bluuebunny/crossref_metadata_2025 huggingface dataset:
A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons alpha and beta and alters macrophage responses.
Authors: Hwang S Y , Hertzog P J , Holland K A , Sumarsono S H , Tymms M J , Hamilton J A , Whitty G , Bertoncello I , Kola I
Published: June 2006

To examine the in vivo role(s) of type I interferons (IFNs) and to determine the role of a component of the type I IFN receptor (IFNAR1) in mediating responses to these IFNs, we generated mice with a null mutation (-/-) in the IFNAR1 gene. Despite compelling evidence for modulation of cell proliferation and differentiation by type I IFNs, there were no gross signs of abnormal fetal development or morphological changes in adult IFNAR1-/- mice. However, abnormalities of hemopoietic cells were detected in IFNAR1 -/- mice. Elevated levels of myeloid lineage cells were detected in peripheral blood and bone marrow by staining with Mac-1 and Gr-1 antibodies. Furthermore, bone marrow macrophages from IFNAR1 -/- mice showed abnormal responses to colony-stimulating factor 1 and lipopolysaccharide. IFNAR1 -/- mice were highly susceptible to viral infection: viral titers were undetected 24 hr after infection of IFNAR1 +/+ mice but were extremely high in organs of IFNAR1 -/- mice, demonstrating that the type I IFN system is a major acute antiviral defence. In cell lines derived from IFNAR1 -/- mice, there was no signaling in response to IFN-alpha or -beta as measured by induction of 2'-5' oligoadenylate synthetase, antiviral, or antiproliferative responses. Importantly, these studies demonstrate that type I IFNs function in the development and responses of myeloid lineage cells, particularly macrophages, and that the IFNAR1 receptor component is essential for antiproliferative and antiviral responses to IFN-alpha and -beta.
Sequence verification of human creatine kinase (43 kDa) isozymes by high-resolution tandem mass spectrometry.
Authors: Wood T D , Chen L H , White C B , Babbitt P C , Kenyon G L , McLafferty F W
Published: June 2006

Amino acid sequencing by recombinant DNA technology, although dramatically useful, is subject to base reading errors, is indirect, and is insensitive to posttranslational processing. Mass spectrometry techniques can provide molecular weight data from even relatively large proteins for such cDNA sequences and can serve as a check of an enzyme's purity and sequence integrity. Multiply-charged ions from electrospray ionization can be dissociated to yield structural information by tandem mass spectrometry, providing a second method for gaining additional confidence in primary sequence confirmation. Here, accurate (+/- 1 Da) molecular weight and molecular ion dissociation information for human muscle and brain creatine kinases has been obtained by electrospray ionization coupled with Fourier-transform mass spectrometry to help distinguish which of several published amino acid sequences for both enzymes are correct. The results herein are consistent with one published sequence for each isozyme, and the heterogeneity indicated by isoelectric focusing due to 1-Da deamidation changes. This approach appears generally useful for detailed sequence verification of recombinant proteins.
Phosphatidylinositol 3-kinase binding to polyoma virus middle tumor antigen mediates elevation of glucose transport by increasing translocation of the GLUT1 transporter.
Authors: Young A T , Dahl J , Hausdorff S F , Bauer P H , Birnbaum M J , Benjamin T L
Published: June 2006

Elevation in the rate of glucose transport in polyoma virus-infected mouse fibroblasts was dependent upon phosphatidylinositol 3-kinase (PI 3-kinase; EC 2.7.1.137) binding to complexes of middle tumor antigen (middle T) and pp60c-src. Wild-type polyoma virus infection led to a 3-fold increase in the rate of 2-deoxyglucose (2DG) uptake, whereas a weakly transforming polyoma virus mutant that encodes a middle T capable of activating pp60c-src but unable to promote binding of PI 3-kinase induced little or no change in the rate of 2DG transport. Another transformation-defective mutant encoding a middle T that retains functional binding of both pp60c-src and PI 3-kinase but is incapable of binding Shc (a protein involved in activation of Ras) induced 2DG transport to wild-type levels. Wortmannin (< or = 100 nM), a known inhibitor of PI 3-kinase, blocked elevation of glucose transport in wild-type virus-infected cells. In contrast to serum stimulation, which led to increased levels of glucose transporter 1 (GLUT1) RNA and protein, wild-type virus infection induced no significant change in levels of either GLUT1 RNA or protein. Nevertheless, virus-infected cells did show increases in GLUT1 protein in plasma membranes. These results point to a posttranslational mechanism in the elevation of glucose transport by polyoma virus middle T involving activation of PI 3-kinase and translocation of GLUT1.
Emergence of multipotent hemopoietic cells in the yolk sac and paraaortic splanchnopleura in mouse embryos, beginning at 8.5 days postcoitus.
Authors: Godin I , Dieterlen-Lièvre F , Cumano A
Published: June 2006

We show by an in vitro approach that multipotent hemopoietic cells can be detected in the body of the mouse embryo between the stages of 10-25 somites (8.5-9.5 days of gestation)--i.e., prior to liver colonization (28-32 pairs of somites). Interestingly, hemopoietic cells appear in parallel in this location, the paraaortic splanchnopleura, and in the yolk sac, where they represent a new generation by reference to the primitive hemopoietic stem cells. Lymphoid cell clones, which could differentiate into mature B cells, were obtained from yolk sac and paraaortic splanchnopleura cell preparations but not from other tissues of the embryonic body. These B-cell precursors were first detected around the stage of 10 somites; thereafter, their initial minute numbers increased in parallel in the yolk sac and the paraaortic splanchnopleura, suggesting that their emergence in the two sites was simultaneous. By single cell manipulation, we show that these precursors can generate B and T lymphocytes and myeloid cells; these precursors can thus be defined as multipotent hemopoietic cells.
Endonuclease-induced, targeted homologous extrachromosomal recombination in Xenopus oocytes.
Authors: Segal D J , Carroll D
Published: June 2006

Homologous recombination in gene targeting in most organisms occurs by an inefficient mechanism. Inducing a double-strand break in the chromosomal target may increase this efficiency by allowing recombination to proceed by the highly efficient single-strand annealing mechanism. A gene targeting experiment was modeled in Xenopus oocytes by using a circular plasmid to mimic the chromosomal target site and a homologous linear molecule (pick-up fragment or PUF) as an analogue of the vector DNA. When those two molecules were simply injected together, no recombination was observed. In contrast, when the circular plasmid was cleaved in vivo by injection of the site-specific endonuclease, I-Sce I, relatively efficient intermolecular recombination occurred, involving up to 17% of the cleaved molecules. Recombination was dependent on the stability of the PUF; product yield was increased by using longer fragments and by injecting larger amounts of linear DNA, both of which increased the lifetime of the PUF in the oocytes. These results demonstrate that in vivo double-strand breaks can induce homologous recombination of reluctant substrates and may be useful in augmenting the efficiency of gene targeting.
Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain.
Authors: Lovenberg T W , Liaw C W , Grigoriadis D E , Clevenger W , Chalmers D T , De Souza E B , Oltersdorf T
Published: June 2006

The present study reports the isolation of a cDNA clone that encodes a second member of the corticotropin-releasing factor (CRF) receptor family, designated as the CRF2 receptor. The cDNA was identified using oligonucleotides of degenerate sequence in a PCR paradigm. A PCR fragment obtained from rat brain was utilized to isolate a full-length cDNA from a rat hypothalamus cDNA library that encoded a 411-amino acid protein with approximately 70% identity to the known CRF1 receptor over the entire coding region. When expressed in mouse Ltk- cells, this receptor stimulates cAMP production in response to CRF and known CRF-like agonists. CRF and the nonmammalian CRF-related peptides sauvagine and urotensin I stimulate adenylate cyclase activity in a dose-dependent manner with a rank order of potency different from that of the CRF1 receptor: sauvagine > urotensin > or = rat/human CRF > ovine CRF. Tissue distribution analysis of the mRNAs by reverse transcriptase-PCR shows CRF2 receptor mRNA is present in rat brain and detectable in lung and heart. In situ hybridization studies indicate specific expression within the brain in the ventromedial nuclei of the hypothalamus, the lateral septum, the amygdala, and entorhinal cortex, but there is unremarkable expression in the pituitary. An additional splice variant of the CRF2 receptor with a different N-terminal domain has been identified by PCR, encoding a putative protein of 431 amino acids. Thus, the data demonstrate the presence of another functional CRF receptor, with significant differences in the pharmacological profile and tissue distribution from the CRF1 receptor, which would predict important functional differences between the two receptors.
Recognition of oxidatively damaged and apoptotic cells by an oxidized low density lipoprotein receptor on mouse peritoneal macrophages: role of membrane phosphatidylserine.
Authors: Sambrano G R , Steinberg D
Published: June 2006

We recently reported that oxidized low density lipoprotein (OxLDL), but not acetyl LDL (AcLDL), inhibited the binding and phagocytosis of nonopsonized, oxidatively damaged red blood cells (OxRBCs) by mouse peritoneal macrophages, implying the involvement of a "scavenger receptor" other than the AcLDL receptor. Numerous studies establish that loss of plasma membrane phospholipid asymmetry, which increases phosphatidylserine expression on the outer leaflet of the membrane, can play a key role in macrophage recognition of damaged and apoptotic cells. We report here that this recognition is in part attributable to the same mouse macrophage receptor that recognizes OxLDL. As described in an accompanying paper, this is a plasma membrane protein of 94-97 kDa. Phosphatidylserine liposomes show strong ligand binding to the same 94- to 97-kDa protein and this binding is inhibited by OxLDL but not by AcLDL. Inhibition of the RBC membrane phospholipid translocase by incubation with sodium vanadate caused a progressive increase in the appearance of phosphatidylserine on the cell surface and a parallel increase in the binding of these RBCs to macrophages, binding that was inhibited by OxLDL. Finally, OxLDL also inhibited the binding of sickled RBCs and apoptotic thymocytes to mouse macrophages. However, the latter was incomplete (approximately 50%), suggesting that other receptors are also involved. We suggest that the OxLDL receptor plays a significant role in recognition of damaged and apoptotic cells.
Activation of Ca2+ signaling in neutrophils by the mast cell-released immunophilin FKBP12.
Authors: Bang H , Müller W , Hans M , Brune K , Swandulla D
Published: June 2006

The immunophilins of the FK506-binding protein (FKBP) family are intracellular proteins that bind the immunosuppresants FK506 and rapamycin. In this study we show that HMC-1 mast cells sensitized with IgE release FKBP12 upon stimulation with anti-IgE. The release is rapid and not affected by actinomycin D or cycloheximide, suggesting that it is due to exocytosis from a storage compartment. FKBP12 from HMC-1 mast cells exhibits biological activity. When applied extracellularly to human neutrophils, it induces transient changes in the intracellular Ca2+ concentration ([Ca2+]i) due to Ca2+ release from intracellular stores. Inhibition of [Ca2+]i changes by ruthenium red and ryanodine indicates that ryanodine receptor/Ca2+ release channels are involved in FKBP12-induced Ca2+ signaling. Neutrophil activation by mast cell-derived FKBP12 is prevented by complexing FKBP12 with FK506 or rapamycin. These results demonstrate that extracellular FKBP12 functions as a cytokine in cell-to-cell communication. They further suggest a pathophysiological role for FKBP12 as a mediator in immediate or type I hypersensitivity and may have implications for novel therapeutic strategies in the treatment of allergic disorders with FK506 and rapamycin.
Short-term Dynamics in the Use of Places: A Space-Time Typology of Visitor Populations in the Netherlands
Authors: Zandvliet Robbert , Dijst Martin
Published: June 2006

In a network society, spurred on by technological, social and economic factors, the process of land use deconcentration has resulted in various new urban forms such as edge cities and edgeless cities. While the consequences of this process for the distribution of the residential population and travel patterns have been extensively described and analysed, there has as yet been little investigation of the effect on visitors' use of places. Using the 1998 Netherlands National Travel Survey, the paper develops a typology of urban, suburban and rural municipalities located in monocentric and polycentric urban systems on the basis of dimensions of diurnal weekday variations in visitor populations. A two-step cluster analysis results in five types of municipality: 'central place', 'contemporary node', 'self-contained', 'mobile children' and 'local children'.
'When the Banks Withdraw, Slum Landlords Take Over' : The Structuration of Neighbourhood Decline through Redlining, Drug Dealing, Speculation and Immigrant Exploitation
Authors: Aalbers Manuel B.
Published: June 2006

Rather than viewing neighbourhood decline as a natural process resulting from the in-flow of low-income households, this study uses a socio-spatial approach that looks at the structuration of neighbourhood decline by emphasising the power of agents/actors, linking the structure of the real estate industry to the development of the neighbourhood. Landlords and banks are not merely automata of the price mechanism that steer the natural operation of the market, but should be seen as intentionally and unintentionally restructuring the local real estate market and thus possibly producing, or contributing to, processes of neighbourhood decline. This paper presents the Tarwewijk (Rotterdam, the Netherlands) as a case study of neighbourhood decline. Attention is paid to the social and physical decline of the neighbourhood, drug dealing, undocumented immigrants and processes impacting the housing market such as speculation, blockbusting, milking and redlining. It is argued that the retreat of 'formal' actors, such as banks and bona fide landlords, stimulates the rise of the underworld in both the housing and drugs markets.
State Aid Formulas and the Local Incentive to Chase (or Shun) Ratables
Authors: Gottlieb Paul D.
Published: June 2006

Most programmes of state aid to local governments in the US are designed to fix problems of interjurisdictional or interpersonal equity, not to address the effect that local tax reliance might have on local land use decisions, such as zoning. As a consequence, little is known about how to design a state aid system that would achieve desirable land use, as opposed to equity, objectives within US states. As a first contribution to this policy literature, the paper compares state aid formulas on their ability to reduce the incentive that local governments have to engage in fiscal zoning and other ratable-oriented behaviour. A set of simulations shows that a state aid formula that guarantees to cover a fixed percentage of local expenditures is preferable to a per capita aid formula in three out of four cases examined and performs better when the level of aid is relatively high. Both types of formula reliably reduce ratable shunning behaviour, but it may take relatively large levels of state aid to curb ratable chasing, due to the increase in local spending caused by the aid itself. The paper ends with a discussion of state aid programmes actually used in New Jersey.
From Giotto to De Chirico to Verrocchio: analyses of paintings and historical bronze alloys availing of portable EDXRF equipment
Authors: Cesareo R. , Ridolfi S. , Castellano A. , Marabelli M. , Buccolieri G. , Quarta S. , Gigante G.E.
Published: June 2006

Energy-dispersive X-ray fluorescence (EDXRF) has been used successfully for some time now in non-destructive diagnostic examinations of art works, especially for paintings and bronze works. Furthermore, such examinations may be carried out with portable equipment, allowing studies in situ. EDXRF-analysis of paintings generally provides the following information: –possible presence of elements on the surface (sulphur, chlorine) due to pollution; –identification of the elements, and therefore giving a good indication of the pigments, employed by the artist; and –identification of previous restoration areas, by detecting the presence of “modern” elements, such as titanium, zinc, cadmium, etc. Recently, the famous Chapel of the Scrovegni painted by Giotto in Padua in 1303–1305 was analysed in detail to obtain all the information described above. Another example of application of EDXRF-analysis to paintings was a recent examination of 11 paintings believed to be by De Chirico the outcome of which was compared with that obtained for 15 paintings certainly by De Chirico. Finally, the bronze statue of Bartolomeo Colleoni was analysed, in order to determine its composition and the presence of sulphur and chlorine on the surface. In this case, the analysis was partially destructive, because small areas of a few square millimetres had to be cleaned for analyses, to avoid interference by the patina.
Neutron tomography for archaeological investigations
Authors: Kardjilov Nikolay , Fiori Fabrizio , Giunta Giuseppe , Hilger André , Rustichelli Franco , Strobl Markus , Banhart John , Triolo Roberto
Published: June 2006

Within the last decade neutron tomography and radiography significantly gained importance. Especially its application in non-destructive testing for industrial components can be underlined. A good example is the automotive and aviation industry, where a high contrast for the used lubricants and adhesive materials is required. In contrast to X-rays, neutrons are able to penetrate thick layers of metals and provide on the other hand a high sensitivity to hydrogen containing materials. In recent years, a large number of applications in other fields like biology, medicine, geology and especially archaeology have been reported. Here the potential of neutron tomography for investigations on archaeological samples shall be outlined and some recent examples will be presented.
Timing, Memory and Disaster: Patriotic Narratives in the Aftermath of the Messina–Reggio Calabria Earthquake, 28 December 1908
Authors: Dickie John
Published: June 2006

The earthquake that struck both coasts of the Straits of Messina on 28 December 1908 was probably the worst natural disaster in the history of the Italian peninsula. It was followed by an extraordinary movement of public grief and solidarity. These extremely widespread manifestations of patriotism in a country that is frequently thought to ‘lack’ national identity give cause to reflect on the way the notion of national identity is used in the Italian context and beyond. The article looks specifically at some of the contrasting ways in which timing and memory simultaneously became patriotic and controversial issues in the Italian press in the aftermath of the catastrophe. It does so through a sustained dialogue with the most influential thinker on nationalism, time and memory: Benedict Anderson. It emerges from the analysis that different constructions of timing and memory are an indicator of the social and political functions of patriotism, which offers ways to manage crisis situations like the earthquake, but at the same time covertly politicizes them.
Debating the Meaning of Fascism in Contemporary Italy
Authors: Ventresca Robert
Published: June 2006

This article takes up the question posed by Claudio Pavone—‘Have the Italians truly known how to come to terms with their past?’—and argues that Italians have indeed grappled with their Fascist past, albeit in varied, contradictory, ambiguous and incomplete ways. This article demonstrates the myriad ways in which Italians—historians, politicians, intellectuals, and segments of the general public—have debated the meaning of Fascism since the fall of Mussolini and the end of the Second World War. What follows below argues that selective remembering and wilful forgetting of the Mussolini regime are nevertheless evidence of an ongoing process of confronting the legacy of Italy's recent past.
Review Article: The significance of neighbourhood context to child and adolescent health and well-being: A systematic review of multilevel studies
Authors: Sellström Eva , Bremberg Sven
Published: June 2006

Growing up in a poor neighbourhood has negative effects on children and adolescents. In the literature it has been concluded that the risk of low birth weight, childhood injury and abuse, and teenage pregnancy or criminality double in poor areas. However, the validity of such studies has been questioned, as they have been associated with ecological or individualistic fallacies. Studies using multilevel technique might thus contribute important knowledge in this field. The present review clarifies the importance of neighbourhood contextual factors in child and adolescent health outcomes, through considering only studies using multilevel technique. Keyword searching of the Medline, ERIC, PsycInfo, Sociological Abstracts, and Social Citation Index databases was performed. Original studies using multilevel technique to examine the effect of neighbourhood characteristics on child and adolescent health outcomes, and focusing on populations in high-income countries were included. Neighbourhood socioeconomic status and social climate were shown to have small to moderate effects on child health outcomes, i.e. birth weight, injuries, behavioural problems, and child maltreatment. On average, 10% of variation in health outcomes was explained by neighbourhood determinants, after controlling for important individual and family variables. This review demonstrates that interventions in underprivileged neighbourhoods can reduce health risks to children, especially in families that lack resources. An analysis of methodological fallacies indicates that observed effects and effect sizes can be underestimated, and that interventions may well have greater impact than this review was able to establish.
Client perceptions of the performance of public and independent not-for-profit primary healthcare
Authors: Laamanen Ritva , Øvretveit John , Sundell Jari , Simonsen-Rehn Nina , Suominen Sakari , Brommels Mats
Published: June 2006

Aims: To compare primary healthcare (PHC) provided by an independent not-for-profit organization (INPO) with that provided by two public municipal organizations (MO1 and MO2), in terms of clients' perceptions of performance, acceptance, and trust. Methods: A survey using a pre-tested questionnaire to all clients visiting a health centre (HC) doctor or nurse during one week in 2000 (n=511, 51% response rate) and 2002 (n=275, 47%). The data were analysed by descriptive statistics and cumulative logistic regression analysis. Results: The INPO differed from both publicly provided services in accessibility, consistency of service, and outcomes. Clients reported lower trust in HC provided by public organizations compared with the INPO. Trust was higher if clients also reported experiencing ``very good'' or ``moderate'' organizational access — or if general satisfaction was ``very high'' or ``moderate'' or if they experienced outcomes as ``very good'' or ``moderate'' compared with the ``very poor or low'' situation. Women reported lower trust in HC than men. When the family doctor was included in the same logistic regression model with the service provider, only the family doctor was a significant explanatory variable. Reported acceptance of private alternative service providers among clients was similar between the study organizations. Conclusions: Clients of the INPO generally rated the service more positively than clients of publicly provided services. The results indicate that trust in HC depends more on a family doctor system than a service provider.
Effects of body fatness and physical activity on cardiovascular risk: Risk prediction using the bioelectrical impedance method
Authors: Calling Susanna , Hedblad Bo , Engström Gunnar , Berglund Göran , Janzon Lars
Published: June 2006

Aims: To explore the effects of body fat percentage (BF%) on incidence of and mortality from cardiovascular disease (CVD) and to study the cardio-protective effect of physical activity in relation to BF%. Methods: A total of 26,942 men and women, aged 45—73 years, without history of CVD were followed up for incidence of coronary events (CE), ischaemic stroke, and CVD mortality over seven years in relation to sex-specific quartiles (Q1—Q4) of BF%. The cardio-protective effect of leisure-time physical activity was studied in relation to BF%. Results: In men, the relative risk (RR) for CE and CVD mortality increased progressively with BF%. RR for CE in Q4 was 1.37 (95% confidence interval: 1.07—1.74), adjusted for age, height, smoking, high alcohol intake, and physical activity, compared with Q1. In women, BF% was significantly associated with incidence of CE and stroke. BF% was more strongly correlated to body mass index (BMI) (r=0.83) and waist circumference (r=0.76) in women than in men (r=0.59 and r=0.66, respectively). BF% was a stronger risk factor than BMI in women, and equally strong as waist circumference. A significant interaction (p=0.013 for incidence of CE, p=0.026 for ischaemic stroke) was found between BF% and sex. The raised cardiovascular risk was reduced by physical activity in subjects with high BF%. Conclusions: BF% is a risk factor for CE, ischaemic stroke, and CVD mortality. An interaction between BF% and sex suggests that BF% is a stronger CVD risk factor in women. The raised cardiovascular risk associated with high BF% is reduced by physical activity.
Democracy or State-Building? 1906–1941
Authors: Gheissari Ali , Nasr Vali
Published: June 2006

This chapter discusses the Constitutional Revolution of 1906-1911 and subsequent efforts to balance the demand for a viable state with the demand for democracy and rule of law. It then traces the rise and triumph of the Iranian state under Reza Shah between 1925 and 1941.
Catholic Higher Education
Authors: Morey Melanie M. , Piderit John J.
Published: June 2006

Relying on empirical evidence from a national study of senior administrators at Catholic colleges and universities across the United States, this book defines the critical religious identity and mission issues facing Catholic colleges and universities as they look to the future. It analyzes and addresses these issues using the rich construct of culture, particularly organizational culture. Adopting cultural concepts of “distinguishability” and “inheritability”, the book provides four different models of how Catholic colleges and universities can operate and successfully compete as religiously distinctive institutions in the higher education market. After specifying the content of the Catholic tradition — intellectual, moral, and social — the book critiques the present performance among institutions in all four models, provides specific policy proposals for attending to religious cultural weakness, and offers principles for effectively leading and managing cultural change. For much of the history of Catholic colleges and universities, nuns, priests, and brothers provided successful Catholic cultural leadership. This book takes a critical look at the way congregations prepared members for knowledgeable, committed, and effective religious cultural leadership, and explains how insights from that model might prove particularly usefully today. The book also explores the cultural collapse of the once highly dynamic Roman Catholic sisterhoods as a cautionary tale about the perils of a cultural change process ineffectively managed.
The Impact of Women in Congress
Authors: Dodson Debra L.
Published: June 2006

This book explores the complex relationship between women’s presence and impact in two strikingly different, consecutive congresses. Drawing on hundreds of elite interviews and archival information, the case studies of three highly visible policy areas (reproductive rights, women’s health, and health care policy) move beyond the question of ‘Do women make a difference?’ to confront the oft-ignored, contested issues surrounding gender difference and impact: its probabilistic nature, contested legitimacy, and disputed meaning. The analysis enhances understanding of how gendered forces at the individual, institutional, and societal levels combine to reinforce and redefine gendered relationships to power in the public sphere, and suggests strategies to strengthen substantive representation of women.
Peace and Justice: A Prologue
Authors: Hoffmann Stanley
Published: June 2006

Why has peace been often unjust, and why has justice been more belligerent than peaceful? Frequently, peace or armistice has served only to put a temporary end to violence, and has left some or all sides feeling dissatisfied. Peace has also been an imposition on the part of the victors of conflict to the end of some notion of order, thus leaving the affected common people to draw their own conclusions without ever being consulted. It is for this reason that justice is often more properly envisioned as the image of a fighter with his sword rather than a balancing scale. In this chapter, Hoffman explores the complexity of how peace and justice might be wedded in international relations, and gives the reader sound starting points for thinking about this conceptual approach.
5 Measuring International Ethics: A Moral Scale of War, Peace, Justice, and Global Care
Authors: Allan Pierre
Published: June 2006

This chapter distinguishes Just Peace from its closest ‘moral’ neighbours — a stable (but usually unjust) peace and positive peace. Drawing on both consequentialist and deontological considerations, Allan develops an international ethical scale to evaluate different acts from a moral standpoint, with different levels of conflict as the baseline of ethical behavior. The more extreme the discord, the worse it is considered on the scale; the more harmonious, the better. Arguing that absolute unhappiness (disappearance of humankind) and absolute happiness (agape-paradise) are not of this world, Allan presents eight intermediary moral situations, each being superseded by the next one in ethical terms: genocide, war, non-war, Just War, stable peace, Just Peace, positive peace, and Global Care. He develops an ethic of ‘global care’ based on feminist theories of care, religious and secular declarations on a global ethic, evolutionary theory arguments, and a critique of a liberal human rights approach.
Agency and Autonomy in Kant's Moral Theory
Authors: Reath Andrews
Published: June 2006

This book contains chapters on various features of Kant's moral psychology and moral theory, with particular emphasis on a conception of rational agency autonomy. The opening chapters explore different elements of Kant's views about motivation, including an account of respect for morality as the distinctive moral motive and a view of the principle of happiness as a representation of the shared structure of non-moral choice. These chapters stress the unity of Kant's moral psychology by arguing that moral and non-moral considerations motivate in essentially the same way. Several of the chapters develop an original approach to Kant's conception of autonomy that emphasizes the political metaphors found throughout Kant's writings on ethics. They argue that autonomy is best interpreted not as a psychological capacity, but as a kind of sovereignty: in claiming that moral agents have autonomy, Kant regards them as a kind of sovereign legislator with the power to give moral law through their willing. The final chapters explore some of the implications of this conception of autonomy elsewhere in Kant's moral thought, arguing that his Formula of Universal Law uses this conception of autonomy to generate substantive moral principles and exploring the connection between Kantian self-legislation and duties to oneself.
A Novel Mutation of POU3F4 Causes Congenital Profound Sensorineural Hearing Loss in a Large Chinese Family
Authors: Wang Qiu‐Ju , Li Qing‐Zhong , Rao Shao‐Qi , Zhao Ya‐Li , Yuan Hu , Yang Wei‐Yan , Han Dong‐yi , Shen Yan
Published: June 2006

Objectives/Hypothesis: It is known that approximately 5% of congenital profound hearing impaired cases are inherited in X‐linked inheritance. This study aimed at identifying its underlying molecular determinant(s) using a large, five‐generation Chinese family with multiple familial cases.

Study Design: Model‐based linkage analysis and positional cloning.

Methods: Model‐based genetic linkage analyses were performed with the use of microsatellite polymorphisms to determine disease locus. Mutation screening was performed within the family and unrelated population‐based controls to establish molecular evidence as to what caused the specific X‐linked inheritance pattern in the family.

Results: Clinical investigations of the pedigree demonstrated the extremely high penetrance in the male members but no penetrance in the female members. Linkage analyses mapped the disease to the chromosomal region Xq13.I‐Xq23 (maximum X‐linkage logarithm of odds score = 3.27). Mutation screening of the candidate genes in the linkage region by direct sequencing revealed a de novo missense substitution (925T>C) in the well‐known deaf gene. POU3F4. Direct sequencing on 240 unrelated controls did not detect any mutation.

Conclusions: Multiple analysis approaches demonstrated that these disorders in the family were caused by a founder mutation in the POU3F4 gene. Our findings provided confirmatory molecular evidence to support that development of congenital profound sensorineural hearing loss in the Chinese population results from a novel mutation in the same gene.
Effects of a Nerve‐Muscle Pedicle on the Denervated Rat Thyroarytenoid Muscle
Authors: Kumai Yoshihiko , Ito Takaaki , Udaka Naoko , Yumoto Eiji
Published: June 2006

Objectives: To evaluate the effects of the nerve‐muscle pedicle (NMP) method on the rat thyroarytenoid (TA) muscle after transection of the recurrent laryngeal nerve (RLN).

Study Design: Quantitative histologic assessment of the TA muscle after NMP implantation.

Methods: Thirty‐six Wistar rats were divided into two groups: animals subjected to transection of the left RLN alone (DNV group) and animals subjected to transection of the left RLN followed by immediate transplantation of a NMP flap containing the sternohyoid (SH) muscle and ansa cervicalis nerve branch (NMP group). Animals were killed 2, 4, and 10 weeks after the treatments. The TA muscle stained with hematoxylin‐eosin was evaluated quantitatively. The pre‐ and postsynaptic structures of the neuromuscular junction (NMJ) in the TA muscle were analyzed histochemically. The myosin heavy chain (MyHC) isoforms were evaluated using immunohistochemistry and reverse‐transcriptase polymerase chain reaction (RT‐PCR).

Results: In the NMP group, the TA muscle fiber recovered to almost normal at 10 weeks, and the ratio of the number of synaptophysin‐positive nerve terminals to that of α‐bungarotoxin‐positive acetylcholine receptors recovered to 79.8 ± 11.8% (P < .05, compared with the control). Immunohistochemistry and the RT‐PCR method after laser capture microdissection revealed the expression of MyHC isoforms type 2B and type 2A; the latter was detected in the SH muscle but not in the normal or denervated TA muscle.

Conclusion: The NMP method was effective for recovering from the atrophic changes of the TA muscle after transection of the RLN. This was attributed to successful reinnervation by reconstruction of the NMJ, which might change MyHC isoform expression.
Limited food induces nepotism in drywood termites
Authors: Korb Judith
Published: June 2006

The evolution of cooperation and altruistic behaviour where individuals forego their own reproduction to help others reproduce can be explained by kin selection. Depending on the costs and benefits provided, altruism can be evolutionarily favoured if it is directed at close relatives. A considerable body of data supports the role of relatedness as a key determinant of cooperation and conflict within societies. However, the role of ecological factors and, in particular, how these costs and benefits interact with relatedness remains poorly understood. By studying 16 colonies, here I show that in a drywood termite ecological factors determine the importance of relatedness. In colonies with limited food supply, nestmates restrict cooperative interactions mainly to close relatives, while non-discriminative cooperation occurs when food is abundant. This shows for the first time directly the interaction between ecological conditions and relatedness in shaping cooperation.
Coactivator cross-talk specifies transcriptional output
Authors: Marr Michael T. , Isogai Yoh , Wright Kevin J. , Tjian Robert
Published: June 2006

Cells often fine-tune gene expression at the level of transcription to generate the appropriate response to a given environmental or developmental stimulus. Both positive and negative influences on gene expression must be balanced to produce the correct level of mRNA synthesis. To this end, the cell uses several classes of regulatory coactivator complexes including two central players, TFIID and Mediator (MED), in potentiating activated transcription. Both of these complexes integrate activator signals and convey them to the basal apparatus. Interestingly, many promoters require both regulatory complexes, although at first glance they may seem to be redundant. Here we have used RNA interference (RNAi) inDrosophilacells to selectively deplete subunits of the MED and TFIID complexes to dissect the contribution of each of these complexes in modulating activated transcription. We exploited the robust response of the metallothionein genes to heavy metal as a model for transcriptional activation by analyzing direct factor recruitment in both heterogeneous cell populations and at the single-cell level. Intriguingly, we find that MED and TFIID interact functionally to modulate transcriptional response to metal. The metal response element-binding transcription factor-1 (MTF-1) recruits TFIID, which then binds promoter DNA, setting up a “checkpoint complex” for the initiation of transcription that is subsequently activated upon recruitment of the MED complex. The appropriate expression level of the endogenous metallothionein genes is achieved only when the activities of these two coactivators are balanced. Surprisingly, we find that the same activator (MTF-1) requires different coactivator subunits depending on the context of the core promoter. Finally, we find that the stability of multi-subunit coactivator complexes can be compromised by loss of a single subunit, underscoring the potential for combinatorial control of transcription activation.
Extinction of conditioned taste aversion depends on functional protein synthesis but not on NMDA receptor activation in the ventromedial prefrontal cortex
Authors: Akirav Irit , Khatsrinov Vicktoria , Vouimba Rose-Marie , Merhav Maayan , Ferreira Guillaume , Rosenblum Kobi , Maroun Mouna
Published: June 2006

We investigated the role of the ventromedial prefrontal cortex (vmPFC) in extinction of conditioned taste aversion (CTA) by microinfusing a protein synthesis inhibitor or N-methyl-d-asparate (NMDA) receptors antagonist into the vmPFC immediately following a non-reinforced extinction session. We found that the protein synthesis blocker anisomycin, but not the NMDA receptors antagonist D,L-2-amino-5-phosphonovaleric acid, impaired CTA extinction in the vmPFC. Anisomycin microinfusion into vmPFC had no effect on CTA acquisition and by itself did not induce CTA. These findings show the necessary role functional protein synthesis is playing in the vmPFC during the learning of CTA extinction.
Darbepoetin‐alpha for the anaemia of myelofibrosis with myeloid metaplasia
Authors: Cervantes Francisco , Alvarez‐Larrán Alberto , Hernández‐Boluda Juan‐Carlos , Sureda Anna , Granell Miquel , Vallansot Rolando , Besses Carles , Montserrat Emili
Published: June 2006

Darbepoetin‐α, a novel hyperglycosylated erythropoiesis‐stimulating protein, was administered to 20 patients with myelofibrosis with myeloid metaplasia and anaemia. The initial weekly dose, 150 μg, was increased to 300 μg when no response was observed after 4–8 weeks. Eight patients (40%) responded to treatment, including six complete and two partial responses, and five maintained their response at a median follow‐up of 12 months (range 4–22). Univariate analysis indicated that older age was the only factor associated with a favourable response to treatment (P = 0.006). None of the patients with appropriate serum erythropoietin levels responded. Treatment was usually well tolerated.
Suspects in the tale of lupus-associated thrombocytopenia
Authors: Ziakas P D , Routsias J G , Giannouli S , Tasidou A , Tzioufas A G , Voulgarelis M
Published: June 2006

Immunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirty-eight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren’s syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues.
Signalling network with a bistable hysteretic switch controls developmental activation of the σF transcription factor in Bacillus subtilis
Authors: Igoshin Oleg A. , Price Chester W. , Savageau Michael A.
Published: June 2006

The sporulation process of the bacterium Bacillus subtilis unfolds by means of separate but co‐ordinated programmes of gene expression within two unequal cell compartments, the mother cell and the smaller forespore. σF is the first compartment‐specific transcription factor activated during this process, and it is controlled at the post‐translational level by a partner‐switching mechanism that restricts σF activity to the forespore. The crux of this mechanism lies in the ability of the anti‐sigma factor SpoIIAB (AB) to form alternative complexes either with σF, holding it in an inactive form, or with the anti‐anti‐sigma factor SpoIIAA (AA) and a nucleotide, either ATP or ADP. In the complex with AB and ATP, AA is phosphorylated on a serine residue and released, making AB available to capture σF in an inactive complex. Subsequent activation of σF requires the intervention of the SpoIIE serine phosphatase to dephosphorylate AA, which can then attack the AB–σF complex to induce the release of σF. By incorporating biochemical, biophysical and genetic data from the literature we have constructed an integrative mathematical model of this partner‐switching network. The model predicts that the self‐enhancing formation of a long‐lived complex of AA, AB and ADP transforms the network into an essentially irreversible hysteretic switch, thereby explaining the sharp, robust and irreversible activation of σF in the forespore compartment. The model also clarifies the contributions of the partly redundant mechanisms that ensure correct spatial and temporal activation of σF, reproduces the behaviour of various mutants and makes strong, testable predictions.
From International Ethics to European Union Policy: A Case Study on Biopiracy in the EU's Biotechnology Directive
Authors: CLOATRE EMILIE
Published: June 2006

This article explores how the question of biopiracy, and the rights of indigenous people in the context of patents over natural resources related to traditional knowledge became articulated within the European Union's law and policy process. It presents how this issue was first introduced into the EU during the negotiation on the Directive 98/44/EC, and which mechanisms transformed this ethical issue into a policy concern. Analyzing the history of this issue within that of Directive 98/44/EC offers significant opportunities for testing the appropriateness of multilevel governance and policy‐network theories to empirical sociolegal research in the EU context.
THE LIMITS OF REGULATORY REFORM IN THE EU
Authors: Vibert Frank
Published: June 2006

The regulatory impact assessment (RIA) may seem like a good mechanism for holding EU regulators to account as it requires them to compute costs and benefits of regulations before implementing them. However, it is too easy to use the RIAs to justify preconceived opinions. To achieve deregulation in the EU it is necessary to have a commitment to liberal markets and the concept of regulatory competition.
DESTROYING A COUNTRY IN ORDER TO SAVE IT: THE FOLLY OF ECONOMIC SANCTIONS AGAINST MYANMAR
Authors: Rarick Charles A.
Published: June 2006

The government of the United States has imposed economic sanctions on the Union of Myanmar, formerly known as Burma, due to the ruling junta’s lack of respect for democracy and human rights. This paper proposes that those sanctions, while well intended, are ineffective, unethical and harmful to the people to whom they are intended to help.
CAN A NEW NUCLEAR PROGRAMME BE JUSTIFIED?
Authors: Robinson Colin , Marshall Eileen
Published: June 2006

The moratorium on the building of new nuclear power stations in the UK that has existed since the 1980s may be ended as a result of government concerns about the security of energy provision and the environmental impact of fossil‐fuel‐based energy supply. This viewpoint argues that the case for nuclear power on both counts is unproven. Moreover, renewed government support for a civil nuclear power programme may be a case of government attempting to pick winners, when the evidence suggests that such decisions are best taken by energy suppliers, producers and consumers.