conserved regulation of a core set of genes involved in the uptake of these metals provides valuable clues to key features of metal metabolism.
Role of endogenous interferon and LPS in the immunomodulatory effects of bovine lactoferrin in murine peritoneal macrophages
Authors: Puddu Patrizia , Carollo Maria Grazia , Belardelli Filippo , Valenti Piera , Gessani Sandra
Published: May 2007

Lactoferrin (Lf) plays an important role in host defense against infection and excessive inflammation. Although the mechanisms underlying its immunomodulatory properties have not been fully elucidated yet, recent evidence suggests that some of these effects may be related to its capacity to form complexes with LPS. We report that the culture of resting mouse peritoneal macrophages (PM) with bovine Lf (bLf), prior to infection with the vesicular stomatitis virus (VSV), resulted in a significant reduction of virus yield with respect to control cultures. The antiviral activity of bLF was related to its capacity of inducing IFN-α/β expression, which in turn inhibited VSV replication. Indeed, the accumulation of IFN-β but not of IFNα1-2 transcripts was up-modulated markedly early after bLf addition. Furthermore, bLf did not exert any antiviral activity in the presence of neutralizing antibodies to IFN-α/β in PM from wild-type mice, as well as in PM from mice genetically defective for the response to IFN. The antiviral activity of bLf relied on its intrinsic capacity to bind LPS, as this protein did not induce IFN expression in PM from LPS-hyporesponsive mice. It is interesting that this LPS-binding property was dispensable for the production of TNF-α, which also occurred in LPS-hyporesponsive mice. Overall, these results indicate that some of the immunomodulatory effects ascribed to Lf may be related to its capacity to favor Type I IFN expression and argue in favor of an important role of the LPS-binding feature and TLR4 in some of the effects ascribed to this molecule.
Memory and Modernity in Democratic Spain: The Difficulty of Coming to Terms with the Spanish Civil War
Authors: Labanyi Jo
Published: May 2007

The essay argues that modernity is best understood not as the cultural expression of capitalist modernization, but as a particular set of relations of present to past. It examines the varying attitudes toward the violent past of the civil war that have characterized Spain since the Franco dictatorship and continuing to the present day. The obsessive memorialization of the Nationalist war dead throughout the Franco dictatorship led, at the time of the transition to democracy, to a desire to break with the past; it was not, as is often argued, a determination to forget, but a decision not to let the past affect the future. Thus attempts toward the end of the Franco dictatorship to deal cinematically with this violent heritage were followed by a ten-year gap, until the appearance in the mid-1980s of a number of novels and films representing the civil war and their escalation since the late 1990s to create a memory boom, which has resulted in the publication of a large number of testimonies. The essay questions whether trauma theory, which has been so important in Holocaust studies, provides an adequate model for understanding the belated appearance of these memories, arguing that the reason is more likely to be a previous lack of willing interlocutors. Nevertheless, it concludes that the present urge to recount every detail of the past is less effective in communicating the horror of the war and its repression than are those accounts—in film at the end of the dictatorship and in fiction in the mid-1980s, with occasional more recent examples—which acknowledge the difficulty of narrativizing the violent past as well as the importance of transgenerational transmission.