bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring the prevalence of regional mutation rates: an analysis of silent substitutions in mammals, fungi, and insects
Authors: Fox Aleah K , Tuch Brian B , Chuang Jeffrey H 
Published: June 2008

Abstract

Background
The patterns of mutation vary both within and across genomes. It has been shown for a few mammals that mutation rates vary within the genome, while for unknown reasons, the sensu stricto yeasts have uniform rates instead. The generality of these observations has been unknown. Here we examine silent site substitutions in a more expansive set (20 mammals, 27 fungi, 4 insects) to determine why some genomes demonstrate this mosaic distribution and why others are uniform.

Results
We applied several intragene and intergene correlation tests to measure regional substitution patterns. Assuming that silent sites are a reasonable approximation to neutrally mutating sequence, our results show that all multicellular eukaryotes exhibit mutational heterogeneity. In striking contrast, all fungi are mutationally uniform – with the exception of three Candida species: C. albicans, C. dubliniensis, and C. tropicalis. We speculate that aspects of replication timing may be responsible for distinguishing these species. Our analysis also reveals classes of genes whose silent sites behave anomalously with respect to the mutational background in many species, indicating prevalent selective pressures. Genes associated with nucleotide binding or gene regulation have consistently low silent substitution rates in every mammalian species, as well as multiple fungi. On the other hand, receptor genes repeatedly exhibit high silent substitution rates, suggesting they have been influenced by diversifying selection.

Conclusion
Our findings provide a framework for understanding the regional mutational properties of eukaryotes, revealing a sharp difference between fungi and multicellular species. They also elucidate common selective pressures acting on eukaryotic silent sites, with frequent evidence for both purifying and diversifying selection.
RAWUL: A new ubiquitin-like domain in PRC1 Ring finger proteins that unveils putative plant and worm PRC1 orthologs
Authors: Sanchez-Pulido Luis , Devos Damien , Sung Zinmay R , Calonje Myriam 
Published: June 2008

Abstract

Background
Polycomb group (PcG) proteins are a set of chromatin-modifying proteins that play a key role in epigenetic gene regulation. The PcG proteins form large multiprotein complexes with different activities. The two best-characterized PcG complexes are the PcG repressive complex 1 (PRC1) and 2 (PRC2) that respectively possess histone 2A lysine 119 E3 ubiquitin ligase and histone 3 lysine 27 methyltransferase activities. While PRC2-like complexes are conserved throughout the eukaryotic kingdoms, PRC1-like complexes have only been described in Drosophila and vertebrates. Since both complexes are required for the gene silencing mechanism in Drosophila and vertebrates, how PRC1 function is realized in organisms that apparently lack PRC1 such as plants, is so far unknown. In vertebrates, PRC1 includes three proteins, Ring1B, Ring1A, and Bmi-1 that form an E3 ubiquitin ligase complex. These PRC1 proteins have an N-terminally located Ring finger domain associated to a poorly characterized conserved C-terminal region.

Results
We obtained statistically significant evidences of sequence similarity between the C-terminal region of the PRC1 Ring finger proteins and the ubiquitin (Ubq)-like family proteins, thus defining a new Ubq-like domain, the RAWUL domain. In addition, our analysis revealed the existence of plant and worm proteins that display the conserved combination of a Ring finger domain at the N-terminus and a RAWUL domain at the C-terminus.

Conclusion
Analysis of the conserved domain architecture among PRC1 Ring finger proteins revealed the existence of long sought PRC1 protein orthologs in these organisms, suggesting the functional conservation of PRC1 throughout higher eukaryotes.
Ex vivo recovery and activation of dysfunctional, anergic, monocyte-derived dendritic cells from patients with operable breast cancer: critical role of IFN-alpha
Authors: Satthaporn Sukchai , Aloysius Mark M , Robins Richard A , Verma Chandan , Chuthapisith Suebwong , Mckechnie Alasdair J , El-Sheemy Mohamad , Vassanasiri Wichai , Valerio David , Clark David , Jibril Jibril A , Eremin Oleg 
Published: June 2008

AbstractBackgroundDendritic cells (DCs) play a crucial role in initiating effective cell-mediated immune responses, but are dysfunctional and anergic in breast cancer. Reversal of this dysfunction and establishment of optimal DC function is a key prerequisite for the induction of effective anti-cancer immune responses.ResultsPeripheral blood DCs (PBDCs) and lymph node DCs (LNDCs) generatedin vitrofrom adherent cultures of peripheral blood monocytes (PBMs) and lymph node monocytes (LNMs), respectively, using the 4 cytokine conditioned medium (CCM) (GM-CSF+IL-4+TNF-α+IFN-α) or 3 CCM (GM-CSF+IL-4+TNF-α) demonstrated a significantly higher degree of recovery and functional capacity in a mixed lymphocyte DC reaction (MLDCR, p < 0.001), expressed significantly higher levels of HLA-DR, CD86, compared with 2 CCM (GM-CSF+IL-4) or medium alone generated DCs from PBMs and LNMs (p < 0.001). The PBDCs generated with 3 CCM or 4 CCM showed a significantly (p < 0.001) enhanced macropinocytotic capability (dextran particles) and induced increased production and secretion of interleukin-12p40 (IL-12p40)in vitro(p < 0.001), compared with PBDCs generated from monocytes using 2 CCM or medium alone. Lipopolysaccharide (LPS) stimulation of PBDCs generated with 4 CCM demonstrated enhanced secretion of IL-6 but not IL-12p70, compared with control DCs unstimulated with LPS (p < 0.001).ConclusionDysfunctional and anergic PBDCs and LNDCs from patients with operable breast cancer can be optimally reversed byex vivoculturing of precursor adherent monocytes using a 4 CCM containing IFN-α. Maximal immunophenotypic recovery and functional reactivation of DCs is seen in the presence of IFN-α. However, 4 CCM containing IFN-α generated-PBDCs, do not produce and secrete IL-12p70in vitro.
Bacteria of the Burkholderia cepacia complex are cyanogenic under biofilm and colonial growth conditions
Authors: Ryall Ben , Lee Xiaoyun , Zlosnik James EA , Hoshino Saiko , Williams Huw D 
Published: June 2008

Abstract

Background
The Burkholderia cepacia complex (Bcc) is a collection of nine genotypically distinct but phenotypically similar species. They show wide ecological diversity and include species that are used for promoting plant growth and bio-control as well species that are opportunistic pathogens of vulnerable patients. Over recent years the Bcc have emerged as problematic pathogens of the CF lung. Pseudomonas aeruginosa is another important CF pathogen. It is able to synthesise hydrogen cyanide (HCN), a potent inhibitor of cellular respiration. We have recently shown that HCN production by P. aeruginosa may have a role in CF pathogenesis. This paper describes an investigation of the ability of bacteria of the Bcc to make HCN.

Results
The genome of Burkholderia cenocepacia has 3 putative HCN synthase encoding (hcnABC) gene clusters. B. cenocepacia and all 9 species of the Bcc complex tested were able to make cyanide at comparable levels to P. aeruginosa, but only when grown surface attached as colonies or during biofilm growth on glass beads. In contrast to P. aeruginosa and other cyanogenic bacteria, cyanide was not detected during planktonic growth of Bcc strains.

Conclusion
All species in the Bcc are cyanogenic when grown as surface attached colonies or as biofilms.
Evidence of platelet activation in multiple sclerosis
Authors: Sheremata William A , Jy Wenche , Horstman Lawrence L , Ahn Yeon S , Alexander J Steven , Minagar Alireza 
Published: June 2008

Abstract

Objective
A fatality in one multiple sclerosis (MS) patient due to acute idiopathic thrombocytopenic purpura (ITP) and a near fatality in another stimulated our interest in platelet function abnormalities in MS. Previously, we presented evidence of platelet activation in a small cohort of treatment-naive MS patients.

Methods
In this report, 92 normal controls and 33 stable, untreated MS patients were studied. Platelet counts, measures of platelet activation [plasma platelet microparticles (PMP), P-selectin expression (CD62p), circulating platelet microaggragtes (PAg)], as well as platelet-associated IgG/IgM, were carried out. In addition, plasma protein S activity was measured.

Results
Compared to controls, PMP were significantly elevated in MS (p < 0.001) and CD62p expression was also markedly elevated (p < 0.001). Both are markers of platelet activation. Platelet-associated IgM, but not IgG, was marginally elevated in MS (p = 0.01). Protein S in MS patients did not differ significantly from normal values.

Conclusion
Platelets are significantly activated in MS patients. The mechanisms underlying this activation and its significance to MS are unknown. Additional study of platelet activation and function in MS patients is warranted.
Effect of prolonging radiation delivery time on retention of gammaH2AX
Authors: Moiseenko Vitali , Banáth Judit P , Duzenli Cheryl , Olive Peggy L 
Published: June 2008

Abstract

Background and purpose
Compared to conventional external beam radiotherapy, IMRT requires significantly more time to deliver the dose. Prolonging dose delivery potentially increases DNA repair which would reduce the biological effect. We questioned whether retention of γH2AX, a measure of lack of repair of DNA damage, would decrease when dose delivery was protracted.

Materials and methods
Exponentially growing SiHa cervical carinoma cells were irradiated with 6 MV photons in a water tank using a VarianEX linear accelerator. Cells held at 37°C received 2 Gy in 0.5 min and 4 Gy in 1 min. To evaluate effect of dose delivery prolongation, 2 and 4 Gy were delivered in 30 and 60 min. After 24 h recovery, cells were analyzed for clonogenic survival and for residual γH2AX as measured using flow cytometry.

Results
Increasing the dose delivery time from 0.5 or 1 min to 30 or 60 min produced a signficant increase in cell survival from 0.45 to 0.48 after 2 Gy, and from 0.17 to 0.20 after 4 Gy. Expression of residual γH2AX decreased from 1.27 to 1.22 relative to background after 2 Gy and 1.46 to 1.39 relative to background after 4 Gy, but differences were not statistically significant. The relative differences in the slopes of residual γH2AX versus dose for acute versus prolonged irradiation bordered on significant (p = 0.055), and the magnitude of the change was consistent with the observed increase in surviving fraction.

Conclusion
These results support the concept that DNA repair underlies the increase in survival observed when dose delivery is prolonged. They also help to establish the limits of sensitivity of residual γH2AX, as measured using flow cytometry, for detecting differences in response to irradiation.
Pathway analysis reveals functional convergence of gene expression profiles in breast cancer
Authors: Shen Ronglai , Chinnaiyan Arul M , Ghosh Debashis 
Published: June 2008

AbstractBackgroundA recent study has shown high concordance of several breast-cancer gene signatures in predicting disease recurrence despite minimal overlap of the gene lists. It raises the question if there are common themes underlying such prediction concordance that are not apparent on the individual gene-level. We therefore studied the similarity of these gene-signatures on the basis of their functional annotations.ResultsWe found the signatures did not identify the same set of genes but converged on the activation of a similar set of oncogenic and clinically-relevant pathways. A clear and consistent pattern across the four breast cancer signatures is the activation of the estrogen-signaling pathway. Other common features include BRCA1-regulated pathway, reck pathways, and insulin signaling associated with the ER-positive disease signatures, all providing possible explanations for the prediction concordance.ConclusionThis work explains why independent breast cancer signatures that appear to perform equally well at predicting patient prognosis show minimal overlap in gene membership.
Fibroepithelioma of pinkus in a 9-year-old boy: a case report
Authors: Pan Zenggang , Huynh Nhi , Sarma Deba P 
Published: June 2008

Abstract
Fibroepithelioma of Pinkus (FEP) is a rare indolent variety of basal cell carcinoma that is typically polypoid and located on the trunk of adult males aged 40–60 years. Basal cell carcinoma (including FEP) is very rare in the pediatric population. We are reporting such a case occurring in a 9-year-old boy.
Inferring mouse gene functions from genomic-scale data using a combined functional network/classification strategy
Authors: Kim Wan Kyu , Krumpelman Chase , Marcotte Edward M 
Published: June 2008

AbstractThe complete set of mouse genes, as with the set of human genes, is still largely uncharacterized, with many pieces of experimental evidence accumulating regarding the activities and expression of the genes, but the majority of genes as yet still of unknown function. Within the context of the MouseFunc competition, we developed and applied two distinct large-scale data mining approaches to infer the functions (Gene Ontology annotations) of mouse genes from experimental observations from available functional genomics, proteomics, comparative genomics, and phenotypic data. The two strategies — the first using classifiers to map features to annotations, the second propagating annotations from characterized genes to uncharacterized genes along edges in a network constructed from the features — offer alternative and possibly complementary approaches to providing functional annotations. Here, we re-implement and evaluate these approaches and their combination for their ability to predict the proper functional annotations of genes in the MouseFunc data set. We show that, when controlling for the same set of input features, the network approach generally outperformed a naïve Bayesian classifier approach, while their combination offers some improvement over either independently. We make our observations of predictive performance on the MouseFunc competition hold-out set, as well as on a ten-fold cross-validation of the MouseFunc data. Across all 1,339 annotated genes in the MouseFunc test set, the median predictive power was quite strong (median area under a receiver operating characteristic plot of 0.865 and average precision of 0.195), indicating that a mining-based strategy with existing data is a promising path towards discovering mammalian gene functions. As one product of this work, a high-confidence subset of the functional mouse gene network was produced — spanning >70% of mouse genes with >1.6 million associations — that is predictive of mouse (and therefore often human) gene function and functional associations. The network should be generally useful for mammalian gene functional analyses, such as for predicting interactions, inferring functional connections between genes and pathways, and prioritizing candidate genes. The network and all predictions are available on the worldwide web.
Consistent probabilistic outputs for protein function prediction
Authors: Obozinski Guillaume , Lanckriet Gert , Grant Charles , Jordan Michael I , Noble William Stafford 
Published: June 2008

AbstractIn predicting hierarchical protein function annotations, such as terms in the Gene Ontology (GO), the simplest approach makes predictions for each term independently. However, this approach has the unfortunate consequence that the predictor may assign to a single protein a set of terms that are inconsistent with one another; for example, the predictor may assign a specific GO term to a given protein ('purine nucleotide binding') but not assign the parent term ('nucleotide binding'). Such predictions are difficult to interpret. In this work, we focus on methods for calibrating and combining independent predictions to obtain a set of probabilistic predictions that are consistent with the topology of the ontology. We call this procedure 'reconciliation'. We begin with a baseline method for predicting GO terms from a collection of data types using an ensemble of discriminative classifiers. We apply the method to a previously described benchmark data set, and we demonstrate that the resulting predictions are frequently inconsistent with the topology of the GO. We then consider 11 distinct reconciliation methods: three heuristic methods; four variants of a Bayesian network; an extension of logistic regression to the structured case; and three novel projection methods - isotonic regression and two variants of a Kullback-Leibler projection method. We evaluate each method in three different modes - per term, per protein and joint - corresponding to three types of prediction tasks. Although the principal goal of reconciliation is interpretability, it is important to assess whether interpretability comes at a cost in terms of precision and recall. Indeed, we find that many apparently reasonable reconciliation methods yield reconciled probabilities with significantly lower precision than the original, unreconciled estimates. On the other hand, we find that isotonic regression usually performs better than the underlying, unreconciled method, and almost never performs worse; isotonic regression appears to be able to use the constraints from the GO network to its advantage. An exception to this rule is the high precision regime for joint evaluation, where Kullback-Leibler projection yields the best performance.
Patients’ Knowledge and Understanding of the Implications of Wearing Dentures. Report of a Survey Conducted at a Dental Institute in the South of India
Authors: Shigli Kamal , Angadi Gangadhar Shivappa , Hegde Pradnya , Hebbal Mamata 
Published: June 2008

Aim The aim of this survey was to assess the knowledge and perceptions of denture treatment among a group of patients who attended the Karnataka Lingayat Education Society's (KLES) Institute of Dental Sciences, Belgaum, Karnataka State, India. Method A questionnaire with four general questions and 14 statements/questions about denture construction and wearing was developed and piloted. Ethical approval was sought and granted. After some revisions, the questionnaire was given to all patients attending KLES over a two-month period. Results All 423 patients who attended KLES in the two-month period completed the questionnaire. Five questionnaires were not analysed because of ambiguity in the answers. The final patient sample was 418 (207 females and 211 males, mean age 40 ± 15.3 years) of whom 140 (33.5%) were dentate and 278 (66.5%) edentulous in either one or both jaws. Among the 278 edentulous patients, 143 (51.4%) had not worn any kind of denture and 135 (48.6%) wore dentures. There was a wide variation in the accuracy of the patients’ knowledge of denture treatment. In particular, more than 20% did not know that complete denture treatment requires five or more visits, that denture wearers may experience oral pain, whether or not dentures may cause more problems than natural teeth, or that dentures may make audible clicks and cause problems when speaking. Conclusion Patient education is an essential element in successful denture treatment. It should begin prior to the treatment, to ensure that the technical capability of the clinician matches the expectations of the patient. The initial appointment needs to be used as an educational tool to raise patients’ level of understanding of prosthetic rehabilitation and how the proposed treatment will meet their needs.
The Emerging Dental Workforce: Short-Term Expectations of, and Influences on Dental Students Graduating from a London Dental School in 2005
Authors: Gallagher Jennifer E , Clarke Wendy , Wilson Nairn HF 
Published: June 2008

Aim The aim of this research was to identify short-term career aspirations and goals of final-year dental students at a London dental school and the perceived factors that influenced these aspirations. Methods Two methods were used to collect data on final-year students’ short-term career plans and influences. Qualitative data were collected through focus groups and analysed using ‘framework methodology’. These findings informed a questionnaire survey of all students at the end of their final undergraduate year. Data were entered into and analysed using a statistical software package. Results Thirty-five students participated in focus groups, with recruitment continuing until data were saturated. Ninety per cent (n=126) of the total population (140) responded to the questionnaire survey; the majority were Asian (70%), female (58%), and aged 23 years (59%). Short-term professional expectations focused around ‘achieving professional status within a social context’, ‘gaining professional experience’, ‘developing independence’ and ‘achieving financial stability’. ‘Achieving financial stability’ was ranked as the most important influence in decision-making about their career in the short term (77%), followed by ‘balance of work and other aspects of life’ (75%) and ‘good lifestyle’ (75%). Four out of ten intended to work towards membership of a Royal College and/or becoming a specialist. Proximity to family (81%) and friends (79%) was an important or very important influence on location in the short term. Asian students were significantly more likely to rate ‘proximity to family’ ( p=0.042), working in an ‘urban area’ ( p=0.001) and ‘opportunities for private care’ ( p=0.043) of greater importance than their White counterparts. Conclusions Short-term aspirations involve ‘achieving professional status within a social context’, and personal, social, professional and financial goals. Location of future practice was significantly associated with ethnicity.
What is the mechanism of psychological change? A qualitative analysis of six individuals who experienced personal change and recovery
Authors: Higginson Sally. , Mansell Warren. 
Published: June 2008

Objective. The mechanism of psychological change, whether this occurs as a result of psychotherapeutic intervention or during natural recovery, remains unknown. The aim of this study was to explore and understand how and why psychological change occurs.Design. This study presents the accounts of six individuals who experienced psychological change and recovery following a significant problem in their lives using the qualitative method of interpretative phenomenological analysis (IPA).Method. A semi‐structured interview covered several aspects of their experience which included details of the problem they faced, how the problem affected their lives, how they were able to overcome the problem, and how they felt about their problem looking back.Results. Four superordinate themes emerged from the analysis: hopelessness and issues of control; the change process; new self versus old self; and putting the problem into perspective.Conclusions. Findings are discussed in relation to existing literature on hopelessness and locus of control, experiential avoidance, acceptance and mindfulness, insight, and adversarial growth. The findings are also discussed in relation to a theory of self‐regulation known as perceptual control theory (PCT). It is proposed that this theory may provide a valid account of the mechanism of psychological change.