bluuebunny/crossref_metadata_2025 huggingface dataset:
Trading Spaces: Carving up Events for Learning Language
Authors: Göksun Tilbe , Hirsh-Pasek Kathy , Michnick Golinkoff Roberta
Published: February 2010

Relational terms (e.g., verbs and prepositions) are the cornerstone of language development, bringing together two distinct fields: linguistic theory and infants’ event processing. To acquire relational terms such as run, walk, in, and on, infants must first perceive and conceptualize components of dynamic events such as containment—support, path—manner, source—goal, and figure—ground. Infants must then uncover how the particular language they are learning encodes these constructs. This review addresses the interaction of language learning with infants’ conceptualization of these nonlinguistic spatial event components. We present the thesis that infants start with language-general nonlinguistic constructs that are gradually refined and tuned to the requirements of their native language. In effect, infants are trading spaces, maintaining their sensitivity to some relational distinctions while dampening other distinctions, depending on how their native language expresses these constructs.
Secular Trends and Personality: Perspectives from Longitudinal and Cross-Cultural Studies—Commentary on Trzesniewski & Donnellan (2010)
Authors: Terracciano Antonio
Published: February 2010

According to cross-temporal meta-analyses (Twenge, 2000, 2001), social trends over the last decades have powerfully influenced the personality profiles of children and students, with effects accounting for 20% of the variance of Neuroticism and Extraversion. However, Trzesniewski and Donnellan (2010, this issue), who examined a large and representative U.S. high-school student sample, found little evidence of secular trends. In this commentary, I emphasize the distinction between cohort and period effects and review findings from longitudinal and cross-cultural studies on the role of social trends and other cultural influences on personality traits. Analyses of adult personality scores from the Baltimore Longitudinal Study of Aging provide little support for powerful secular effects on Neuroticism and Extraversion; evidence supports a secular trend of declining trust, along with additional small effects on other facets of personality. Analyses of personality scores from around the world suggest that social and cultural differences account for about 5% of the variance on major dimensions of personality. The integration of findings from multiple perspectives provides useful insights into the role of the environment on personality traits.
It is Developmental Me, Not Generation Me: Developmental Changes are more Important than Generational Changes in Narcissism—Commentary on Trzesniewski & Donnellan (2010)
Authors: Roberts Brent W. , Edmonds Grant , Grijalva Emily
Published: February 2010

In this article, we make two points about the ongoing debate concerning the purported increase in narcissistic tendencies in college students over the last 30 years. First, we show that when new data on narcissism are folded into preexisting meta-analytic data, there is no increase in narcissism in college students over the last few decades. Second, we show, in contrast, that age changes in narcissism are both replicable and comparatively large in comparison to generational changes in narcissism. This leads to the conclusion that every generation is Generation Me, as every generation of younger people are more narcissistic than their elders.
Large Gallstones Resulting in Obstruction
Authors: Bolinger Krista
Published: February 2010

Generally, health care professionals are taught that gallstones found within the gallbladder that are large in size create no potential complications for the patient. However, there are rare instances when a gallstone that is greater than 2 cm can pass from the gallbladder and cause problems. When a large gallstone does pass, a gallstone ileus can occur, forming a fistula and intestinal obstruction. This rare pathology may be difficult to initially detect by sonography, but the use of sonography when comparing with computed tomography can aid in finalizing this unique pathology.
DraGnET: Software for storing, managing and analyzing annotated draft genome sequence data
Authors: Duncan Stacy , Sirkanungo Ruchita , Miller Leslie , Phillips Gregory J
Published: February 2010

Background

New "next generation" DNA sequencing technologies offer individual researchers the ability to rapidly generate large amounts of genome sequence data at dramatically reduced costs. As a result, a need has arisen for new software tools for storage, management and analysis of genome sequence data. Although bioinformatic tools are available for the analysis and management of genome sequences, limitations still remain. For example, restrictions on the submission of data and use of these tools may be imposed, thereby making them unsuitable for sequencing projects that need to remain in-house or proprietary during their initial stages. Furthermore, the availability and use of next generation sequencing in industrial, governmental and academic environments requires biologist to have access to computational support for the curation and analysis of the data generated; however, this type of support is not always immediately available.

Results

To address these limitations, we have developed DraGnET (Draft Genome Evaluation Tool). DraGnET is an open source web application which allows researchers, with no experience in programming and database management, to setup their own in-house projects for storing, retrieving, organizing and managing annotated draft and complete genome sequence data. The software provides a web interface for the use of BLAST, allowing users to perform preliminary comparative analysis among multiple genomes. We demonstrate the utility of DraGnET for performing comparative genomics on closely related bacterial strains. Furthermore, DraGnET can be further developed to incorporate additional tools for more sophisticated analyses.

Conclusions

DraGnET is designed for use either by individual researchers or as a collaborative tool available through Internet (or Intranet) deployment. For genome projects that require genome sequencing data to initially remain proprietary, DraGnET provides the means for researchers to keep their data in-house for analysis using local programs or until it is made publicly available, at which point it may be uploaded to additional analysis software applications. The DraGnET home page is available at http://www.dragnet.cvm.iastate.edu and includes example files for examining the functionalities, a link for downloading the DraGnET setup package and a link to the DraGnET source code hosted with full documentation on SourceForge.
Green-to-red photoconvertible fluorescent proteins: tracking cell and protein dynamics on standard wide-field mercury arc-based microscopes
Authors: Baker Susan M , Buckheit Robert W , Falk Matthias M
Published: February 2010

Background

Green fluorescent protein (GFP) and other FP fusions have been extensively utilized to track protein dynamics in living cells. Recently, development of photoactivatable, photoswitchable and photoconvertible fluorescent proteins (PAFPs) has made it possible to investigate the fate of discrete subpopulations of tagged proteins. Initial limitations to their use (due to their tetrameric nature) were overcome when monomeric variants, such as Dendra, mEos, and mKikGR were cloned/engineered.

Results

Here, we report that by closing the field diaphragm, selective, precise and irreversible green-to-red photoconversion (330-380 nm illumination) of discrete subcellular protein pools was achieved on a wide-field fluorescence microscope equipped with standard DAPI, Fluorescein, and Rhodamine filter sets and mercury arc illumination within 5-10 seconds. Use of a DAPI-filter cube with long-pass emission filter (LP420) allowed the observation and control of the photoconversion process in real time. Following photoconversion, living cells were imaged for up to 5 hours often without detectable phototoxicity or photobleaching.

Conclusions

We demonstrate the practicability of this technique using Dendra2 and mEos2 as monomeric, photoconvertible PAFP representatives fused to proteins with low (histone H2B), medium (gap junction channel protein connexin 43), and high (α-tubulin; clathrin light chain) dynamic cellular mobility as examples. Comparable efficient, irreversible green-to-red photoconversion of selected portions of cell nuclei, gap junctions, microtubules and clathrin-coated vesicles was achieved. Tracking over time allowed elucidation of the dynamic live-cycle of these subcellular structures. The advantage of this technique is that it can be performed on a standard, relatively inexpensive wide-field fluorescence microscope with mercury arc illumination. Together with previously described laser scanning confocal microscope-based photoconversion methods, this technique promises to further increase the general usability of photoconvertible PAFPs to track the dynamic movement of cells and proteins over time.
Evolution of spliceosomal introns following endosymbiotic gene transfer
Authors: Ahmadinejad Nahal , Dagan Tal , Gruenheit Nicole , Martin William , Gabaldón Toni
Published: February 2010

Background

Spliceosomal introns are an ancient, widespread hallmark of eukaryotic genomes. Despite much research, many questions regarding the origin and evolution of spliceosomal introns remain unsolved, partly due to the difficulty of inferring ancestral gene structures. We circumvent this problem by using genes originated by endosymbiotic gene transfer, in which an intron-less structure at the time of the transfer can be assumed.

Results

By comparing the exon-intron structures of 64 mitochondrial-derived genes that were transferred to the nucleus at different evolutionary periods, we can trace the history of intron gains in different eukaryotic lineages. Our results show that the intron density of genes transferred relatively recently to the nuclear genome is similar to that of genes originated by more ancient transfers, indicating that gene structure can be rapidly shaped by intron gain after the integration of the gene into the genome and that this process is mainly determined by forces acting specifically on each lineage. We analyze 12 cases of mitochondrial-derived genes that have been transferred to the nucleus independently in more than one lineage.

Conclusions

Remarkably, the proportion of shared intron positions that were gained independently in homologous genes is similar to that proportion observed in genes that were transferred prior to the speciation event and whose shared intron positions might be due to vertical inheritance. A particular case of parallel intron gain in the nad7 gene is discussed in more detail.
Identification and characterization of Tc1/mariner-like DNA transposons in genomes of the pathogenic fungi of the Paracoccidioides species complex
Authors: Marini Marjorie M , Zanforlin Tamiris , Santos Patrícia C , Barros Roberto RM , Guerra Anne CP , Puccia Rosana , Felipe Maria SS , Brigido Marcelo , Soares Célia MA , Ruiz Jerônimo C , Silveira José F , Cisalpino Patrícia S
Published: February 2010

Background

Paracoccidioides brasiliensis (Eukaryota, Fungi, Ascomycota) is a thermodimorphic fungus, the etiological agent of paracoccidioidomycosis, the most important systemic mycoses in Latin America. Three isolates corresponding to distinct phylogenetic lineages of the Paracoccidioides species complex had their genomes sequenced. In this study the identification and characterization of class II transposable elements in the genomes of these fungi was carried out.

Results

A genomic survey for DNA transposons in the sequence assemblies of Paracoccidioides, a genus recently proposed to encompass species P. brasiliensis (harboring phylogenetic lineages S1, PS2, PS3) and P. lutzii (Pb01-like isolates), has been completed. Eight new Tc1/mariner families, referred to as Trem (Tr ansposable e lement m ariner), labeled A through H were identified. Elements from each family have 65-80% sequence similarity with other Tc1/mariner elements. They are flanked by 2-bp TA target site duplications and different termini. Encoded DDD-transposases, some of which have complete ORFs, indicated that they could be functionally active. The distribution of Trem elements varied between the genomic sequences characterized as belonging to P. brasiliensis (S1 and PS2) and P. lutzii. TremC and H elements would have been present in a hypothetical ancestor common to P. brasiliensis and P. lutzii, while TremA, B and F elements were either acquired by P. brasiliensis or lost by P. lutzii after speciation. Although TremD and TremE share about 70% similarity, they are specific to P. brasiliensis and P. lutzii, respectively. This suggests that these elements could either have been present in a hypothetical common ancestor and have evolved divergently after the split between P. brasiliensis and P. Lutzii, or have been independently acquired by horizontal transfer.

Conclusions

New families of Tc1/mariner DNA transposons in the genomic assemblies of the Paracoccidioides species complex are described. Families were distinguished based on significant BLAST identities between transposases and/or TIRs. The expansion of Trem in a putative ancestor common to the species P. brasiliensis and P. lutzii would have given origin to TremC and TremH, while other elements could have been acquired or lost after speciation had occurred. The results may contribute to our understanding of the organization and architecture of genomes in the genus Paracoccidioides.
The ecology of nasal colonization of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus: the role of competition and interactions with host's immune response
Authors: Margolis Elisa , Yates Andrew , Levin Bruce R
Published: February 2010

Background

The first step in invasive disease caused by the normally commensal bacteria Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae is their colonization of the nasal passages. For any population to colonize a new habitat it is necessary for it to be able to compete with the existing organisms and evade predation. In the case of colonization of these species the competition is between strains of the same and different species of bacteria and the predation is mediated by the host's immune response. Here, we use a neonatal rat model to explore these elements of the ecology of nasal colonization by these occasionally invasive bacteria.

Results

When neonatal rats are colonized by any one of these species the density of bacteria in the nasal passage rapidly reaches a steady-state density that is species-specific but independent of inoculum size. When novel populations of H. influenzae and S. pneumoniae are introduced into the nasal passages of neonatal rats with established populations of the same species, residents and invaders coexisted. However, this was not the case for S. aureus - the established population inhibited invasion of new S. aureus populations. In mixed-species introductions, S. aureus or S. pneumoniae facilitated the invasion of another H. influenzae population; for other pairs the interaction was antagonistic and immune-mediated. For example, under some conditions H. influenzae promoted an immune response which limited the invasion of S. pneumoniae.

Conclusions

Nasal colonization is a dynamic process with turnover of new strains and new species. These results suggest that multiple strains of either H. influenzae or S. pneumoniae can coexist; in contrast, S. aureus strains require a host to have no other S. aureus present to colonize. Levels of colonization (and hence the possible risk of invasive disease) by H. influenzae are increased in hosts pre-colonized with either S. aureus or S. pneumoniae.
Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?
Authors: Steele Peter , Strange Geoff , Wlodarczyk John , Dalton Brad , Stewart Simon , Gabbay Eli , Keogh Anne
Published: February 2010

Background

Pulmonary arterial hypertension (PAH) has witnessed dramatic treatment advances over the past decade. However, with the exception of epoprostenol, data from short-term randomized controlled trials (RCTs) have not shown a benefit of these drugs on survival. There remains a need to differentiate between available therapies and current endpoint responses which in turn, could be used to guide treatment selection and provide long-term prognostic information for patients.

Methods

We performed a systematic literature search of MEDLINE and EMBASE databases for RCTs of PAH-specific therapy published between January 1980 and May 2009. Articles were selected if they contained a placebo comparator and described hemodynamic changes from baseline. We applied the weighted mean change in hemodynamic variables to the equation developed by the National Institutes of Health (NIH) Registry to estimate long-term survival with each therapy.

Results

Ten RCTs involving 1,635 patients met the inclusion criteria. Suitable hemodynamic data were identified for bosentan, sitaxentan, sildenafil, epoprostenol, beraprost and treprostinil. 77.6% of patients were female and the mean (SD) age was 46.5 ± 4.9 years. 55.5% of patients had idiopathic PAH (iPAH), 23.9% PAH related to connective tissue disease, and 18.2% PAH related to congenital heart disease. Based on the effects observed in short-term trials and, relative to placebo, all analyzed therapies improved survival. The estimated 1-year survival was 78.4%, 77.8%, 76.1%, 75.8%, 75.2%, and 74.1% for epoprostenol, bosentan, treprostinil, sitaxentan, sildenafil, and beraprost, respectively. These estimates are considerably lower than the 1-year observed survival reported in several open-label and registry studies with PAH-specific therapies: 88% - 97%.

Conclusion

When applied to the NIH Registry equation, hemodynamic changes from baseline appear to underestimate the survival benefits observed with long-term PAH therapy.
Evidence for waning of latency in a cohort study of tuberculosis
Authors: Wiker Harald G , Mustafa Tehmina , Bjune Gunnar A , Harboe Morten
Published: February 2010

Background

To investigate how the risk of active tuberculosis disease is influenced by time since original infection and to determine whether the risk of reactivation of tuberculosis increases or decreases with age.

Methods

Cohort analysis of data for the separate ten year birth cohorts of 1876-1885 to 1959-1968 obtained from Statistics Norway and the National Tuberculosis Registry. These data were used to calculate the rates and the changes in the rates of bacillary (or active) tuberculosis. Data on bacillary tuberculosis for adult (20+) age groups were obtained from the National Tuberculosis Registry and Statistics Norway from 1946 to 1974. Most cases during this period arose due to reactivation of remote infection. Participants in this part of the analysis were all reported active tuberculosis cases in Norway from 1946 to 1974 as recorded in the National Tuberculosis Registry.

Results

Tuberculosis decreased at a relatively steady rate when following individual birth cohorts, but with a tendency of slower decline as time passed since infection. A mean estimate of this rate of decline was 57% in a 10 year period.

Conclusions

The risk of reactivation of latent tuberculosis decreases with age. This decline may reflect the rate at which latent tuberculosis is eliminated from a population with minimal transmission of tubercle bacilli. A model for risk of developing active tuberculosis as a function of time since infection shows that the rate at which tuberculosis can be eliminated from a society can be quite substantial if new infections are effectively prevented. The findings clearly indicate that preventative measures against transmission of tuberculosis will be the most effective. These results also suggest that the total population harbouring live tubercle bacilli and consequently the future projection for increased incidence of tuberculosis in the world is probably overestimated.
Different screening strategies (single or dual) for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis
Authors: Pooran Anil , Booth Helen , Miller Robert F , Scott Geoff , Badri Motasim , Huggett Jim F , Rook Graham , Zumla Alimuddin , Dheda Keertan
Published: February 2010

Background

Previous health economic studies recommend either a dual screening strategy [tuberculin skin test (TST) followed by interferon-γ-release assay (IGRA)] or a single one [IGRA only] for latent tuberculosis infection (LTBI), the former largely based on claims that it is more cost-effective. We sought to examine that conclusion through the use of a model that accounts for the additional costs of adverse drug reactions and directly compares two commercially available versions of the IGRA: the Quantiferon-TB-Gold-In-Tube (QFT-GIT) and T-SPOT.TB.

Methods

A LTBI screening model directed at screening contacts was used to perform a cost-effectiveness analysis, from a UK healthcare perspective, taking into account the risk of isoniazid-related hepatotoxicity and post-exposure TB (2 years post contact) using the TST, QFT-GIT and T-SPOT.TB IGRAs.

Results

Examining costs alone, the TST/IGRA dual screening strategies (TST/T-SPOT.TB and TST/QFT-GIT; £162,387 and £157,048 per 1000 contacts, respectively) cost less than their single strategy counterparts (T-SPOT.TB and QFT-GIT; £203,983 and £202,921 per 1000 contacts) which have higher IGRA test costs and greater numbers of persons undergoing LTBI treatment. However, IGRA alone strategies direct healthcare interventions and costs more accurately to those that are truly infected.

Subsequently, less contacts need to be treated to prevent an active case of TB (T-SPOT.TB and QFT-GIT; 61.7 and 69.7 contacts) in IGRA alone strategies. IGRA single strategies also prevent more cases of post-exposure TB. However, this greater effectiveness does not outweigh the lower incremental costs associated with the dual strategies. Consequently, when these costs are combined with effectiveness, the IGRA dual strategies are more cost-effective than their single strategy counterparts. Comparing between the IGRAs, T-SPOT.TB-based strategies (single and dual; £39,712 and £37,206 per active TB case prevented, respectively) were more cost-effective than the QFT-GIT-based strategies (single and dual; £42,051 and £37,699 per active TB case prevented, respectively). Using the TST alone was the least cost-effective (£47,840 per active TB case prevented). Cost effectiveness values were sensitive to changes in LTBI prevalence, IGRA test sensitivities/specificities and IGRA test costs.

Conclusion

A dual strategy is more cost effective than a single strategy but this conclusion is sensitive to screening test assumptions and LTBI prevalence.
An efficacy trial of brief lifestyle intervention delivered by generalist community nurses (CN SNAP trial)
Authors: Laws Rachel A , Chan Bibiana C , Williams Anna M , Davies Gawaine Powell , Jayasinghe Upali W , Fanaian Mahnaz , Harris Mark F ,   the CN SNAP Project Team
Published: February 2010

Background

Lifestyle risk factors, in particular smoking, nutrition, alcohol consumption and physical inactivity (SNAP) are the main behavioural risk factors for chronic disease. Primary health care (PHC) has been shown to be an effective setting to address lifestyle risk factors at the individual level. However much of the focus of research to date has been in general practice. Relatively little attention has been paid to the role of nurses working in the PHC setting. Community health nurses are well placed to provide lifestyle intervention as they often see clients in their own homes over an extended period of time, providing the opportunity to offer intervention and enhance motivation through repeated contacts. The overall aim of this study is to evaluate the impact of a brief lifestyle intervention delivered by community nurses in routine practice on changes in clients' SNAP risk factors.

Methods/Design

The trial uses a quasi-experimental design involving four generalist community nursing services in NSW Australia. Services have been randomly allocated to an 'early intervention' group or 'late intervention' (comparison) group. 'Early intervention' sites are provided with training and support for nurses in identifying and offering brief lifestyle intervention for clients during routine consultations. 'Late intervention site' provide usual care and will be offered the study intervention following the final data collection point. A total of 720 generalist community nursing clients will be recruited at the time of referral from participating sites. Data collection consists of 1) telephone surveys with clients at baseline, three months and six months to examine change in SNAP risk factors and readiness to change 2) nurse survey at baseline, six and 12 months to examine changes in nurse confidence, attitudes and practices in the assessment and management of SNAP risk factors 3) semi-structured interviews/focus with nurses, managers and clients in 'early intervention' sites to explore the feasibility, acceptability and sustainability of the intervention.

Discussion

The study will provide evidence about the effectiveness and feasibility of brief lifestyle interventions delivered by generalist community nurses as part of routine practice. This will inform future community nursing practice and PHC policy.

Trial Registration

ACTRN12609001081202
The cross-reactivity of the enterovirus 71 to human brain tissue and identification of the cross-reactivity related fragments
Authors: Jia Chun Shi , Liu Jiang Ning , Li Wan Bo , Ma Chun Mei , Lin Shu Zhu , Hao Yi , Gao Xue Zhong , Liu Xiao Lin , Xu Yan Feng , Zhang Lian Feng , Qin Chuan
Published: February 2010

Background

EV71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis. However, the neurological destruction mechanism was remained to be clarified. This study described the cross reaction between EV71 induced IgG and human brain tissue.

Results

Cross reaction of the IgG from 30 EV71 infected patients' sera to human tissues of cerebra was observed, which suggested that some EV71 antigens could induce IgG cross-reactivity to human cerebra. To identify the regions of EV71 virus that containing above antigens, the polypeptide of virus was divided into 19 peptides by expression in prokaryotes cell. Mouse anti-sera of these peptides was prepared and applied in immunohistochemical staining with human adult and fetus brain tissue, respectively. The result indicated the 19 peptides can be classified into three groups: strong cross-reactivity, weak cross-reactivity and no cross-reactivity with human brain tissue according the cross reaction activity. Then, the increased Blood Brain Barrier (BBB) permeability and permits IgG entry in neonatal mice after EV71 infection was determined.

Conclusion

EV71 induced IgG could enter BBB and cross-reacted with brain tissue in EV71 infected neonatal mice, and then the peptides of EV71 that could induce cross-reactivity with brain tissue were identified, which should be avoided in future vaccine designing.
Hepatic steatosis in hepatitis C is a storage disease due to HCV interaction with microsomal triglyceride transfer protein (MTP)
Authors: Mirandola Silvia , Bowman David , Hussain Mahmood M , Alberti Alfredo
Published: February 2010

Liver steatosis is a frequent histological feature in patients chronically infected with hepatitis C virus (HCV). The relationship between HCV and hepatic steatosis seems to be the result of both epigenetic and genetic factors. In vivo and in vitro studies have shown that HCV can alter intrahepatic lipid metabolism by affecting lipid synthesis, oxidative stress, lipid peroxidation, insulin resistance and the assembly and secretion of VLDL. Many studies suggest that HCV-related steatosis might be the result of a direct interaction between the virus and MTP. It has been demonstrated that MTP is critical for the secretion of HCV particles and that inhibition of its lipid transfer activity reduces HCV production. However, higher degrees of hepatic steatosis were found in chronic hepatitis C patients carrying the T allele of MTP -493G/T polymorphism that seems to be associated with increased MTP transcription. We propose here that liver steatosis in hepatitis C could be a storage disease induced by the effects of the virus and of its proteins on the intracellular lipid machinery and on MTP. Available data support the hypothesis that HCV may modulate MTP expression and activity through a number of mechanisms such as inhibition of its activity and transcriptional control. Initial up regulation could favour propagation of HCV while down regulation in chronic phase could cause impairment of triglyceride secretion and excessive lipid accumulation, with abnormal lipid droplets facilitating the "storage" of virus particles for persistent infection.
Quality assurance for Chinese herbal formulae: standardization of IBS-20, a 20-herb preparation
Authors: Ip Siu-Po , Zhao Ming , Xian Yanfang , Chen Mengli , Zong Yuying , Tjong Yung-Wui , Tsai Sam-Hip , Sung Joseph JY , Bensoussan Alan , Berman Brian , Fong Harry HS , Che Chun-Tao
Published: February 2010

Background

The employment of well characterized test samples prepared from authenticated, high quality medicinal plant materials is key to reproducible herbal research. The present study aims to demonstrate a quality assurance program covering the acquisition, botanical validation, chemical standardization and good manufacturing practices (GMP) production of IBS-20, a 20-herb Chinese herbal formula under study as a potential agent for the treatment of irritable bowel syndrome.

Methods

Purity and contaminant tests for the presence of toxic metals, pesticide residues, mycotoxins and microorganisms were performed. Qualitative chemical fingerprint analysis and quantitation of marker compounds of the herbs, as well as that of the IBS-20 formula was carried out with high-performance liquid chromatography (HPLC). Extraction and manufacture of the 20-herb formula were carried out under GMP. Chemical standardization was performed with liquid chromatography-mass spectrometry (LC-MS) analysis. Stability of the formula was monitored with HPLC in real time.

Results

Quality component herbs, purchased from a GMP supplier were botanically and chemically authenticated and quantitative HPLC profiles (fingerprints) of each component herb and of the composite formula were established. An aqueous extract of the mixture of the 20 herbs was prepared and formulated into IBS-20, which was chemically standardized by LC-MS, with 20 chemical compounds serving as reference markers. The stability of the formula was monitored and shown to be stable at room temperature.

Conclusion

A quality assurance program has been developed for the preparation of a standardized 20-herb formulation for use in the clinical studies for the treatment of irritable bowel syndrome (IBS). The procedures developed in the present study will serve as a protocol for other poly-herbal Chinese medicine studies.
A reference guide for tree analysis and visualization
Authors: Pavlopoulos Georgios A , Soldatos Theodoros G , Barbosa-Silva Adriano , Schneider Reinhard
Published: February 2010

The quantities of data obtained by the new high-throughput technologies, such as microarrays or ChIP-Chip arrays, and the large-scale OMICS-approaches, such as genomics, proteomics and transcriptomics, are becoming vast. Sequencing technologies become cheaper and easier to use and, thus, large-scale evolutionary studies towards the origins of life for all species and their evolution becomes more and more challenging. Databases holding information about how data are related and how they are hierarchically organized expand rapidly. Clustering analysis is becoming more and more difficult to be applied on very large amounts of data since the results of these algorithms cannot be efficiently visualized. Most of the available visualization tools that are able to represent such hierarchies, project data in 2D and are lacking often the necessary user friendliness and interactivity. For example, the current phylogenetic tree visualization tools are not able to display easy to understand large scale trees with more than a few thousand nodes. In this study, we review tools that are currently available for the visualization of biological trees and analysis, mainly developed during the last decade. We describe the uniform and standard computer readable formats to represent tree hierarchies and we comment on the functionality and the limitations of these tools. We also discuss on how these tools can be developed further and should become integrated with various data sources. Here we focus on freely available software that offers to the users various tree-representation methodologies for biological data analysis.
Establishment and Characterization of a Novel Head and Neck Squamous Cell Carcinoma Cell Line USC-HN1
Authors: Liebertz Daniel J , Lechner Melissa G , Masood Rizwan , Sinha Uttam K , Han Jing , Puri Raj K , Correa Adrian J , Epstein Alan L
Published: February 2010

Background

Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal malignancy. Publically available cell lines are mostly of lingual origin, or have not been carefully characterized. Detailed characterization of novel HNSCC cell lines is needed in order to provide researchers a concrete keystone on which to build their investigations.

Methods

The USC-HN1 cell line was established from a primary maxillary HNSCC biopsy explant in tissue culture. The immortalized cells were then further characterized by heterotransplantation in Nude mice; immunohistochemical staining for relevant HNSCC biomarkers; flow cytometry for surface markers; cytogenetic karyotypic analysis; human papillomavirus and Epstein-Barr virus screening; qRT-PCR for oncogene and cytokine analysis; investigation of activated, cleaved Notch1 levels; and detailed 35,000 gene microarray analysis.

Results

Characterization experiments confirmed the human HNSCC origin of USC-HN1, including a phenotype similar to the original tumor. Viral screening revealed no HPV or EBV infection, while western blotting displayed significant upregulation of activated, cleaved Notch1.

Conclusions

USC-HN1, a novel immortalized cell line has been derived from a maxillary HNSCC. Characterization studies have shown that the cell line is of HNSCC origin and displays many of the same markers previously reported in the literature. USC-HN1 is available for public research and will further the investigation of HNSCC and the development of new therapeutic modalities.
Paternal age increases the risk for autism in an Iranian population sample
Authors: Sasanfar Roksana , Haddad Stephen A , Tolouei Ala , Ghadami Majid , Yu Dongmei , Santangelo Susan L
Published: February 2010

Background

Autism is a neurodevelopmental disorder which is known to have a strong genetic component and is most likely oligogenic. However, the necessary role of environmental factors has been well documented. Prior research suggests that parental characteristics, such as age and level of education, may be associated with a risk of autism. Parental age has been shown to be associated with many disorders, such as schizophrenia, childhood cancer and fetal death. However, results from studies of parental age and autism are inconsistent.

Methods

In the present study, we investigated the association of autism with parental age in 179 autism cases and 1611 matched cohort children from Iran. Each case was matched with nine cohort controls on parental education, sex, order of birth, consanguineous marriage, urbanism and province of residence. The Cox regression model was used to carry out conditional logistic regression on the matched data.

Results

There was a significant association between higher paternal age, but not maternal age, and an increasing risk of autism. An analysis of the combined effect of parental age and education also revealed that parents with higher education had an increased risk of having autistic children, with a dose-response effect of parental age.

Conclusions

This study, which is the first epidemiological study of autism in Iran, provides evidence of the association of paternal age and risk of autism.
Novel Proapoptotic Effect of Hepatocyte Growth Factor: Synergy with Palmitate to Cause Pancreatic β-Cell Apoptosis
Authors: González-Pertusa José A. , Dubé John , Valle Shelley R. , Rosa Taylor C. , Takane Karen K. , Mellado-Gil José M. , Perdomo Germán , Vasavada Rupangi C. , García-Ocaña Adolfo
Published: February 2010

Increasing evidence suggests that elevation of plasma fatty acids that often accompanies insulin resistance contributes to β-cell insufficiency in obesity-related type 2 diabetes. Circulating levels of hepatocyte growth factor (HGF) are increased in humans with metabolic syndrome and obesity. HGF is known to protect β-cells against streptozotocin and during islet engraftment. However, whether HGF is a β-cell prosurvival factor in situations of excessive lipid supply has not been deciphered. Mice overexpressing HGF in the β-cell [rat insulin type II promoter (RIP)-HGF transgenic mice] fed with standard chow display improved glucose homeostasis and increased β-cell mass and proliferation compared with normal littermates. However, after 15 wk of high-fat feeding, glucose homeostasis and β-cell expansion and proliferation are indistinguishable between normal and transgenic mice. Interestingly, RIP-HGF transgenic mouse β-cells and normal β-cells treated with HGF display increased sensitivity to palmitate-mediated apoptosis in vitro. Palmitate completely eliminates Akt and Bad phosphorylation in RIP-HGF transgenic mouse islets. HGF-overexpressing islets also show significantly decreased AMP-activated protein kinase-α and acetyl-coenzyme A carboxylase phosphorylation, diminished fatty acid oxidation, increased serine palmitoyltransferase expression, and enhanced ceramide formation compared with normal islets. Importantly, human islets overexpressing HGF also display increased β-cell apoptosis in the presence of palmitate. Treatment of both mouse and human islet cells with the de novo ceramide synthesis inhibitors myriocin and fumonisin B1 abrogates β-cell apoptosis induced by HGF and palmitate. Collectively, these studies indicate that HGF can be detrimental for β-cell survival in an environment with excessive fatty acid supply.
New Insights into Sexual Dimorphism during Progression of Heart Failure and Rhythm Disorders
Authors: Thireau Jérôme , Aimond Franck , Poisson Denise , Zhang BeiLi , Bruneval Patrick , Eder Véronique , Richard Sylvain , Babuty Dominique
Published: February 2010

Neurohormonal imbalance is a key determinant of the progression of heart failure (HF), which results in an elevated risk of mortality. A better understanding of mechanisms involved may influence treatment strategies. The incidence and prevalence of HF are lower in women. We explored sexual dimorphism in the progression of HF using a mice model of neurohormonal-dependent HF. Male and female mice overexpressing the human β2-adrenergic receptor (TG4 strain) develop HF. We compared TG4 animals with age-matched wild-type controls. Cardiac function was studied in vivo by echocardiography and electrocardiography. Histological studies were performed. Conduction parameters were assessed by intracardiac electrophysiological exploration, as was the occurrence of spontaneous and inducible arrhythmias. The patch-clamp technique was used to determine the cellular electrophysiological profile. The role of hormonal status in HF progression was investigated by surgical gonadectomy. High mortality rate was observed in TG4 mice with a dramatic difference between males and females. Male TG4 mice exhibited intraventricular conduction abnormalities, as measured by infrahisian interval and QRS durations potentially determining reentrant circuits and increasing susceptibility to arrhythmia. The severity of HF was correlated with the degree of fibrosis, which was modulated by the gonadal hormones. Action potentials recorded from male and female left ventricular cardiomyocytes were indistinguishable, although both sexes exhibited delayed repolarization when compared with their wild-type counterparts. In conclusion, female TG4 mice were better protected than males against cardiac remodeling and rhythm disorders. A link between fibrosis, conduction time, and mortality was established in relation with sex hormones.
SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification
Authors: Hattori Takako , Müller Catharina , Gebhard Sonja , Bauer Eva , Pausch Friederike , Schlund Britta , Bösl Michael R. , Hess Andreas , Surmann-Schmitt Cordula , von der Mark Helga , de Crombrugghe Benoit , von der Mark Klaus
Published: February 2010

SOX9 is a transcription factor of the SRY family that regulates sex determination, cartilage development and numerous other developmental events. In the foetal growth plate, Sox9 is highly expressed in chondrocytes of the proliferating and prehypertrophic zone but declines abruptly in the hypertrophic zone, suggesting that Sox9 downregulation in hypertrophic chondrocytes might be a necessary step to initiate cartilage-bone transition in the growth plate. In order to test this hypothesis, we generated transgenic mice misexpressing Sox9 in hypertrophic chondrocytes under the control of a BAC-Col10a1 promoter. The transgenic offspring showed an almost complete lack of bone marrow in newborns, owing to strongly retarded vascular invasion into hypertrophic cartilage and impaired cartilage resorption, resulting in delayed endochondral bone formation associated with reduced bone growth. In situ hybridization analysis revealed high levels of Sox9 misexpression in hypertrophic chondrocytes but deficiencies of Vegfa, Mmp13, RANKL and osteopontin expression in the non-resorbed hypertrophic cartilage, indicating that Sox9 misexpression in hypertrophic chondrocytes inhibits their terminal differentiation. Searching for the molecular mechanism of SOX9-induced inhibition of cartilage vascularization, we discovered that SOX9 is able to directly suppress Vegfa expression by binding to SRY sites in the Vegfa gene. Postnatally, bone marrow formation and cartilage resorption in transgenic offspring are resumed by massive invasion of capillaries through the cortical bone shaft, similar to secondary ossification. These findings imply that downregulation of Sox9 in the hypertrophic zone of the normal growth plate is essential for allowing vascular invasion, bone marrow formation and endochondral ossification.
Interplay of auxin, KANADI and Class III HD-ZIP transcription factors in vascular tissue formation
Authors: Ilegems Michael , Douet Véronique , Meylan-Bettex Marlyse , Uyttewaal Magalie , Brand Lukas , Bowman John L. , Stieger Pia A.
Published: February 2010

Class III HD-ZIP and KANADI gene family members have complementary expression patterns in the vasculature and their gain-of-function and loss-of-function mutants have complementary vascular phenotypes. This suggests that members of the two gene families are involved in the establishment of the spatial arrangement of phloem, cambium and xylem. In this study, we have investigated the role of these two gene families in vascular tissue differentiation, in particular their interactions with the plant hormone auxin. We have analyzed the vasculature of plants that have altered expression levels of Class III HD-ZIP and KANADI transcription factors in provascular cells. Removal of either KANADI or Class III HD-ZIP expression in procambium cells led to a wider distribution of auxin in internal tissues, to an excess of procambium cell recruitment and to increased cambium activity. Ectopic expression of KANADI1 in provascular cells inhibited procambium cell recruitment due to negative effects of KANADI1 on expression and polar localization of the auxin efflux-associated protein PIN-FORMED1. Ectopic expression of Class III HD-ZIP genes promoted xylem differentiation. We propose that Class III HD-ZIP and KANADI transcription factors control cambium activity: KANADI proteins by acting on auxin transport, and Class III HD-ZIP proteins by promoting axial cell elongation and xylem differentiation.
Genetic Screening: A Conceptual Framework for Programmes and Policy-Making
Authors: Andermann Anne , Blancquaert Ingeborg , Déry Véronique
Published: February 2010

Objective

Policy-makers are faced with increasing pressures from a range of different stakeholders to introduce or expand genetic screening programmes. A shared understanding is therefore needed of the many factors influencing these complex policy decisions. Our aim was to develop a theoretical framework that highlights the multiple components and influences involved in genetic screening and the policy-making process.

Methods

As part of a larger research programme, existing policy frameworks relating to genetic screening were identified through a review of the literature. Major themes were identified and synthesized into an overarching framework, which was further refined through discussions with key informants.

Results

The framework consists of three parts. The first part conceptualizes genetic screening as an integrated public health programme. The second part describes the policy-making process at each stage in the life cycle of the programme. The third part depicts the broader context within which policy-making occurs.

Conclusion

This framework can support policy-makers by fostering a common understanding and facilitating dialogue with stakeholders. The framework has also been used as the conceptual foundation for the development of a more elaborate decision-guide.
When Policy Meets the Personal: General Practice Nurses in Australia
Authors: Pearce Christopher , Hall Sally , Phillips Christine
Published: February 2010

Objective

A significant focus of current health policy in Australia is to expand both the number and role of general practice nurses. Multiple new payment incentives have been instituted to encourage the use of practice nurses. This study explored the way these policies have framed their work.

Methods

Multimethod research using observation, workspace photographs and interviews with nurses, doctors and managers collected through rapid appraisal in 25 practices in two states, followed by case studies of the role of nurses in seven practices over one year.

Results

Many respondents reported unanticipated benefits in general practice functioning and teamwork as a result of employing a nurse, though this had not been a policy aim. Within funding constraints, nurses created new roles and manipulated old roles to fit their personal understanding of patient care. Policy initiatives targeting practice nurses are often based around tasks and system issues, rather than the personal creation of care and quality that patients require and nurses seek. Incentives in this study were targeted at both the uptake of nurses and specific nursing activities.

Conclusion

Policy development and funding structures would benefit from better understanding of nurses as agents of connectivity (rather than simply as performers of tasks) as well as the nature of teamwork in practices.