bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between lamb survival and prion protein genotype: analysis of data for ten sheep breeds in Great Britain
Authors: Gubbins Simon , Cook Charlotte J , Hyder Kieran , Boulton Kay , Davis Carol , Thomas Eurion , Haresign Will , Bishop Stephen C , Villanueva Beatriz , Eglin Rachel D 
Published: February 2009

Abstract

Background
Selective breeding programmes, based on prion protein (PrP) genotype, have been introduced throughout the European Union to reduce the risk of sheep transmissible spongiform encephalopathies (TSEs). These programmes could have negative consequences on other important traits, such as fitness and production traits, if the PrP gene has pleiotropic effects or is in linkage disequilibrium with genes affecting these traits. This paper presents the results of an investigation into associations between lamb survival and PrP genotype in ten mainstream sheep breeds in Great Britain (GB). In addition, the reasons for lamb deaths were examined in order to identify any associations between these and PrP genotype.

Results
Survival times from birth to weaning were analysed for over 38000 lambs (2427 dead and 36096 live lambs) from 128 flocks using Cox proportional hazard models for each breed, including additive animal genetic effects. No significant associations between PrP genotype and lamb survival were identified, except in the Charollais breed for which there was a higher risk of mortality in lambs of the ARR/VRQ genotype compared with those of the ARR/ARR genotype. Significant effects of birth weight, litter size, sex, age of dam and year of birth on survival were also identified. For all breeds the reasons for death changed significantly with age; however, no significant associations between reason for death and PrP genotype were found for any of the breeds.

Conclusion
This study found no evidence to suggest that a selective breeding programme based on PrP genotype will have a detrimental effect on lamb survival. The only significant effect of PrP genotype identified was likely to be of little consequence because an increased risk of mortality was associated with a genotype that is selected against in current breeding strategies.
Enhanced relapse prevention for bipolar disorder: a qualitative investigation of value perceived for service users and care coordinators
Authors: Pontin Eleanor , Peters Sarah , Lobban Fiona , Rogers Anne , Morriss Richard K 
Published: February 2009

Abstract

Background
Enhanced relapse prevention (ERP) is a psychological intervention delivered by mental health professionals to help individuals with bipolar disorder (BD) recognise and manage early warning signs for mania and depression. ERP has an emerging evidence base and is recommended as good practice for mental health professionals. However, without highly perceived value to both those receiving (services users) or delivering it (health professionals), implementation will not occur. The aim of this study is to determine what values of ERP are perceived by service users (SUs) and mental health professionals (care coordinators, CCs) providing community case management.

Methods
A nested qualitative study design was employed as part of a randomised controlled trial of ERP. Semi-structured interviews were conducted with a purposive sub-sample of 21 CCs and 21 SUs, and an iterative approach used to develop a framework of conceptual categories that was applied systematically to the data.

Results
The process of implementing and receiving ERP was valued by both SUs and CCs for three similar sets of reasons: improved understanding of BD (where a knowledge deficit of BD was perceived), enhanced working relationships, and improved ways of managing the condition. There were some differences in the implications these had for both CCs and SUs who also held some reservations.

Conclusion
CCs and SUs perceive similar value in early warning signs interventions to prevent relapse, and these have particular benefits to them. If this perceived value is maintained, CCs and SUs in routine practice may use ERP long-term.
An image processing approach to computing distances between RNA secondary structures dot plots
Authors: Ivry Tor , Michal Shahar , Avihoo Assaf , Sapiro Guillermo , Barash Danny 
Published: February 2009

Abstract

Background
Computing the distance between two RNA secondary structures can contribute in understanding the functional relationship between them. When used repeatedly, such a procedure may lead to finding a query RNA structure of interest in a database of structures. Several methods are available for computing distances between RNAs represented as strings or graphs, but none utilize the RNA representation with dot plots. Since dot plots are essentially digital images, there is a clear motivation to devise an algorithm for computing the distance between dot plots based on image processing methods.

Results
We have developed a new metric dubbed 'DoPloCompare', which compares two RNA structures. The method is based on comparing dot plot diagrams that represent the secondary structures. When analyzing two diagrams and motivated by image processing, the distance is based on a combination of histogram correlations and a geometrical distance measure. We introduce, describe, and illustrate the procedure by two applications that utilize this metric on RNA sequences. The first application is the RNA design problem, where the goal is to find the nucleotide sequence for a given secondary structure. Examples where our proposed distance measure outperforms others are given. The second application locates peculiar point mutations that induce significant structural alternations relative to the wild type predicted secondary structure. The approach reported in the past to solve this problem was tested on several RNA sequences with known secondary structures to affirm their prediction, as well as on a data set of ribosomal pieces. These pieces were computationally cut from a ribosome for which an experimentally derived secondary structure is available, and on each piece the prediction conveys similarity to the experimental result. Our newly proposed distance measure shows benefit in this problem as well when compared to standard methods used for assessing the distance similarity between two RNA secondary structures.

Conclusion
Inspired by image processing and the dot plot representation for RNA secondary structure, we have managed to provide a conceptually new and potentially beneficial metric for comparing two RNA secondary structures. We illustrated our approach on the RNA design problem, as well as on an application that utilizes the distance measure to detect conformational rearranging point mutations in an RNA sequence.
Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon
Authors: Wang Bei , Waclaw Ronald R , Allen Zegary J , Guillemot Francois , Campbell Kenneth 
Published: February 2009

Abstract
Background
The homeobox gene Gsx2 (formerly Gsh2) is known to regulate patterning in the lateral ganglionic eminence (LGE) of the embryonic telencephalon. In its absence, the closely related gene Gsx1 (previously known as Gsh1) can partially compensate in the patterning and differentiation of ventral telencephalic structures, such as the striatum. However, the cellular and molecular mechanisms underlying this compensation remain unclear.

Results
We show here that in the Gsx2 mutants Gsx1 is expressed in only a subset of the ventral telencephalic progenitors that normally express Gsx2. Based on the similarities in the expression of Gsx1 and Ascl1 (Mash1) within the Gsx2 mutant LGE, we examined whether Ascl1 plays an integral part in the Gsx1-based recovery. Ascl1 mutants show only modest alterations in striatal development; however, in Gsx2;Ascl1 double mutants, striatal development is severely affected, similar to that seen in the Gsx1;Gsx2 double mutants. This is despite the fact that Gsx1 is expressed, and even expands, in the Gsx2;Ascl1 mutant LGE, comparable to that seen in the Gsx2 mutant. Finally, Notch signaling has recently been suggested to be required for normal striatal development. In spite of the fact that Notch signaling is severely disrupted in Ascl1 mutants, it actually appears to be improved in the Gsx2;Ascl1 double mutants.

Conclusion
These results, therefore, reveal a non-proneural requirement of Ascl1 that together with Gsx1 compensates for the loss of Gsx2 in a subset of LGE progenitors.
Rhombomere-specific analysis reveals the repertoire of genetic cues expressed across the developing hindbrain
Authors: Chambers David , Wilson Leigh Jane , Alfonsi Fabienne , Hunter Ewan , Saxena Uma , Blanc Eric , Lumsden Andrew 
Published: February 2009

Abstract
Background
The Hox family of homeodomain transcription factors comprises pivotal regulators of cell specification and identity during animal development. However, despite their well-defined roles in the establishment of anteroposterior pattern and considerable research into their mechanism of action, relatively few target genes have been identified in the downstream regulatory network. We have sought to investigate this issue, focussing on the developing hindbrain and the cranial motor neurons that arise from this region. The reiterated anteroposterior compartments of the developing hindbrain (rhombomeres (r)) are normally patterned by the combinatorial action of distinct Hox genes. Alteration in the normal pattern of Hox cues in this region results in a transformation of cellular identity to match the remaining Hox profile, similar to that observed in Drosophila homeotic transformations.

Results
To define the repertoire of genes regulated in each rhombomere, we have analysed the transcriptome of each rhombomere from wild-type mouse embryos and not those where pattern is perturbed by gain or loss of Hox gene function. Using microarray and bioinformatic methodologies in conjunction with other confirmatory techniques, we report here a detailed and comprehensive set of potential Hox target genes in r2, r3, r4 and r5. We have demonstrated that the data produced are both fully reflective and predictive of rhombomere identity and, thus, may represent some the of Hox targets. These data have been interrogated to generate a list of candidate genes whose function may contribute to the generation of neuronal subtypes characteristic of each rhombomere. Interestingly, the data can also be classified into genetic motifs that are predicted by the specific combinations of Hox genes and other regulators of hindbrain anteroposterior identity. The sets of genes described in each or combinations of rhombomeres span a wide functional range and suggest that the Hox genes, as well as other regulatory inputs, exert their influence across the full spectrum of molecular machinery.

Conclusion
We have performed a systematic survey of the transcriptional status of individual segments of the developing mouse hindbrain and identified hundreds of previously undescribed genes expressed in this region. The functional range of the potential candidate effectors or upstream modulators of Hox activity suggest multiple unexplored mechanisms. In particular, we present evidence of a potential new retinoic acid signalling system in ventral r4 and propose a model for the refinement of identity in this region. Furthermore, the rhombomeres demonstrate a molecular relationship to each other that is consistent with known observations about neurogenesis in the hindbrain. These findings give the first genome-wide insight into the complexity of gene expression during patterning of the developing hindbrain.
A novel PTCH1 germline mutation distinguishes basal cell carcinoma from basaloid follicular hamartoma: a case report
Authors: Hellani Ali , Baghdadi Hiba , Dabbour Nidal , Almassri Nidal , Abu-Amero Khaled K 
Published: February 2009

Abstract

Introduction
Nevoid basal cell carcinoma syndrome is a rare autosomal dominant disorder characterized by numerous basal cell carcinomas, odontogenic keratocysts of the jaws and developmental defects. The disorder results from mutations in the PTCH1 gene.

Case presentation
A 15-year-old boy presented to our dental clinic with multiple jaw cysts. The patient had broad confluent eyebrows, a broad base of the nose, frontal bossing and palmoplantar pits. Examination of the jaw cysts revealed many keratinizing cysts without granular cell layers a finding that raised the suspicion of nevoid basal cell carcinoma. Radiological examinations showed calcification of the falx cerebri, spina bifida, bifid thoracic ribs and frontal bossing. Histopathological examination showed basaloid proliferation in the upper dermis with follicular differentiation surrounded by a loose mucinous stroma and retraction artifacts. These features make it difficult to differentiate between nevoid basal cell carcinoma and basaloid follicular hamartoma, especially the presence of these findings on a non-hairy area. BCL-2 staining was positive in the periphery of the basaloid proliferation, which is typical of basaloid follicular hamartoma, and not in a diffuse pattern, which is typical of nevoid basal cell carcinoma. The proband's siblings and parents were healthy with no family history of this condition in the extended family. Since histology was equivocal and palmoplantar pits are seen in both basaloid follicular hamartoma and nevoid basal cell carcinoma, molecular genetic investigation was necessary to differentiate between the two potential diagnoses. After sequencing the entire PTCH1 gene, we detected a single nucleotide deletion (c.1291delC) in codon 431 of the PTCH protein, which resulted in a premature stop translation at residue 431. This de novo mutation was not detected in both parents and in 100 normal volunteers of matching ethnicity.

Conclusion
Screening the PTCH1 gene for mutations helped to differentiate between basaloid follicular hamartoma and nevoid basal cell carcinoma and confirmed the diagnosis.
Diurnal variation of the human adipose transcriptome and the link to metabolic disease
Authors: Loboda Andrey , Kraft Walter K , Fine Bernard , Joseph Jeffrey , Nebozhyn Michael , Zhang Chunsheng , He Yudong , Yang Xia , Wright Christopher , Morris Mark , Chalikonda Ira , Ferguson Mark , Emilsson Valur , Leonardson Amy , Lamb John , Dai Hongyue , Schadt Eric , Greenberg Howard E , Lum Pek Yee 
Published: February 2009

AbstractBackgroundCircadian (diurnal) rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation.MethodsThe present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted.ResultsThe results indicated that diurnal rhythm was the most significant driver of gene expression variation in the human adipose tissue, with at least 25% of the genes having had significant changes in their expression levels during the course of the day. The mRNA expression levels of core clock genes at a specific time of day were consistent across multiple subjects on different days in all three arms, indicating robust diurnal regulation irrespective of potential confounding factors. The genes essential for energy metabolism and tissue physiology were part of the diurnal signature. We hypothesize that the diurnal transition of the expression of energy metabolism genes reflects the shift in the adipose tissue from an energy-expending state in the morning to an energy-storing state in the evening. Consistent with this hypothesis, the diurnal transition was delayed by fasting and treatment with sibutramine. Finally, anin silicocomparison of the diurnal signature with data from the publicly-available Connectivity Map demonstrated a significant association with transcripts that were repressed by mTOR inhibitors, suggesting a possible link between mTOR signaling, diurnal gene expression and metabolic regulation.ConclusionDiurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose tissue and should be considered in the selection of novel targets for the treatment of obesity and other metabolic disorders.
Heavy metal exposure reverses genetic resistance to Chlamydia-induced arthritis
Authors: Inman Robert D , Chiu Basil 
Published: February 2009

Abstract
Introduction
We have previously observed that Brown Norway (BN) rats display a relative resistance to experimental Chlamydia-induced arthritis. In the present study, we examine an environmental toxin, mercuric chloride (HgCl2), as a modulator of this innate resistance to arthritis.

Methods
To assess the effect of the heavy metal exposure, one group of rats received two subcutaneous injections of HgCl2 (1 mg/kg) 48 hours apart. Seven days later, the animals received the intra-articular injection of synoviocyte-packaged Chlamydia.

Results
Histopathology revealed that BN rats receiving only Chlamydia had a minimal cellular infiltration in the joint, which was predominantly mononuclear in character. In contrast, mercury-exposed rats had a marked exacerbation of the histopathological severity of the arthritis, and the infiltration was predominantly neutrophilic. Mercury exposure was also associated with marked enhancement in IgE levels and an alteration in IgG2a/IgG1 ratio, reflecting a Th2 shift. The local cytokine profile in the joint was markedly altered after mercury exposure, with a suppression of tumour necrosis factor-alpha and interferon-gamma but an enhancement of vascular endothelial growth factor. This was associated with decreased host clearance capacity reflected in enhanced bacterial load in both the spleen and the joint and was accompanied by enhanced detection of microbial antigens in the synovial tissues by immunohistological staining.

Conclusions
Genetically defined cytokine production in the joint defines the severity of reactive arthritis by dictating the local clearance of the pathogen. This interplay can be altered dramatically by heavy metal exposure, which results in suppression of protective cytokines in the microenvironment of the joint.
Routine delirium monitoring in a UK critical care unit
Authors: Page Valerie J , Navarange Sachin , Gama Sibu , McAuley Danny F 
Published: February 2009

Abstract
Introduction
Delirium in the intensive care unit (ICU) is associated with increased morbidity and mortality. Using an assessment tool has been shown to improve the ability of clinicians in the ICU to detect delirium. The confusion assessment method for the ICU (CAM-ICU) is a validated delirium-screening tool for critically ill intubated patients. The aim of this project was to establish the feasibility of routine delirium screening using the CAM-ICU and to identify the incidence of delirium in a UK critical care unit.

Methods
Routine CAM-ICU monitoring was implemented in a mixed critical care unit in January 2007 following a two-month educational and promotional campaign. Guidelines for the management of delirium were introduced. During a two-month prospective audit in September and October 2007, the daily CAM-ICU was recorded by the bedside nurse for consecutive level 2 and level 3 patients admitted to the mixed medical/surgical critical care ward in a district general hospital. This was repeated in January 2008. Patient outcome was recorded. The records of an additional cohort of ventilated patients were reviewed retrospectively to determine compliance with routine CAM-ICU assessments.

Results
Seventy-one patients were included in the observational cohort, with 60 patients in the retrospective cohort. In the prospective group it was not possible to assess for delirium with the CAM-ICU in nine patients due to persistent coma or inability to understand simple instructions. Excluding elective post-operative patients, the incidence of delirium was 45% in patients who could be assessed; in the 27 ventilated patients who could be assessed it was 63%. From the retrospective data compliance with the CAM-ICU assessment was 92%. The incidence of delirium in this retrospective group of ventilated patients who could be assessed was 65%.

Conclusions
We have demonstrated that delirium screening is feasible in a UK ICU population. The high incidence of delirium and the impact on outcomes in this UK cohort of patients is in line with previous reports.
Fast genomic μChIP-chip from 1,000 cells
Authors: Dahl John Arne , Reiner Andrew H , Collas Philippe 
Published: February 2009

AbstractGenome-wide location analysis of histone modifications and transcription factor binding relies on chromatin immunoprecipitation (ChIP) assays. These assays are, however, time-consuming and require large numbers of cells, hindering their application to the analysis of many interesting cell types. We report here a fast microChIP (μChIP) assay for 1,000 cells in combination with microarrays to produce genome-scale surveys of histone modifications. μChIP-chip reliably reproduces data obtained by large-scale assays: H3K9ac and H3K9m3 enrichment profiles are conserved and nucleosome-free regions are revealed.
EpiGRAPH: user-friendly software for statistical analysis and prediction of (epi)genomic data
Authors: Bock Christoph , Halachev Konstantin , Büch Joachim , Lengauer Thomas 
Published: February 2009

AbstractThe EpiGRAPH web service http://epigraph.mpi-inf.mpg.de/ enables biologists to uncover hidden associations in vertebrate genome and epigenome datasets. Users can upload sets of genomic regions and EpiGRAPH will test multiple attributes (including DNA sequence, chromatin structure, epigenetic modifications and evolutionary conservation) for enrichment or depletion among these regions. Furthermore, EpiGRAPH learns to predictively identify similar genomic regions. This paper demonstrates EpiGRAPH's practical utility in a case study on monoallelic gene expression and describes its novel approach to reproducible bioinformatic analysis.
The role of the GPR91 ligand succinate in hematopoiesis
Authors: Hakak Yaron , Lehmann-Bruinsma Karin , Phillips Shirley , Le Thuy , Liaw Chen , Connolly Daniel T , Behan Dominic P 
Published: February 2009

AbstractRegulation of cellular metabolism by the citric acid cycle occurs in the mitochondria. However, the citric acid cycle intermediate succinate was shown recently to be a ligand for the G-protein-coupled receptor GPR91. Here, we describe a role for succinate and its receptor in the stimulation of hematopoietic progenitor cell (HPC) growth. GPR91 mRNA and protein expression were detected in human bone marrow CD34+ progenitor cells, as well as in erythroid and megakaryocyte cultures and the erythroleukemic cell line TF-1. Treatment of these cell cultures with succinate resulted in increased proliferation rates. The proliferation response of TF-1 cells was pertussis toxin (PTX)-sensitive, suggesting a role for Gi signaling. Proliferation was also blocked when TF-1 cells were transfected with small interfering RNA specific for GPR91. Succinate stimulated activation of the Erk MAPK pathway and inositol phosphate accumulation in a PTX-sensitive manner. Pretreatment of TF-1 cells with the Erk1/2 kinase (MEK) inhibitor PD98059 blocked the proliferation response. Succinate treatment additionally protected TF-1 cells from cell death induced by serum deprivation. Finally, in vivo administration of succinate was found to elevate the levels of hemoglobin, platelets, and neutrophils in a mouse model of chemotherapy-induced myelosuppression. These results suggest that succinate-GPR91 signaling is capable of promoting HPC development.