bluuebunny/crossref_metadata_2025_split huggingface dataset:
A recessive genetic screen for host factors required for retroviral infection in a library of insertionally mutated Blm-deficient embryonic stem cells
Authors: Wang Wei , Bradley Allan 
Published: April 2007

Abstract
Background
Host factors required for retroviral infection are potential targets for the modulation of diseases caused by retroviruses. During the retroviral life cycle, numerous cellular factors interact with the virus and play an essential role in infection. Cultured embryonic stem (ES) cells are susceptible to retroviral infection, therefore providing access to all of the genes required for this process to take place. In order to identify the host factors involved in retroviral infection, we designed and implemented a scheme for identifying ES cells that are resistant to retroviral infection and subsequent cloning of the mutated gene.

Results
A library of mutant ES cells was established by genome-wide insertional mutagenesis in Blm-deficient ES cells, and a screen was performed by superinfection of the library at high multiplicity with a recombinant retrovirus carrying a positive and negative selection cassette. Stringent negative selection was then used to exclude the infected ES cells. We successfully recovered five independent clones of ES cells that are resistant to retroviral infection. Analysis of the mutations in these clones revealed four different homozygous and one compound heterozygous mutation in the mCat-1 locus, which confirms that mCat-1 is the ecotropic murine leukemia virus receptor in ES cells.

Conclusion
We have demonstrated the feasibility and reliability of this recessive genetic approach to identifying critical genes required for retroviral infection in ES cells; the approach provides a unique opportunity to recover other cellular factors required for retroviral infection. The resulting insertionally mutated Blm-deficient ES cell library might also provide access to essential host cell components that are required for infection and replication for other types of virus.
Evolution of protein complexes by duplication of homomeric interactions
Authors: Pereira-Leal Jose B , Levy Emmanuel D , Kamp Christel , Teichmann Sarah A 
Published: April 2007

Abstract
Background
Cellular functions are accomplished by the concerted actions of functional modules. The mechanisms driving the emergence and evolution of these modules are still unclear. Here we investigate the evolutionary origins of protein complexes, modules in physical protein-protein interaction networks.

Results
We studied protein complexes in Saccharomyces cerevisiae, complexes of known three-dimensional structure in the Protein Data Bank and clusters of pairwise protein interactions in the networks of several organisms. We found that duplication of homomeric interactions, a large class of protein interactions, frequently results in the formation of complexes of paralogous proteins. This route is a common mechanism for the evolution of complexes and clusters of protein interactions. Our conclusions are further confirmed by theoretical modelling of network evolution. We propose reasons for why this is favourable in terms of structure and function of protein complexes.

Conclusion
Our study provides the first insight into the evolution of functional modularity in protein-protein interaction networks, and the origins of a large class of protein complexes.
A major zebrafish polymorphism resource for genetic mapping
Authors: Bradley Kevin M , Elmore J Bradford , Breyer Joan P , Yaspan Brian L , Jessen Jason R , Knapik Ela W , Smith Jeffrey R 
Published: April 2007

AbstractWe have identified 645,088 candidate polymorphisms in zebrafish and observe a single nucleotide polymorphism (SNP) validation rate of 71% to 86%, improving with polymorphism confidence score. Variant sites are non-random, with an excess of specific novel T- and A-rich motifs. We positioned half of the polymorphisms on zebrafish genetic and physical maps as a resource for positional cloning. We further demonstrate bulked segregant analysis using the anchored SNPs as a method for high-throughput genetic mapping in zebrafish.
Global transcriptome analysis of murine embryonic stem cell-derived cardiomyocytes
Authors: Doss Michael Xavier , Winkler Johannes , Chen Shuhua , Hippler-Altenburg Rita , Sotiriadou Isaia , Halbach Marcel , Pfannkuche Kurt , Liang Huamin , Schulz Herbert , Hummel Oliver , Hübner Norbert , Rottscheidt Ruth , Hescheler Jürgen , Sachinidis Agapios 
Published: April 2007

Abstract
Background
Characterization of gene expression signatures for cardiomyocytes derived from embryonic stem cells will help to define their early biologic processes.

Results
A transgenic α-myosin heavy chain (MHC) embryonic stem cell lineage was generated, exhibiting puromycin resistance and expressing enhanced green fluorescent protein (EGFP) under the control of the α-MHC promoter. A puromycin-resistant, EGFP-positive, α-MHC-positive cardiomyocyte population was isolated with over 92% purity. RNA was isolated after electrophysiological characterization of the cardiomyocytes. Comprehensive transcriptome analysis of α-MHC-positive cardiomyocytes in comparison with undifferentiated α-MHC embryonic stem cells and the control population from 15-day-old embryoid bodies led to identification of 884 upregulated probe sets and 951 downregulated probe sets in α-MHC-positive cardiomyocytes. A subset of upregulated genes encodes cytoskeletal and voltage-dependent channel proteins, and proteins that participate in aerobic energy metabolism. Interestingly, mitosis, apoptosis, and Wnt signaling-associated genes were downregulated in the cardiomyocytes. In contrast, annotations for genes upregulated in the α-MHC-positive cardiomyocytes are enriched for the following Gene Ontology (GO) categories: enzyme-linked receptor protein signaling pathway (GO:0007167), protein kinase activity (GO:0004672), negative regulation of Wnt receptor signaling pathway (GO:0030178), and regulation of cell size (O:0008361). They were also enriched for the Biocarta p38 mitogen-activated protein kinase signaling pathway and Kyoto Encyclopedia of Genes and Genomes (KEGG) calcium signaling pathway.

Conclusion
The specific pattern of gene expression in the cardiomyocytes derived from embryonic stem cells reflects the biologic, physiologic, and functional processes that take place in mature cardiomyocytes. Identification of cardiomyocyte-specific gene expression patterns and signaling pathways will contribute toward elucidating their roles in intact cardiac function.
Adenovirus type 5 exerts genome-wide control over cellular programs governing proliferation, quiescence, and survival
Authors: Miller Daniel L , Myers Chad L , Rickards Brenden , Coller Hilary A , Flint S Jane 
Published: April 2007

Abstract
Background
Human adenoviruses, such as serotype 5 (Ad5), encode several proteins that can perturb cellular mechanisms that regulate cell cycle progression and apoptosis, as well as those that mediate mRNA production and translation. However, a global view of the effects of Ad5 infection on such programs in normal human cells is not available, despite widespread efforts to develop adenoviruses for therapeutic applications.

Results
We used two-color hybridization and oligonucleotide microarrays to monitor changes in cellular RNA concentrations as a function of time after Ad5 infection of quiescent, normal human fibroblasts. We observed that the expression of some 2,000 genes, about 10% of those examined, increased or decreased by a factor of two or greater following Ad5 infection, but were not altered in mock-infected cells. Consensus k-means clustering established that the temporal patterns of these changes were unexpectedly complex. Gene Ontology terms associated with cell proliferation were significantly over-represented in several clusters. The results of comparative analyses demonstrate that Ad5 infection induces reversal of the quiescence program and recapitulation of the core serum response, and that only a small subset of the observed changes in cellular gene expression can be ascribed to well characterized functions of the viral E1A and E1B proteins.

Conclusion
These findings establish that the impact of adenovirus infection on host cell programs is far greater than appreciated hitherto. Furthermore, they provide a new framework for investigating the molecular functions of viral early proteins and information relevant to the design of conditionally replicating adenoviral vectors.
Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile
Authors: Rossi Leonardo , Salvetti Alessandra , Marincola Francesco M , Lena Annalisa , Deri Paolo , Mannini Linda , Batistoni Renata , Wang Ena , Gremigni Vittorio 
Published: April 2007

Abstract
Background
Mammalian stem cells are difficult to access experimentally; model systems that can regenerate offer an alternative way to characterize stem cell related genes. Planarian regeneration depends on adult pluripotent stem cells - the neoblasts. These cells can be selectively destroyed using X-rays, enabling comparison of organisms lacking stem cells with wild-type worms.

Results
Using a genomic approach we produced an oligonucleotide microarray chip (the Dj600 chip), which was designed using selected planarian gene sequences. Using this chip, we compared planarians treated with high doses of X-rays (which eliminates all neoblasts) with wild-type worms, which led to identification of a set of putatively neoblast-restricted genes. Most of these genes are involved in chromatin modeling and RNA metabolism, suggesting that epigenetic modifications and post-transcriptional regulation are pivotal in neoblast regulation. Comparing planarians treated with low doses of X-rays (after which some radiotolerant neoblasts re-populate the planarian body) with specimens irradiated with high doses and unirradiated control worms, we identified a group of genes that were upregulated as a consequence of low-dose X-ray treatment. Most of these genes encode proteins that are known to regulate the balance between death and survival of the cell; our results thus suggest that genetic programs that control neoblast cytoprotection, proliferation, and migration are activated by low-dose X-rays.

Conclusion
The broad differentiation potential of planarian neoblasts is unparalleled by any adult stem cells in the animal kingdom. In addition to our validation of the Dj600 chip as a valuable platform, our work contributes to elucidating the molecular mechanisms that regulate the self-renewal and differentiation of neoblasts.
Gene expression patterns during adaptation of a helminth parasite to different environmental niches
Authors: Jolly Emmitt R , Chin Chen-Shan , Miller Steve , Bahgat Mahmoud M , Lim KC , DeRisi Joseph , McKerrow James H 
Published: April 2007

Abstract
Background
Schistosome bloodflukes are complex trematodes responsible for 200 million cases of schistosomiasis worldwide. Their life cycle is characterized by a series of remarkable morphological and biochemical transitions between an invertebrate host, an aquatic environment, and a mammalian host. We report a global transcriptional analysis of how this parasite alters gene regulation to adapt to three distinct environments.

Results
Utilizing a genomic microarray made of 12,000 45-50-mer oligonucleotides based on expressed sequence tags, three different developmental stages of the schistosome parasite were analyzed by pair-wise comparisons of transcript hybridization signals. This analysis resulted in the identification of 1,154 developmentally enriched transcripts.

Conclusion
This study expands the repertoire of schistosome genes analyzed for stage-specific expression to over 70% of the predicted genome. Among the new associations identified are the roles of robust protein synthesis and programmed cell death in development of cercariae in the sporocyst stages, the relative paucity of cercarial gene expression outside of energy production, and the remarkable diversity of adult gene expression programs that reflect adaptation to the host bloodstream and an average lifespan that may approach 10 years.
Value of standard personality assessments in informing clinical decision-making in a medium secure unit
Authors: Duggan Conor , Mason Lauren , Banerjee Penny , Milton John 
Published: April 2007

BackgroundAssessing those with personality disorder for treatment in secure settings is known to be unsatisfactory.AimTo examine the utility of a standardised assessment of offenders with personality disorder referred for treatment in secure care in a naturalistic study.MethodA consecutive series of 89 men were assessed with a battery of four recommended instruments measuring personality and risk. Decisions on whether or not to admit were based on a multidisciplinary discussion informed by these assessments.ResultsOf the 89 comprehensively assessed referrals, 60 (67%) were offered admission. High scores on the Psychopathy Checklist–Revised (especially on Factor 1) was the only measure that was associated with rejection. Of 44 patients discharged, 29 (66%) failed to complete treatment; none of the pre-admission assessments distinguished ‘completers' from ‘non-completers'. Although skills were acquired on the unit, follow-up of 24 men in the community showed that this had only a marginal effect on re-offending rate (58%).ConclusionsCurrent recommended assessment methods appear unsatisfactory in identifying those who either (a) complete treatment or (b) benefit from treatment. Our results throw doubt on their value.
Altered memory and affective instability in prisoners assessed for dangerous and severe personality disorder
Authors: Kirkpatrick Tim , Joyce Eileen , Milton John , Duggan Conor , Tyrer Peter , Rogers Robert D. 
Published: April 2007

BackgroundPrevious studies of borderline personality disorder report neuropsychological impairments in several domains, including memory. No studies have compared memory functioning in high-risk prisoners with borderline personality disorder with similar prisoners with other personality disorders.AimsTo explore mnemonic impairments in prisoners undergoing personality assessment as part of the dangerous and severe personality disorder initiative or detained in a medium secure facility.MethodWe investigated memory function in 18 prisoners with borderline personality disorder and 18 prisoners with other personality disorders.ResultsPrisoners with borderline personality disorder exhibited a pattern of multi-modal impairments in the immediate and delayed recall of verbal and visual information, with some association with affective instability. These deficits were not associated with the severity of personality disturbance.ConclusionsThese data suggest that memory deficits have some specificity in relation to the constituent traits of borderline personality disorder and indicate that neuropsychological assessment may be a source of useful adjunctive information for distinguishing between the cognitive and psychological difficulties of individual prisoners.
Developmental trajectories associated with juvenile sexually abusive behaviour and emerging severe personality disorder in childhood: 3-year study
Authors: Vizard Eileen , Hickey Nicole , McCrory Eamon 
Published: April 2007

BackgroundLittle is known about the developmental trajectories of juveniles presenting with sexually abusive behaviour or emerging severe personality disorder traits.AimsTo investigate whether ‘age at onset’ of sexually abusive behaviour and whether emerging severe personality disorder traits are associated with specific developmental profiles.MethodA retrospective file review of 280 juveniles presenting with sexually abusive behaviour was conducted and follow-up Offenders Index data were analysed.ResultsJuveniles with early onset (<11 years) of sexually abusive behaviour had higher levels of psychosocial adversity and early childhood antisocial behaviour compared with those with late onset. Emerging severe personality disorder traits were associated with higher levels of psychosocial adversity, antisocial behaviour, convictions and predatory sexually abusive behaviour.ConclusionsPreliminary evidence supports the existence of distinct developmental trajectories within this population and points to a key role for traits of emerging severe personality disorder.
Aetiology of the relationship between callous-unemotional traits and conduct problems in childhood
Authors: Viding Essi , Frick Paul J. , Plomin Robert 
Published: April 2007

BackgroundA callous and unemotional disposition is an indicator of early-onset antisocial behaviour.AimsTo investigate the extent to which genetic influences contribute to the overlap between callous–unemotional traits and conduct problems in a large population sample of 7-year-old twins.MethodTeachers provided ratings of callous-unemotional traits and conduct problems for 3434 twin pairs from the Twins Early Development Study. Model-fitting analyses were performed across the continuum of scores and at the extremes.ResultsThe phenotypic relationship was primarily genetically mediated, both across the continuum and at the extremes and was substantial.ConclusionsAt 7 years of age, genetic influences on callous–unemotional traits overlap substantially with genetic influences on conduct problems. This combination should guide selection criteria in future molecular genetic studies.
Understanding the structure of the Psychopathy Checklist – Revised
Authors: Cooke David J. , Michie Christine , Skeem Jennifer 
Published: April 2007

SummaryPsychopathy is the key construct in the Dangerous and Severe Personality Disorder (DSPD) Programme. The Psychopathy Checklist – Revised is used as a primary means of selection for the programme. The Checklist confounds two distinct constructs – personality disorder and criminal behaviour. This confound is important both practically and theoretically. For example, under the criteria for DSPD it is necessary to demonstrate that personality disorder has afunctional link with future risk of criminal behaviour. The confound has been exacerbated recently by claims that criminal behaviour is a core feature of psychopathic disorder. This contention is based on inappropriate analytical methods. In this paper we examine the source of this confound and illustrate how inappropriate methods can mislead.
Critical developments in the assessment of personality disorder
Authors: Tyrer Peter , Coombs Natalie , Ibrahimi Fatema , Mathilakath Anand , Bajaj Priya , Ranger Maja , Rao Bharti , Din Raana 
Published: April 2007

BackgroundThe assessment of personality disorder is currently inaccurate, largely unreliable, frequently wrong and in need of improvement.AimsTo describe the errors inherent in the current systems and to indicate recent ways of improving personality assessment.MethodHistorical review, description of recent developments, including temporal stability, and of studies using document-derived assessment.ResultsStudies of interrater agreement and accuracy of diagnosis in complex patients with independently established personality status using document-derived assessment (PAS–DOC) with a four personality cluster classification, showed very good agreement between raters for the flamboyant cluster B group of personalities, generally good agreement for the anxious/dependent cluster C group and inhibited (obsessional) cluster D group, but only fair agreement for the withdrawn cluster A group. Overall diagnostic accuracy was 71%.ConclusionsPersonality function or diathesis, a fluctuating state, is a better description than personality disorder. The best form of assessment is one that uses longitudinal repeated measures using a four-dimensional system.
Assessment and treatment of violence-prone forensic clients: an integrated approach
Authors: Wong Stephen C. P. , Gordon Audrey , Gu Deqiang 
Published: April 2007

BackgroundA risk-reduction treatment programme complemented by a focused assessment, both guided by the risk–need–responsivity principles, is suggested as the preferred treatment for violence-prone individuals with personality disorder.AimsViolence Reduction Programme (VRP) and Violence Risk Scale (VRS) were used to illustrate the design and implementation of such an approach. Participants from a similarly designed Aggressive Behaviour Control Programme were used to illustrate the principles discussed and to test programme efficacy.MethodThe VRS was used to assess risk/need and treatment readiness, and DSM–III/IV psychiatric diagnoses of 203 federal offenders.ResultsParticipants had a high probability of violent recidivism and many violence-linked criminogenic needs, similar to offenders with high PCL–R scores. Most had antisocial personality disorder and substance use disorders; in terms of treatment-readiness, most were in the contemplation stage of change. Outcome evaluation results support the objectives of the VRP.ConclusionsIntegrating risk–need–responsivity principles in assessment and treatment can provide useful guidelines for intervention with violence-prone forensic clients with personality disorder.
Mental health of US Gulf War veterans 10 years after the war
Authors: Toomey Rosemary , Kang Han K. , Karlinsky Joel , Baker Dewleen G. , Vasterling Jennifer J. , Alpern Renee , Reda Domenic J. , Henderson William G. , Murphy Frances M. , Eisen Seth A. 
Published: April 2007

BackgroundGulf War veterans reported multiple psychological symptoms immediately after the war; the temporal course of these symptoms remains unclear.AimsTo assess the prevalence of war-era onset mental disorders in US veterans deployed to the Gulf War and in non-deployed veterans 10 years after the war.MethodMental disorders were diagnosed using structured clinical interviews. Standard questionnaires assessed symptoms and quality of life.ResultsGulf War-era onset mental disorders were more prevalent in deployed veterans (18.1%, n=1061) compared with non-deployed veterans (8.9%, n=1128). The prevalence of depression and anxiety declined 10 years later in both groups, but remained higher in the deployed group, who also reported more symptoms and a lower quality of life than the non-deployed group. Remission of depression may be related to the presence of comorbid psychiatric disorders and level of education. Remission of anxiety was related to treatment with medication.ConclusionsGulf War deployment was associated with an increased prevalence of mental disorders, psychological symptoms and a lower quality of life beginning during the war and persisting at a lower rate 10 years later.
Dementia Screening Questionnaire for Individuals with Intellectual Disabilities
Authors: Deb Shoumitro , Hare Monika , Prior Lindsay , Bhaumik Sabyasachi 
Published: April 2007

BackgroundMany adults with Down's syndrome develop Alzheimer's dementia relatively early in their lives, but accurate clinical diagnosis remains difficult.AimsTo develop a user-friendly observer-rated dementia screening questionnaire with strong psychometric properties for adults with intellectual disabilities.MethodWe used qualitative methods to gather information from carers of people with Down's syndrome about the symptoms of dementia. This provided the items for the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID), which we then tested for its psychometric properties.ResultsThe DSQIID was administered to carers of 193 adults with Down's syndrome, 117 of whom were examined by clinicians who confirmed a diagnosis of dementia for 49 according to modified ICD–10 criteria. We established that a total score of 20 provides maximum sensitivity (0.92) and optimum specificity (0.97) for screening. The DSQIID has sound internal consistency (α = 0.91) for all its 53 items, and good test–retest and interrater reliability. We established a good construct validity by dividing the items into four factors.ConclusionsThe DSQIID is a valid, reliable and user-friendly observer-rated questionnaire for screening for dementia among adults with Down's syndrome.