bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Class, Contextualism, and Empathic Accuracy
Authors: Kraus Michael W. , Côté Stéphane , Keltner Dacher
Published: October 2010

Recent research suggests that lower-class individuals favor explanations of personal and political outcomes that are oriented to features of the external environment. We extended this work by testing the hypothesis that, as a result, individuals of a lower social class are more empathically accurate in judging the emotions of other people. In three studies, lower-class individuals (compared with upper-class individuals) received higher scores on a test of empathic accuracy (Study 1), judged the emotions of an interaction partner more accurately (Study 2), and made more accurate inferences about emotion from static images of muscle movements in the eyes (Study 3). Moreover, the association between social class and empathic accuracy was explained by the tendency for lower-class individuals to explain social events in terms of features of the external environment. The implications of class-based patterns in empathic accuracy for well-being and relationship outcomes are discussed.
Determination of Gurson–Tvergaard–Needleman Model Parameters for Failure of a Polymeric Material
Authors: Oral Alpay , Anlas Gunay , Lambros John
Published: October 2010

In this work, the Gurson–Tvergaard–Needleman model, commonly used for metallic materials, is applied to the failure of a polymeric material – specifically a polyethylene carbon monoxide copolymer, which is an enhanced photodegradable material. Gurson–Tvergaard–Needleman model parameters for this material are obtained using the Nelder–Mead simplex method when correlating experimental and numerical results of both tensile and fracture specimens. Results show that the Gurson–Tvergaard–Needleman model can also be used for polymeric materials with selection of proper parameters that are quite different from the ones proposed for metallic materials.
Choices of approaches in e-moderation: Conclusions from a grounded theory study
Authors: Vlachopoulos Panos , Cowan John
Published: October 2010

Much has been published in recent years about the desirable nature of facilitated interactions in online discussions for educational purposes. However, little has been reported about the roles that tutors actually adopt in real-life learning contexts, how these range between ‘tutoring, ‘managing’ and ‘facilitating’, and what the distinctions between these three roles may be. In this article choices of priorities in e-moderation, which were made in three naturalistic (real-life) case studies by three higher education practitioners, are identified and discussed. These contrasting approaches were captured and analysed using grounded theory principles. The article also discusses the occasions when the facilitation was less effective than might have been desired. It finally summarizes the potential of various approaches within e-moderation — and some of the attendant risks. The finding is that principles and practices developed for face-to-face support of student-directed learning were found equally applicable in e-moderated online group work, despite several significant differences between the two types of setting.
Recovering From Strain and Enduring Pain
Authors: Jones Janelle M. , Jetten Jolanda
Published: October 2010

Recent research suggests that multiple group memberships can be a source of resilience in the face of various life challenges (e.g., illness, injury, life transitions, performance demands). In two studies the authors examined whether multiple group memberships promote resilience in the face of novel physical challenges. They found that belonging to multiple groups was associated with faster heart rate recovery for novice bobsleigh, luge, and skeleton athletes (Study 1) and that the salience of a greater number of group memberships led to greater endurance on a cold-pressor task (Study 2). Importantly, these effects were unchanged when controlling for individual differences in responses to the challenge, challenge perceptions, and group membership importance. The authors argue that multiple group memberships reflect an important psychological resource from which individuals draw strength when faced with life challenges and speculate as to the mechanisms underlying this effect.
Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity
Authors: Metzler Kathleen D. , Fuchs Tobias A. , Nauseef William M. , Reumaux Dominique , Roesler Joachim , Schulze Ilka , Wahn Volker , Papayannopoulos Venizelos , Zychlinsky Arturo
Published: October 2010

The granule enzyme myeloperoxidase (MPO) plays an important role in neutrophil antimicrobial responses. However, the severity of immunodeficiency in patients carrying mutations in MPO is variable. Serious microbial infections, especially with Candida species, have been observed in a subset of completely MPO-deficient patients. Here we show that neutrophils from donors who are completely deficient in MPO fail to form neutrophil extracellular traps (NETs), indicating that MPO is required for NET formation. In contrast, neutrophils from partially MPO-deficient donors make NETs, and pharmacological inhibition of MPO only delays and reduces NET formation. Extracellular products of MPO do not rescue NET formation, suggesting that MPO acts cell-autonomously. Finally, NET-dependent inhibition of Candida albicans growth is compromised in MPO-deficient neutrophils. The inability to form NETs may contribute in part to the host defense defects observed in completely MPO-deficient individuals.
The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells
Authors: Martinez-Garcia Eva , Popovic Relja , Min Dong-Joon , Sweet Steve M. M. , Thomas Paul M. , Zamdborg Leonid , Heffner Aaron , Will Christine , Lamy Laurence , Staudt Louis M. , Levens David L. , Kelleher Neil L. , Licht Jonathan D.
Published: October 2010

The multiple myeloma SET domain (MMSET) protein is overexpressed in multiple myeloma (MM) patients with the translocation t(4;14). Although studies have shown the involvement of MMSET/Wolf-Hirschhorn syndrome candidate 1 in development, its mode of action in the pathogenesis of MM is largely unknown. We found that MMSET is a major regulator of chromatin structure and transcription in t(4;14) MM cells. High levels of MMSET correlate with an increase in lysine 36 methylation of histone H3 and a decrease in lysine 27 methylation across the genome, leading to a more open structural state of the chromatin. Loss of MMSET expression alters adhesion properties, suppresses growth, and induces apoptosis in MM cells. Consequently, genes affected by high levels of MMSET are implicated in the p53 pathway, cell cycle regulation, and integrin signaling. Regulation of many of these genes required functional histone methyl-transferase activity of MMSET. These results implicate MMSET as a major epigenetic regulator in t(4;14)+ MM.
Mutational dynamics of murine angiogenin duplicates
Authors: Codoñer Francisco M , Alfonso-Loeches Silvia , Fares Mario A
Published: October 2010

Background

Angiogenin (Ang) is a protein involved in angiogenesis by inducing the formation of blood vessels. The biomedical importance of this protein has come from findings linking mutations in Ang to cancer progression and neurodegenerative diseases. These findings highlight the evolutionary constrain on Ang amino acid sequence. However, previous studies comparing human Angiogenin with homologs from other phylogenetically related organisms have led to the conclusion that Ang presents a striking variability. Whether this variability has an adaptive value per se remains elusive. Understanding why many functional Ang paralogs have been preserved in mouse and rat and identifying functional divergence mutations at these copies may explain the relationship between mutations and function. In spite of the importance of testing this hypothesis from the evolutionarily and biomedical perspectives, this remains yet unaccomplished. Here we test the main mutational dynamics driving the evolution and function of Ang paralogs in mammals.

Results

We analysed the phylogenetic asymmetries between the different Ang gene copies in mouse and rat in the context of vertebrate Ang phylogeny. This analysis shows strong evidence in support of accelerated evolution in some Ang murine copies (mAng). This acceleration is not due to non-functionalisation because constraints on amino acid replacements remain strong. We identify many of the amino acid sites involved in signal localization and nucleotide binding by Ang to have evolved under diversifying selection. Compensatory effects of many of the mutations at these paralogs and their key structural location in or nearby important functional regions support a possible functional shift (functional divergence) in many Ang copies. Similarities between 3D-structural models for mAng copies suggest that their divergence is mainly functional.

Conclusions

We identify the main evolutionary dynamics shaping the variability of Angiogenin in vertebrates and highlight the plasticity of this protein after gene duplication. Our results suggest functional divergence among mAng paralogs. This puts forward mAng as a good system candidate for testing functional plasticity of such an important protein while stresses caution when using mouse as a model to infer the consequences of mutations in the single Ang copy of humans.
Annotation and comparative analysis of the glycoside hydrolase genes in Brachypodium distachyon
Authors: Tyler Ludmila , Bragg Jennifer N , Wu Jiajie , Yang Xiaohan , Tuskan Gerald A , Vogel John P
Published: October 2010

Background

Glycoside hydrolases cleave the bond between a carbohydrate and another carbohydrate, a protein, lipid or other moiety. Genes encoding glycoside hydrolases are found in a wide range of organisms, from archea to animals, and are relatively abundant in plant genomes. In plants, these enzymes are involved in diverse processes, including starch metabolism, defense, and cell-wall remodeling. Glycoside hydrolase genes have been previously cataloged forOryza sativa(rice), the model dicotyledonous plantArabidopsis thaliana, and the fast-growing treePopulustrichocarpa(poplar). To improve our understanding of glycoside hydrolases in plants generally and in grasses specifically, we annotated the glycoside hydrolase genes in the grassesBrachypodiumdistachyon(an emerging monocotyledonous model) andSorghum bicolor(sorghum). We then compared the glycoside hydrolases across species, at the levels of the whole genome and individual glycoside hydrolase families.

Results

We identified 356 glycoside hydrolase genes inBrachypodiumand 404 in sorghum. The corresponding proteins fell into the same 34 families that are represented in rice,Arabidopsis, and poplar, helping to define a glycoside hydrolase family profile which may be common to flowering plants. For several glycoside hydrolase familes (GH5, GH13, GH18, GH19, GH28, and GH51), we present a detailed literature review together with an examination of the family structures. This analysis of individual families revealed both similarities and distinctions between monocots and eudicots, as well as between species. Shared evolutionary histories appear to be modified by lineage-specific expansions or deletions. Within GH families, theBrachypodiumand sorghum proteins generally cluster with those from other monocots.

Conclusions

This work provides the foundation for further comparative and functional analyses of plant glycoside hydrolases. Defining theBrachypodiumglycoside hydrolases sets the stage forBrachypodiumto be a grass model for investigations of these enzymes and their diverse rolesin planta. Insights gained fromBrachypodiumwill inform translational research studies, with applications for the improvement of cereal crops and bioenergy grasses.
A novel multifunctional oligonucleotide microarray for Toxoplasma gondii
Authors: Bahl Amit , Davis Paul H , Behnke Michael , Dzierszinski Florence , Jagalur Manjunatha , Chen Feng , Shanmugam Dhanasekaran , White Michael W , Kulp David , Roos David S
Published: October 2010

Background

Microarrays are invaluable tools for genome interrogation, SNP detection, and expression analysis, among other applications. Such broad capabilities would be of value to many pathogen research communities, although the development and use of genome-scale microarrays is often a costly undertaking. Therefore, effective methods for reducing unnecessary probes while maintaining or expanding functionality would be relevant to many investigators.

Results

Taking advantage of available genome sequences and annotation for Toxoplasma gondii (a pathogenic parasite responsible for illness in immunocompromised individuals) and Plasmodium falciparum (a related parasite responsible for severe human malaria), we designed a single oligonucleotide microarray capable of supporting a wide range of applications at relatively low cost, including genome-wide expression profiling for Toxoplasma, and single-nucleotide polymorphism (SNP)-based genotyping of both T. gondii and P. falciparum. Expression profiling of the three clonotypic lineages dominating T. gondii populations in North America and Europe provides a first comprehensive view of the parasite transcriptome, revealing that ~49% of all annotated genes are expressed in parasite tachyzoites (the acutely lytic stage responsible for pathogenesis) and 26% of genes are differentially expressed among strains. A novel design utilizing few probes provided high confidence genotyping, used here to resolve recombination points in the clonal progeny of sexual crosses. Recent sequencing of additional T. gondii isolates identifies >620 K new SNPs, including ~11 K that intersect with expression profiling probes, yielding additional markers for genotyping studies, and further validating the utility of a combined expression profiling/genotyping array design. Additional applications facilitating SNP and transcript discovery, alternative statistical methods for quantifying gene expression, etc. are also pursued at pilot scale to inform future array designs.

Conclusions

In addition to providing an initial global view of the T. gondii transcriptome across major lineages and permitting detailed resolution of recombination points in a historical sexual cross, the multifunctional nature of this array also allowed opportunities to exploit probes for purposes beyond their intended use, enhancing analyses. This array is in widespread use by the T. gondii research community, and several aspects of the design strategy are likely to be useful for other pathogens.
Effects of polymerase, template dilution and cycle number on PCR based 16 S rRNA diversity analysis using the deep sequencing method
Authors: Wu Jin-Ya , Jiang Xiao-Tao , Jiang Yun-Xia , Lu Su-Ying , Zou Fei , Zhou Hong-Wei
Published: October 2010

Background

The primer and amplicon length have been found to affect PCR based estimates of microbial diversity by pyrosequencing, while other PCR conditions have not been addressed using any deep sequencing method. The present study determined the effects of polymerase, template dilution and PCR cycle number using the Solexa platform.

Results

The PfuUltra II Fusion HS DNA Polymerase (Stratagene) with higher fidelity showed lower amount of PCR artifacts and determined lower taxa richness than the Ex Taq (Takara). More importantly, the two polymerases showed different efficiencies for amplifying some of very abundant sequences, and determined significantly different community structures. As expected, the dilution of the DNA template resulted in a reduced estimation of taxa richness, particularly at the 200 fold dilution level, but the community structures were similar for all dilution levels. The 30 cycle group increased the PCR artifacts while comparing to the 25 cycle group, but the determined taxa richness was lower than that of the 25 cycle group. The PCR cycle number did not changed the microbial community structure significantly.

Conclusions

These results highlight the PCR conditions, particularly the polymerase, have significant effect on the analysis of microbial diversity with next generation sequencing methods.
Mitochondrially-targeted expression of a cytoplasmic male sterility-associated orf220 gene causes male sterility in Brassica juncea
Authors: Yang Jinghua , Liu Xunyan , Yang Xiaodong , Zhang Mingfang
Published: October 2010

Background

The novel chimeric open reading frame (orf) resulting from the rearrangement of a mitochondrial genome is generally thought to be a causal factor in the occurrence of cytoplasmic male sterility (CMS). Both positive and negative correlations have been found between CMS-associatedorfsand the occurrence of CMS when CMS-associatedorfswere expressed and targeted at mitochondria. Someorfscause male sterility or semi-sterility, while some do not. Little is currently known about how mitochondrial factor regulates the expression of the nuclear genes involved in male sterility. The purpose of this study was to investigate the biological function of a candidate CMS-associatedorf220gene, newly isolated from cytoplasmic male-sterile stem mustard, and show how mitochondrial retrograde regulated nuclear gene expression is related to male sterility.

Results

It was shown that the ORF220 protein can be guided to the mitochondria using the mitochondrial-targeting sequence of theβsubunit of F1-ATPase (atp2-1). Transgenic stem mustard plants expressed the chimeric gene containing theorf220gene and a mitochondrial-targeting sequence of theβsubunit of F1-ATPase (atp2-1). Transgenic plants were male-sterile, most being unable to produce pollen while some could only produce non-vigorous pollen. The transgenic stem mustard plants also showed aberrant floral development identical to that observed in the CMS stem mustard phenotype. Results obtained from oligooarray analysis showed that some genes related to mitochondrial energy metabolism were down-regulated, indicating a weakening of mitochondrial function in transgenic stem mustard. Some genes related to pollen development were shown to be down-regulated in transgenic stem mustard and the expression of some transcription factor genes was also altered.

Conclusion

The work presented furthers our understanding of how the mitochondrially-targeted expression of CMS-associatedorf220gene causes male sterility through retrograde regulation of nuclear gene expression inBrassica juncea.
The Ve-mediated resistance response of the tomato to Verticillium dahliae involves H2O2, peroxidase and lignins and drives PALgene expression
Authors: Gayoso Carmen , Pomar Federico , Novo-Uzal Esther , Merino Fuencisla , Martínez de Ilárduya Óskar
Published: October 2010

Background

Verticillium dahliae is a fungal pathogen that infects a wide range of hosts. The only known genes for resistance to Verticillium in the Solanaceae are found in the tomato (Solanum lycopersicum) Ve locus, formed by two linked genes, Ve1 and Ve2. To characterize the resistance response mediated by the tomato Ve gene, we inoculated two nearly isogenic tomato lines, LA3030 (ve/ve) and LA3038 (Ve/Ve), with V. dahliae.

Results

We found induction of H2O2 production in roots of inoculated plants, followed by an increase in peroxidase activity only in roots of inoculated resistant plants. Phenylalanine-ammonia lyase (PAL) activity was also increased in resistant roots 2 hours after inoculation, while induction of PAL activity in susceptible roots was not seen until 48 hours after inoculation. Phenylpropanoid metabolism was also affected, with increases in ferulic acid, p-coumaric acid, vanillin and p-hydroxybenzaldehyde contents in resistant roots after inoculation. Six tomato PAL cDNA sequences (PAL1 - PAL6) were found in the SolGenes tomato EST database. RT-PCR analysis showed that these genes were expressed in all organs of the plant, albeit at different levels. Real-time RT-PCR indicated distinct patterns of expression of the different PAL genes in V. dahliae-inoculated roots. Phylogenetic analysis of 48 partial PAL cDNAs corresponding to 19 plant species grouped angiosperm PAL sequences into four clusters, suggesting functional differences among the six tomato genes, with PAL2 and PAL6 presumably involved in lignification, and the remaining PAL genes implicated in other biological processes.

An increase in the synthesis of lignins was found 16 and 28 days after inoculation in both lines; this increase was greater and faster to develop in the resistant line. In both resistant and susceptible inoculated plants, an increase in the ratio of guaiacyl/syringyl units was detected 16 days after inoculation, resulting from the lowered amount of syringyl units in the lignins of inoculated plants.

Conclusions

The interaction between the tomato and V. dahliae triggered a number of short- and long-term defensive mechanisms. Differences were found between compatible and incompatible interactions, including onset of H2O2 production and activities of peroxidase and PAL, and phenylpropanoid metabolism and synthesis of lignins.
Bacteremic community-acquired pneumonia due to Klebsiella pneumoniae: Clinical and microbiological characteristics in Taiwan, 2001-2008
Authors: Lin Yi-Tsung , Jeng Yuan-Yu , Chen Te-Li , Fung Chang-Phone
Published: October 2010

Background

Klebsiella pneumoniae is the major cause of community-acquired pyogenic infections in Taiwan. This retrospective study evaluated the clinical and microbiological characteristics of bacteremic community-acquired pneumonia due to K. pneumoniae in Taiwanese adults.

Methods

The clinical characteristics of bacteremic community-acquired pneumonia (CAP) in adults due to K. pneumoniae were compared to those of adults with bacteremic CAP due to Streptococcus pneumoniae at a tertiary medical center in Taiwan from 2001-2008. Risk factors for mortality of bacteremic CAP due to K. pneumoniae were analyzed. All clinical isolates of K. pneumoniae were examined for capsular serotypes, hypermucoviscosity phenotype, aerobactin and rmpA gene.

Results

K. pneumoniae was the dominant cause of bacteremic CAP and was associated with a more fulminant course and a worse prognosis than bacteremic CAP due to Streptococcus pneumoniae. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality. Serotype K1 and K2 comprised around half of all isolates. There were no significant differences in the clinical characteristics of patients with bacteremic CAP due to K1/K2 and non-K1/K2 isolates. Hypermucoviscosity phenotype as well as the aerobactin and rmpA genes were highly prevalent in the K. pneumoniae isolates.

Conclusions

K. pneumoniae continued to be the dominant cause of bacteremic CAP in Taiwanese adults during 2001-2008. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality from K. pneumoniae bacteremic CAP. Serotypes K1/K2 comprised around half of all isolates, but did not predispose patients to a poor clinical outcome. Physicians should be aware of the poor prognosis of any patient with bacteremic K. pneumoniae CAP and monitor these patients more closely.
Use of antenatal care services in Kassala, eastern Sudan
Authors: Ali Abdel Aziem A , Osman Mohammed M , Abbaker Ameer O , Adam Ishag
Published: October 2010

Background

Antenatal care is named as one of the four pillars initiatives of the Safe Motherhood Initiative. While many of routine antenatal care procedure have little effect on maternal mortality and morbidity, some of these have been ascertained as beneficial. The aim of this study was to investigate coverage of antenatal care and identify factors associated with inadequacy of antenatal care in Kassala, eastern Sudan.

Methods

A cross-sectional community-based study was carried out in Kassala, eastern Sudan during September-October 2009. Household surveys were conducted. Structured questionnaires were used to gather data from women who had been pregnant within the last year, or pregnant more than 14 weeks.

Results

Out of 900 women investigated for antenatal care coverage, 811(90%) women had at least one visit. Only 11% of the investigated women had ≥ four antenatal visits, while 10.0% had not attended at all. Out of 811 women who attended at least one visit, 483 (59.6%), 303 (37.4%) and 25 (3.1%) women attended antenatal care in the first, second and third trimester, respectively. In logistic regression analyses, while maternal age and residence were not associated with inadequacy of antenatal care (<2 visits), high parity (OR = 2.0, CI = 1.1-3.5; P = 0.01) and husband education ≤ secondary level (OR = 2.4, CI = 1.3-4.2; P = 0.002) were associated with inadequacy of antenatal care.

Conclusions

Antenatal care showed a low coverage in Kassala, eastern Sudan. This low coverage was associated with high parity and low husband education.
Herbal compound "Songyou Yin" reinforced the ability of interferon-alfa to inhibit the enhanced metastatic potential induced by palliative resection of hepatocellular carcinoma in nude mice
Authors: Huang Xiu-Yan , Huang Zi-Li , Wang Lu , Xu Yong-Hua , Huang Xin-Yu , Ai Kai-Xing , Zheng Qi , Tang Zhao-You
Published: October 2010

Background

Liver resection is a widely accepted treatment for hepatocellular carcinoma (HCC). Our previous clinical study showed that the rate of palliative resection was 34.0% (1958-2008, 2754 of 8107). However, the influence of palliative resection on tumor metastasis remains controversial. The present study was conducted to evaluate the effect of palliative resection on residual HCC and to explore interventional approaches.

Methods

Palliative resection was done in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Tumor growth, invasion, metastasis, lifespan, and some molecular alterations were examined in vivo and in vitro. Mice that underwent palliative resection were treated with the Chinese herbal compound "Songyou Yin," interferon-alfa-1b (IFN-α), or their combination to assess their effects.

Results

In the palliative resection group, the number of lung metastatic nodules increased markedly as compared to the sham operation group (14.3 ± 4.7 versus 8.7 ± 3.6, P < 0.05); tumor matrix metalloproteinase 2 (MMP2) activity was elevated by 1.4-fold, with up-regulation of vascular endothelial growth factor (VEGF) and down-regulation of tissue inhibitor of metalloproteinase 2 (TIMP2). The sera of mice undergoing palliative resection significantly enhanced cell invasiveness by 1.3-fold. After treatment, tumor volume was 1205.2 ± 581.3 mm3, 724.9 ± 337.6 mm3, 507.6 ± 367.0 mm3, and 245.3 ± 181.2 mm3 in the control, "Songyou Yin," IFN-α, and combination groups, respectively. The combined therapy noticeably decreased the MMP2/TIMP2 ratio and prolonged the lifespan by 42.2%. Moreover, a significant (P < 0.001) reduction of microvessel density was found: 43.6 ± 8.5, 34.5 ± 5.9, 23.5 ± 5.6, and 18.2 ± 8.0 in the control and treatment groups, respectively.

Conclusion

Palliative resection-stimulated HCC metastasis may occur, in part, by up-regulation of VEGF and MMP2/TIMP2. "Songyou Yin" reinforced the ability of IFN-α to inhibit the metastasis-enhancing potential induced by palliative resection, which indicated its potential postoperative use in patients with HCC.
Pressure pain sensitivity maps of the neck-shoulder and the low back regions in men and women
Authors: Binderup Asbjørn T , Arendt-Nielsen Lars , Madeleine Pascal
Published: October 2010

Background

Musculoskeletal pain in the low back and neck-shoulder regions is a major problem among the working population all over the world. The prevalence of musculoskeletal pain is found to be higher among women. Women also have lower pressure pain thresholds (PPTs) than men. Pressure pain topography aims at mapping the spatial distribution of PPT within a muscle in an attempt to track changes in mechanical sensitivity. In order to assess gender differences in the pain topography, it is necessary to map the distribution in both healthy men and women. The aim of this study was to assess PPT maps from the cervico-thoracic and lumbar regions in men and women.

Methods

Eleven men and eleven women without any known musculoskeletal disorders participated in the study. PPT was measured twice at 36 points over the trapezius muscle of the dominant arm, at 36 points over the trapezius muscle on the contralateral side and at 12 points over the spine between the left and right trapezius. Further, 11 points were measured over the erector spinae muscle on the left side of the spine between the first and the fifth lumbar vertebrae, 11 on the right side and 5 points on the spine itself. The measurements on each trapezius muscle were divided according to anatomical subdivisions. Three-way and two-way ANOVAs were used to analyse the differences in PPTs with the following factors: gender, locations and sub-divisions (only for cervico-thoracic region).

Results

There were no differences between left and right side in neither the cervico-thoracic nor the lumbar region, but there were (large effect) differences between the subdivisions in the trapezius with the lowest values in the upper part (P < 0.001; partial η2 = 0.19). Women had (small effect) lower PPT in both cervico-thoracic and lumbar regions (P ≤ 0.001; partial η2 = 0.02 for both regions), but gender had no effect on neither location nor subdivisions.

Conclusions

The pain topography was not found to be different between genders in the cervico-thoracic and lumbar regions. This study can be used as basis for further clinical studies on musculoskeletal disorders.
Hunter disease eClinic:interactive, computer-assisted, problem-based approach to independent learning about a rare genetic disease
Authors: Al-Jasmi Fatma , Moldovan Laura , Clarke Joe TR
Published: October 2010

Background

Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II).

Aim

To develop interactive teaching software functioning as a virtual clinic for the management of MPS II.

Implementation and Results

The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca), was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available.

Conclusions

The Hunter disease eClinic employs a CBT model providing the trainee with realistic clinical problems, coupled with comprehensive basic and clinical reference information by instantaneous access to an electronic textbook, the eBook. The program was rated highly by attendees at national and international presentations. It provides a potential model for use as an educational approach to other rare genetic diseases.
FasL and FADD delivery by a glioma-specific and cell cycle-dependent HSV-1 amplicon virus enhanced apoptosis in primary human brain tumors
Authors: Ho Ivy A , Ng Wai H , Lam Paula Y
Published: October 2010

Background

Glioblastoma multiforme is the most malignant cancer of the brain and is notoriously difficult to treat due to the highly proliferative and infiltrative nature of the cells. Herein, we explored the combination treatment of pre-established human glioma xenograft using multiple therapeutic genes whereby the gene expression is regulated by both cell-type and cell cycle-dependent transcriptional regulatory mechanism conferred by recombinant HSV-1 amplicon vectors.

Results

We demonstrated for the first time that Ki67-positive proliferating primary human glioma cells cultured from biopsy samples were effectively induced into cell death by the dual-specific function of the pG8-FasL amplicon vectors. These vectors were relatively stable and exhibited minimal cytotoxicity in vivo. Intracranial implantation of pre-transduced glioma cells resulted in better survival outcome when compared with viral vectors inoculated one week post-implantation of tumor cells, indicating that therapeutic efficacy is dependent on the viral spread and mode of viral vectors administration. We further showed that pG8-FasL amplicon vectors are functional in the presence of commonly used treatment regimens for human brain cancer. In fact, the combined therapies of pG8-FasL and pG8-FADD in the presence of temozolomide significantly improved the survival of mice bearing intracranial high-grade gliomas.

Conclusion

Taken together, our results showed that the glioma-specific and cell cycle-dependent HSV-1 amplicon vector is potentially useful as an adjuvant therapy to complement the current gene therapy strategy for gliomas.
Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro
Authors: Liao Xinhua , Che Xiangming , Zhao Wei , Zhang Danjie , Long Houlong , Chaudhary Prakash , LI Haijun
Published: October 2010

Background

The National Comprehensive Cancer Network (NCCN) guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because gastric cancer demonstrates limited sensitivity to radiotherapy, a radiosensitizer might therefore be useful to enhance the radiosensitivity of patients with advanced gastric carcinoma. In this study, we evaluated if propranolol, a β-adrenoceptor (β-AR) antagonist, could enhance radiosensitivity and explored its precise molecular mechanism in gastric cancer cells.

Methods

Human gastric adenocarcinoma cell lines (SGC-7901 and BGC-823) were treated with or without propranolol and exposed to radiation. Cell viability and clonogenic survival assays were performed, and cell apoptosis was evaluated with flow cytometry. In addition, the expression of nuclear factor κB (NF-κB), vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and epidermal growth factor receptor (EGFR) were detected by western blot and real-time reverse transcription polymerase chain reaction (PCR).

Results

Propranolol combined with radiation decreased cell viability and clonogenic survivability. Furthermore, it also induced apoptosis in both cell lines tested, as determined by Annexin V staining. In addition, treatment with propranolol decreased the level of NF-κB and, subsequently, down-regulated VEGF, COX-2, and EGFR expression.

Conclusions

Taken together, these results suggested that propranolol enhanced the sensitivity of gastric cancer cells to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway.
Information propagation within the Genetic Network of Saccharomyces cerevisiae
Authors: Chowdhury Sharif , Lloyd-Price Jason , Smolander Olli-Pekka , Baici Wayne CV , Hughes Timothy R , Yli-Harja Olli , Chua Gordon , Ribeiro Andre S
Published: October 2010

Background

A gene network's capacity to process information, so as to bind past events to future actions, depends on its structure and logic. From previous and new microarray measurements in Saccharomyces cerevisiae following gene deletions and overexpressions, we identify a core gene regulatory network (GRN) of functional interactions between 328 genes and the transfer functions of each gene. Inferred connections are verified by gene enrichment.

Results

We find that this core network has a generalized clustering coefficient that is much higher than chance. The inferred Boolean transfer functions have a mean p-bias of 0.41, and thus similar amounts of activation and repression interactions. However, the distribution of p-biases differs significantly from what is expected by chance that, along with the high mean connectivity, is found to cause the core GRN of S. cerevisiae's to have an overall sensitivity similar to critical Boolean networks. In agreement, we find that the amount of information propagated between nodes in finite time series is much higher in the inferred core GRN of S. cerevisiae than what is expected by chance.

Conclusions

We suggest that S. cerevisiae is likely to have evolved a core GRN with enhanced information propagation among its genes.
Collagen-induced arthritis in common marmosets: a new nonhuman primate model for chronic arthritis
Authors: Vierboom Michel PM , Breedveld Elia , Kondova Ivanela , 't Hart Bert A
Published: October 2010

Introduction

There is an ever-increasing need for animal models to evaluate efficacy and safety of new therapeutics in the field of rheumatoid arthritis (RA). Particularly for the early preclinical evaluation of human-specific biologicals targeting the progressive phase of the disease, there is a need for relevant animal models. In response to this requirement we set out to develop a model of collagen-induced arthritis (CIA) in a small-sized nonhuman primate species (300 to 400 g at adult age); that is, the common marmoset (Callithrix jacchus).

Methods

Twenty-two animals divided into three experiments were immunized with collagen type II (CII) of either bovine or chicken origin with different immunization strategies. The animals were analyzed for clinical manifestation of arthritis, hematology and clinical chemistry, immunological responses against CII and histopathological features of the arthritis.

Results

Clinically manifest arthritis was observed in almost 100% (21 out of 22) of the animals. Fifty percent of the animals developed semi-acute CIA while the other 50% displayed a more chronic disease. Both cellular (CD3/CD4 and CD3/CD8) and humoral responses (IgM and IgG) against CII were involved in the development of the disease. Besides mild histopathological changes in bone and cartilage, severe inflammation in extraarticular tissues like periosteum and subcutaneous tissues was observed.

Conclusions

This new model in marmosets more closely resembles chronic RA with respect to the chronic disease course and pathomorphological presentation than the more acute monophasic and destructive CIA model in macaques. This model can therefore fill a niche in preclinical testing of new human specific therapeutics.
“Sensitive but Unclassified”: Secrecy and the Counterterrorist State
Authors: Masco Joseph
Published: October 2010

This essay tracks the conversion of the United States from a countercommunist to a counterterrorist state formation via an examination of the expanding logics of state secrecy. Starting with analysis of a new category of state information known as “sensitive but unclassified,” the essay theorizes a secrecy/threat matrix as a core project of the national security state. In doing so, it assesses the ideological linkages between “weapons of mass destruction” and the “secret” from the Cold War through the “war on terror.” The essay argues that the long-term effect of state secrecy is to fundamentally devalue knowledge and expertise and assesses the impact of such devaluation on the democratic state form.
Introduction: Transgressing Boundaries
Authors: Fassin Éric , Surkis Judith
Published: October 2010

A public scandal that followed the 2005 exhibition of Tanja Ostojić's remake of Courbet's L'origine du monde revealed the contemporary sexual politics of the European Union. This essay analyzes how what was at stake in this “obscenity” was not the sex but rather the sexualization of Europe that the politics of immigration entail. This explicit representation uncovered the logic of inclusion and exclusion that defines today the boundaries of sexual democracy.
Pitx2 defines alternate pathways acting through MyoD during limb and somitic myogenesis
Authors: L'Honoré Aurore , Ouimette Jean-François , Lavertu-Jolin Marisol , Drouin Jacques
Published: October 2010

The MyoD gene is part of the core regulatory network that governs skeletal myogenesis and acts as an essential determinant of the myogenic cell fate. Although generic regulatory networks converging on this gene have been described, the specific mechanisms leading to MyoD expression in muscles of different ontology remain misunderstood. We now show that the homeobox gene Pitx2 is required for initial activation of the MyoD gene in limb muscle precursors through direct binding of Pitx2 to the MyoD core enhancer. Whereas Myf5 and Mrf4 are dispensable for limb muscle progenitor fate, inactivation of Myf5 and Mrf4 in Pitx2 mutants results in a drastic decrease of limb MyoD expression. Thus, Pitx2 and Myf5 define parallel genetic pathways for limb myogenesis. We show a similar dependence on Pitx2 and Myf5(Mrf4) in myotome, where MyoD expression is initially activated by Myf5 and Mrf4. In their absence, MyoD expression is eventually rescued by a Pax3-dependent mechanism. We now provide evidence that Pitx2 contributes to the rescue of MyoD expression and that it acts downstream of Pax3. We thus propose that myogenic differentiation of somite-derived muscle cells relies on two parallel genetic pathways, with the Pitx2 pathway being of primary importance for limb myogenesis but the Myf5 and Mrf4 pathway predominating in myotome. Muscle-specific wiring of regulatory networks composed of similar transcription factors thus underlies development of distinct skeletal muscles.
Hox11genes establish synovial joint organization and phylogenetic characteristics in developing mouse zeugopod skeletal elements
Authors: Koyama Eiki , Yasuda Tadashi , Minugh-Purvis Nancy , Kinumatsu Takashi , Yallowitz Alisha R. , Wellik Deneen M. , Pacifici Maurizio
Published: October 2010

Hox11 genes are essential for zeugopod skeletal element development but their roles in synovial joint formation remain largely unknown. Here, we show that the elbow and knee joints of mouse embryos lacking all Hox11 paralogous genes are specifically remodeled and reorganized. The proximal ends of developing mutant ulna and radius elements became morphologically similar and formed an anatomically distinct elbow joint. The mutant ulna lacked the olecranon that normally attaches to the triceps brachii muscle tendon and connects the humerus to the ulna. In its place, an ulnar patella-like element developed that expressed lubricin on its ventral side facing the joint and was connected to the triceps muscle tendon. In mutant knees, both tibia and fibula fully articulated with an enlarged femoral epiphyseal end that accommodated both elements, and the neo-tripartite knee joint was enclosed in a single synovial cavity and displayed an additional anterior ligament. The mutant joints also exhibited a different organization of the superficial zone of articular cartilage that normally exerts an anti-friction function. In conclusion, Hox11 genes co-regulate and coordinate the development of zeugopod skeletal elements and adjacent elbow and knee joints, and dictate joint identity, morphogenesis and anatomical and functional organization. Notably, the ulnar patella and tripartite knee joints in the mouse mutants actually characterize several lower vertebrates, including certain reptiles and amphibians. The re-emergence of such anatomical structures suggests that their genetic blueprint is still present in the mouse genome but is normally modified to the needs of the mammalian joint-formation program by distinct Hox11 function.
The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex
Authors: Werth Max , Walentin Katharina , Aue Annekatrin , Schönheit Jörg , Wuebken Anne , Pode-Shakked Naomi , Vilianovitch Larissa , Erdmann Bettina , Dekel Benjamin , Bader Michael , Barasch Jonathan , Rosenbauer Frank , Luft Friedrich C. , Schmidt-Ott Kai M.
Published: October 2010

Differentiation of epithelial cells and morphogenesis of epithelial tubes or layers is closely linked with the establishment and remodeling of the apical junctional complex, which includes adherens junctions and tight junctions. Little is known about the transcriptional control of apical junctional complex components. Here, we show that the transcription factor grainyhead-like 2 (Grhl2), an epithelium-specific mammalian homolog of Drosophila Grainyhead, is essential for adequate expression of the adherens junction gene E-cadherin and the tight junction gene claudin 4 (Cldn4) in several types of epithelia, including gut endoderm, surface ectoderm and otic epithelium. We have generated Grhl2 mutant mice to demonstrate defective molecular composition of the apical junctional complex in these compartments that coincides with the occurrence of anterior and posterior neural tube defects. Mechanistically, we show that Grhl2 specifically associates with cis-regulatory elements localized at the Cldn4 core promoter and within intron 2 of the E-cadherin gene. Cldn4 promoter activity in epithelial cells is crucially dependent on the availability of Grhl2 and on the integrity of the Grhl2-associated cis-regulatory element. At the E-cadherin locus, the intronic Grhl2-associated cis-regulatory region contacts the promoter via chromatin looping, while loss of Grhl2 leads to a specific decrease of activating histone marks at the E-cadherin promoter. Together, our data provide evidence that Grhl2 acts as a target gene-associated transcriptional activator of apical junctional complex components and, thereby, crucially participates in epithelial differentiation.
How to Make Antimicrobial Stewardship Work: Practical Considerations for Hospitals of All Sizes
Authors: Patel Dimple , Macdougall Conan
Published: October 2010

Implementation of an antimicrobial stewardship program in a hospital is complicated by a variety of challenges. Key issues facing stewardship personnel include recruiting personnel and building relationships, establishing program metrics, selecting stewardship strategies, working with clinicians, reporting results, and adapting the program. These issues can present different challenges at community hospitals and academic medical centers. Strategies for overcoming these challenges require accounting for the unique characteristics of each institution.
Book Reviews
Authors: Esopenko Carrie.
Published: October 2010

The student's guide to cognitive neuroscience 2nd edition Ward Jamie New York: Psychology Press, 2010. $53.96. ISBN 978‐1‐84872‐003‐9
Factors behind the Historic Defeat of Japan's Liberal Democratic Party in 2009
Authors: Maeda Ko
Published: October 2010

This study seeks to identify the factors that caused the historic defeat of Japan's longdominant party in the 2009 election. Employing district-level data, I show that a large national swing occurred that overrode district-specific characteristics, and that the electoral coordination of opposition parties helped bring about victory.
The Rise and Fall of Anti-American Sentiment in South Korea: Deconstructing Hegemonic Ideas and Threat Perception
Authors: Jung Heon Joo
Published: October 2010

This article examines anti-American sentiment in South Korea by taking a closer look at the ways in which hegemonic ideas of anti-North Korea and pro-U.S. have been deconstructed. It argues that the extent to which South Koreans perceive a North Korean threat exerts a significant influence on anti-American sentiment in South Korea.