bluuebunny/crossref_metadata_2025 huggingface dataset:
Enrichment of Sca1+ hematopoietic progenitors in polycythemic mice inhibits leukemogenesis
Authors: Usenko Tatiana , Li You-Jun , Haeri Mehran , Li Yanmei , Vecchiarelli-Federico Laura M. , Zhao Xiaojun , Prchal Josef T. , Ben-David Yaacov
Published: July 2009

Polycythemia vera (PV) is a myeloproliferative disorder characterized by a pronounced increase in the number of erythroid cells. However, despite this aberrant proliferation, the incidence of erythroleukemia is paradoxically rare in PV patients. In this study, we show that the progression of Friend virus–induced erythroleukemia is delayed in a mouse model of primary familial congenital polycythemia in which the wild-type Epo-receptor (EpoR) gene is replaced with a truncated human EPOR gene. Herein, we show that these mice exhibit enrichment of Sca1+/cKit− progenitors and several mature immune cells, such as dendritic cells and macrophages. In cotransplantation experiments, Sca1+/cKit− progenitors inhibit the tumorigenicity of Sca1−/cKit+ erythroleukemic cells. A cell line established from Sca1+/cKit− progenitors is also capable of inhibiting leukemic proliferation in culture and in mice. This phenomenon of leukemic inhibition, also detected in the serum of PV patients, is partially attributed to increased nitric oxide secretion. In addition, the administration of erythropoietin into leukemic mice induces a polycythemia-like state associated with the expansion of Sca1+/cKit− progenitors and derivative immune cells, thereby inhibiting leukemia progression. This study indicates that a combination therapy incorporating the enrichment of Sca1+/cKit− progenitors may serve as a novel approach for the treatment of leukemia.
Comparative chromosome mapping of repetitive sequences. Implications for genomic evolution in the fish, Hoplias malabaricus
Authors: Cioffi Marcelo B , Martins Cesar , Bertollo Luiz AC
Published: July 2009

Background

Seven karyomorphs of the fish, Hoplias malabaricus (A-G) were previously included in two major groups, Group I (A, B, C, D) and Group II (E, F, G), based on their similar karyotype structure. In this paper, karyomorphs from Group I were analyzed by means of distinct chromosomal markers, including silver-stained nucleolar organizer regions (Ag-NORs) and chromosomal location of repetitive sequences (18S and 5S rDNA, and satellite 5SHind III-DNA), through fluorescence in situ hybridization (FISH), in order to evaluate the evolutionary relationships among them.

Results

The results showed that several chromosomal markers had conserved location in the four karyomorphs. In addition, some other markers were only conserved in corresponding chromosomes of karyomorphs A-B and C-D. These data therefore reinforced and confirmed the proposed grouping of karyomorphs A-D in Group I and highlight a closer relationship between karyomorphs A-B and C-D. Moreover, the mapping pattern of some markers on some autosomes and on the chromosomes of the XY and X1X2Y systems provided new evidence concerning the possible origin of the sex chromosomes.

Conclusion

The in situ investigation of repetitive DNA sequences adds new informative characters useful in comparative genomics at chromosomal level and provides insights into the evolutionary relationships among Hoplias malabaricus karyomorphs.
Whole genome expression analysis within the angiotensin II-apolipoprotein E deficient mouse model of abdominal aortic aneurysm
Authors: Rush Catherine , Nyara Moses , Moxon Joseph V , Trollope Alexandra , Cullen Bradford , Golledge Jonathan
Published: July 2009

Background

An animal model commonly used to investigate pathways and potential therapeutic interventions relevant to abdominal aortic aneurysm (AAA) involves subcutaneous infusion of angiotensin II within the apolipoprotein E deficient mouse. The aim of this study was to investigate genes differentially expressed in aneurysms forming within this mouse model in order to assess the relevance of this model to human AAA.

Results

Using microarrays we identified genes relevant to aneurysm formation within apolipoprotein E deficient mice. Firstly we investigated genes differentially expressed in the aneurysm prone segment of the suprarenal aorta in these mice. Secondly we investigated genes that were differentially expressed in the aortas of mice developing aneurysms relative to those that did not develop aneurysms in response to angiotensin II infusion. Our findings suggest that a host of inflammation and extracellular matrix remodelling pathways are upregulated within the aorta in mice developing aneurysms. Kyoto Encyclopedia of Genes and Genome categories enriched in the aortas of mice with aneurysms included cytokine-cytokine receptor interaction, leukocyte transendothelial migration, natural killer cell mediated cytotoxicity and hematopoietic cell lineage. Genes associated with extracellular matrix remodelling, such as a range of matrix metalloproteinases were also differentially expressed in relation to aneurysm formation.

Conclusion

This study is the first report describing whole genome expression arrays in the apolipoprotein E deficient mice in relation to aneurysm formation. The findings suggest that the pathways believed to be critical in human AAA are also relevant to aneurysm formation in this mouse model. The findings therefore support the value of this model to investigate interventions and mechanisms of human AAA.
Deep sampling of the Palomero maize transcriptome by a high throughput strategy of pyrosequencing
Authors: Vega-Arreguín Julio C , Ibarra-Laclette Enrique , Jiménez-Moraila Beatriz , Martínez Octavio , Vielle-Calzada Jean Philippe , Herrera-Estrella Luis , Herrera-Estrella Alfredo
Published: July 2009

Background

In-depth sequencing analysis has not been able to determine the overall complexity of transcriptional activity of a plant organ or tissue sample. In some cases, deep parallel sequencing of Expressed Sequence Tags (ESTs), although not yet optimized for the sequencing of cDNAs, has represented an efficient procedure for validating gene prediction and estimating overall gene coverage. This approach could be very valuable for complex plant genomes. In addition, little emphasis has been given to efforts aiming at an estimation of the overall transcriptional universe found in a multicellular organism at a specific developmental stage.

Results

To explore, in depth, the transcriptional diversity in an ancient maize landrace, we developed a protocol to optimize the sequencing of cDNAs and performed 4 consecutive GS20–454 pyrosequencing runs of a cDNA library obtained from 2 week-old Palomero Toluqueño maize plants. The protocol reported here allowed obtaining over 90% of informative sequences. These GS20–454 runs generated over 1.5 Million reads, representing the largest amount of sequences reported from a single plant cDNA library. A collection of 367,391 quality-filtered reads (30.09 Mb) from a single run was sufficient to identify transcripts corresponding to 34% of public maize ESTs databases; total sequences generated after 4 filtered runs increased this coverage to 50%. Comparisons of all 1.5 Million reads to the Maize Assembled Genomic Islands (MAGIs) provided evidence for the transcriptional activity of 11% of MAGIs. We estimate that 5.67% (86,069 sequences) do not align with public ESTs or annotated genes, potentially representing new maize transcripts. Following the assembly of 74.4% of the reads in 65,493 contigs, real-time PCR of selected genes confirmed a predicted correlation between the abundance of GS20–454 sequences and corresponding levels of gene expression.

Conclusion

A protocol was developed that significantly increases the number, length and quality of cDNA reads using massive 454 parallel sequencing. We show that recurrent 454 pyrosequencing of a single cDNA sample is necessary to attain a thorough representation of the transcriptional universe present in maize, that can also be used to estimate transcript abundance of specific genes. This data suggests that the molecular and functional diversity contained in the vast native landraces remains to be explored, and that large-scale transcriptional sequencing of a presumed ancestor of the modern maize varieties represents a valuable approach to characterize the functional diversity of maize for future agricultural and evolutionary studies.
Comparative genomics of the emerging human pathogen Photorhabdus asymbiotica with the insect pathogen Photorhabdus luminescens
Authors: Wilkinson Paul , Waterfield Nicholas R , Crossman Lisa , Corton Craig , Sanchez-Contreras Maria , Vlisidou Isabella , Barron Andrew , Bignell Alexandra , Clark Louise , Ormond Douglas , Mayho Matthew , Bason Nathalie , Smith Frances , Simmonds Mark , Churcher Carol , Harris David , Thompson Nicholas R , Quail Michael , Parkhill Julian , ffrench-Constant Richard H
Published: July 2009

Background

The Gram-negative bacterium Photorhabdus asymbiotica (Pa) has been recovered from human infections in both North America and Australia. Recently, Pa has been shown to have a nematode vector that can also infect insects, like its sister species the insect pathogen P. luminescens (Pl). To understand the relationship between pathogenicity to insects and humans in Photorhabdus we have sequenced the complete genome of Pa strain ATCC43949 from North America. This strain (formerly referred to as Xenorhabdus luminescens strain 2) was isolated in 1977 from the blood of an 80 year old female patient with endocarditis, in Maryland, USA. Here we compare the complete genome of Pa ATCC43949 with that of the previously sequenced insect pathogen P. luminescens strain TT01 which was isolated from its entomopathogenic nematode vector collected from soil in Trinidad and Tobago.

Results

We found that the human pathogen Pa had a smaller genome (5,064,808 bp) than that of the insect pathogen Pl (5,688,987 bp) but that each pathogen carries approximately one megabase of DNA that is unique to each strain. The reduced size of the Pa genome is associated with a smaller diversity in insecticidal genes such as those encoding the Toxin complexes (Tc's), Makes caterpillars floppy (Mcf) toxins and the Photorhabdus Virulence Cassettes (PVCs). The Pa genome, however, also shows the addition of a plasmid related to pMT1 from Yersinia pestis and several novel pathogenicity islands including a novel Type Three Secretion System (TTSS) encoding island. Together these data suggest that Pa may show virulence against man via the acquisition of the pMT1-like plasmid and specific effectors, such as SopB, that promote its persistence inside human macrophages. Interestingly the loss of insecticidal genes in Pa is not reflected by a loss of pathogenicity towards insects.

Conclusion

Our results suggest that North American isolates of Pa have acquired virulence against man via the acquisition of a plasmid and specific virulence factors with similarity to those shown to play roles in pathogenicity against humans in other bacteria.
Expressional dynamics of minisatellite 33.15 tagged spermatozoal transcriptome in Bubalus bubalis
Authors: Srivastava Jyoti , Premi Sanjay , Kumar Sudhir , Ali Sher
Published: July 2009

Background

Transcriptionally quiescent spermatozoa have been established to be a repository of mRNA coding for several functionally essential cellular proteins. This entourage of mRNA is envisaged to be involved in post-fertilization and early embryogenesis. Minisatellites tagged with mRNA transcripts have been implicated with gene organization, regulation and function. However, the organization and expression of the minisatellite tagged transcript diversity, particularly in spermatozoa, remains unclear.

Results

In the present study, we identified and characterized 12 mRNA transcripts from the spermatozoa of water buffaloBubalus bubalisemploying minisatellite associated sequence amplification (MASA) and a consensus sequence of 33.15 repeat loci. Of these 33.15 tagged transcripts, only one was found to be homologous to Bovine steroid 21-hydroxylase (P-450-c21) gene. Other ten transcripts showed significant similarity with various mRNAs or chromosomal contigs across the species. The remaining one construed to be novel since this was unreported in the database (NCBI GenBank). All these uncharacterized and known transcripts showed highest expression in testis and spermatozoa compared to that in somatic tissues and ovary. Of these 12 mRNA transcripts, 4 showed differential expression in the forebrain and hindbrain of buffalo. Moreover, genes corresponding to all the 33.15 tagged spermatozoal transcripts were found to be conserved across 13 other species analyzed.

Conclusion

Our results show MASA as an important tool to capture mRNA transcript diversity tagged with minisatellites in the spermatozoa. Comprehensive characterization of these transcripts is envisaged to augment our understanding on the genes involved in testicular functions and sustenance of a viable paternal genome during pre- and post- fertilization events and early stages of development. Prospects of this approach in genome analysis in general and comparative genomics in particular are highlighted.
Comparison of feature selection and classification for MALDI-MS data
Authors: Liu Qingzhong , Sung Andrew H , Qiao Mengyu , Chen Zhongxue , Yang Jack Y , Yang Mary Qu , Huang Xudong , Deng Youping
Published: July 2009

Introduction

In the classification of Mass Spectrometry (MS) proteomics data, peak detection, feature selection, and learning classifiers are critical to classification accuracy. To better understand which methods are more accurate when classifying data, some publicly available peak detection algorithms for Matrix assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) data were recently compared; however, the issue of different feature selection methods and different classification models as they relate to classification performance has not been addressed. With the application of intelligent computing, much progress has been made in the development of feature selection methods and learning classifiers for the analysis of high-throughput biological data. The main objective of this paper is to compare the methods of feature selection and different learning classifiers when applied to MALDI-MS data and to provide a subsequent reference for the analysis of MS proteomics data.

Results

We compared a well-known method of feature selection, Support Vector Machine Recursive Feature Elimination (SVMRFE), and a recently developed method, Gradient based Leave-one-out Gene Selection (GLGS) that effectively performs microarray data analysis. We also compared several learning classifiers including K-Nearest Neighbor Classifier (KNNC), Naïve Bayes Classifier (NBC), Nearest Mean Scaled Classifier (NMSC), uncorrelated normal based quadratic Bayes Classifier recorded as UDC, Support Vector Machines, and a distance metric learning for Large Margin Nearest Neighbor classifier (LMNN) based on Mahanalobis distance. To compare, we conducted a comprehensive experimental study using three types of MALDI-MS data.

Conclusion

Regarding feature selection, SVMRFE outperformed GLGS in classification. As for the learning classifiers, when classification models derived from the best training were compared, SVMs performed the best with respect to the expected testing accuracy. However, the distance metric learning LMNN outperformed SVMs and other classifiers on evaluating the best testing. In such cases, the optimum classification model based on LMNN is worth investigating for future study.
Interviewee Transcript Review: assessing the impact on qualitative research
Authors: Hagens Victoria , Dobrow Mark J , Chafe Roger
Published: July 2009

Background

This paper assesses interviewee transcript review (ITR) as a technique for improving the rigour of interview-based, qualitative research. ITR is a process whereby interviewees are provided with verbatim transcripts of their interviews for the purposes of verifying accuracy, correcting errors or inaccuracies and providing clarifications. ITR, in various forms, is widely used among qualitative researchers, however there is limited methodological guidance on how it should be employed and little is known about its actual impact on the transcript, the data, the interviewee or the researcher.

Methods

ITR was incorporated into a qualitative research study in which 51 key informant interviews were conducted with a range of senior stakeholders within the Canadian health care system. The changes made by interviewees to their transcripts were systematically tracked and categorized using a set of mutually exclusive categories.

Results

The study found that ITR added little to the accuracy of the transcript and may create complications if the goal of the researcher is to produce a transcript which reflects precisely what was said at the time of the interview. The advantages of ITR are that it allows interviewees the opportunity to edit or clarify information provided in the original interview, with many interviewees providing corrections, clarifications, and in some cases, adding new material to their transcripts. There are also potential disadvantages, such as a bias created by inconsistent data sources or the loss of data when an interviewee chooses to remove valuable material. The impact of ITR on the interviewee may be both positive and negative, depending on the specific circumstances and the nature of the study. The impact of ITR on the researcher was minimal in this study, but is again subject to specific circumstances of the research context.

Conclusion

While ITR is employed by many researchers across numerous fields, the advantages of its use may be relatively small in terms of verifying the accuracy of qualitative interview transcripts. Researchers are advised to carefully consider both the potential advantages and disadvantages of ITR outlined in this paper before deciding to incorporate the practice within their qualitative study designs.
Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes
Authors: Feder Jeanette , Ovadia Ofer , Blech Ilana , Cohen Josef , Wainstein Julio , Harman-Boehm Ilana , Glaser Benjamin , Mishmar Dan
Published: July 2009

Background

Although mitochondrial dysfunction is consistently manifested in patients with Type 2 Diabetes mellitus (T2DM), the association of mitochondrial DNA (mtDNA) sequence variants with T2DM varies among populations. These differences might stem from differing environmental influences among populations. However, other potentially important considerations emanate from the very nature of mitochondrial genetics, namely the notable high degree of partitioning in the distribution of human mtDNA variants among populations, as well as the interaction of mtDNA and nuclear DNA-encoded factors working in concert to govern mitochondrial function. We hypothesized that association of mtDNA genetic variants with T2DM could be revealed while controlling for the effect of additional inherited factors, reflected in family history information.

Methods

To test this hypothesis we set out to investigate whether mtDNA genetic variants will be differentially associated with T2DM depending on the diabetes status of the parents. To this end, association of mtDNA genetic backgrounds (haplogroups) with T2DM was assessed in 1055 Jewish patients with and without T2DM parents ('DP' and 'HP', respectively).

Results

Haplogroup J1 was found to be 2.4 fold under-represented in the 'HP' patients (p = 0.0035). These results are consistent with a previous observation made in Finnish T2DM patients. Moreover, assessing the haplogroup distribution in 'DP' versus 'HP' patients having diabetic siblings revealed that haplogroup J1 was virtually absent in the 'HP' group.

Conclusion

These results imply the involvement of inherited factors, which modulate the susceptibility of haplogroup J1 to T2DM.
Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression
Authors: Yasuoka Hironao , Kodama Rieko , Tsujimoto Masahiko , Yoshidome Katsuhide , Akamatsu Hiroki , Nakahara Masaaki , Inagaki Michiya , Sanke Tokio , Nakamura Yasushi
Published: July 2009

Background

Neuropilin-2 (Nrp2) is a receptor for vascular endothelial growth factor-C (VEGF-C), which is a well-known lymphangiogenic factor and plays an important role in lymph node metastasis of various human cancers, including breast cancer. Recently, Nrp2 was shown to play a role in cancer by promoting tumor cell metastasis. CXC chemokine receptor 4 (CXCR4) also promotes tumor metastasis. In the previous studies, we demonstrated that VEGF-C and cytoplasmic CXCR4 expressions were correlated with poorer patient prognosis (BMC Cancer 2008,8:340; Breast Cancer Res Treat 2005, 91:125–132).

Methods

The relationship between Nrp2 expression and lymph node metastasis, VEGF-C expression, CXCR4 expression, and other established clinicopathological variables (these data were cited in our previous papers), including prognosis, was analyzed in human breast cancer. Effects of neutralizing anti-Nrp2 antibody on CXCR4 expression and chemotaxis were assessed in MDA-MB-231 breast cancer cells.

Results

Nrp2 expression was observed in 53.1% (60 of 113) of the invasive breast carcinomas. Nrp2 expression was significantly correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival. In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival. Neutralizing anti-Nrp2 antibody blocks cytoplasmic CXCR4 expression and CXCR4-induced migration in MDA-MB-231 cells.

Conclusion

Nrp2 expression was correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer. Our data also showed a role for Nrp2 in regulating cytoplasmic CXCR4 expression in vitro.
Determinants of household demand for bed nets in a rural area of southern Mozambique
Authors: Chase Claire , Sicuri Elisa , Sacoor Charfudin , Nhalungo Delino , Nhacolo Ariel , Alonso Pedro L , Menéndez Clara
Published: July 2009

Background

A key to making insecticide-treated nets (ITNs) a long-term, sustainable solution to the spread of malaria is understanding what drives their purchase and use. Few studies have analysed the determinants of demand for bed nets for malaria prevention at the household level, and in particular, how demand for nets compares with demand for other mosquito prevention methods.

Methods

This study uses a household survey to assess the determinants of demand for bed nets in an area of endemic malaria transmission in rural, southern Mozambique. The study looks at willingness to pay (WTP) for bed nets, net ownership, usage, and past purchase behaviour, alongside expenditure and frequency of use of alternate methods for malaria prevention.

Results

While overall net ownership in the sample is low, the evidence fails to suggest that poorer households are less likely to own bed nets, when controlling for covariates, nor does the likelihood of receiving a free net depend on socioeconomic status (SES). Formal schooling and market knowledge seem to indicate higher average willingness to pay, while use of alternate methods for malaria prevention, and receipt of Indoor Residual Spraying (IRS) are found to decrease demand for bed nets.

Conclusion

For long-term sustainability of ITNs to be realized, results suggest that either full or partial subsidies may be necessary in some contexts to encourage households to obtain and use nets. Given the possible substitution effects of combined malaria control interventions, and the danger of not taking into consideration household preferences for malaria prevention, successful malaria control campaigns should invest a portion of their funds towards educating recipients of IRS and users of other preventive methods on the importance of net use even in the absence of mosquitoes.
Esophagopericardial fistula as a rare complication after total gastrectomy for cancer
Authors: Dafnios Nikolaos , Anastasopoulos Georgios , Marinis Athanasios , Polydorou Andreas , Gkiokas Georgios , Fragulidis Georgios , Athanasopoulos Panayiotis , Theodosopoulos Theodosios
Published: July 2009

Background

Esophagopericardial fistula is a rare but life-threatening complication of benign, malignant or traumatic esophageal disease. It is most commonly associated with benign etiology and carries a high mortality rate which increases with delay in diagnosis.

Case presentation

We present a case of an esophagopericardial fistula as a rare complication in a 53-year-old male patient, 7 months after total gastrectomy for an adenocarcinoma of the esophagogastric junction.

Conclusion

The prognosis of esophagopericardial fistula is poor, especially when it is associated with malignancy.
Thrombotic genetic risk factors and warfarin pharmacogenetic variants in São Miguel's healthy population (Azores)
Authors: Branco Claudia C , Pereirinha Tânia , Cabral Rita , Pacheco Paula R , Mota-Vieira Luisa
Published: July 2009

Background

The Azorean population presents the highest standardized mortality rate for cardiovascular diseases (CVD) when compared to mainland Portugal and other populations. Since thrombosis is a common cause of CVD, we assessed four polymorphisms in three thrombotic risk genes – F5 (G1691A), F2 (G20210A) and MTHFR (C677T, A1298C), in 469 healthy blood donors from São Miguel Island (Azores). We also analysed the CYP2C9 (C430T, A1075C) and VKORC1 (G1639A) variants in fifty-eight individuals with predisposition to thrombosis (possessing at least one variation in F5 or F2 genes and one in MTHFR) to evaluate their warfarin drug response genetic profiles.

Results

Among the 469 individuals, the data showed that thrombotic risk allele frequencies – 1691A (4.9%), 20210A (1.8%), 677T (41.7%) and 1298C (24.8%) – were similar to other Caucasians, but significantly different from mainland Portuguese (χ2, p < 0.001). The combined analysis of these variants identified twenty-two different genetic profiles (genotype order: F5, F2, MTHFR C677T and A1298C). Complete homozygosity for all wild-type alleles (GG GG CC AA) was present in 11.7%, being GG GG CT AA (22.4%) the most frequent profile. The results also demonstrated that 12.4% (58 out of 469) of São Miguel islanders have increased genetic predisposition to thrombosis. Subsequently, we evaluated these individuals for their warfarin response genetic profiles. The data showed that seven out of fifty-eight individuals are poor metabolizers (two with CYP2C9*2/*2 and five with CYP2C9*2/*3 genotypes). VKORC1 polymorphism analysis identified twelve individuals (20.7%) with AA genotype, who probably will require lower doses of warfarin. The joint analysis of CYP2C9 and VKORC1 revealed that 79.3% (46 out of 58) of the individuals carry at least one polymorphism in these genes. Within these, twenty-five individuals (43.1%) need intermediate and/or low doses of warfarin, if treatment is started.

Conclusion

The present study demonstrated, for the first time, that São Miguel, and possibly the Azores population, shows significant differences on allele frequencies of thrombotic risk factors when compared to mainland Portugal. This research constitutes a primary approach for future studies on CVD, as well as for the implementation of warfarin dosing protocols using the patient's genotypic information.
Assessment of environmental correlates of physical activity: development of a European questionnaire
Authors: Spittaels Heleen , Foster Charlie , Oppert Jean-Michel , Rutter Harry , Oja Pekka , Sjöström Michael , De Bourdeaudhuij Ilse
Published: July 2009

Background

Research on the influence of the physical environment on physical activity is rapidly expanding and different measures of environmental perceptions have been developed, mostly in the US and Australia. The purpose of this paper is to (i) provide a literature review of measures of environmental perceptions recently used in European studies and (ii) develop a questionnaire for population monitoring purposes in the European countries.

Methods

This study was done within the framework of the EU-funded project 'Instruments for Assessing Levels of Physical Activity and Fitness (ALPHA)', which aims to propose standardised instruments for physical activity and fitness monitoring across Europe. Quantitative studies published from 1990 up to November 2007 were systematically searched in Pubmed, Web of Science, TRIS and Geobase. In addition a survey was conducted among members of the European network for the promotion of Health-Enhancing Physical Activity (HEPA Europe) and European members of the International Physical Activity and Environment Network (IPEN) to identify published or ongoing studies. Studies were included if they were conducted among European general adult population (18+y) and used a questionnaire to assess perceptions of the physical environment. A consensus meeting with an international expert group was organised to discuss the development of a European environmental questionnaire.

Results

The literature search resulted in 23 European studies, 15 published and 8 unpublished. In these studies, 13 different environmental questionnaires were used. Most of these studies used adapted versions of questionnaires that were developed outside Europe and that focused only on the walkability construct: The Neighborhood Environment Walkability Scale (NEWS), the abbreviated version of the NEWS (ANEWS) and the Neighborhood Quality of Life Study (NQLS) questionnaire have been most commonly used. Based on the results of the literature review and the output of the meeting with international experts, a European environmental questionnaire with 49 items was developed.

Conclusion

There is need for a greater degree of standardization in instruments/methods used to assess environmental correlates of physical activity, taking into account the European-specific situation. A first step in this process is taken by the development of a European environmental questionnaire.
The chemiluminescence based Ziplex® automated workstation focus array reproduces ovarian cancer Affymetrix GeneChip® expression profiles
Authors: Quinn Michael CJ , Wilson Daniel J , Young Fiona , Dempsey Adam A , Arcand Suzanna L , Birch Ashley H , Wojnarowicz Paulina M , Provencher Diane , Mes-Masson Anne-Marie , Englert David , Tonin Patricia N
Published: July 2009

Background

As gene expression signatures may serve as biomarkers, there is a need to develop technologies based on mRNA expression patterns that are adaptable for translational research. Xceed Molecular has recently developed a Ziplex® technology, that can assay for gene expression of a discrete number of genes as a focused array. The present study has evaluated the reproducibility of the Ziplex system as applied to ovarian cancer research of genes shown to exhibit distinct expression profiles initially assessed by Affymetrix GeneChip® analyses.

Methods

The new chemiluminescence-based Ziplex® gene expression array technology was evaluated for the expression of 93 genes selected based on their Affymetrix GeneChip® profiles as applied to ovarian cancer research. Probe design was based on the Affymetrix target sequence that favors the 3' UTR of transcripts in order to maximize reproducibility across platforms. Gene expression analysis was performed using the Ziplex Automated Workstation. Statistical analyses were performed to evaluate reproducibility of both the magnitude of expression and differences between normal and tumor samples by correlation analyses, fold change differences and statistical significance testing.

Results

Expressions of 82 of 93 (88.2%) genes were highly correlated (p < 0.01) in a comparison of the two platforms. Overall, 75 of 93 (80.6%) genes exhibited consistent results in normal versus tumor tissue comparisons for both platforms (p < 0.001). The fold change differences were concordant for 87 of 93 (94%) genes, where there was agreement between the platforms regarding statistical significance for 71 (76%) of 87 genes. There was a strong agreement between the two platforms as shown by comparisons of log2 fold differences of gene expression between tumor versus normal samples (R = 0.93) and by Bland-Altman analysis, where greater than 90% of expression values fell within the 95% limits of agreement.

Conclusion

Overall concordance of gene expression patterns based on correlations, statistical significance between tumor and normal ovary data, and fold changes was consistent between the Ziplex and Affymetrix platforms. The reproducibility and ease-of-use of the technology suggests that the Ziplex array is a suitable platform for translational research.
Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB
Authors: Li Chun-Yan , Li Bao-Xiu , Liang Yi , Peng Rui-Qing , Ding Ya , Xu Da-Zhi , Zhang Xin , Pan Zhi-Zhong , Wan De-Sen , Zeng Yi-Xin , Zhu Xiao-Feng , Zhang Xiao-Shi
Published: July 2009

Background

Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors.

Patients and methods

Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed.

Results

The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5%) were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%). Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth.

Conclusion

The fact that a higher percentage CD133+ cells were strongly associated with a poorer prognosis in patients with locally advanced colon cancer implicated that CD133+ cancer cells contribute to the tumor progression, and the overpopulation hypothesis of cancer stem cell seems reasonable.
Molt-inhibiting hormone stimulates vitellogenesis at advanced ovarian developmental stages in the female blue crab, Callinectes sapidus 2: novel specific binding sites in hepatopancreas and cAMP as a second messenger
Authors: Zmora Nilli , Sagi Amir , Zohar Yonathan , Chung J Sook
Published: July 2009

The finding that molt-inhibiting hormone (MIH) regulates vitellogenesis in the hepatopancreas of mature Callinectes sapidus females, raised the need for the characterization of its mode of action. Using classical radioligand binding assays, we located specific, saturable, and non-cooperative binding sites for MIH in the Y-organs of juveniles (J-YO) and in the hepatopancreas of vitellogenic adult females. MIH binding to the hepatopancreas membranes had an affinity 77 times lower than that of juvenile YO membranes (KD values: 3.22 × 10-8 and 4.19 × 10-10 M/mg protein, respectively). The number of maximum binding sites (BMAX) was approximately two times higher in the hepatopancreas than in the YO (BMAX values: 9.24 × 10-9 and 4.8 × 10-9 M/mg protein, respectively). Furthermore, MIH binding site number in the hepatopancreas was dependent on ovarian stage and was twice as high at stage 3 than at stages 2 and 1. SDS-PAGE separation of [125I] MIH or [125I] crustacean hyperglycemic hormone (CHH) crosslinked to the specific binding sites in the membranes of the J-YO and hepatopancreas suggests a molecular weight of ~51 kDa for a MIH receptor in both tissues and a molecular weight of ~61 kDa for a CHH receptor in the hepatopancreas. The use of an in vitro incubation of hepatopancreas fragments suggests that MIH probably utilizes cAMP as a second messenger in this tissue, as cAMP levels increased in response to MIH. Additionally, 8-Bromo-cAMP mimicked the effects of MIH on vitellogenin (VtG) mRNA and heterogeneous nuclear (hn) VtG RNA levels. The results imply that the functions of MIH in the regulation of molt and vitellogenesis are mediated through tissue specific receptors with different kinetics and signal transduction. MIH ability to regulate vitellogenesis is associated with the appearance of MIH specific membrane binding sites in the hepatopancreas upon pubertal/final molt.
Molt-inhibiting hormone stimulates vitellogenesis at advanced ovarian developmental stages in the female blue crab, Callinectes sapidus 1: an ovarian stage dependent involvement
Authors: Zmora Nilli , Trant John , Zohar Yonathan , Chung J Sook
Published: July 2009

To understand the hormonal coordination of the antagonism between molting and reproduction in crustaceans, the terminally anecdysial mature female Callinectes sapidus was used as a model. The regulatory roles of crustacean hyperglycemic hormone (CHH) and molt-inhibiting hormone (MIH) in vitellogenesis were examined. A competitive specific RIA was used to measure the levels of MIH and CHH in the hemolymphs of mature females at pre- and mid- vitellogenic stages, and their effects on vitellogenesis at early (early 2, E2) and mid vitellogenesis (3) stages were determined in vitro. A hepatopancreas fragments incubation system was developed and the levels of vitellogenin (VtG), as well as VtG mRNA and heterogeneous nuclear (hn)VtG RNA were determined using RIA or QPCR, respectively. MIH titers were four times higher at mid-vitellogenesis than at pre-vitellogenesis, while CHH levels in the hemolymph were constant. In the in vitro incubation experiments, MIH increased both VtG mRNA levels and secretion at ovarian stage 3. At stage E2, however, MIH resulted in a mixed response: downregulation of VtG mRNA and upregulation of hnVtG RNA. CHH had no effect on any of the parameters. Actinomycin D blocked the stimulatory effects of MIH in stage 3 animals on VtG mRNA and VtG, while cycloheximide attenuated only VtG levels, confirming the MIH stimulatory effect at this stage. MIH is a key endocrine regulator in the coordination of molting and reproduction in the mature female C. sapidus, which simultaneously inhibits molt and stimulates vitellogenesis.
Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to tumorigenesis
Authors: Osmundson Evan C , Ray Dipankar , Moore Finola E , Kiyokawa Hiroaki
Published: July 2009

The execution of the mitotic program with high fidelity is dependent upon precise spatiotemporal regulation of posttranslational protein modifications. For example, the timely polyubiquitination of critical mitotic regulators by Anaphase Promoting Complex/Cyclosome (APC/C) is essential for the metaphase to anaphase transition and mitotic exit. The spindle assembly checkpoint prevents unscheduled activity of APC/C-Cdc20 in early mitosis, allowing bipolar attachment of kinetochores to mitotic spindle and facilitating equal segregation of sister chromatids. The critical effector of the spindle checkpoint, Mitotic arrest deficient 2 (Mad2), is recruited to unattached kinetochores forming a complex with other regulatory proteins to efficiently and cooperatively inhibit APC/C-Cdc20. A weakened and/or dysfunctional spindle checkpoint has been linked to the development of genomic instability in both cell culture and animal models, and evidence suggests that aberrant regulation of the spindle checkpoint plays a critical role in human carcinogenesis. Recent studies have illuminated a network of both degradative and non-degradative ubiquitination events that regulate the metaphase to anaphase transition and mitotic exit. Within this context, our recent work showed that the HECT (Homologous to E6-AP C-terminus)-family E3 ligase Smurf2 (Smad specific ubiquitin regulatory factor 2), known as a negative regulator of transforming growth factor-beta (TGF-β) signaling, is required for a functional spindle checkpoint by promoting the functional localization and stability of Mad2. Here we discuss putative models explaining the role of Smurf2 as a new regulator in the spindle checkpoint. The dynamic mitotic localization of Smurf2 to the centrosome and other critical mitotic structures provides implications about mitotic checkpoint control dependent on various ubiquitination events. Finally, deregulated Smurf2 activity may contribute to carcinogenesis by perturbed mitotic control.
Retinal waves are likely to instruct the formation of eye-specific retinogeniculate projections
Authors: Feller Marla B
Published: July 2009

Prior to eye-opening and the development of visual responses, the retina exhibits highly correlated spontaneous firing pattens termed retinal waves. Disruption of the normal spontaneous firing pattern either genetically or pharmacologically prevents the eye-specific refinement of retinogeniculate afferents. Here I provide the evidence that retinal waves play an instructive role in this process. In addition, I argue that a full understanding requires an identification of the features of retinal activity that drive the refinement as well as an understanding of mechanisms that transform these signals into axonal rearrangements.
Retinal waves are unlikely to instruct the formation of eye-specific retinogeniculate projections
Authors: Chalupa Leo M
Published: July 2009

In all mammalian species the projections of the two eyes to the dorsal lateral geniculate nucleus are initially overlapping before gradually forming the eye-specific domains evident at maturity. It is widely thought that retinal waves of neuronal activity play an instructional role in this developmental process. Here, I discuss the myriad reasons why retinal waves are unlikely to have such a role, and suggest that eye-specific molecular cues in combination with neuronal activity are most probably involved in the formation of eye-specific retinogeniculate projections.
A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases
Authors: Peineau Stéphane , Nicolas Céline S , Bortolotto Zuner A , Bhat Ratan V , Ryves W Jonathan , Harwood Adrian J , Dournaud Pascal , Fitzjohn Stephen M , Collingridge Graham L
Published: July 2009

Background

The signalling mechanisms involved in the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression (LTD) in the hippocampus are poorly understood. Numerous studies have presented evidence both for and against a variety of second messengers systems being involved in LTD induction. Here we provide the first systematic investigation of the involvement of serine/threonine (ser/thr) protein kinases in NMDAR-LTD, using whole-cell recordings from CA1 pyramidal neurons.

Results

Using a panel of 23 inhibitors individually loaded into the recorded neurons, we can discount the involvement of at least 57 kinases, including PKA, PKC, CaMKII, p38 MAPK and DYRK1A. However, we have been able to confirm a role for the ser/thr protein kinase, glycogen synthase kinase 3 (GSK-3).

Conclusion

The present study is the first to investigate the role of 58 ser/thr protein kinases in LTD in the same study. Of these 58 protein kinases, we have found evidence for the involvement of only one, GSK-3, in LTD.
Comparison of three methods of extravascular lung water volume measurement in patients after cardiac surgery
Authors: Maddison Benjamin , Wolff Christopher , Findlay George , Radermacher Peter , Hinds Charles , Pearse Rupert M
Published: July 2009

Introduction

Measurement of extravascular lung water (EVLW) by using the lithium-thermal (Li-thermal) and single-thermal indicator dilution methods was compared with the indocyanine green-thermal (ICG-thermal) method in humans.

Methods

Single-center observational study involving patients undergoing cardiac surgery with cardiopulmonary bypass. Paired measurements were taken 1, 2, 4, and 6 hours after surgery. Bland-Altman analysis was used to calculate bias and limits of agreement. Data are presented as mean (SD) or median (IQR).

Results

Seventeen patients were recruited (age, 69 years (54 to 87 years); Parsonnet score 10 (0 to 29)). Sixteen ICG-thermal measurements were excluded after blinded assessment because of poor-quality indicator dilution curves. EVLW volume as measured by the ICG-thermal technique was 4.6 (1.9) ml/kg, compared with 5.3 (1.4) ml/kg for the single-thermal method. Measurements taken with the Li-thermal method were clearly erroneous (-7.6 (7.4) ml/kg). In comparison with simultaneous measurements with the ICG-thermal method, single-thermal measurements had an acceptable degree of bias, but limits of agreement were poor (bias, -0.3 ml/kg (2.3)). Li-thermal measurements compared poorly with the ICG-thermal reference method (bias, 13.2 ml/kg (14.4)).

Conclusions

The principal finding of this study was that the prototype Li-thermal method did not provide reliable measurements of EVLW volume when compared with the ICG-thermal reference technique. Although minimal bias was associated with the single-thermal method, limits of agreement were approximately 45% of the normal value of EVLW volume. The Li-thermal method performed very poorly because of the overestimation of mean indicator transit time by using an external lithium ion electrode. These findings suggest that the assessment of lung water content by lithium-indicator dilution is not sufficiently reliable for clinical use in individual patients.