bluuebunny/crossref_metadata_2025 huggingface dataset:
MausDB: An open source application for phenotype data and mouse colony management in large-scale mouse phenotyping projects
Authors: Maier Holger , Lengger Christoph , Simic Bruno , Fuchs Helmut , Gailus-Durner Valérie , Hrabé de Angelis Martin
Published: March 2008

Background

Large-scale, comprehensive and standardized high-throughput mouse phenotyping has been established as a tool of functional genome research by the German Mouse Clinic and others. In all these projects, vast amounts of data are continuously generated and need to be stored, prepared for data-mining procedures and eventually be made publicly available. Thus, central storage and integrated management of mouse phenotype data, genotype data, metadata and linked external data are highly important. Requirements most probably depend on the individual mouse housing unit or project and the demand for either very specific individual database solutions or very flexible solutions that can be easily adapted to local demands. Not every group has the resources and/or the know-how to develop software for this purpose. A database application has been developed for the German Mouse Clinic in order to meet all requirements mentioned above.

Results

We present MausDB, the German Mouse Clinic web-based database application that integrates standard mouse colony management, phenotyping workflow scheduling features and mouse phenotyping result data management. It links mouse phenotype data with genotype data, metadata and external data such as public web databases, which is a prerequisite for comprehensive data analysis and mining. We describe how this can be achieved with a lean and user-friendly system built on open standards.

Conclusion

MausDB is suited for large-scale, high-throughput phenotyping facilities but can also be used exclusively for mouse colony management within smaller units or projects. The system is successfully used as the primary mouse and data management tool of the German Mouse Clinic and other mouse facilities. We offer MausDB to the scientific community as open source software to provide a system for storage of data from functional genomics projects in a well-structured, easily accessible form.
Xenopus importin beta validates human importin beta as a cell cycle negative regulator
Authors: Delmar Valerie A , Chan Rene C , Forbes Douglass J
Published: March 2008

Background

Human importin beta has been used in all Xenopus laevis in vitro nuclear assembly and spindle assembly studies. This disconnect between species raised the question for us as to whether importin beta was an authentic negative regulator of cell cycle events, or a dominant negative regulator due to a difference between the human and Xenopus importin beta sequences. No Xenopus importin beta gene was yet identified at the time of those studies. Thus, we first cloned, identified, and tested the Xenopus importin beta gene to address this important mechanistic difference. If human importin beta is an authentic negative regulator then we would expect human and Xenopus importin beta to have identical negative regulatory effects on nuclear membrane fusion and pore assembly. If human importin beta acts instead as a dominant negative mutant inhibitor, we should then see no inhibitory effect when we added the Xenopus homologue.

Results

We found that Xenopus importin beta acts identically to its human counterpart. It negatively regulates both nuclear membrane fusion and pore assembly. Human importin beta inhibition was previously found to be reversible by Ran for mitotic spindle assembly and nuclear membrane fusion, but not nuclear pore assembly. During the present study, we observed that this differing reversibility varied depending on the presence or absence of a tag on importin beta. Indeed, when untagged importin beta, either human or Xenopus, was used, inhibition of nuclear pore assembly proved to be Ran-reversible.

Conclusion

We conclude that importin beta, human or Xenopus, is an authentic negative regulator of nuclear assembly and, presumably, spindle assembly. A difference in the Ran sensitivity between tagged and untagged importin beta in pore assembly gives us mechanistic insight into nuclear pore formation.
The receptor for Granulocyte-colony stimulating factor (G-CSF) is expressed in radial glia during development of the nervous system
Authors: Kirsch Friederike , Krüger Carola , Schneider Armin
Published: March 2008

Background

Granulocyte colony-stimulating (G-CSF) factor is a well-known hematopoietic growth factor stimulating the proliferation and differentiation of myeloid progenitors. Recently, we uncovered that G-CSF acts also as a neuronal growth factor in the brain, which promotes adult neural precursor differentiation and enhances regeneration of the brain after insults. In adults, the receptor for G-CSF is predominantly expressed in neurons in many brain areas. We also described expression in neurogenic regions of the adult brain, such as the subventricular zone and the subgranular layer of the dentate gyrus. In addition, we found close co-localization of the G-CSF receptor and its ligand G-CSF. Here we have conducted a systematic expression analysis of G-CSF receptor and its ligand in the developing embryo.

Results

Outside the central nervous system (CNS) we found G-CSF receptor expression in blood vessels, muscles and their respective precursors and neurons. The expression of the G-CSF receptor in the developing CNS was most prominent in radial glia cells.

Conclusion

Our data imply that in addition to the function of G-CSF and its receptor in adult neurogenesis, this system also has a role in embryonic neurogenesis and nervous system development.
Identification and characterization of PhoP regulon members in Yersinia pestis biovar Microtus
Authors: Li Yingli , Gao He , Qin Long , Li Bei , Han Yanping , Guo Zhaobiao , Song Yajun , Zhai Junhui , Du Zongmin , Wang Xiaoyi , Zhou Dongsheng , Yang Ruifu
Published: March 2008

Background

The transcription regulator PhoP has been shown to be important for Y. pestis survival in macrophages and under various in vitro stresses. However, the mechanism by which PhoP promotes bacterial intracellular survival is not fully understood. Our previous microarray analysis suggested that PhoP governed a wide set of cellular pathways in Y. pestis. A series of biochemical experiments were done herein to study members of the PhoP regulon of Y. pestis biovar Microtus.

Results

By using gel mobility shift assay and quantitative RT-PCR, a total of 30 putative transcription units were characterized as direct PhoP targets. The primer extension assay was further used to determine the transcription start sites of 18 PhoP-dependent promoters and to localize the -10 and -35 elements. The DNase I footprinting was used to identify the PhoP-binding sites within 17 PhoP-dependent promoters, enabling the identification of PhoP box and matrix that both represented the conserved signals for PhoP recognition in Y. pestis. Data presented here providing a good basis for modeling PhoP-promoter DNA interactions that is crucial to the PhoP-mediated transcriptional regulation.

Conclusion

The proven direct PhoP targets include nine genes encoding regulators and 21 genes or operons with functions of detoxification, protection against DNA damages, resistance to antimicrobial peptides, and adaptation to magnesium limitation. We can presume that PhoP is a global regulator that controls a complex regulatory cascade by a mechanism of not only directly controlling the expression of specific genes, but also indirectly regulating various cellular pathways by acting on a set of dedicated regulators. These results help us gain insights into the PhoP-dependent mechanisms by which Y. pestis survives the antibacterial strategies employed by host macrophages.
Impaired barrier function by dietary fructo-oligosaccharides (FOS) in rats is accompanied by increased colonic mitochondrial gene expression
Authors: Rodenburg Wendy , Keijer Jaap , Kramer Evelien , Vink Carolien , van der Meer Roelof , Bovee-Oudenhoven Ingeborg MJ
Published: March 2008

Background

Dietary non-digestible carbohydrates stimulate the gut microflora and are therefore presumed to improve host resistance to intestinal infections. However, several strictly controlled rat infection studies showed that non-digestible fructo-oligosaccharides (FOS) increase, rather than decrease, translocation ofSalmonellatowards extra-intestinal sites. In addition, it was shown that FOS increases intestinal permeability already before infection. The mechanism responsible for this adverse effect of FOS is unclear. Possible explanations are altered mucosal integrity due to changes in tight junctions or changes in expression of defense molecules such as antimicrobials and mucins. To examine the mechanisms underlying weakening of the intestinal barrier by FOS, a controlled dietary intervention study was performed. Two groups of 12 rats were adapted to a diet with or without FOS. mRNA was collected from colonic mucosa and changes in gene expression were assessed for each individual rat using Agilent rat whole genome microarrays.

Results

Among the 997 FOS induced genes we observed less mucosal integrity related genes than expected with the clear permeability changes. FOS did not induce changes in tight junction genes and only 8 genes related to mucosal defense were induced by FOS. These small effects are unlikely the cause for the clear increase in intestinal permeability that is observed. FOS significantly increased expression of 177 mitochondria-related genes. More specifically, induced expression of genes involved in all five OXPHOS complexes and the TCA cycle was observed. These results indicate that dietary FOS influences intestinal mucosal energy metabolism. Furthermore, increased expression of 113 genes related to protein turnover, including proteasome genes, ribosomal genes and protein maturation related genes, was seen. FOS upregulated expression of the peptide hormone proglucagon gene, in agreement with previous studies, as well as three other peptide hormone genes; peptide YY, pancreatic polypeptide and cholecystokinin.

Conclusion

We conclude that altered energy metabolism may underly colonic barrier function disruption due to FOS feeding in rats.
Predicted transcription factor binding sites as predictors of operons in Escherichia coli and Streptomyces coelicolor
Authors: Laing Emma , Sidhu Khushwant , Hubbard Simon J
Published: March 2008

Background

As a polycistronic transcriptional unit of one or more adjacent genes, operons play a key role in regulation and function in prokaryotic biology, and a better understanding of how they are constituted and controlled is needed. Recent efforts have attempted to predict operonic status in sequenced genomes using a variety of techniques and data sources. To date, non-homology based operon prediction strategies have mainly used predicted promoters and terminators present at the extremities of transcriptional unit as predictors, with reasonable success. However, transcription factor binding sites (TFBSs), typically found upstream of the first gene in an operon, have not yet been evaluated.

Results

Here we apply a method originally developed for the prediction of TFBSs in Escherichia coli that minimises the need for prior knowledge and tests its ability to predict operons in E. coli and the 'more complex', pharmaceutically important, Streptomyces coelicolor. We demonstrate that through building genome specific TFBS position-specific-weight-matrices (PSWMs) it is possible to predict operons in E. coli and S. coelicolor with 83% and 93% accuracy respectively, using only TFBS as delimiters of operons. Additionally, the 'palindromicity' of TFBS footprint data of E. coli is characterised.

Conclusion

TFBS are proposed as novel independent features for use in prokaryotic operon prediction (whether alone or as part of a set of features) given their efficacy as operon predictors in E. coli and S. coelicolor. We also show that TFBS footprint data in E. coli generally contains inverted repeats with significantly (p < 0.05) greater palindromicity than random sequences. Consequently, the palindromicity of putative TFBSs predicted can also enhance operon predictions.
Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population
Authors: Yamaguchi Yuka , Moritani Maki , Tanahashi Toshihito , Osabe Dai , Nomura Kyoko , Fujita Yuka , Keshavarz Parvaneh , Kunika Kiyoshi , Nakamura Naoto , Yoshikawa Toshikazu , Ichiishi Eiichiro , Shiota Hiroshi , Yasui Natsuo , Inoue Hiroshi , Itakura Mitsuo
Published: March 2008

Background

Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between D15S118 and D15S117 in a Japanese population using a region-wide case-control association test.

Methods

A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed.

Results

SNP2140 (rs2412747) (C/T) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal p value (p = 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07–1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing.

Conclusion

The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations.
Angiogenic, hyperpermeability and vasodilator network in utero-placental units along pregnancy in the guinea-pig (Cavia porcellus)
Authors: Valdés Gloria , Erices Rafaela , Chacón Cecilia , Corthorn Jenny
Published: March 2008

Background

The angiogenic and invasive properties of the cytotrophoblast are crucial to provide an adequate area for feto-maternal exchange. The present study aimed at identifying the localization of interrelated angiogenic, hyperpermeability and vasodilator factors in the feto-maternal interface in pregnant guinea-pigs.

Methods

Utero-placental units were collected from early to term pregnancy. VEGF, Flt-1, KDR, B2R and eNOS were analyzed by immunohistochemistry, and the intensity of the signals in placenta and syncytial streamers was digitally analysed. Flt1 and eNOS content of placental homogenates was determined by western blotting. Statistical analysis used one-way analysis of variance and Tukey's Multiple Comparison post-hoc test.

Results

In the subplacenta, placental interlobium and labyrinth VEGF, Flt-1, KDR, B2R and eNOS were expressed in all stages of pregnancy. Syncytial streamers in all stages of gestation, and cytotrophoblasts surrounding myometrial arteries in early and mid pregnancy – and replacing the smooth muscle at term – displayed immunoreactivity for VEGF, Flt-1, KDR, eNOS and B2R. In partly disrupted mesometrial arteries in late pregnancy cytotrophoblasts and endothelial cells expressed VEGF, Flt-1, KDR, B2R and eNOS. Sections incubated in absence of the first antibody, or in presence of rabbit IgG fraction and mouse IgG serum, yielded no staining. According to the digital analysis, Flt-1 increased in the placental interlobium in days 40 and 60 as compared to day 20 (P = 0.016), and in the labyrinth in day 60 as compared to days 20 and 40 (P = 0.026), while the signals for VEGF, KDR, B2R, and eNOS showed no variations along pregnancy. In syncytial streamers the intensity of VEGF immunoreactivity was increased in day 40 in comparison to day 20 (P = 0.027), while that of B2R decreased in days 40 and 60 as compared to day 20 (P = 0.011); VEGF, Flt-1, KDR, B2R and eNOS expression showed no variations. Western blots for eNOS and Flt-1 in placental homogenates showed no significant temporal differences along pregnancy.

Conclusion

The demonstration of different angiogenic, hyperpermeability and vasodilator factors in the same cellular protagonists of angiogenesis and invasion in the pregnant guinea-pig, supports the presence of a functional network, and strengthens the argument that this species provides an adequate model to understand human pregnancy.
S4HARA: System for HIV/AIDS resource allocation
Authors: Lasry Arielle , Carter Michael W , Zaric Gregory S
Published: March 2008

Background

HIV/AIDS resource allocation decisions are influenced by political, social, ethical and other factors that are difficult to quantify. Consequently, quantitative models of HIV/AIDS resource allocation have had limited impact on actual spending decisions. We propose a decision-support System for HIV/AIDS Resource Allocation (S4HARA) that takes into consideration both principles of efficient resource allocation and the role of non-quantifiable influences on the decision-making process for resource allocation.

Methods

S4HARA is a four-step spreadsheet-based model. The first step serves to identify the factors currently influencing HIV/AIDS allocation decisions. The second step consists of prioritizing HIV/AIDS interventions. The third step involves allocating the budget to the HIV/AIDS interventions using a rational approach. Decision-makers can select from several rational models of resource allocation depending on availability of data and level of complexity. The last step combines the results of the first and third steps to highlight the influencing factors that act as barriers or facilitators to the results suggested by the rational resource allocation approach. Actionable recommendations are then made to improve the allocation. We illustrate S4HARA in the context of a primary healthcare clinic in South Africa.

Results

The clinic offers six types of HIV/AIDS interventions and spends US$750,000 annually on these programs. Current allocation decisions are influenced by donors, NGOs and the government as well as by ethical and religious factors. Without additional funding, an optimal allocation of the total budget suggests that the portion allotted to condom distribution be increased from 1% to 15% and the portion allotted to prevention and treatment of opportunistic infections be increased from 43% to 71%, while allocation to other interventions should decrease.

Conclusion

Condom uptake at the clinic should be increased by changing the condom distribution policy from a pull system to a push system. NGOs and donors promoting antiretroviral programs at the clinic should be sensitized to the results of the model and urged to invest in wellness programs aimed at the prevention and treatment of opportunistic infections. S4HARA differentiates itself from other decision support tools by providing rational HIV/AIDS resource allocation capabilities as well as consideration of the realities facing authorities in their decision-making process.
Porphyromonas gingivalisinduces CCR5-dependent transfer of infectious HIV-1 from oral keratinocytes to permissive cells
Authors: Giacaman Rodrigo A , Asrani Anil C , Gebhard Kristin H , Dietrich Elizabeth A , Vacharaksa Anjalee , Ross Karen F , Herzberg Mark C
Published: March 2008

Background

Systemic infection with HIV occurs infrequently through the oral route. The frequency of occurrence may be increased by concomitant bacterial infection of the oral tissues, since co-infection and inflammation of some cell types increases HIV-1 replication. A putative periodontal pathogen,Porphyromonas gingivalisselectively up-regulates expression of the HIV-1 coreceptor CCR5 on oral keratinocytes. We, therefore, hypothesized thatP. gingivalismodulates the outcome of HIV infection in oral epithelial cells.

Results

Oral and tonsil epithelial cells were pre-incubated withP. gingivalis, and inoculated with either an X4- or R5-type HIV-1. Between 6 and 48 hours post-inoculation,P. gingivalisselectively increased the infectivity of R5-tropic HIV-1 from oral and tonsil keratinocytes; infectivity of X4-tropic HIV-1 remained unchanged. Oral keratinocytes appeared to harbor infectious HIV-1, with no evidence of productive infection. HIV-1 was harbored at highest levels during the first 6 hours after HIV exposure and decreased to barely detectable levels at 48 hours. HIV did not appear to co-localize withP. gingivalis, which increased selective R5-tropic HIV-1transinfection from keratinocytes to permissive cells. When CCR5 was selectively blocked, HIV-1transinfection was reduced.

Conclusion

P. gingivalisup-regulation of CCR5 increasestransinfection of harbored R5-tropic HIV-1 from oral keratinocytes to permissive cells. Oral infections such as periodontitis may, therefore, increase risk for oral infection and dissemination of R5-tropic HIV-1.
A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study
Authors: Frestedt Joy L , Zenk John L , Kuskowski Michael A , Ward Loren S , Bastian Eric D
Published: March 2008

Background

This study evaluated a specialized whey fraction (Prolibra™, high in leucine, bioactive peptides and milk calcium) for use as a dietary supplement to enhance weight loss.

Methods

This was a randomized, double-blind, parallel-arm, 12-week study. Caloric intake was reduced 500 calories per day. Subjects consumed Prolibra or an isocaloric ready-to-mix beverage 20 minutes before breakfast and 20 minutes before dinner. Body fat and lean muscle tissue were measured by dual-energy x-ray absorptiometry (DEXA). Body weight and anthropometric measurements were recorded every 4 weeks. Blood samples were taken at the beginning and end of the study. Statistical analyses were performed on all subjects that completed (completer analysis) and all subjects that lost at least 2.25 kg of body weight (responder analysis). Within group significance was determined at P < 0.05 using a two-tailed paired t-test and between group significance was determined using one way analysis of covariance with baseline data as a covariate.

Results

Both groups lost a significant amount of weight and the Prolibra group tended to lose more weight than the control group; however the amount of weight loss was not significantly different between groups after 12 weeks. Prolibra subjects lost significantly more body fat compared to control subjects for both the completer (2.81 vs. 1.62 kg P = 0.03) and responder (3.63 vs. 2.11 kg, P = 0.01) groups. Prolibra subjects lost significantly less lean muscle mass in the responder group (1.07 vs. 2.41 kg, P = 0.02). The ratio of fat to lean loss (kg fat lost/kg lean lost) was much larger for Prolibra subjects for both completer (3.75 vs. 1.05) and responder (3.39 vs. 0.88) groups.

Conclusion

Subjects in both the control and treatment group lost a significant amount of weight with a 500 calorie reduced diet. Subjects taking Prolibra lost significantly more body fat and showed a greater preservation of lean muscle compared to subjects consuming the control beverage. Because subjects taking Prolibra lost 6.1% of their body fat mass, and because a 5% reduction of body fat mass has been shown to reduce the risk of obesity related disease, the results have practical significance.
Atypically distributed cutaneous lesions of Norwegian scabies in an HIV-positive man in South India: a case report
Authors: Vignesh Ramachandran , Shankar Esaki Muthu , Devaleenal Bella , Balakrishnan Pachamuthu , Thousen Shieh Mark , Sekar Ramalingam , Solomon Suniti , Kumarasamy Nagalingeswaran
Published: March 2008

Introduction

Immune-compromised subjects, especially those with underlying HIV disease, are prone to be infected with Norwegian scabies, where the cutaneous lesions are classically distributed over the extremities.

Case presentation

We report the case of an HIV-positive 16-year-old man with severe crusted Norwegian scabies initially misdiagnosed as a dermal fungal infection. The patient had extensive, generalized, thick, hyperkeratotic, crusting, yellowish papule lesions distributed on the entire body from his scalp to his toes.

The patient was started with Ivermectin and topical Permethrin, which eventually resulted in complete resolution. Interestingly, despite quarantining efforts, one of the patient's acquaintances and a healthcare worker acquired the symptoms of itching.

Conclusion

This atypical presentation of Norwegian scabies emphasizes the need to include scabies in the differential diagnosis when HIV-infected patients present with crusted, generalized cutaneous lesions.
Utilitarianism without Consequentialism: The Case of John Stuart Mill
Authors: Jacobson Daniel
Published: March 2008

This essay argues, flouting paradox, that Mill was a utilitarian but not a consequentialist. First, it contends that there is logical space for a view that deserves to be called utilitarian despite its rejection of consequentialism; second, that this logical space is, in fact, occupied by John Stuart Mill. The key to understanding Mill's unorthodox utilitarianism and the role it plays in his moral philosophy is to appreciate his sentimentalist metaethics—especially his account of wrongness in terms of fitting guilt and resentment. Mill recognizes a fundamental moral asymmetry between the agent and others, which conflicts intractably with a presupposition of consequentialism. This allows him to differentiate three potentially conflicting evaluative spheres: morality, prudence, and aesthetics. This essay's account of Mill's utilitarianism coheres with his defense of individual liberty and his embrace of supererogation, both of which elude traditional interpretations.
Rethinking Working-Class Literature: Feminism, Globalization, and Socialist Ethics
Authors: Perera Sonali
Published: March 2008

According to a corpus of representative texts and standard minimal Marxist definitions, the “proletariat” of proletarian literature is, by definition, revolutionary, and by implication, male; this is the specific subset of the working class entrusted with the historic mission of abolishing the class system. Women's texts of nonrevolutionary socialism from across the global North-South divide, however, confront us with new figures and concepts for thinking unorganized resistance, everyday exigencies, and the shape of the ethical within globalization. This essay studies the conventions and notations of such proletarian internationalist feminist texts from the global South, focusing specifically on the figure of a dispersed collective subject. It brings together contemporary protest literature published by Dabindu--a collective comprised of garment factory worker-activists and feminists from the free trade zone regions of Sri Lanka--with Tillie Olsen's classic field-defining literature from the proletarian moment in the U.S. Can we speak of a collective subject of feminism within economic globalization? Whose interest does staking a claim for such a heterogeneous class subject--one that figures “unity in dispersal”--serve? What are the conditions and constraints for conceptualizing historical agency and class struggle according to these terms, given that we occupy a conjuncture that has been described by some in epochal terms as the “feminization of the proletariat,” by others as the “NGO-ization of feminism”? Toward answering these questions, “Rethinking Working-Class Literature” turns to the methodological resources of Marxism and comparative literature. This essay ultimately seeks to articulate the terms of a feminist class politics in the shadow of economisms like “comparative advantage” and “outsourcing.”
Turn the Beat Around: Sadomasochism, Temporality, History
Authors: Freeman Elizabeth
Published: March 2008

Through a close analysis of Isaac Julien's short film The Attendant, this essay argues that sadomasochistic sex practice ought to be understood in temporal terms, as a play of pause against surprise, suspension against shock. In The Attendant, Freeman contends, Julien rethinks S/M precisely this way, thereby linking it with the possibilities of film as a particularly indexical, intercorporeal medium for shocking and reorganizing the senses. This rethinking of screen as a kind of skin in turn enables Julien to confront sadomasochistic role playing, in which players take up the signs and tools of historically specific injustices such as the Inquisition, the Holocaust, and especially the transatlantic slave trade. Rather than condemning this kind of role playing--especially as it takes place between black and white men--Julien offers sadomasochism as an embodied way to feel historical or to engage viscerally with the past. He thereby opens up new registers for taking in and taking account of the historical, registers that refuse to concede pleasure in the name of trauma, which has been treated as the more properly political affect by most criticism.
The in-Tensions of Extensions: Compagnie Marie Chouinard'sbODY Remix gOLDBERG vARIATIONS
Authors: Thain Alanna
Published: March 2008

This essay explores the affective intensity of movement in a recent choreography by noted French Canadian choreographer Marie Chouinard. In bODY rEMIX/ gOLDBERG vARIATIONS, dancers perform with all manners of prosthetics and bodily extensions--crutches, ski poles, coat racks, pointe shoes worn by men and women, on one or two feet or on hands--to a score that remixes Glenn Gould's recordings of the Goldberg Variations with his recorded interviews. Drawing on Gilles Deleuze, José Gil, and André Lepecki, I argue that despite its engagement with forms of extension, the use of prosthetics in Chouinard's bODY rEMIX fundamentally explores the intensive movement of affect, particularly through its engagement with suspense (as the generation of an ambiguous image in the tension between extensive and intensive movement) and the sound image. This exploration of the in-tensions of extensions, when, rather than simply extending into the world, movement develops a centrifugal force, likewise argues that the movement of affective intensity is the way in which the body activates its inherent capacity for change. Extension is a fundamental attitude of the dancing body; dancing “projects lines into the invisible” in a movement of outward intentionality. Yet that movement is always doubled and deviated by a responsive (not simply reactive) intensity of movement, a dynamic activation of the body's potential charged by the encounter that pushes against and reworks the constitution of the very bodies that compose it, a movement of a different quality whose effects cannot simply be determined by a reverse calculation from extension.
Descartes, Individualism, and the Fetal Subject
Authors: Wilkin Rebecca
Published: March 2008

The fetus was able to think and was conscious of doing so, Descartes claimed in his Response to Antoine Arnauld's Objection to the Meditationes de prima philosophia (1641). This essay traces the fortunes of the cogitating fetus in Descartes's published works and correspondence, showing that he eventually came to use the example of the fetus to exemplify what he meant by the “union” of mind and body. Although Descartes is usually considered a dualist, particularly in feminist criticism, he took for granted that we experience ourselves as mind/body composites. The fetus presented an extreme version of the experiences devolving from mind/body union. Far from suggesting that fetuses, like born human beings, were individuals (as they are portrayed in pro-life rhetoric), Descartes invited his readers to consider that born human beings, like fetuses, comprised embodied minds, connected to and in varying degrees dependent on other people. This investigation of the “fetal subject” in Cartesian metaphysics reveals a relational side to the Cartesian “cogito,” a surprising revelation insofar as Descartes often takes the blame (or credit--depending on one's adherence to liberal ideals) for providing the foundations of an individualistic conception of personhood.
Requirement for Foxd3 in the maintenance of neural crest progenitors
Authors: Teng Lu , Mundell Nathan A. , Frist Audrey Y. , Wang Qiaohong , Labosky Patricia A.
Published: March 2008

Understanding the molecular mechanisms of stem cell maintenance is crucial for the ultimate goal of manipulating stem cells for the treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3-/-embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue-specific deletion of Foxd3 in the neural crest, we show that Foxd3flox/-; Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo.
Live imaging of theDictyosteliumcell cycle reveals widespread S phase during development, a G2 bias in spore differentiation and a premitotic checkpoint
Authors: Muramoto Tetsuya , Chubb Jonathan R.
Published: March 2008

The regulation of the Dictyostelium cell cycle has remained ambiguous owing to difficulties in long-term imaging of motile cells and a lack of markers for defining cell cycle phases. There is controversy over whether cells replicate their DNA during development, and whether spores are in G1 or G2 of the cell cycle. We have introduced a live-cell S-phase marker into Dictyostelium cells that allows us to precisely define cycle phase. We show that during multicellular development, a large proportion of cells undergo nuclear DNA synthesis. Germinating spores enter S phase only after their first mitosis, indicating that spores are in G2. In addition, we demonstrate that Dictyostelium heterochromatin is copied late in S phase and replicates via accumulation of replication factors, rather than recruitment of DNA to pre-existing factories. Analysis of variability in cycle times indicates that regulation of the cycle manifests at a single random transition in G2, and we present the first identified checkpoint in Dictyostelium, which operates at the G2-M transition in response to DNA damage.
Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation
Authors: Emmons Jillian , Townley-Tilson W.H. Davin , Deleault Kristen M. , Skinner Stephen J. , Gross Robert H. , Whitfield Michael L. , Brooks Seth A.
Published: March 2008

Dendritic cells provide a critical link between innate and adaptive immunity and are essential to prime a naive T-cell response. The transition from immature dendritic cells to mature dendritic cells involves numerous changes in gene expression; however, the role of post-transcriptional changes in this process has been largely ignored. Tristetraprolin is an AU-rich element mRNA-binding protein that has been shown to regulate the stability of a number of cytokines and chemokines of mRNAs. Using TTP immunoprecipitations and Affymetrix GeneChips, we identified 393 messages as putative TTP mRNA targets in human dendritic cells. Gene ontology analysis revealed that ∼25% of the identified mRNAs are associated with protein synthesis. We also identified six MHC Class I alleles, five MHC Class II alleles, seven chemokine and chemokine receptor genes, indoleamine 2,3 dioxygenase, and CD86 as putative TTP ligands. Real-time PCR was used to validate the GeneChip data for 15 putative target genes and functional studies performed for six target genes. These data establish that TTP regulates the expression of DUSP1, IDO, SOD2, CD86, and MHC Class I-B and F via the 3′-untranslated region of each gene. A novel finding is the demonstration that TTP can interact with and regulate the expression of non-AU-rich element-containing messages. The data implicate TTP as having a broader role in regulating and limiting the immune response than previously suspected.
Cap-dependent eukaryotic initiation factor-mRNA interactions probed by cross-linking
Authors: Lindqvist Lisa , Imataka Hiroaki , Pelletier Jerry
Published: March 2008

Cap-dependent ribosome recruitment to eukaryotic mRNAs during translation initiation is stimulated by the eukaryotic initiation factor (eIF) 4F complex and eIF4B. eIF4F is a heterotrimeric complex composed of three subunits: eIF4E, a 7-methyl guanosine cap binding protein; eIF4A, a DEAD-box RNA helicase; and eIF4G. The interactions of eIF4E, eIF4A, and eIF4B with mRNA have previously been monitored by chemical- and UV-based cross-linking approaches aimed at characterizing the initial protein/mRNA interactions that lead to ribosome recruitment. These studies have led to a model whereby eIF4E interacts with the 7-methyl guanosine cap structure in an ATP-independent manner, followed by an ATP-dependent interaction of eIF4A and eIF4B. Herein, we apply a splint-ligation-mediated approach to generate 4-thiouridine-containing mRNA adjacent to a radiolabel group that we utilize to monitor cap-dependent cross-linking of proteins adjacent to, and downstream from, the cap structure. Using this approach, we demonstrate interactions between eIF4G, eIF4H, and eIF3 subunits with the mRNA during the cap recognition process.
miR-148 targets human DNMT3b protein coding region
Authors: Duursma Anja M. , Kedde Martijn , Schrier Mariette , le Sage Carlos , Agami Reuven
Published: March 2008

MicroRNAs (miRNAs) are small noncoding RNA molecules of 20–24 nucleotides that regulate gene expression. In animals, miRNAs form imperfect interactions with sequences in the 3′ Untranslated region (3′UTR) of mRNAs, causing translational inhibition and mRNA decay. In contrast, plant miRNAs mostly associate with protein coding regions. Here we show that human miR-148 represses DNA methyltransferase 3b (Dnmt3b) gene expression through a region in its coding sequence. This region is evolutionary conserved and present in the Dnmt3b splice variants Dnmt3b1, Dnmt3b2, and Dnmt3b4, but not in the abundantly expressed Dnmt3b3. Whereas overexpression of miR-148 results in decreased DNMT3b1 expression, short-hairpin RNA-mediated miR-148 repression leads to an increase in DNMT3b1 expression. Interestingly, mutating the putative miR-148 target site in Dnmt3b1 abolishes regulation by miR-148. Moreover, endogenous Dnmt3b3 mRNA, which lacks the putative miR-148 target site, is resistant to miR-148-mediated regulation. Thus, our results demonstrate that the coding sequence of Dnmt3b mediates regulation by the miR-148 family. More generally, we provide evidence that coding regions of human genes can be targeted by miRNAs, and that such a mechanism might play a role in determining the relative abundance of different splice variants.
Development of Reusable Bid Evaluation Models for the Portuguese Electric Transmission Company
Authors: Bana e Costa Carlos A. , Lourenço João C. , Chagas Manuel P. , Bana e Costa João C.
Published: March 2008

Bid evaluation is the process of selecting a contractor from a number of bidders. The decision analysis models currently in use at the Portuguese Electric Transmission Company (REN) to evaluate bids were developed through a decision-conferencing process supported by the MACBETH multicriteria approach and software. This paper presents the various components of this interactive sociotechnical process. Given the number of contracts awarded by REN each year, it was crucial that the models be reusable in similar calls for tenders; this required substantial care in structuring the criteria, with a focus on constructed scales, and building value function models based on qualitative pairwise comparison judgments of difference in attractiveness. Also of particular interest is the approach for weighing benefits against costs.
Interpretation of the Risk Tolerance Coefficient in Terms of Maximum Acceptable Loss
Authors: Delquié Philippe
Published: March 2008

Users (or would-be users) of exponential expected utility often seek a concrete, intuitive meaning for the risk tolerance coefficient (RT) that they can grasp and explain to others easily. This paper shows an interpretation of RT as the maximum loss the decision maker is willing to be exposed to at a stated probability level, regardless of the upside potential. As an example, if you are facing a portfolio of projects having a 1 in 20 chance of total loss and you indicate that L is the maximum loss you would tolerate, then your risk tolerance is L/3. Other such examples, which may be better suited to other situations, are presented. In some contexts, this interpretation may be congruent with the way individuals naturally think about their risk-taking propensity, for example, as willingness to be exposed to losses or as in value-at-risk. This interpretation can also be helpful in determining whether assuming exponential utility is adequate for the situation being analyzed, and in eliciting the value of RT. The merits of this approach for thinking about RT are discussed.
Decision-Analytic Approach to Knockout Auctions
Authors: Gerchak Yigal
Published: March 2008

Society seems to have developed several ingenious schemes for allocating jointly owned indivisible items. One such scheme, occasionally used to divide estates among heirs, is a knockout auction (Engelbrecht-Wiggans 1994). In a knockout auction, the joint owners bid for the item; the highest bidder obtains it and pays the others their share of the winning bid. This paper follows the advice of Raiffa and Rothkopf to view auctions from a decision-analytic point of view, and analyzes the optimal bid of an expected-utility maximizing participant in a knockout auction who is uncertain about the bids of others, and contrasts it to the properties of optimal declarations in buy-sell agreements, derived in Gerchak and Fuller (1992).
Getting the Right Mix of Experts
Authors: Merrick Jason R. W.
Published: March 2008

The Bayesian approach to combining expert opinions is well developed, providing a decision maker's posterior beliefs after receiving advice from people with deep knowledge in a given subject. A necessary part of these models is the inclusion of dependencies between the experts' judgments, often justified by an overlap in the information on which the experts base their judgments. In this paper, we propose a hierarchical structure different than those previously proposed, where the mixing distribution is treated nonparametrically with a Dirichlet process. This makes our overall model a Dirichlet process mixture and allows for experts' model parameters to be equal in the mixture. We apply this approach to published expert judgment data, demonstrating that the decision maker's posterior distributions on the quantities of interest are not restricted to specific parametric forms, even allowing for multiple modes, and are thus more intuitively appealing.
From the Editor…
Authors: Keller L. Robin
Published: March 2008

This issue of Decision Analysis begins with an article by Philippe Delquié, “Interpretation of the Risk Tolerance Coefficient in Terms of Maximum Acceptable Loss.” The risk tolerance coefficient is an exponential utility function's parameter, which is positive for risk averse decision makers. Next is an article titled “Optimal Betting Strategies for Simultaneous Games,” by Andrew Grant, David Johnstone, and Oh Kang Kwon, which examines how to bet on two or more games (such as sports events or political outcomes) at once. Our third paper, “Decision-Analytic Approach to Knockout Auctions,” by Yigal Gerchak, examines an approach for bidding on a single jointly owned indivisible item (such as a cherished item in an estate with multiple heirs). Our fourth paper develops a method for evaluating bids. Carlos A. Bana e Costa, João C. Lourenço, Manuel P. Chagas, and João C. Bana e Costa use a multiple objective value function approach in their article “Development of Reusable Bid Evaluation Models for the Portuguese Electric Transmission Company.” We end with an article by Jason R. W. Merrick which presents an approach for “Getting the Right Mix of Experts” when they give possibly correlated probability judgments.
The Color of Discipline: Civil Rights and Black Sexuality
Authors: Russell Thaddeus
Published: March 2008

In the discourse of the civil rights movement, "full citizenship" was constructed upon heterosexuality and in opposition to non-heteronormative behaviors. Prior to the ascendancy of the movement in the 1950s, African-American working-class culture was far more open to homosexuality and non-heteronormative behavior than was the black middle class, which led the movement, or than white culture generally. This black working-class openness was one indication of a broader evasion of the repression required of "good Americans," as black homosexuals came to represent all the elements of African-American working-class culture that civil rights leaders identified as obstacles to the attainment of citizenship. At the height of the movement for integration, black queerness was replaced in public discourse and popular culture by black heteronormativity.
Gas Masks, Pogo, and the Ecological Indian: Earth Day and the Visual Politics of American Environmentalism
Authors: Dunaway Finis
Published: March 2008

This essay offers a new way of understanding a pivotal moment in the history of U.S. environmentalism: the time surrounding the first celebration of Earth Day in 1970. By exploring a wide array of visual images produced during this period and paying particular attention to pictures of people wearing gas masks, the comic strip character Pogo, and the figure of the Ecological Indian, the article examines the complex relationship between the mass media and multiple forms of environmentalism. These images personalized the sense of risk and responsibility by presenting all Americans as equally vulnerable to pollution and equally to blame for environmental degradation. When placed in dialogue with both mainstream and subaltern environmental movements as well as with public policy, the images reveal a paradox embedded in the environmental politics of the era: the state expanded its environmental regulatory agenda, even as the visual media repeatedly emphasized individual responsibility for the environmental crisis. This essay explains how these seemingly opposing trends actually reinforced one another and how they bequeathed a problematic legacy to U.S. environmentalism. Ultimately, the media, mainstream environmental groups, and public policy all failed to consider the links between social inequality and the disproportionate experience of risk among racialized minorities. Across these different fields, subaltern perspectives were submerged, drowned out by the repeated insistence upon universal danger and culpability. Earth Day, often described as a moment of origins for modern environmentalism, thus helped frame and validate a particular conception of the movement as a cause that promised to unite the nation but that lacked a social edge.