bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introducing W.A.T.E.R.S.: a Workflow for the Alignment, Taxonomy, and Ecology of Ribosomal Sequences
Authors: Hartman Amber L , Riddle Sean , McPhillips Timothy , Ludäscher Bertram , Eisen Jonathan A 
Published: June 2010

Abstract

Background
For more than two decades microbiologists have used a highly conserved microbial gene as a phylogenetic marker for bacteria and archaea. The small-subunit ribosomal RNA gene, also known as 16 S rRNA, is encoded by ribosomal DNA, 16 S rDNA, and has provided a powerful comparative tool to microbial ecologists. Over time, the microbial ecology field has matured from small-scale studies in a select number of environments to massive collections of sequence data that are paired with dozens of corresponding collection variables. As the complexity of data and tool sets have grown, the need for flexible automation and maintenance of the core processes of 16 S rDNA sequence analysis has increased correspondingly.

Results
We present WATERS, an integrated approach for 16 S rDNA analysis that bundles a suite of publicly available 16 S rDNA analysis software tools into a single software package. The "toolkit" includes sequence alignment, chimera removal, OTU determination, taxonomy assignment, phylogentic tree construction as well as a host of ecological analysis and visualization tools. WATERS employs a flexible, collection-oriented 'workflow' approach using the open-source Kepler system as a platform.

Conclusions
By packaging available software tools into a single automated workflow, WATERS simplifies 16 S rDNA analyses, especially for those without specialized bioinformatics, programming expertise. In addition, WATERS, like some of the newer comprehensive rRNA analysis tools, allows researchers to minimize the time dedicated to carrying out tedious informatics steps and to focus their attention instead on the biological interpretation of the results. One advantage of WATERS over other comprehensive tools is that the use of the Kepler workflow system facilitates result interpretation and reproducibility via a data provenance sub-system. Furthermore, new "actors" can be added to the workflow as desired and we see WATERS as an initial seed for a sizeable and growing repository of interoperable, easy-to-combine tools for asking increasingly complex microbial ecology questions.
Inactivation of Dicer1 in Steroidogenic factor 1-positive cells reveals tissue-specific requirement for Dicer1in adrenal, testis, and ovary
Authors: Huang Chen-Che J , Yao Humphrey HC 
Published: June 2010

Abstract
Background
The synthesis of microRNA (miRNA) is a multi-step process that requires the action of the ribonuclease Dicer1. Dicer1 is responsible for the final processing of miRNA and has been implicated in cellular processes such as proliferation, apoptosis, and differentiation. Mouse embryos lacking Dicer1 die in early embryogenesis. In this study, we investigated whether Dicer1 is required for development of adrenal, testis, and ovary in mouse embryos.

Results
To target Dicer1 deletion specifically in developing adrenals and gonads, we used Steroidogenic factor 1-cre (Sf1/Cre) line in which Cre recombinase is active in the progenitor cells of adrenals and gonads. Lack of Dicer1 in the SF1-positive cells did not affect formation and early differentiation of the adrenals and gonads. However, increasing numbers of apoptotic cells were first detected in the Dicer1 knockout adrenal cortex at 18.5 days post coitum (dpc), followed by apoptosis of somatic cells and germ cells in the testis at postnatal day 0. Affected adrenal and testes underwent complete degeneration 48 hrs after the onset of apoptosis. However, ovaries were not affected at least until postnatal day 5, when the animals died due to adrenal insufficiency.

Conclusions
Dicer1 is dispensable for formation and differentiation of fetal tissues derived from the SF1-positive adrenogonadal primordium. Dicer1 is essential for maintaining cell survival in adrenal and testis; however, development of the ovary from fetal stages to postnatal day 5 does not require the presence of Dicer1. Our results reveal a tissue-specific requirement of Dicer1 and microRNAs. Future research is needed to understand how the tissue-specific role of Dicer1 is established.
GT1b-induced neurotoxicity is mediated by the Akt/GSK-3/tau signaling pathway but not caspase-3 in mesencephalic dopaminergic neurons
Authors: Chung Eun S , Bok Eugene , Sohn Sunghyang , Lee Young D , Baik Hyung H , Jin Byung K 
Published: June 2010

Abstract

Background
Gangliosides, sialic acid-containing glycosphingolipids exist in mammalian cell membranes particularly neuronal membranes. The trisialoganglioside (GT1b) is one of the major brain gangliosides and acts as an endogenous regulator in the brain. We previously showed GT1b induces mesencephalic dopaminergic (DA) neuronal death, both in vivo and in vitro. We further investigate the underlying mechanisms of GT1b neurotoxicity.

Results
Consistent with earlier findings, GT1b attenuated the DA neuron number and dopamine uptake level in mesencephalic cultures. Morphological evidence revealed GT1b-induced chromatin condensation and nuclear fragmentation as well as an increased number of TUNEL-positive cells, compared to control cultures. Interestingly, while GT1b enhanced caspase-3 activity, DEVD, a caspase-3 inhibitor, failed to rescue DA neuronal death. Immunoblot analysis revealed that GT1b inactivates Akt through dephosphorylation at both Ser473 and Thr308, subsequent dephosphorylation of GSK-3β, a substrate of Akt, and hyperphosphorylation of tau, downstream of GSK-3β. Moreover, a GSK-3β specific inhibitor, L803-mt, attenuated tau phosphorylation and rescued DA neurons from cell death in mesencephalic cultures.

Conclusion
Our data provide novel evidence that a Akt/GSK-3β/tau-dependent, but not caspase-3 signaling pathway plays a pivotal role in GT1b-mediated neurotoxic actions on mesencephalic DA neurons.
Inoculated mammary carcinoma-associated fibroblasts: contribution to hormone independent tumor growth
Authors: Fabris Victoria T , Sahores Ana , Vanzulli Silvia I , Colombo Lucas , Molinolo Alfredo A , Lanari Claudia , Lamb Caroline A 
Published: June 2010

Abstract

Background
Increasing evidence has underscored the role of carcinoma associated fibroblasts (CAF) in tumor growth. However, there are controversial data regarding the persistence of inoculated CAF within the tumors. We have developed a model in which murine metastatic ductal mammary carcinomas expressing estrogen and progesterone receptors transit through different stages of hormone dependency. Hormone dependent (HD) tumors grow only in the presence of progestins, whereas hormone independent (HI) variants grow without hormone supply. We demonstrated previously that CAF from HI tumors (CAF-HI) express high levels of FGF-2 and that FGF-2 induced HD tumor growth in vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can induce HD tumor growth.

Methods
Purified EPI cells of HD and HI tumors were inoculated alone, or together with CAF-HI, into female BALB/c mice and tumor growth was evaluated. In another set of experiments, purified EPI-HI alone or combined with CAF-HI or CAF-HI-GFP were inoculated into BALB/c or BALB/c-GFP mice. We assessed whether inoculated CAF-HI persisted within the tumors by analyzing inoculated or host CAF in frozen sections of tumors growing in BALB/c or BALB/c-GFP mice. The same model was used to evaluate early stages of tumor development and animals were euthanized at 2, 7, 12 and 17 days after EPI-HI or EPI-HI+CAF-HI inoculation. In angiogenesis studies, tumor vessels were quantified 5 days after intradermal inoculation.

Results
We found that admixed CAF-HI failed to induce epithelial HD tumor growth, but instead, enhanced HI tumor growth (p < 0.001). Moreover, inoculated CAF-HI did not persist within the tumors. Immunofluorescence studies showed that inoculated CAF-HI disappeared after 13 days. We studied the mechanisms by which CAF-HI increased HI tumor growth, and found a significant increase in angiogenesis (p < 0.05) in the co-injected mice at early time points.

Conclusions
Inoculated CAF-HI do not persist within the tumor mass although they play a role during the first stages of tumor formation promoting angiogenesis. This angiogenic environment is unable to replace the hormone requirement of HD tumors that still need the hormone to recruit the stroma from the host.
Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST) evaluating the human-bovine (WC3) reassortant pentavalent rotavirus vaccine (RV5)
Authors: Itzler Robbin , Koch Gary , Matson David O , Gothefors Leif , Van Damme Pierre , DiNubile Mark J , Heaton Penny M 
Published: June 2010

AbstractBackgroundThe Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance.MethodsData on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses.ResultsIn the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED) visits 88.9% (95% CI: 84.9, 91.9) for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6) reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0% (95% CI: 81.7, 95.5) and 95.9% (95% CI: 92.2, 97.8) among parents contacted every 2 weeks (number evaluable = 4,451) and every 6 weeks (number evaluable = 52,683) respectively.ConclusionsOur analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations and ED visits based on the MITT analyses were generally consistent with the PP analyses. The rate of events for subgroups with different intensities of surveillance differed but the effect of RV5 on the relative rate reductions were consistent with the results that have already been published.Trial RegistrationClinicalTrials.gov number, NCT00090233
Compliance with herpes zoster vaccination in young and adult individuals in two regions of Italy
Authors: Parlato Antonino , Spica Vincenzo Romano , Ciccozzi Massimo , Farchi Francesca , Gallè Francesca , Di Onofrio Valeria , Franco Elisabetta , Liguori Giorgio 
Published: June 2010

Abstract

Background
The purpose of this work was to explore the knowledge and acceptance of Varicella Zoster Virus (VZV)-Herpes Zoster (HZ) vaccination in the general Italian population, where the HZ vaccine has not yet been distributed, using a prevalence study of subjects from two regions in Italy.

Methods
A group of 3,173 individuals were interviewed using a questionnaire. The youngest age group (≤ 20 year) was composed of students interviewed at university. The middle age group (21-40 years) and the older age group (≥ 41 years) were interviewed by general practitioners in their office.

Results
In both regions, the majority of subjects had been infected with varicella, and only 165 (5.2%) subjects reported receiving the VZV vaccination. Regarding HZ, 2,749 (86.6%) individuals stated that they knew of the virus and 2,233 (70%) were willing to be vaccinated against HZ. The majority of people willing to be vaccinated were in the middle and older age groups (36.6% and 44.7%, respectively).

Conclusion
Compliance versus vaccination results were satisfactory and probably, with the upcoming availability of the HZ vaccine in Italy, adults will be favourably disposed towards vaccination.
A novel anti-virulence gene revealed by proteomic analysis in Shigella flexneri 2a
Authors: Zhao Ge , Zhu Li , Feng Erling , Cao Xiaoyu , Shang Na , Liu Xiankai , Liao Xiang , Ying Tianyi , Wang Jie , Chen Huipeng , Wang Hengliang 
Published: June 2010

Abstract

Background

Shigella flexneri is a gram-negative, facultative pathogen that causes the majority of communicable bacterial dysenteries in developing countries. The virulence factors of S. flexneri have been shown to be produced at 37 degrees C but not at 30 degrees C. To discover potential, novel virulence-related proteins of S. flexneri, we performed differential in-gel electrophoresis (DIGE) analysis to measure changes in the expression profile that are induced by a temperature increase.

Results
The ArgT protein was dramatically down-regulated at 37 degrees C. In contrast, the ArgT from the non-pathogenic E. coli did not show this differential expression as in S. flexneri, which suggested that argT might be a potential anti-virulence gene. Competitive invasion assays in HeLa cells and in BALB/c mice with argT mutants were performed, and the results indicated that the over-expression of ArgTY225D would attenuate the virulence of S. flexneri. A comparative proteomic analysis was subsequently performed to investigate the effects of ArgT in S. flexneri at the molecular level. We show that HtrA is differentially expressed among different derivative strains.

Conclusion
Gene argT is a novel anti-virulence gene that may interfere with the virulence of S. flexneri via the transport of specific amino acids or by affecting the expression of the virulence factor, HtrA.
Small molecule screening in zebrafish: an in vivo approach to identifying new chemical tools and drug leads
Authors: Taylor Kerrie L , Grant Nicola J , Temperley Nicholas D , Patton E Elizabeth 
Published: June 2010

Abstract
In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads, and explore new applications for known drugs. Here, we discuss some of the advantages of using zebrafish in chemical biology, and describe some important and creative examples of small molecule screening, drug discovery and target identification.
Pearsonema (syn Capillaria) plica associated cystitis in a Fennoscandian arctic fox (Vulpes lagopus: a case report
Authors: Fernández-Aguilar Xavier , Mattsson Roland , Meijer Tomas , Osterman-Lind Eva , Gavier-Widén Dolores 
Published: June 2010

AbstractThe bladderwormPearsonema (syn Capillaria) plicaaffects domestic dogs and wild carnivores worldwide. A high prevalence in red foxes (Vulpes vulpes) has been reported in many European countries.P. plicainhabits the lower urinary tract and is considered to be of low pathogenic significance in dogs mostly causing asymptomatic infections. However, a higher level of pathogenicity has been reported in foxes. A severe cystitis associated with numerous bladderworms was found in a captive arctic fox (Vulpes lagopus) originating from the endangered Fennoscandian arctic fox population. To our knowledge this is the first description ofP. plicainfection in an arctic fox.
Is there an association between PEPFAR funding and improvement in national health indicators in Africa? A retrospective study
Authors: Duber Herbert C , Coates Thomas J , Szekeras Greg , Kaji Amy H , Lewis Roger J 
Published: June 2010

BackgroundThe US President's Emergency Plan for AIDS Relief (PEPFAR) was reauthorized in June 2008 with a three‐fold increase in funds, and a broader, more explicit mandate to improve health in the low‐ and middle‐income countries that it funded. However, the ability of a disease‐specific, or vertical, programme to have a spill‐over effect and improve health outcomes has been questioned. In this study, we sought to examine associations between being designated as a PEPFAR focus country (and receiving increased PEPFAR funding) and non‐HIV‐specific health outcomes in the World Health Organization (WHO) Africa Region, the area most affected by the HIV/AIDS epidemic.MethodsA retrospective analysis of publicly available health outcomes data published by the World Health Organization was performed for all countries in the WHO Africa Region. Fractional changes in health indicators between 2000 and 2006 were calculated, and PEPFAR focus and non‐focus countries were then compared.ResultsOverall, countries in the WHO Africa Region showed a small worsening in health outcomes status when all indicators were analyzed together and weighted equally. However, more health indicators improved than worsened over this six‐year period. A comparison of PEPFAR focus and non‐focus countries found no significant difference in the fractional change among 13 of 14 health indicators during the study period.ConclusionsThis study suggests that vertical programmes, even one that is the scale of PEPFAR, may have little or no impact on health outcomes not explicitly targeted.
Development of a Model-Based Roentgen Stereophotogrammetric Analysis System to Measure Polyethylene Wear in Unicompartmental Arthroplasty
Authors: Simpson D J , Kendrick B J L , Kaptein B L , Price A J , Murray D W , Gill H S 
Published: June 2010

One of the most important causes of failure in unicompartmental knee replacement (UKR) is polyethylene wear. The aim of this study was to develop and assess a novel Roentgen stereophotogrammetric analysis (RSA)-based method for the measurement of linear wear suitable for UKR. Model-based RSA was used to estimate the linear wear of polyethylene bearings in UKR. A phantom was used to validate the method using in vitro measured bearing thicknesses and the linear wear of ten control bearings was estimated in vivo. Computer aided design (CAD) models for the UKRs were used in the model-based RSA system. There was no statistically significant difference between the estimated and measured bearing thicknesses using the CAD models ( p = 0.386). The precision of the linear wear measurement, expressed as the standard deviation of the difference between the estimated and measured bearing thickness was 0.163 mm. The bias (mean difference) was 0.030 mm. The use of RSA to measure in vivo wear in a UKR has been shown to be accurate in a phantom, and has been verified with in vivo measured controls. The technique does not require surgical implantation of marker balls and can be used retrospectively.
Glucose Meter Performance Criteria for Tight Glycemic Control Estimated by Simulation Modeling
Authors: Karon Brad S , Boyd James C , Klee George G 
Published: June 2010

AbstractBackground: Glucose meter analytical performance criteria required for safe and effective management of patients on tight glycemic control (TGC) are not currently defined. We used simulation modeling to relate glucose meter performance characteristics to insulin dosing errors during TGC.Methods: We used 29 920 glucose values from patients on TGC at 1 institution to represent the expected distribution of glucose values during TGC, and we used 2 different simulation models to relate glucose meter analytical performance to insulin dosing error using these 29 920 initial glucose values and assuming 10%, 15%, or 20% total allowable error (TEa) criteria.Results: One-category insulin dosing errors were common under all error conditions. Two-category insulin dosing errors occurred more frequently when either 20% or 15% TEa was assumed compared with 10% total error. Dosing errors of 3 or more categories, those most likely to result in hypoglycemia and thus patient harm, occurred infrequently under all error conditions with the exception of 20% TEa.Conclusions: Glucose meter technologies that operate within a 15% total allowable error tolerance are unlikely to produce large (≥3-category) insulin dosing errors during TGC. Increasing performance to 10% TEa should reduce the frequency of 2-category insulin dosing errors, although additional studies are necessary to determine the clinical impact of such errors during TGC. Current criteria that allow 20% total allowable error in glucose meters may not be optimal for patient management during TGC.
Nonparametric Bayesian Variable Selection With Applications to Multiple Quantitative Trait Loci Mapping With Epistasis and Gene–Environment Interaction
Authors: Zou Fei , Huang Hanwen , Lee Seunggeun , Hoeschele Ina 
Published: June 2010

AbstractThe joint action of multiple genes is an important source of variation for complex traits and human diseases. However, mapping genes with epistatic effects and gene–environment interactions is a difficult problem because of relatively small sample sizes and very large parameter spaces for quantitative trait locus models that include such interactions. Here we present a nonparametric Bayesian method to map multiple quantitative trait loci (QTL) by considering epistatic and gene–environment interactions. The proposed method is not restricted to pairwise interactions among genes, as is typically done in parametric QTL analysis. Rather than modeling each main and interaction term explicitly, our nonparametric Bayesian method measures the importance of each QTL, irrespective of whether it is mostly due to a main effect or due to some interaction effect(s), via an unspecified function of the genotypes at all candidate QTL. A Gaussian process prior is assigned to this unknown function. In addition to the candidate QTL, nongenetic factors and covariates, such as age, gender, and environmental conditions, can also be included in the unspecified function. The importance of each genetic factor (QTL) and each nongenetic factor/covariate included in the function is estimated by a single hyperparameter, which enters the covariance function and captures any main or interaction effect associated with a given factor/covariate. An initial evaluation of the performance of the proposed method is obtained via analysis of simulated and real data.
Natural Diversity in Flowering Responses ofArabidopsis thalianaCaused by Variation in a Tandem Gene Array
Authors: Rosloski Sarah Marie , Jali Sathya Sheela , Balasubramanian Sureshkumar , Weigel Detlef , Grbic Vojislava 
Published: June 2010

AbstractTandemly arrayed genes that belong to gene families characterize genomes of many organisms. Gene duplication and subsequent relaxation of selection can lead to the establishment of paralogous cluster members that may evolve along different trajectories. Here, we report on the structural variation in MADS AFFECTING FLOWERING 2 (MAF2) gene, one member of the tandemly duplicated cluster of MADS-box-containing transcription factors in Arabidopsis thaliana. The altered gene structure at the MAF2 locus is present as a moderate-frequency polymorphism in Arabidopsis and leads to the extensive diversity in transcript patterns due to alternative splicing. Rearrangements at the MAF2 locus are associated with an early flowering phenotype in BC5 lines. The lack of suppression of flowering time in a MAF2-insertion line expressing the MAF2-specific artificial miRNA suggests that these MAF2 variants are behaving as loss-of-function alleles. The variation in gene architecture is also associated with segregation distortion, which may have facilitated the spread and the establishment of the corresponding alleles throughout the Eurasian range of the A. thaliana population.