bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remote messaging: exploring graphic manifestations of human relationships to the terrain through site markers and cognitive mapping in Ladakh, India
Authors: Norwood Angela D. 
Published: August 2009

This article explores the role of design in Ladakh, a remote region in northwestern India that was opened to tourism and trade only 35 years ago. The shift in the prevailing socio-economic structure is manifested within the region's forms of visual communication, spanning a continuum from photographic advertising to hand-painted wayfinding systems. One questions the cumulative effects these graphic artifacts have on local people's perception of the region and their identities integrated with it. Workshops were conducted in which participants were introduced to the abstract visual language of maps then sketched their home villages. Content analysis of these externalized cognitive maps reveals a consistency of visual representation strategies across all participants. References to natural and man-made features reflect reverence for the land and an understanding of agrarian systems. Currently graphic design in Ladakh is in service to profit outside interests. The author seeks a role for design that values the local constituency as well.
EvoRSR: an integrated system for exploring evolution of RNA structural robustness
Authors: Shu Wenjie , Ni Ming , Bo Xiaochen , Zheng Zhiqiang , Wang Shengqi 
Published: August 2009

Abstract

Background
Robustness, maintaining a constant phenotype despite perturbations, is a fundamental property of biological systems that is incorporated at various levels of biological complexity. Although robustness has been frequently observed in nature, its evolutionary origin remains unknown. Current hypotheses suggest that robustness originated as a direct consequence of natural selection, as an intrinsic property of adaptations, or as a congruent correlate of environment robustness. To elucidate the evolutionary origins of robustness, a convenient computational package is strongly needed.

Results
In this study, we developed the open-source integrated system EvoRSR (Evolution of RNA Structural Robustness) to explore the evolution of robustness based on biologically important landscapes induced by RNA folding. EvoRSR is object-oriented, modular, and freely available at http://biotech.bmi.ac.cn/EvoRSR under the GNU/GPL license. We present an overview of EvoRSR package and illustrate its features with the miRNA gene cel-mir-357.

Conclusion
EvoRSR is a novel and flexible package for exploring the evolution of robustness. Accordingly, EvoRSR can be used for future studies to investigate the evolution and origin of robustness and to address other common questions about robustness. While the current EvoRSR environment is a versatile analysis framework, future versions can include features to enhance evolutionary studies of robustness.
Integrating microarray analysis and the soybean genome to understand the soybeans iron deficiency response
Authors: O'Rourke Jamie A , Nelson Rex T , Grant David , Schmutz Jeremy , Grimwood Jane , Cannon Steven , Vance Carroll P , Graham Michelle A , Shoemaker Randy C 
Published: August 2009

Abstract

Background
Soybeans grown in the upper Midwestern United States often suffer from iron deficiency chlorosis, which results in yield loss at the end of the season. To better understand the effect of iron availability on soybean yield, we identified genes in two near isogenic lines with changes in expression patterns when plants were grown in iron sufficient and iron deficient conditions.

Results
Transcriptional profiles of soybean (Glycine max, L. Merr) near isogenic lines Clark (PI548553, iron efficient) and IsoClark (PI547430, iron inefficient) grown under Fe-sufficient and Fe-limited conditions were analyzed and compared using the Affymetrix® GeneChip® Soybean Genome Array. There were 835 candidate genes in the Clark (PI548553) genotype and 200 candidate genes in the IsoClark (PI547430) genotype putatively involved in soybean's iron stress response. Of these candidate genes, fifty-eight genes in the Clark genotype were identified with a genetic location within known iron efficiency QTL and 21 in the IsoClark genotype. The arrays also identified 170 single feature polymorphisms (SFPs) specific to either Clark or IsoClark. A sliding window analysis of the microarray data and the 7X genome assembly coupled with an iterative model of the data showed the candidate genes are clustered in the genome. An analysis of 5' untranslated regions in the promoter of candidate genes identified 11 conserved motifs in 248 differentially expressed genes, all from the Clark genotype, representing 129 clusters identified earlier, confirming the cluster analysis results.

Conclusion
These analyses have identified the first genes with expression patterns that are affected by iron stress and are located within QTL specific to iron deficiency stress. The genetic location and promoter motif analysis results support the hypothesis that the differentially expressed genes are co-regulated. The combined results of all analyses lead us to postulate iron inefficiency in soybean is a result of a mutation in a transcription factor(s), which controls the expression of genes required in inducing an iron stress response.
The cyclin-dependent kinase inhibitor 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole induces nongenotoxic, DNA replication-independent apoptosis of normal and leukemic cells, regardless of their p53 status
Authors: Turinetto Valentina , Porcedda Paola , Orlando Luca , De Marchi Mario , Amoroso Antonio , Giachino Claudia 
Published: August 2009

Abstract

Background
Current chemotherapy of human cancers focuses on the DNA damage pathway to induce a p53-mediated cellular response leading to either G1 arrest or apoptosis. However, genotoxic treatments may induce mutations and translocations that result in secondary malignancies or recurrent disease. In addition, about 50% of human cancers are associated with mutations in the p53 gene. Nongenotoxic activation of apoptosis by targeting specific molecular pathways thus provides an attractive therapeutic approach.

Methods
Normal and leukemic cells were evaluated for their sensitivity to 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) through cell viability and caspase activation tests. The apoptotic pathway induced by DRB was analysed by immunfluorescence and immunoblot analysis. H2AX phosphorylation and cell cycle analysis were performed to study the dependance of apoptosis on DNA damage and DNA replication, respectively. To investigate the role of p53 in DRB-induced apoptosis, specific p53 inhibitors were used. Statistical analysis on cell survival was performed with the test of independence.

Results
Here we report that DRB, an inhibitor of the transcriptional cyclin-dependent kinases (CDKs) 7 and 9, triggers DNA replication-independent apoptosis in normal and leukemic human cells regardless of their p53 status and without inducing DNA damage. Our data indicate that (i) in p53-competent cells, apoptosis induced by DRB relies on a cytosolic accumulation of p53 and subsequent Bax activation, (ii) in the absence of p53, it may rely on p73, and (iii) it is independent of ATM and NBS1 proteins. Notably, even apoptosis-resistant leukemic cells such as Raji were sensitive to DRB.

Conclusion
Our results indicate that DRB represents a potentially useful cancer chemotherapeutic strategy that employs both the p53-dependent and -independent apoptotic pathways without inducing genotoxic stress, thereby decreasing the risk of secondary malignancies.
Yeast artificial chromosomes employed for random assembly of biosynthetic pathways and production of diverse compounds in Saccharomyces cerevisiae
Authors: Naesby Michael , Nielsen Søren VS , Nielsen Curt AF , Green Trine , Tange Thomas Ø , Simón Ernesto , Knechtle Philipp , Hansson Anders , Schwab Markus S , Titiz Olca , Folly Christophe , Archila Roberto E , Maver Milena , van Sint Fiet Stephan , Boussemghoune Thiamo , Janes Michael , Kumar A S Sathish , Sonkar Shailendra P , Mitra Partha P , Benjamin V Ajai Kumar , Korrapati Nimitha , Suman Inala , Hansen Esben H , Thybo Tanja , Goldsmith Neil , Sorensen Alexandra Santana 
Published: August 2009

AbstractBackgroundNatural products are an important source of drugs and other commercially interesting compounds, however their isolation and production is often difficult. Metabolic engineering, mainly in bacteria and yeast, has sought to circumvent some of the associated problems but also this approach is impeded by technical limitations. Here we describe a novel strategy for production of diverse natural products, comprising the expression of an unprecedented large number of biosynthetic genes in a heterologous host.ResultsAs an example, genes from different sources, representing enzymes of a seven step flavonoid pathway, were individually cloned into yeast expression cassettes, which were then randomly combined on Yeast Artificial Chromosomes and used, in a single transformation of yeast, to create a variety of flavonoid producing pathways. Randomly picked clones were analysed, and approximately half of them showed production of the flavanone naringenin, and a third of them produced the flavonol kaempferol in various amounts. This reflected the assembly of 5–7 step multi-species pathways converting the yeast metabolites phenylalanine and/or tyrosine into flavonoids, normally only produced by plants. Other flavonoids were also produced that were either direct intermediates or derivatives thereof. Feeding natural and unnatural, halogenated precursors to these recombinant clones demonstrated the potential to further diversify the type of molecules that can be produced with this technology.ConclusionThe technology has many potential uses but is particularly suited for generating high numbers of structurally diverse compounds, some of which may not be amenable to chemical synthesis, thus greatly facilitating access to a huge chemical space in the search for new commercially interesting compounds
Intrinsic expression of host genes and intronic miRNAs in prostate carcinoma cells
Authors: Sikand Kavleen , Slane Stephen D , Shukla Girish C 
Published: August 2009

Abstract

Background
Recent data show aberrant and altered expression of regulatory noncoding micro (mi) RNAs in prostate cancer (PCa). A large number of miRNAs are encoded in organized intronic clusters within many protein coding genes. While expression profiling studies of miRNAs are common place, little is known about the host gene and their resident miRNAs coordinated expression in PCa cells. Furthermore, whether expression of a subset of miRNAs is distinct in androgen-responsive and androgen-independent cells is not clear. Here we have examined the expression of mature miRNAs of miR 17–92, miR 106b-25 and miR 23b-24 clusters along with their host genes C13orf25, MCM7 and AMPO respectively in PCa cell lines.

Results
The expression profiling of miRNAs and host genes was performed in androgen-sensitive MDA PCa 2b and LNCaP as well as in androgen-refractory PC-3 and DU 145 cell culture models of PCa. No significant correlation between the miRNA expression and the intrinsic hormone-responsive property of PCa cells was observed. Androgen-sensitive MDA PCa 2b cells exhibited the highest level of expression of most miRNAs studied in this report. We found significant expression variations between host genes and their resident miRNAs. The expressions of C13orf25 and miR 17–92 cluster as well as MCM7 and miR 106b-25 cluster did not reveal statistically significant correlation, thus suggesting that host genes and resident miRNAs may be expressed independent of each other.

Conclusion
Our results suggest that miRNA expression profiles may not predict intrinsic hormone-sensitive environment of PCa cells. More importantly, our data indicate the possibility of additional novel mechanisms for intronic miRNA processing in PCa cells.
Tumor biology and cancer therapy – an evolving relationship
Authors: Seufferlein Thomas , Ahn Johann , Krndija Denis , Lother Ulrike , Adler Guido , von Wichert Götz 
Published: August 2009

Abstract
The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pathways underlie cancer, and not just altered genes. Thus, an effective therapeutic agent will sometimes have to target downstream parts of a signaling pathway or physiological effects rather than individual genes. In addition, over the past few years increasing evidence has suggested that solid tumors represent a very heterogeneous group of cells with different susceptibility to cancer therapy. Thus, since therapeutic concepts and pathophysiological understanding are continuously evolving a combination of current concepts in tumor therapy and tumor biology is needed. This review aims to present current problems of cancer therapy by highlighting exemplary results from recent clinical trials with colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying reasons.
Psychosocial correlates of eating behavior in children and adolescents: a review
Authors: McClain Arianna D , Chappuis Courtney , Nguyen-Rodriguez Selena T , Yaroch Amy L , Spruijt-Metz Donna 
Published: August 2009

Abstract

Background
Understanding the correlates of dietary intake is necessary in order to effectively promote healthy dietary behavior among children and adolescents. A literature review was conducted on the correlates of the following categories of dietary intake in children and adolescents: Fruit, Juice and Vegetable Consumption, Fat in Diet, Total Energy Intake, Sugar Snacking, Sweetened Beverage Consumption, Dietary Fiber, Other Healthy Dietary Consumption, and Other Less Healthy Dietary Consumption in children and adolescents.

Methods
Cross-sectional and prospective studies were identified from PubMed, PsycINFO and PsycArticles by using a combination of search terms. Quantitative research examining determinants of dietary intake among children and adolescents aged 3–18 years were included. The selection and review process yielded information on country, study design, population, instrument used for measuring intake, and quality of research study.

Results
Seventy-seven articles were included. Many potential correlates have been studied among children and adolescents. However, for many hypothesized correlates substantial evidence is lacking due to a dearth of research. The correlates best supported by the literature are: perceived modeling, dietary intentions, norms, liking and preferences. Perceived modeling and dietary intentions have the most consistent and positive associations with eating behavior. Norms, liking, and preferences were also consistently and positively related to eating behavior in children and adolescents. Availability, knowledge, outcome expectations, self-efficacy and social support did not show consistent relationships across dietary outcomes.

Conclusion
This review examined the correlates of various dietary intake; Fruit, Juice and Vegetable Consumption, Fat in Diet, Total Energy Intake, Sugar Snacking, Sweetened Beverage Consumption, Dietary Fiber, Other Healthy Dietary Consumption, and Other Less Healthy Dietary Consumption in cross-sectional and prospective studies for children and adolescents. The correlates most consistently supported by evidence were perceived modeling, dietary intentions, norms, liking and preferences. More prospective studies on the psychosocial determinants of eating behavior using broader theoretical perspectives should be examined in future research.
Mechanisms of the action of povidone-iodine against human and avian influenza A viruses: its effects on hemagglutination and sialidase activities
Authors: Sriwilaijaroen Nongluk , Wilairat Prapon , Hiramatsu Hiroaki , Takahashi Tadanobu , Suzuki Takashi , Ito Morihiro , Ito Yasuhiko , Tashiro Masato , Suzuki Yasuo 
Published: August 2009

Abstract

Background
Influenza virus infection causes significant morbidity and mortality and has marked social and economic impacts throughout the world. The influenza surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), act cooperatively to support efficient influenza A virus replication and provide the most important targets for anti-influenza chemotherapy. In this study, povidone-iodine (PVP-I), which has a broad-spectrum microbicidal property, was examined for its inhibitory effects against influenza virus infection in MDCK cells and the mechanisms of PVP-I action on HA and NA were revealed.

Results
Results obtained using a novel fluorescence- and chromogenic-based plaque inhibition assay showed that 1.56 mg/ml PVP-I inhibited infections in MDCK cells of human (8 strains) and avian (5 strains) influenza A viruses, including H1N1, H3N2, H5N3 and H9N2, from 23.0–97.5%. A sialidase inhibition assay revealed that PVP-I inhibited N1, N2 and N3 neuraminidases with IC50 values of 9.5–212.1 μg/ml by a mixed-type inhibition mechanism. Receptor binding inhibition and hemagglutinin inhibition assays indicated that PVP-I affected viral hemagglutinin rather than host-specific sialic acid receptors.

Conclusion
Mechanisms of reduction of viral growth in MDCK cells by PVP-I involve blockade of viral attachment to cellular receptors and inhibition of viral release and spread from infected cells. Therefore, PVP-I is useful to prevent infection and limit spread of human and avian influenza viruses.
Multiple functions of precursor BDNF to CNS neurons: negative regulation of neurite growth, spine formation and cell survival
Authors: Koshimizu Hisatsugu , Kiyosue Kazuyuki , Hara Tomoko , Hazama Shunsuke , Suzuki Shingo , Uegaki Koichi , Nagappan Guhan , Zaitsev Eugene , Hirokawa Takatsugu , Tatsu Yoshiro , Ogura Akihiko , Lu Bai , Kojima Masami 
Published: August 2009

AbstractBackgroundProneurotrophins and mature neurotrophins elicit opposite effects via the p75 neurotrophin receptor (p75NTR) and Trk tyrosine kinase receptors, respectively; however the molecular roles of proneurotrophins in the CNS are not fully understood.ResultsBased on two rare single nucleotide polymorphisms (SNPs) of thehuman brain-derived neurotrophic factor (BDNF)gene, we generated R125M-, R127L- and R125M/R127L-BDNF, which have amino acid substitution(s) near the cleavage site between the pro- and mature-domain of BDNF. Western blot analyses demonstrated that these BDNF variants are poorly cleaved and result in the predominant secretion of proBDNF. Using these cleavage-resistant proBDNF (CR-proBDNF) variants, the molecular and cellular roles of proBDNF on the CNS neurons were examined. First, CR-proBDNF showed normal intracellular distribution and secretion in cultured hippocampal neurons, suggesting that inhibition of proBDNF cleavage does not affect intracellular transportation and secretion of BDNF. Second, we purified recombinant CR-proBDNF and tested its biological effects using cultured CNS neurons. Treatment with CR-proBDNF elicited apoptosis of cultured cerebellar granule neurons (CGNs), while treatment with mature BDNF (matBDNF) promoted cell survival. Third, we examined the effects of CR-proBDNF on neuronal morphology using more than 2-week cultures of basal forebrain cholinergic neurons (BFCNs) and hippocampal neurons. Interestingly, in marked contrast to the action of matBDNF, which increased the number of cholinergic fibers and hippocampal dendritic spines, CR-proBDNF dramatically reduced the number of cholinergic fibers and hippocampal dendritic spines, without affecting the survival of these neurons.ConclusionThese results suggest that proBDNF has distinct functions in different populations of CNS neurons and might be responsible for specific physiological cellular processes in the brain.
Mechanism of action of lenalidomide in hematological malignancies
Authors: Kotla Venumadhav , Goel Swati , Nischal Sangeeta , Heuck Christoph , Vivek Kumar , Das Bhaskar , Verma Amit 
Published: August 2009

AbstractImmunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide is a 4-amino-glutamyl analogue of thalidomide that lacks the neurologic side effects of sedation and neuropathy and has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma. Lenalidomide has been shown to be an immunomodulator, affecting both cellular and humoral limbs of the immune system. It has also been shown to have anti-angiogenic properties. Newer studies demonstrate its effects on signal transduction that can partly explain its selective efficacy in subsets of MDS. Even though the exact molecular targets of lenalidomide are not well known, its activity across a spectrum of neoplastic conditions highlights the possibility of multiple target sites of action.
Development and initial validation of the Bedside Paediatric Early Warning System score
Authors: Parshuram Christopher S , Hutchison James , Middaugh Kristen 
Published: August 2009

Abstract
Introduction
Adverse outcomes following clinical deterioration in children admitted to hospital wards is frequently preventable. Identification of children for referral to critical care experts remains problematic. Our objective was to develop and validate a simple bedside score to quantify severity of illness in hospitalized children.

Methods
A case-control design was used to evaluate 11 candidate items and identify a pragmatic score for routine bedside use. Case-patients were urgently admitted to the intensive care unit (ICU). Control-patients had no 'code blue', ICU admission or care restrictions. Validation was performed using two prospectively collected datasets.

Results
Data from 60 case and 120 control-patients was obtained. Four out of eleven candidate-items were removed. The seven-item Bedside Paediatric Early Warning System (PEWS) score ranges from 0–26. The mean maximum scores were 10.1 in case-patients and 3.4 in control-patients. The area under the receiver operating characteristics curve was 0.91, compared with 0.84 for the retrospective nurse-rating of patient risk for near or actual cardiopulmonary arrest. At a score of 8 the sensitivity and specificity were 82% and 93%, respectively. The score increased over 24 hours preceding urgent paediatric intensive care unit (PICU) admission (P < 0.0001). In 436 urgent consultations, the Bedside PEWS score was higher in patients admitted to the ICU than patients who were not admitted (P < 0.0001).

Conclusions
We developed and performed the initial validation of the Bedside PEWS score. This 7-item score can quantify severity of illness in hospitalized children and identify critically ill children with at least one hours notice. Prospective validation in other populations is required before clinical application.