bluuebunny/crossref_metadata_2025 huggingface dataset:
Complementary RNA amplification methods enhance microarray identification of transcripts expressed in the C. elegans nervous system
Authors: Watson Joseph D , Wang Shenglong , Von Stetina Stephen E , Spencer W Clay , Levy Shawn , Dexheimer Phillip J , Kurn Nurith , Heath Joe Don , Miller David M
Published: February 2008

Background

DNA microarrays provide a powerful method for global analysis of gene expression. The application of this technology to specific cell types and tissues, however, is typically limited by small amounts of available mRNA, thereby necessitating amplification. Here we compare microarray results obtained with two different methods of RNA amplification to profile gene expression in the C. elegans larval nervous system.

Results

We used the mRNA-tagging strategy to isolate transcripts specifically from C. elegans larval neurons. The WT-Ovation Pico System (WT-Pico) was used to amplify 2 ng of pan-neural RNA to produce labeled cDNA for microarray analysis. These WT-Pico-derived data were compared to microarray results obtained with a labeled aRNA target generated by two rounds of In Vitro Transcription (IVT) of 25 ng of pan-neural RNA. WT-Pico results in a higher fraction of present calls than IVT, a finding consistent with the proposal that DNA-DNA hybridization results in lower mismatch signals than the RNA-DNA heteroduplexes produced by IVT amplification. Microarray data sets from these samples were compared to a reference profile of all larval cells to identify transcripts with elevated expression in neurons. These results were validated by the high proportion of known neuron-expressed genes detected in these profiles and by promoter-GFP constructs for previously uncharacterized genes in these data sets. Together, the IVT and WT-Pico methods identified 2,173 unique neuron-enriched transcripts. Only about half of these transcripts (1,044), however, are detected as enriched by both IVT and WT-Pico amplification.

Conclusion

We show that two different methods of RNA amplification, IVT and WT-Pico, produce valid microarray profiles of gene expression in the C. elegans larval nervous system with a low rate of false positives. However, our results also show that each method of RNA amplification detects a unique subset of bona fide neural-enriched transcripts and thus a wider array of authentic neural genes are identified by the combination of these data sets than by the microarray profiles obtained with either method of RNA amplification alone. With its relative ease of implementation and greater sensitivity, WT-Pico is the preferred method of amplification for cases in which sample RNA is limiting.
Characterization and partial purification of Candida albicans Secretory IL-12 Inhibitory Factor
Authors: Wang Mingyue , Mukherjee Pranab K , Chandra Jyotsna , Lattif Ali Abdul , McCormick Thomas S , Ghannoum Mahmoud A
Published: February 2008

Background

We have previously shown that supernatant fromCandida albicans(CA) culture contains a Secretory Interleukin (IL)-12 Inhibitory Factor (CA-SIIF), which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not been performed.

Results

In this study, we demonstrate that the IL-12 inhibitory activity of CA-SIIF was serum-independent, based on the reduction of IL-12 levels in monocytes stimulated under serum-independent conditions. The minimal inhibitory dose of CA-SIIF was found to be 200 μg/ml. Investigation of CA-SIIF's effect on macrophages IL-12 productionin vitroandin vivoalso showed that CA-SIIF inhibited IL-12 production by murine macrophages bothin vitro(from 571 ± 24 pg/ml to 387 ± 87 pg/ml; P = 0.05) andin vivo(from 262 ± 6 pg/ml to 144 ± 30 pg/ml;P< 0.05). In addition to IL-12, cytokine array analysis revealed that CA-SIIF induced differential production of other cytokines also. In this regard, reduction in levels were observed for IL-8, IL-10, IL-13, monocyte chemoattractant protein (MCP)-1, MCP-2, macrophage inflammatory protein (MIP)-1, RANTES, etc. In contrast, levels of other chemokines e.g. MCP-4, MIF and MIP-3α (P< 0.05) were increased. We also found that CA-SIIF suppressed the maturation of human monocytes to dendritic cells (CD1a expression = 13 ± 3% vs 36 ± 2% of the control;P< 0.01). Next, to identify the biochemical nature of CA-SIIF, we separated this factor into a Concanavalin A (ConA)-binding glycoprotein fraction (CA-SIIF-GP) and a non-ConA-binding protein fraction (CA-SIIF-NGP) using ConA affinity chromatography. Both fractions were then tested for this inhibitory effect on human monocyte IL-12 production. CA-SIIF-GP produced a higher inhibitory effect on IL-12 production compared to CA-SIIF-NGP and CA-SIIF crude (P< 0.01), proving that CA-SIIF is a glycoprotein in nature.

Conclusion

CA-SIIF is a glycoprotein which exhibits serum-independent inhibition of IL-12 production from monocytesin vitroandin vivo, and also modulates differentiation of monocytes into dendritic cells. These results suggest important role for CA-SIIF in interactions ofC. albicanswith the host immune system.
Development of a novel system for isolating genes involved in predator-prey interactions using host independent derivatives of Bdellovibrio bacteriovorus 109J
Authors: Medina Adrian A , Shanks Robert M , Kadouri Daniel E
Published: February 2008

Background

Bdellovibrio bacteriovorus is a gram-negative bacterium that preys upon other gram-negative bacteria. Although the life cycle of Bdellovibrio has been extensively investigated, very little is known about the mechanisms involved in predation.

Results

Host-Independent (HI) mutants of B. bacteriovorus were isolated from wild-type strain 109J. Predation assays confirmed that the selected HI mutants retained their ability to prey on host cells grown planktonically and in a biofilm. A mariner transposon library of B. bacteriovorus HI was constructed and HI mutants that were impaired in their ability to attack biofilms were isolated. Transposon insertion sites were determined using arbitrary polymerase chain reaction. Ten HI transposon mutants mapped to genes predicted to be involved in mechanisms previously implicated in predation (flagella, pili and chemotaxis) were further examined for their ability to reduce biofilms.

Conclusion

In this study we describe a new method for isolating genes that are required for Bdellovibrio biofilm predation. Focusing on mechanisms that were previously attributed to be involved in predation, we demonstrate that motility systems are required for predation of bacterial biofilms. Furthermore, genes identified in this study suggest that surface gliding motility may also play a role in predation of biofilms consistent with Bdellovibrios occupying a biofilm niche. We believe that the methodology presented here will open the way for future studies on the mechanisms involved in Bdellovibrio host-prey interaction and a greater insight of the biology of this unique organism.
Inter- and intraobserver reliability of the MTM-classification for proximal humeral fractures: A prospective study
Authors: Bahrs Christian , Schmal Hagen , Lingenfelter Erich , Rolauffs Bernd , Weise Kuno , Dietz Klaus , Helwig Peter
Published: February 2008

Background

A precise modular topographic-morphological (MTM) classification for proximal humeral fractures may address current classification problems. The classification was developed to evaluate whether a very detailed classification exceeding the analysis of fractured parts may be a valuable tool.

Methods

Three observers classified plain radiographs of 22 fractures using both a simple version (fracture displacement, number of parts) and an extensive version (individual topographic fracture type and morphology) of the MTM classification. Kappa-statistics were used to determine reliability.

Results

An acceptable reliability was found for the simple version classifying fracture displacement and fractured main parts. Fair interobserver agreement was found for the extensive version with individual topographic fracture type and morphology.

Conclusion

Although the MTM-classification covers a wide spectrum of fracture types, our results indicate that the precise topographic and morphological description is not delivering reproducible results. Therefore, simplicity in fracture classification may be more useful than extensive approaches, which are not adequately reliable to address current classification problems.
Solubility enhancement of aggregation-prone heterologous proteins by fusion expression using stress-responsive Escherichia coliprotein, RpoS
Authors: Park Jin-Seung , Han Kyung-Yeon , Lee Jong-Ho , Song Jong-Am , Ahn Keum-Young , Seo Hyuk-Seong , Sim Sang-Jun , Kim Seung-Wook , Lee Jeewon
Published: February 2008

Background

The most efficient method for enhancing solubility of recombinant proteins appears to use the fusion expression partners. Although commercial fusion partners including maltose binding protein and glutathione-S-transferase have shown good performance in enhancing the solubility, they cannot be used for the proprietory production of commercially value-added proteins and likely cannot serve as universal helpers to solve all protein solubility and folding issues. Thus, novel fusion partners will continue to be developed through systematic investigations including proteome mining presented in this study.

Results

We analyzed theEscherichia coliproteome response to the exogenous stress of guanidine hydrochloride using 2-dimensional gel electrophoresis and found that RpoS (RNA polymerase sigma factor) was significantly stress responsive. While under the stress condition the total number of soluble proteins decreased by about 7 %, but a 6-fold increase in the level of RpoS was observed, indicating that RpoS is a stress-induced protein. As an N-terminus fusion expression partner, RpoS increased significantly the solubility of many aggregation-prone heterologous proteins inE. colicytoplasm, indicating that RpoS is a very effective solubility enhancer for the synthesis of many recombinant proteins. RpoS was also well suited for the production of a biologically active fusion mutant ofPseudomonas putidacutinase.

Conclusion

RpoS is highly effective as a strong solubility enhancer for aggregation-prone heterologous proteins when it is used as a fusion expression partner in anE. coliexpression system. The results of these findings may, therefore, be useful in the production of other biologically active industrial enzymes, as successfully demonstrated by cutinase.
Household cost of malaria overdiagnosis in rural Mozambique
Authors: Hume Jen CC , Barnish Guy , Mangal Tara , Armázio Luiz , Streat Elizabeth , Bates Imelda
Published: February 2008

Background

It is estimated that over 70% of patients with suspected malaria in sub-Saharan Africa, diagnose and manage their illness at home without referral to a formal health clinic. Of those patients who do attend a formal health clinic, malaria overdiagnosis rates are estimated to range between 30–70%.

Methods

This paper details an observational cohort study documenting the number and cost of repeat consultations as a result of malaria overdiagnosis at two health care providers in a rural district of Mozambique. 535 adults and children with a clinical diagnosis of malaria were enrolled and followed over a 21 day period to assess treatment regimen, symptoms, number and cost of repeat visits to health providers in patients misdiagnosed with malaria compared to those with confirmed malaria (determined by positive bloodfilm reading).

Results

Diagnosis based solely on clinical symptoms overdiagnosed 23% of children (<16y) and 31% of adults with malaria. Symptoms persisted (p = 0.023) and new ones developed (p < 0.001) in more adults than children in the three weeks following initial presentation. Adults overdiagnosed with malaria had more repeat visits (67% v 46%, p = 0.01–0.06) compared to those with true malaria. There was no difference in costs between patients correctly or incorrectly diagnosed with malaria. Median costs over three weeks were $0.28 for those who had one visit and $0.76 for ≥ 3 visits and were proportionally highest among the poorest (p < 0.001)

Conclusion

Overdiagnosis of malaria results in a greater number of healthcare visits and associated cost for adult patients. Additionally, it is clear that the poorest individuals pay significantly more proportionally for their healthcare making it imperative that the treatment they receive is correct in order to prevent wastage of limited economic resources. Thus, investment in accurate malaria diagnosis and appropriate management at primary level is critical for improving health outcomes and reducing poverty.
Correlation between β-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma
Authors: Austinat Madeleine , Dunsch Ruediger , Wittekind Christian , Tannapfel Andrea , Gebhardt Rolf , Gaunitz Frank
Published: February 2008

Aberrant Wnt-signaling caused by mutants of β-catenin, a key regulator of the canonical Wnt-signaling pathway, is frequently detected in cancer. Only recently, it was suggested that in hepatocellular carcinoma (HCC) the expression of the target gene glutamine synthetase (GS) is a highly reliable marker for the identification of β-catenin mutations. In order to prove this hypothesis, 52 samples from human hepatocellular carcinomas were analysed for the activation of β-catenin and the expression of GS. In total, 45 samples stained positive for cytoplasmic/nuclear β-catenin. A strong correlation between expression of GS and activated β-catenin (100% of nuclear and 84% of cytosolic) was found. However, among 35 GS positive tumors that were analysed for β-catenin mutations no mutations were detected in 25 GS-positive carcinomas although 24 out of the 25 carcinomas exhibited at least abnormal expression of β-catenin. Since the mutational analysis identified 9 different point mutations of the β-catenin gene including the rare mutation H36P and the yet unknown mutation P44A it was asked whether these mutations may differently effect β-catenin target genes. Therefore, expression plasmids for different mutations were constructed and cotransfected with the TOP-flash luciferase reporter and a reporter carrying the GS-5'-enhancer. The experiments confirmed that there are differences between different β-catenin target sequences and different β-catenin mutations. In addition, the failure that the endogenous expression of GS in GS-negative cells was not induced by the transient transfection experiment indicated that the effect of β-catenin on the GS-5'-enhancer is only one aspect of gene activation induced by β-catenin.
Failure to detect the 22q11.2 duplication syndrome rearrangement among patients with schizophrenia
Authors: Brunet Anna , Armengol Lluís , Pelaez Trini , Guillamat Roser , Vallès Vicenç , Gabau Elisabeth , Estivill Xavier , Guitart Miriam
Published: February 2008

Chromosome aberrations have long been studied in an effort to identify susceptibility genes for schizophrenia. Chromosome 22q11.2 microdeletion is associated with DiGeorge and Velocardiofacial syndromes (DG/VCF) and provides the most convincing evidence of an association between molecular cytogenetic abnormality and schizophrenia. In addition, this region is one of the best replicated linkage findings for schizophrenia. Recently, the reciprocal microduplication on 22q11.2 has been reported as a new syndrome. Preliminary data indicates that individuals with these duplications also suffer from neuropsychiatric disorders. In this study we have investigated the appropriateness of testing schizophrenia patients for the 22q11.2 microduplication. We used multiplex ligation-dependent probe amplification (MLPA) to measure copy number changes on the 22q11.2 region in a sample of 190 patients with schizophrenia. Our results corroborate the prevalence of the 22q11.2 microdeletion in patients with schizophrenia and clinical features of DG/VCFS and do not suggest an association between 22q11.2 microduplication and schizophrenia.
Mammary tuberculosis mimicking breast cancer: a case report
Authors: Maroulis Ioannis , Spyropoulos Charalambos , Zolota Vasiliki , Tzorakoleftherakis Evaggelos
Published: February 2008

Introduction

The incidence of tuberculosis is rising worldwide and rare manifestations of the past are seen more often nowadays. Mammary tuberculosis is a rare clinical entity, often mimicking breast cancer or abscesses of benign or malignant origin. Clinical awareness is necessary during diagnostic work-up for establishing the correct diagnosis and treatment.

Case presentation

We present a case of breast tuberculosis diagnosed in a 73 year old woman at our institution. The patient presented with a palpable mass of the right breast with clinical, laboratory and mammographic findings indicative of breast carcinoma. The patient underwent lumpectomy and sentinel lymph node biopsy. Frozen section of the tumor and the sentinel node revealed "granulomatous inflammation", while gross examination confirmed the diagnosis of tuberculous mastitis. The patient received anti-tuberculosis therapy for six months with no side effects or any further complications.

Conclusion

Breast tuberculosis is an obscure disease often mistaken for carcinoma or pyogenic abscess of the breast, especially if well-defined clinical features are absent. A high index of suspicion is required because the disease can usually be treated conservatively with current antituberculous modalities while surgical intervention is reserved for rare cases only.
Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2using five methods: results from a population-based study of young breast cancer patients
Authors: Lee Eunjung , McKean-Cowdin Roberta , Ma Huiyan , Chen Zhengjia , Van Den Berg David , Henderson Brian E , Bernstein Leslie , Ursin Giske
Published: February 2008

Introduction

Efforts are ongoing to determine the significance of unclassified variants (UVs) in the breast cancer susceptibility genes BRCA1/BRCA2, but no study has systematically assessed whether women carrying the suspected deleterious UVs have characteristics commonly seen among women carrying known deleterious or disease-causing mutations in BRCA1/BRCA2.

Methods

We sequenced BRCA1/BRCA2 in 1,469 population-based female breast cancer patients diagnosed between the ages of 20 and 49 years. We used existing literature to classify variants into known deleterious mutations, polymorphic variants, and UVs. The UVs were further classified as high risk or low risk based on five methods: allele frequency, Polyphen algorithm, sequence conservation, Grantham matrix scores, and a combination of the Grantham matrix score and sequence conservation. Furthermore, we examined whether patients who carry the variants classified as high risk using these methods have risk characteristics similar to patients with known deleterious BRCA1/BRCA2 mutations (early age at diagnosis, family history of breast cancer or ovarian cancer, and negative estrogen receptor/progesterone receptor).

Results

We identified 262 distinct BRCA1/BRCA2 variants, including 147 UVs, in our study population. The BRCA1 UV carriers, but not the BRCA2 UV carriers, who were classified as high risk using each classification method were more similar to the deleterious mutation carriers with respect to family history than those carriers classified as low risk. For example, the odds ratio of having a first-degree family history for the high-risk women classified using Polyphen was 3.39 (95% confidence interval = 1.16 to 9.94) compared with normal/polymorphic BRCA1 carriers. The corresponding odds ratio of low-risk women was 1.53 (95% confidence interval = 1.07 to 2.18). The odds ratio for high-risk women defined by allele frequency was 2.00 (95% confidence interval = 1.14 to 3.51), and that of low-risk women was 1.30 (95% confidence interval = 0.87 to 1.93).

Conclusion

The results suggest that the five classification methods yielded similar results. Polyphen was particularly better at isolating BRCA1 UV carriers likely to have a family history of breast cancer or ovarian cancer, and may therefore help to classify BRCA1 UVs. Our study suggests that these methods may not be as successful in classifying BRCA2 UVs.
A comparison of the CAM-ICU and the NEECHAM Confusion Scale in intensive care delirium assessment: an observational study in non-intubated patients
Authors: Van Rompaey Bart , Schuurmans Marieke J , Shortridge-Baggett Lillie M , Truijen Steven , Elseviers Monique , Bossaert Leo
Published: February 2008

Background

Several reports indicate a high incidence of intensive care delirium. To develop strategies to prevent this complication, validated instruments are needed. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is widely used. A binary result diagnoses delirium. The Neelon and Champagne (NEECHAM) Confusion Scale recently has been validated for use in the ICU and has a numeric assessment. This scale allows the patients to be classified in four categories: non-delirious, at risk, confused, and delirious. In this study, we investigated the results of the NEECHAM scale in comparison with the CAM-ICU.

Methods

A consecutive sample of 172 non-intubated patients in a mixed ICU was assessed after a stay in the ICU for at least 24 hours. All adult patients with a Glasgow Coma Scale score of greater than 9 were included. A nurse researcher simultaneously assessed both scales once daily in the morning. A total of 599 paired observations were made.

Results

The CAM-ICU showed a 19.8% incidence of delirium. The NEECHAM scale detected incidence rates of 20.3% for delirious, 24.4% for confused, 29.7% for at risk, and 25.6% for normal patients. The majority of the positive CAM-ICU patients were detected by the NEECHAM scale. The sensitivity of the NEECHAM scale was 87% and the specificity was 95%. The positive predictive value and the negative predictive value were 79% and 97%, respectively. The diagnostic capability in cardiac surgery patients proved to be lower than in other patients.

Conclusion

In non-intubated patients, the NEECHAM scale identified most cases of delirium which were detected by the CAM-ICU. Additional confused patients were identified in the categorical approach of the scale. The NEECHAM scale proved to be a valuable screening tool compared with the CAM-ICU in the early detection of intensive care delirium by nurses.
Abundant and species-specific DINE-1 transposable elements in 12 Drosophila genomes
Authors: Yang Hsiao-Pei , Barbash Daniel A
Published: February 2008

Background

Miniature inverted-repeat transposable elements (MITEs) are non-autonomous DNA-mediated transposable elements (TEs) derived from autonomous TEs. Unlike in many plants or animals, MITEs and other types of DNA-mediated TEs were previously thought to be either rare or absent in Drosophila. Most other TE families in Drosophila exist at low or intermediate copy number (around < 100 per genome).

Results

We present evidence here that the dispersed repeat Drosophila interspersed element 1 (DINE-1; also named INE-1 and DNAREP1) is a highly abundant DNA-mediated TE containing inverted repeats found in all 12 sequenced Drosophila genomes. All DINE-1s share a similar sequence structure, but are more homogeneous within species than they are among species. The inferred phylogenetic relationship of the DINE-1 consensus sequence from each species is generally consistent with the known species phylogeny, suggesting vertical transmission as the major mechanism for DINE-1 propagation. Exceptions observed in D. willistoni and D. ananassae could be due to either horizontal transfer or reactivation of ancestral copies. Our analysis of pairwise percentage identity of DINE-1 copies within species suggests that the transpositional activity of DINE-1 is extremely dynamic, with some lineages showing evidence for recent transpositional bursts and other lineages appearing to have silenced their DINE-1s for long periods of time. We also find that all species have many DINE-1 insertions in introns and adjacent to protein-coding genes. Finally, we discuss our results in light of a recent proposal that DINE-1s belong to the Helitron family of TEs.

Conclusion

We find that all 12 Drosophila species with whole-genome sequence contain the high copy element DINE-1. Although all DINE-1s share a similar structure, species-specific variation in the distribution of average pairwise divergence suggests that DINE-1 has gone through multiple independent cycles of activation and suppression. DINE-1 also has had a significant impact on gene structure evolution.
Systems biology meets stress ecology: linking molecular and organismal stress responses in Daphnia magna
Authors: Heckmann Lars-Henrik , Sibly Richard M , Connon Richard , Hooper Helen L , Hutchinson Thomas H , Maund Steve J , Hill Christopher J , Bouetard Anthony , Callaghan Amanda
Published: February 2008

Background

Ibuprofen and other nonsteroidal anti-inflammatory drugs have been designed to interrupt eicosanoid metabolism in mammals, but little is known of how they affect nontarget organisms. Here we report a systems biology study that simultaneously describes the transcriptomic and phenotypic stress responses of the model crustacean Daphnia magna after exposure to ibuprofen.

Results

Our findings reveal intriguing similarities in the mode of action of ibuprofen between vertebrates and invertebrates, and they suggest that ibuprofen has a targeted impact on reproduction at the molecular, organismal, and population level in daphnids. Microarray expression and temporal real-time quantitative PCR profiles of key genes suggest early ibuprofen interruption of crustacean eicosanoid metabolism, which appears to disrupt signal transduction affecting juvenile hormone metabolism and oogenesis.

Conclusion

Combining molecular and organismal stress responses provides a guide to possible chronic consequences of environmental stress for population health. This could improve current environmental risk assessment by providing an early indication of the need for higher tier testing. Our study demonstrates the advantages of a systems approach to stress ecology, in which Daphnia will probably play a major role.
The Writing Workshop of François Quesnay and the Making of Physiocracy
Authors: Théré Christine , Charles Loïc
Published: February 2008

Using archival materials, we investigate the scientific practices of François Quesnay and the individuals who worked with him in relation to their social background. Our contention is that, before 1764, the group of authors who shared Quesnay's commitment to an agrarian economic theory are best described as the “writing workshop” of François Quesnay rather than as the “physiocratic” school. Quesnay organized and supervised the work of these individuals, who assisted him in a manner clearly reminiscent of that of workshops of artists from late medieval and early modern Europe. On the one hand, Quesnay tightly controlled the work of those (the Marquis de Mirabeau, Pattullo, Du Pont de Nemours) who published economic writings, correcting and even rewriting whole parts of their texts. On the other hand, he commanded other writers/individuals to collect data and execute and verify calculations, most notably for his tableaux économiques. In other words, the production of political and economic writings was structured by a detailed division of labor organized by Quesnay, who acted as the master of a writing workshop. After the death of Madame de Pompadour, Quesnay's prominent patroness, in 1764, the situation changed. Quesnay's aura of power at court disappeared and with it, his writing workshop. The center of gravity of physiocracy moved from Versailles to Paris, and the workshop was gradually replaced by the physiocratic school.
Adam Smith, the Last of the Former Virtue Ethicists
Authors: McCloskey Deirdre
Published: February 2008

Smith was mainly an ethical philosopher, though he practiced what was considered for a long time after Smith an obsolete sort of ethical philosophy, known nowadays as “virtue ethics.” Since 1790 most ethical theory as practiced in departments of philosophy has derived instead from Kant or Bentham, but virtue ethics has recently come back. From the Seven Primary Virtues, Smith chose five to admire especially. He chose all four of the pagan and stoic virtues of courage, temperance, justice, and prudence. To these he added, as virtue number five, a part of the Christian virtue of love, the part admired by his teacher Francis Hutcheson. Smith was not, as has often been claimed, a Stoic, because he was always a pluralist, and would not reduce the good life to, say, Stoic temperance alone. Smith's choice of the virtues makes sense of his writings and career. And it reveals a flaw, shared with Hume: the banishment of the monkish virtues of hope and faith, necessary for human flourishing.
Linking Strategic Interaction and Bargaining Theory: The Harsanyi-Schelling Debate on the Axiom of Symmetry
Authors: Innocenti Alessandro
Published: February 2008

This paper analyzes the early contributions of John Harsanyi and Thomas C. Schelling to bargaining theory. In the 1950s, Harsanyi draws Nash's solution to two-person cooperative games from the bargaining model proposed by Zeuthen (1930), and Schelling proposes a multifaceted theory of conflict that, without dismissing the assumption of rational behavior, points out some of its paradoxical consequences. Harsanyi's and Schelling's contrasting views on the axiom of symmetry, as postulated by Nash (1950), are then presented. This debate explains why, although in the early 1960s two different approaches to link strategic interaction and bargaining theory were proposed, only Harsanyi's insights were fully developed later.
Becoming-Obscure: A Constant in the Development of Modern Chinese Poetry
Authors: Yongguo Chen
Published: February 2008

Both historically and theoretically, this essay traces the development of modern Chinese poetry, including the Chinese symbolists of the 1920s, the modernists of the 1930s, the Nine Leaves of the 1940s, the obscurists of the 1970s, and the post-obscurists of the Third Generation of the 1980s, to the Western source from which the Chinese New Poets learned the techniques of modern Western poetry and introduced them into China by way of adaptation and imitation. At that point a new leaf was turned in the history of Chinese poetry: the mingling of the foreign elements, especially the obscurant that was constant in Western poetry, with vernacular Chinese expression gave birth to the New Poetry.
The Best Colleague
Authors: Bauerlein Mark
Published: February 2008

Elizabeth Fox-Genovese died in January 2007. She was a renowned scholar and important public intellectual, but in this reminiscence Mark Bauerlein recalls her as something else: a model colleague. Despite the many attacks on her work and the difficulties she encountered in her professional life, she always conducted herself with respect and high-mindedness. Never did Bauerlein witness her give in to gossip and vitriol. She was an example of the best of higher education, and academia is a diminished place without her.
Malory and Modernity
Authors: Richmond Colin
Published: February 2008

This essay takes the Morte Darthur of Sir Thomas Malory as a test case for the applicability of Thomas Kuhn's notion of “paradigm shifts” to the history of culture. While Kuhn apparently found inspiration in the disciplines of cultural and art history for his idea that scientific progress is noncumulative, the arts and humanities (unlike the sciences) must deal with the ideas of (and the evidence for) “Renaissance” and “renascence,” “resistance” and “reaction.” A poet such as Malory may achieve a permanent place in literary history and on required-reading lists by resisting a shift in paradigm, whereas a scientist who resists will effectively disappear. Thus, the Morte Darthur set the terms for modern literature in English by holding fast to those of the Middle Ages. This essay argues that Malory was “modern” in that the Morte Darthur would not have been written except for the events in England and France of 1454–85 but that what was most modern about him was his resistance to concomitant changes in English society.
Lrig3 regulates neural crest formation inXenopusby modulating Fgf and Wnt signaling pathways
Authors: Zhao Hui , Tanegashima Kosuke , Ro Hyunju , Dawid Igor B.
Published: February 2008

Leucine-rich repeats and immunoglobulin-like domains 3(Lrig3) was identified by microarray analysis among genes that show differential expression during gastrulation in Xenopus laevis. Lrig3 was expressed in the neural plate and neural crest (NC) at neurula stages, and in NC derivatives and other dorsal structures during tailbud stages. A prominent consequence of the morpholino-induced inhibition of Lrig3 expression was impaired NC formation, as revealed by the suppression of marker genes, including Slug, Sox9 and Foxd3. In the NC induction assay involving Chordin plus Wnt3a-injected animal caps, Lrig3 morpholino inhibited expression of Slug, Sox9 and Foxd3, but not of Pax3 and Zic1. In line with this, Lrig3 knockdown prevented NC marker induction by Pax3 and Zic1, suggesting that Lrig3 acts downstream of these two genes in NC formation. Injection of Lrig3 and Wnt3a led to low-level induction of NC markers and enhanced induction of Fgf3,Fgf4 and Fgf8 in animal caps, suggesting a positive role for Lrig3 in Wnt signaling. Lrig3 could attenuate Fgf signaling in animal caps,did interact with Fgf receptor 1 in cultured cells and, according to context,decreased or increased the induction of NC markers by Fgf. We suggest that Lrig3 functions in NC formation in Xenopus by modulating the Wnt and Fgf signaling pathways.
Ascl1 is required for oligodendrocyte development in the spinal cord
Authors: Sugimori Michiya , Nagao Motoshi , Parras Carlos M. , Nakatani Hiroko , Lebel Mélanie , Guillemot François , Nakafuku Masato
Published: February 2008

Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification of oligodendrocyte progenitors (OLPs) begins early in development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. How these distinct steps are controlled remains unclear. Our previous study demonstrated an important role of the helix-loop-helix (HLH) transcription factor Ascl1 in early generation of OLPs in the developing spinal cord. Here,we show that Ascl1 is also involved in terminal differentiation of oligodendrocytes late in development. Ascl1-/- mutant mice showed a deficiency in differentiation of myelin-expressing oligodendrocytes at birth. In vitro culture studies demonstrate that the induction and maintenance of co-expression of Olig2 and Nkx2-2 in OLPs, and thyroid hormone-responsive induction of myelin proteins are impaired in Ascl1-/- mutants. Gain-of-function studies further showed that Ascl1 collaborates with Olig2 and Nkx2-2 in promoting differentiation of OLPs into oligodendrocytes in vitro. Overexpression of Ascl1, Olig2 and Nkx2-2 alone stimulated the specification of OLPs, but the combinatorial action of Ascl1 and Olig2 or Nkx2-2 was required for further promoting their differentiation into oligodendrocytes. Thus, Ascl1 regulates multiple aspects of oligodendrocyte development in the spinal cord.
Nanometer-scale organization of the alpha subunits of the receptors for IL2 and IL15 in human T lymphoma cells
Authors: de Bakker Bärbel I. , Bodnár Andrea , van Dijk Erik M. H. P. , Vámosi György , Damjanovich Sándor , Waldmann Thomas A. , van Hulst Niek F. , Jenei Attila , Garcia-Parajo María F.
Published: February 2008

Interleukin 2 and interleukin 15 (IL2 and IL15, respectively) provide quite distinct contributions to T-cell-mediated immunity, despite having similar receptor composition and signaling machinery. As most of the proposed mechanisms underlying this apparent paradox attribute key significance to the individual α-chains of IL2 and IL15 receptors, we investigated the spatial organization of the receptors IL2Rα and IL15Rα at the nanometer scale expressed on a human CD4+ leukemia T cell line using single-molecule-sensitive near-field scanning optical microscopy (NSOM). In agreement with previous findings, we here confirm clustering of IL2Rα and IL15Rα at the submicron scale. In addition to clustering, our single-molecule data reveal that a non-negligible percentage of the receptors are organized as monomers. Only a minor fraction of IL2Rα molecules reside outside the clustered domains, whereas ∼30% of IL15Rα molecules organize as monomers or small clusters, excluded from the main domain regions. Interestingly, we also found that the packing densities per unit area of both IL2Rα and IL15Rα domains remained constant, suggesting a `building block' type of assembly involving repeated structures and composition. Finally, dual-color NSOM demonstrated co-clustering of the two α-chains. Our results should aid understanding the action of the IL2R-IL15R system in T cell function and also might contribute to the more rationale design of IL2R- or IL15R-targeted immunotherapy agents for treating human leukemia.
Human Capital and Institutional Effects in the Compensation of Information Technology Professionals in the United States
Authors: Mithas Sunil , Krishnan M. S.
Published: February 2008

This paper studies the influence of supply-side and demand-side factors on the compensation of information technology (IT) professionals and considers the human capital and institutional explanations. We focus on returns to an MBA and the IT-related experience of IT professionals and use the largest data set of IT professionals that has been compiled to date in the United States to answer our research questions. We find that firms pay a significant premium for an MBA. Although firms value the IT experience of IT professionals, they value an MBA significantly more. The results of this study cast doubt on the belief that IT skills have a large firm-specific component. Although IT experience is valued more than non-IT experience for IT professionals, firms value IT experience at other firms much more than they value firm-specific IT experience. Likewise, contrary to popular perception, we do not find evidence for complementarities between an MBA education and IT experience. Among institutional effects, firms in IT and IT-intensive industries pay significantly more to IT professionals than do other firms, and dot-com firms also paid a significant premium in 1999 and 2000. However, these firms do not value an MBA or firm-specific IT experience any more than other firms. We discuss the implications of these findings for further research, for firms' compensation practices, and for individual IT professionals.
Evidence of the camera perspective bias in authentic videotaped interrogations: Implications for emerging reform in the criminal justice system
Authors: Lassiter G. Daniel , Ware Lezlee J. , Ratcliff Jennifer J. , Irvin Clinton R.
Published: February 2008

Objective. Numerous previous experiments have established the existence of a camera perspective bias in evaluations of videotaped interrogations/confessions: videotapes that make the suspect more visually conspicuous than the interrogator(s) by virtue of focusing the camera on the suspect yield assessments of voluntariness and judgments of guilt that are greater than those found when alternative presentation formats are used. One limitation of this body of research is that all the interrogations/confessions used to date were simulations; therefore, no evidence currently demonstrates that the camera perspective bias importantly generalizes to authentic videotapes recorded by police and depicting actual suspects and interrogators. Two experiments addressed this issue.

Methods. Experiment 1 compared judgments of voluntariness based on viewing two authentic videotaped confessions – one recorded with the camera focused on the suspect, the other with the camera focused equally on the suspect and interrogator – with those based on listening only to the audio or reading only a transcript. Experiment 2 compared judgments of voluntariness and guilt of an originally equal‐focus videotaped confession that was edited to produce suspect‐focus and interrogator‐focus versions.

Results. In Experiment 1, participants judged the videotape version of the confession to be more voluntary than either the audio only or transcript versions, but only for the suspect‐focus videotape. In Experiment 2, participants viewing the suspect‐focus version of the confession (relative to the interrogator‐focus version) judged it to be more voluntary and the suspect more likely to be guilty.

Conclusion. The present research further strengthens the policy implications of the literature on camera perspective bias by providing evidence that the bias manifests with authentic interrogations/confessions as well as with simulations.
Human rights and forensic psychology
Authors: Ward Tony
Published: February 2008

Objectives. Human rights serve to orientate practitioners to the necessary conditions for a minimally worthwhile life for service users, the prerequisites for a life of dignity and a chance at happiness, and the opportunity to incorporate into their life plans cherished values and goals. In this introduction to the special section paper, I discuss the basic concept of human rights and outline their relevance for clinical practice with offenders.

Method. I explore the core values associated with human rights and suggest that one of their primary functions is to protect the internal and external conditions of individuals' agency and their pursuit of better lives.

Conclusion. I briefly outline the three articles comprising this special section of LCP on human rights that address issues of risk, therapeutic jurisprudence, and the rights of detained persons.
Molecular Actions of 1,25-Dihydroxyvitamin D3 on Genes Involved in Calcium Homeostasis
Authors: Pike J Wesley , Zella Lee A , Meyer Mark B , Fretz Jackie A , Kim Sungtae
Published: February 2008

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] functions in vertebrate organisms as a primary regulator of calcium and phosphorus homeostasis, an activity that is achieved through direct actions on gene expression in intestine, kidney, and bone. Recent studies have identified novel genes such as TRPV5, TRPV6, and RANKL whose products are integral to the maintenance of extracellular calcium. The objective of this progress report/review is to describe our recent results that identify the mechanisms of 1,25(OH)2D3 action on the expression of TRPV6 and RANKL. A series of molecular, cellular, and in vivo studies have been conducted to define the molecular mechanisms that control the expression of TRPV6 and RANKL. Cell culture–based assays, chromatin immunoprecipitation (ChIP) and ChIP-DNA microarray (ChIP-chip) methods, and a series of molecular techniques were used to identify and characterize upstream regions of mouse and human TRPV6 and RANKL genes. We discovered that these genes were regulated by at least five separate enhancer regions. In the TRPV6 gene, these enhancers were all located within 5 kb of the transcriptional start site (TSS), and each contained one or more vitamin D regulatory elements (VDREs). In the RANKL gene, these regulatory regions span over 80 kb of upstream sequence, the most distal 76 kb from the TSS. This regulatory region is central to the regulation of RANKL expression in vitro and in vivo. Our studies identified key regulatory regions within the TRPV6 and RANKL genes that are essential for their individual expression in the intestine and bone, respectively.
Vitamin D and Skin Physiology: A D-Lightful Story
Authors: Holick Michael F , Chen Tai C , Lu Zhiren , Sauter Edward
Published: February 2008

Throughout evolution, exposure to sunlight and the photosynthesis of vitamin D3 in the skin has been critically important for the evolution of land vertebrates. During exposure to sunlight, the solar UVB photons with energies 290–315 nm are absorbed by 7-dehydrocholesterol in the skin and converted to previtamin D3. Previtamin D3 undergoes a rapid transformation within the plasma membrane to vitamin D3. Excessive exposure to sunlight will not result in vitamin D intoxication because both previtamin D3 and vitamin D3 are photolyzed to several noncalcemic photoproducts. During the winter at latitudes above ∼35°, there is minimal, if any, previtamin D3 production in the skin. Altitude also has a significant effect on vitamin D3 production. At 27° N in November, very little (∼0.5%) previtamin D3 synthesis was detected in Agra (169 m) and Katmandu (1400 m). There was an ∼2- and 4-fold increase in previtamin D3 production at ∼3400 m and at Everest base camp (5300 m), respectively. Increased skin pigmentation, application of a sunscreen, aging, and clothing have a dramatic effect on previtamin D3 production in the skin. It is estimated that exposure in a bathing suit to 1 minimal erythemal dose (MED) is equivalent to ingesting between 10,000 and 25,000 IU of vitamin D2. The importance of sunlight for providing most humans with their vitamin D requirement is well documented by the seasonal variation in circulating levels of 25-hydroxyvitamin D [25(OH)D]. Vitamin D deficiency [i.e., 25(OH)D < 20 ng/ml] is common in both children and adults worldwide. Exposure to lamps that produce UVB radiation is an excellent source for producing vitamin D3 in the skin and is especially efficacious in patients with fat malabsorption syndromes. The major cause of vitamin D deficiency globally is an underappreciation of sunlight's role in providing humans with their vitamin D3 requirement. Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D3 compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being.