bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNP identification, verification, and utility for population genetics in a non-model genus
Authors: Williams Larissa M , Ma Xin , Boyko Adam R , Bustamante Carlos D , Oleksiak Marjorie F 
Published: April 2010

Abstract

Background
By targeting SNPs contained in both coding and non-coding areas of the genome, we are able to identify genetic differences and characterize genome-wide patterns of variation among individuals, populations and species. We investigated the utility of 454 sequencing and MassARRAY genotyping for population genetics in natural populations of the teleost, Fundulus heteroclitus as well as closely related Fundulus species (F. grandis, F. majalis and F. similis).

Results
We used 454 pyrosequencing and MassARRAY genotyping technology to identify and type 458 genome-wide SNPs and determine genetic differentiation within and between populations and species of Fundulus. Specifically, pyrosequencing identified 96 putative SNPs across coding and non-coding regions of the F. heteroclitus genome: 88.8% were verified as true SNPs with MassARRAY. Additionally, putative SNPs identified in F. heteroclitus EST sequences were verified in most (86.5%) F. heteroclitus individuals; fewer were genotyped in F. grandis (74.4%), F. majalis (72.9%), and F. similis (60.7%) individuals. SNPs were polymorphic and showed latitudinal clinal variation separating northern and southern populations and established isolation by distance in F. heteroclitus populations. In F. grandis, SNPs were less polymorphic but still established isolation by distance. Markers differentiated species and populations.

Conclusions
In total, these approaches were used to quickly determine differences within the Fundulus genome and provide markers for population genetic studies.
Microarray analysis of Shigella flexneri-infected epithelial cells identifies host factors important for apoptosis inhibition
Authors: Faherty Christina S , Merrell D Scott , Semino-Mora Cristina , Dubois Andre , Ramaswamy Aishwarya V , Maurelli Anthony T 
Published: April 2010

Abstract

Background

Shigella flexneri inhibits apoptosis in infected epithelial cells. In order to understand the pro-survival effects induced by the bacteria, we utilized apoptosis-specific microarrays to analyze the changes in eukaryotic gene expression in both infected and uninfected cells in the presence and absence of staurosporine, a chemical inducer of the intrinsic pathway of apoptosis. The goal of this research was to identify host factors that contribute to apoptosis inhibition in infected cells.

Results
The microarray analysis revealed distinct expression profiles in uninfected and infected cells, and these changes were altered in the presence of staurosporine. These profiles allowed us to make comparisons between the treatment groups. Compared to uninfected cells, Shigella- infected epithelial cells, both in the presence and absence of staurosporine, showed significant induced expression of JUN, several members of the inhibitor of apoptosis gene family, nuclear factor κB and related genes, genes involving tumor protein 53 and the retinoblastoma protein, and surprisingly, genes important for the inhibition of the extrinsic pathway of apoptosis. We confirmed the microarray results for a selection of genes using in situ hybridization analysis.

Conclusion
Infection of epithelial cells with S. flexneri induces a pro-survival state in the cell that results in apoptosis inhibition in the presence and absence of staurosporine. The bacteria may target these host factors directly while some induced genes may represent downstream effects due to the presence of the bacteria. Our results indicate that the bacteria block apoptosis at multiple checkpoints along both pathways so that even if a cell fails to prevent apoptosis at an early step, Shigella will block apoptosis at the level of caspase-3. Apoptosis inhibition is most likely vital to the survival of the bacteria in vivo. Future characterization of these host factors is required to fully understand how S. flexneri inhibits apoptosis in epithelial cells.
A jackknife-like method for classification and uncertainty assessment of multi-category tumor samples using gene expression information
Authors: Zhang Wensheng , Robbins Kelly , Wang Yupeng , Bertrand Keith , Rekaya Romdhane 
Published: April 2010

Abstract

Background
The use of gene expression profiling for the classification of human cancer tumors has been widely investigated. Previous studies were successful in distinguishing several tumor types in binary problems. As there are over a hundred types of cancers, and potentially even more subtypes, it is essential to develop multi-category methodologies for molecular classification for any meaningful practical application.

Results
A jackknife-based supervised learning method called paired-samples test algorithm (PST), coupled with a binary classification model based on linear regression, was proposed and applied to two well known and challenging datasets consisting of 14 (GCM dataset) and 9 (NC160 dataset) tumor types. The results showed that the proposed method improved the prediction accuracy of the test samples for the GCM dataset, especially when t-statistic was used in the primary feature selection. For the NCI60 dataset, the application of PST improved prediction accuracy when the numbers of used genes were relatively small (100 or 200). These improvements made the binary classification method more robust to the gene selection mechanism and the size of genes to be used. The overall prediction accuracies were competitive in comparison to the most accurate results obtained by several previous studies on the same datasets and with other methods. Furthermore, the relative confidence R(T) provided a unique insight into the sources of the uncertainty shown in the statistical classification and the potential variants within the same tumor type.

Conclusion
We proposed a novel bagging method for the classification and uncertainty assessment of multi-category tumor samples using gene expression information. The strengths were demonstrated in the application to two bench datasets.
Salmo salar and Esox lucius full-length cDNA sequences reveal changes in evolutionary pressures on a post-tetraploidization genome
Authors: Leong Jong S , Jantzen Stuart G , von Schalburg Kristian R , Cooper Glenn A , Messmer Amber M , Liao Nancy Y , Munro Sarah , Moore Richard , Holt Robert A , Jones Steven JM , Davidson William S , Koop Ben F 
Published: April 2010

Abstract

Background
Salmonids are one of the most intensely studied fish, in part due to their economic and environmental importance, and in part due to a recent whole genome duplication in the common ancestor of salmonids. This duplication greatly impacts species diversification, functional specialization, and adaptation. Extensive new genomic resources have recently become available for Atlantic salmon (Salmo salar), but documentation of allelic versus duplicate reference genes remains a major uncertainty in the complete characterization of its genome and its evolution.

Results
From existing expressed sequence tag (EST) resources and three new full-length cDNA libraries, 9,057 reference quality full-length gene insert clones were identified for Atlantic salmon. A further 1,365 reference full-length clones were annotated from 29,221 northern pike (Esox lucius) ESTs. Pairwise dN/dS comparisons within each of 408 sets of duplicated salmon genes using northern pike as a diploid out-group show asymmetric relaxation of selection on salmon duplicates.

Conclusions
9,057 full-length reference genes were characterized in S. salar and can be used to identify alleles and gene family members. Comparisons of duplicated genes show that while purifying selection is the predominant force acting on both duplicates, consistent with retention of functionality in both copies, some relaxation of pressure on gene duplicates can be identified. In addition, there is evidence that evolution has acted asymmetrically on paralogs, allowing one of the pair to diverge at a faster rate.
Using epitope predictions to evaluate efficacy and population coverage of the Mtb72f vaccine for tuberculosis
Authors: McNamara Lucy A , He Yongqun , Yang Zhenhua 
Published: April 2010

Abstract

Background
The Mtb72f subunit vaccine for tuberculosis, currently in clinical trials, is hoped to provide improved protection compared to the current BCG vaccine. It is not clear, however, whether Mtb72f would be equally protective in the different human populations suffering from a high burden of tuberculosis. Previous work by Hebert and colleagues demonstrated that the PPE18 protein of Mtb72f had significant variability in a sample of clinical M. tuberculosis isolates. However, whether this variation might impact the efficacy of Mtb72f in the context of the microbial and host immune system interactions remained to be determined. The present study assesses Mtb72f's predicted efficacy in people with different DRB1 genotypes to predict whether the vaccine will protect against diverse clinical strains of M. tuberculosis in a diverse host population.

Results
We evaluated the binding of epitopes in the vaccine to different alleles of the human DRB1 Class II MHC protein using freely available epitope prediction programs and compared protein sequences from clinical isolates to the sequences included in the Mtb72f vaccine. This analysis predicted that the Mtb72f vaccine would be less effective for several DRB1 genotypes, due either to limited vaccine epitope binding to the DRB1 proteins or to binding primarily by unconserved PPE18 epitopes. Furthermore, we found that these less-protective DRB1 alleles are found at a very high frequency in several populations with a high burden of tuberculosis.

Conclusion
Although the Mtb72f vaccine candidate has shown promise in animal and clinical trials thus far, it may not be optimally effective in some genotypic backgrounds. Due to variation in both M. tuberculosis protein sequences and epitope-binding capabilities of different HLA alleles, certain human populations with a high burden of tuberculosis may not be optimally protected by the Mtb72f vaccine. The efficacy of the Mtb72f vaccine should be further examined in these particular populations to determine whether additional protective measures might be necessary for these regions.
Mental health in the aged: prevalence, covariates and related neuroendocrine, cardiovascular and inflammatory factors of successful aging
Authors: Lacruz Maria E , Emeny Rebecca T , Bickel Horst , Cramer Barbara , Kurz Alexander , Bidlingmaier Martin , Huber Dorothea , Klug Günther , Peters Annette , Ladwig Karl H 
Published: April 2010

Abstract

Background
Although aging is accompanied by diminished functioning, many elderly individuals preserve a sense of well-being. While the concept of "successful aging" has been popular for many decades, little is known about its psycho-physiologic and endocrine underpinnings. KORA-Age is a population-based, longitudinal study designed to determine the prevalence of successfully aged men and women between 65 and 94 years old in the MONICA/KORA Augsburg cohort of randomly selected inhabitants. Specifically, we aim to identify predictors of successful aging and to elucidate bio-psychosocial mechanisms that maintain mental health and successful adaptation despite adverse experiences of life and aging.

Methods/Design
Components of successful aging were assessed in a telephone survey of 4,127 participants (2008-2009) enrolled in the MONICA/KORA cohort, on average, 13 years earlier. Psychosocial, somatic and behavioural predictors are used to determine factors that contribute to successful aging. An age-stratified random sub-sample (n = 1,079) participated in a personal interview where further psychological mechanisms that may underlie successful adaptation (resilience, social support, attachment) were examined. The interactions among neuroendocrine systems in the aging process are investigated by studying the cortisol/dehydroepiandrosterone-sulfate ratio, the level of insulin-like growth factor I, and oxytocin.

Discussion
Longitudinal determinants of successful aging can be assessed based on a follow-up of an average of 13 years. A comprehensive analysis of biological as well as physio-psychological information provides a unique opportunity to investigate relevant outcomes such as resilience and frailty in the elderly population.
Who will increase their physical activity? Predictors of change in objectively measured physical activity over 12 months in the ProActive cohort
Authors: Simmons Rebecca K , van Sluijs Esther MF , Hardeman Wendy , Sutton Stephen , Griffin Simon J ,   the ProActive project team
Published: April 2010

Abstract

Background
The aim was to identify predictors of change in objectively measured physical activity over 12 months in the ProActive cohort to improve understanding of factors influencing change in physical activity.

Methods

ProActive is a physical activity promotion trial that took place in Eastern England (1999-2004). 365 offspring of people with type 2 diabetes underwent measurement of physical activity energy expenditure (PAEE) using heart rate monitoring, fitness, and anthropometric and biochemical status at baseline and 1 year (n = 321). Linear regression was used to quantify the associations between baseline demographic, clinical, psychosocial and behavioural variables and change in PAEE over 12 months. This study is registered as ISRCTN61323766.

Results

ProActive participants significantly increased their PAEE by 0.6 kj/min (SD 4.2, p = 0.006) over one year, the equivalent of around 20 minutes brisk walking/day. Male sex and higher fitness at baseline predicted increase in PAEE. No significant associations were found for any other variables. Very few baseline demographic, clinical, psychosocial and behavioural predictors were associated with change in objectively measured physical activity.

Conclusions
Traditional baseline determinants of self-reported physical activity targeted by behavioural interventions may be relatively weak predictors of change in objectively measured physical activity. Further research is needed to improve our understanding of factors influencing change in physical activity to inform the development and targeting of interventions.
Mentoring programs for medical students - a review of the PubMed literature 2000 - 2008
Authors: Frei Esther , Stamm Martina , Buddeberg-Fischer Barbara 
Published: April 2010

Abstract

Background
Although mentoring is acknowledged as a key to successful and satisfying careers in medicine, formal mentoring programs for medical students are lacking in most countries. Within the framework of planning a mentoring program for medical students at Zurich University, an investigation was carried out into what types of programs exist, what the objectives pursued by such programs are, and what effects are reported.

Methods
A PubMed literature search was conducted for 2000 - 2008 using the following keywords or their combinations: mentoring, mentoring program, medical student, mentor, mentee, protégé, mentorship. Although a total of 438 publications were identified, only 25 papers met the selection criteria for structured programs and student mentoring surveys.

Results
The mentoring programs reported in 14 papers aim to provide career counseling, develop professionalism, increase students' interest in research, and support them in their personal growth. There are both one-to-one and group mentorships, established in the first two years of medical school and continuing through graduation. The personal student-faculty relationship is important in that it helps students to feel that they are benefiting from individual advice and encourages them to give more thought to their career choices. Other benefits are an increase in research productivity and improved medical school performance in general. Mentored students also rate their overall well-being as higher. - The 11 surveys address the requirements for being an effective mentor as well as a successful mentee. A mentor should empower and encourage the mentee, be a role model, build a professional network, and assist in the mentee's personal development. A mentee should set agendas, follow through, accept criticism, and be able to assess performance and the benefits derived from the mentoring relationship.

Conclusion
Mentoring is obviously an important career advancement tool for medical students. In Europe, more mentoring programs should be developed, but would need to be rigorously assessed based on evidence of their value in terms of both their impact on the career paths of juniors and their benefit for the mentors. Medical schools could then be monitored with respect to the provision of mentorships as a quality characteristic.
Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits
Authors: Amran Adel A , Zakaria Zaiton , Othman Faizah , Das Srijit , Raj Santhana , Nordin Nor-Anita M M 
Published: April 2010

Abstract

Background

Piper sarmentosum (P.s) has flavonoid component in its leaves which has antioxidative effect. To date, its effect on atherosclerosis has not been studied histologically.

Aim
The study aimed to investigate the effect of P.s on atherosclerotic changes in hypercholesterolemic rabbits.

Methods
Forty two male New Zealand white rabbits were divided into seven groups. C - control group fed normal rabbit chow, CH - cholesterol diet (1% cholesterol), W1 - 1% cholesterol with water extract of P.s (62.5 mg/kg), W2 - 1% cholesterol with water extract of P.s (125 mg/kg), W3 - 1% cholesterol with water extract of P.s (250 mg/kg), W4 - 1% cholesterol with water extract of P.s (500 mg/kg) and Smv - 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg). All rabbits were treated for 10 weeks. Following 10 weeks of supplementation, the animals were sacrificed and the aortic tissue was taken for histological study.

Results
Rabbits fed only with high cholesterol diet 1% cholesterol (CH) showed focal fatty streak lesions compared to the C group and 1% cholesterol supplemented with simvistatin drug (Smv) group. Atherosclerotic lesions in the 1% cholesterol group supplemented with P.s (500 mg/kg) i.e. W4 group showed significant reduction (30 ± 6.0%, p < 0.05) in fatty streak compared to the high cholesterol group (85.6 ± 4.1%) under Sudan IV stain. The atherosclerotic lesions under transmission electron microscope showed reduction in foam cells in the treatment groups compared to the CH groups.

Conclusion
Administration of P.s extract has protective effect against atheroscleros
A health economic model for evaluating a vaccine for the prevention of herpes zoster and post-herpetic neuralgia in the UK
Authors: Moore Lee , Remy Vanessa , Martin Monique , Beillat Maud , McGuire Alistair 
Published: April 2010

Abstract

Background
A live-attenuated vaccine aimed at preventing herpes zoster (HZ) and its main complication, post-herpetic neuralgia (PHN) is available in Europe for immunocompetent adults aged 50 years and more. The study objective is to assess the cost effectiveness of a vaccination program for this population in the UK.

Methods
A state-transition Markov model has been developed to simulate the natural history of HZ and PHN and to estimate the lifetime effects of vaccination in the UK. Several health states are defined including good health, HZ, PHN, and death. HZ and PHN health states are further divided to reflect pain severity.

Results
The model predicts that a vaccination strategy for those aged over 50 years would lead to an incremental cost-effectiveness ratio of £13,077 per QALY gained from the NHS perspective, when compared to the current strategy of no vaccination. Age-group analyses show that the lowest ICERs (£10,984 and £10,275 for NHS) are observed when vaccinating people between 60-64 and 65-69 years of age. Sensitivity analyses showed that results are sensitive to the duration of vaccine protection, discount rate, utility decrements and pain severity split used.

Conclusions
Using the commonly accepted threshold of £30,000 per QALY gained in the UK, most scenarios of vaccination programmes preventing HZ and PHN, including the potential use of a repeat dose, may be considered cost-effective by the NHS, especially within the 60 to 69 age-groups.
Clinical significance of EGFR, Her-2 and EGF in oral squamous cell carcinoma: a case control study
Authors: Bernardes Vanessa F , Gleber-Netto Frederico O , Sousa Sílvia F , Silva Tarcília A , Aguiar Maria Cássia F 
Published: April 2010

Abstract

Background
The erbB receptors and their ligands are involved in the pathogenesis and progression of oral squamous cell carcinoma (OSCC). Although EGFR and Her-2 are frequently overexpressed in OSCC, few studies evaluated these proteins in saliva and their association with the tumor, which may represent potential usefulness in a clinical setting.

Methods
The levels of EGFR, Her-2, and EGF were evaluated in saliva of 46 patients with OSCC before and after the surgical removal of the lesion, as well as in matched healthy controls. The relationship of salivary levels and EGFR and Her-2 immunoexpression in tumor samples with clinicopathological features was analyzed.

Results
EGFR and Her-2 salivary levels did not show difference between to pre-surgery and control groups, however, both demonstrated an increase after surgical removal of the tumor. No association was detectable among receptor salivary levels, tissue expression and clinicopathological features. EGF levels in pre-surgery group were significantly lower when compared to the control group.

Conclusions
EGFR and Her-2 were not considered to be valuable salivary tumor markers in OSCC, however, lower levels of EGF in saliva may suggest a higher susceptibility for OSCC development.