bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative persistence of AAV serotype 1 vector genomes in dystrophic muscle
Authors: Pacak Christina A , Conlon Thomas , Mah Cathryn S , Byrne Barry J 
Published: October 2008

Abstract
The purpose of this study was to assess the behavior of pseudotyped recombinant adeno-associated virus type 1 (rAAV2/1) vector genomes in dystrophic skeletal muscle. A comparison was made between a therapeutic vector and a reporter vector by injecting the hindlimb in a mouse model of Limb Girdle Muscular Dystrophy Type 2D (LGMD-2D) prior to disease onset. We hypothesized that the therapeutic vector would establish long-term persistence through prevention of myofiber turnover. In contrast, the reporter vector genome copy number would diminish over time due to disease-associated muscle degradation.
One day old alpha sarcoglycan knockout mice (sgca
-/-) were injected with 1 × 1011 vector genomes of rAAV2/1-tMCK-sgca in one hindlimb and the same dose of rAAV2/1-tMCK-LacZ in the contra lateral hindlimb. Newborn mice are tolerant of the foreign transgene allowing for long-term expression of both the marker and the therapeutic gene in the null background. At 2 time-points following vector administration, hindlimb muscles were harvested and analyzed for LacZ or sarcoglycan expression. Our data demonstrate prolonged vector genome persistence in skeletal muscle from the hindlimbs injected with the therapeutic transgene as compared to hindlimbs injected with the reporter gene. We observed loss of vector genomes in skeletal muscles that were there were not protected by the benefits of therapeutic gene transfer. In comparison, the therapeutic vector expressing sarcoglycan led to reduction or elimination of myofiber loss. Mitigating the membrane instability inherent in dystrophic muscle was able to prolong the life of individual myofibers.
Physical and in silico approaches identify DNA-PK in a Tax DNA-damage response interactome
Authors: Ramadan Emad , Ward Michael , Guo Xin , Durkin Sarah S , Sawyer Adam , Vilela Marcelo , Osgood Christopher , Pothen Alex , Semmes Oliver J 
Published: October 2008

Abstract

Background
We have initiated an effort to exhaustively map interactions between HTLV-1 Tax and host cellular proteins. The resulting Tax interactome will have significant utility toward defining new and understanding known activities of this important viral protein. In addition, the completion of a full Tax interactome will also help shed light upon the functional consequences of these myriad Tax activities. The physical mapping process involved the affinity isolation of Tax complexes followed by sequence identification using tandem mass spectrometry. To date we have mapped 250 cellular components within this interactome. Here we present our approach to prioritizing these interactions via an in silico culling process.

Results
We first constructed an in silico Tax interactome comprised of 46 literature-confirmed protein-protein interactions. This number was then reduced to four Tax-interactions suspected to play a role in DNA damage response (Rad51, TOP1, Chk2, 53BP1). The first-neighbor and second-neighbor interactions of these four proteins were assembled from available human protein interaction databases. Through an analysis of betweenness and closeness centrality measures, and numbers of interactions, we ranked proteins in the first neighborhood. When this rank list was compared to the list of physical Tax-binding proteins, DNA-PK was the highest ranked protein common to both lists. An overlapping clustering of the Tax-specific second-neighborhood protein network showed DNA-PK to be one of three bridge proteins that link multiple clusters in the DNA damage response network.

Conclusion
The interaction of Tax with DNA-PK represents an important biological paradigm as suggested via consensus findings in vivo and in silico. We present this methodology as an approach to discovery and as a means of validating components of a consensus Tax interactome.
Vectors for multi-color bimolecular fluorescence complementation to investigate protein-protein interactions in living plant cells
Authors: Lee Lan-Ying , Fang Mei-Jane , Kuang Lin-Yun , Gelvin Stanton B 
Published: October 2008

Abstract

Background
The investigation of protein-protein interactions is important for characterizing protein function. Bimolecular fluorescence complementation (BiFC) has recently gained interest as a relatively easy and inexpensive method to visualize protein-protein interactions in living cells. BiFC uses "split YFP" tags on proteins to detect interactions: If the tagged proteins interact, they may bring the two split fluorophore components together such that they can fold and reconstitute fluorescence. The sites of interaction can be monitored using epifluorescence or confocal microscopy. However, "conventional" BiFC can investigate interactions only between two proteins at a time. There are instances when one may wish to offer a particular "bait" protein to several "prey" proteins simultaneously. Preferential interaction of the bait protein with one of the prey proteins, or different sites of interaction between the bait protein and multiple prey proteins, may thus be observed.

Results
We have constructed a series of gene expression vectors, based upon the pSAT series of vectors, to facilitate the practice of multi-color BiFC. The bait protein is tagged with the C-terminal portion of CFP (cCFP), and prey proteins are tagged with the N-terminal portions of either Venus (nVenus) or Cerulean (nCerulean). Interaction of cCFP-tagged proteins with nVenus-tagged proteins generates yellow fluorescence, whereas interaction of cCFP-tagged proteins with nCerulean-tagged proteins generates blue fluorescence. Additional expression of mCherry indicates transfected cells and sub-cellular structures. Using this system, we have determined in both tobacco BY-2 protoplasts and in onion epidermal cells that Agrobacterium VirE2 protein interacts with the Arabidopsis nuclear transport adapter protein importin α-1 in the cytoplasm, whereas interaction of VirE2 with a different importin α isoform, importin α-4, occurs predominantly in the nucleus.

Conclusion
Multi-color BiFC is a useful technique to determine interactions simultaneously between a given" bait" protein and multiple "prey" proteins in living plant cells. The vectors we have constructed and tested will facilitate the study of protein-protein interactions in many different plant systems.
Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study
Authors: Liu Zheng , Fu Qiang , Lv Jiaju , Wang Facheng , Ding Kejia 
Published: October 2008

Abstract

Background
p27Kip1 plays a major role as a negative regulator of the cell cycle. The regulation of p27Kip1 degradation is mediated by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. However, little is known regarding the prognostic utility of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma.

Methods
Immunohistochemistry was performed for p27Kip1, Skp2 and Cks1 in tissue microarrays of 482 renal cell carcinomas with follow-up. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance.

Results
Immunoreactivity of p27Kip1, Skp2 and Cks1 was noted in 357, 71 and 82 patients, respectively. Skp2 and Cks1 expression were not noted in chromophobe cancers. A strong correlation was found between Skp2 and Cks1 expression (P < 0.001), both of which were inversely related to p27Kip1 levels (P = 0.006 and P < 0.001), especially in primary and clear-cell cancers. Low p27Kip1 expression and Skp2 expression were correlated with larger tumor size and higher stage, as well as tumor necrosis. Cks1 expression was only correlated with tumor size. In univariate analysis, low p27Kip1 expression, Skp2 and Cks1 expression were all associated with a poor prognosis, while in multivariate analysis, only low p27Kip1 expression were independent prognostic factors for both cancer specific survival and recurrence-free survival in patients with RCC.

Conclusion
Our results suggest that immunohistochemical expression levels of p27Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma.
Breast cancer proteomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1
Authors: Neubauer Hans , Clare Susan E , Wozny Wojciech , Schwall Gerhard P , Poznanović Slobodan , Stegmann Werner , Vogel Ulrich , Sotlar Karl , Wallwiener Diethelm , Kurek Raffael , Fehm Tanja , Cahill Michael A 
Published: October 2008

Abstract
Introduction
Breast tumors lacking the estrogen receptor-α (ER-α) have increased incidence of resistance to therapy and poorer clinical prognosis.

Methods
Whole tissue sections from 16 cryopreserved breast cancer tumors that were either positive or negative for the ER (eight ER positive and eight ER negative) were differentially analyzed by multiplex imaging of two-dimensional PAGE gels using 54 cm isoelectric focusing. Differentially detected spots of Progesterone Receptor Membrane Component 1 (PGRMC1) were shown to differ in phosphorylation status by differential two dimensional polyacrylamide gel electrophoresis of phosphatase-treated tumor proteins. Site directed mutagenesis was used to create putative phosphorylation site point mutants in PGRMC1. Stable transfectants of these mutants in MCF7 cells were assayed for their survival after oxidative stress, and for AKT kinase phosphorylation. Immune fluorescence using anti-PGRMC1 monoclonal antibody 5G7 was performed on breast cancer tissue microarrays.

Results
Proteins significantly differentially abundant between estrogen receptor negative and estrogen receptor positive tumors at the 0.1% level were consistent with published profiles, suggesting an altered keratin pool, and increased inflammation and wound responses in estrogen receptor negative tumors. Two of three spots of PGRMC1 were more abundant in estrogen receptor negative tumors. Phosphatase treatment of breast tumor proteins indicated that the PGRMC1 isoforms differed in their phosphorylation status. Simultaneous mutation of PGRMC1 serine-56 and serine-181 fully abrogated the sensitivity of stably transfected MCF7 breast cancer cells to peroxide-induced cell death. Immune fluorescence revealed that PGRMC1 was primarily expressed in ER-negative basal epithelial cells of mammary ductules. Even in advanced tumors, high levels of ER or PGRMC1 were almost mutually exclusive in individual cells. In five out of five examined ductal in situ breast cancers of comedo type, PGRMC1 was expressed in glucose transporter 1 negative or positive poorly oxygenated cells surrounding the necrotic core, surrounded by a more distal halo of ER-positive cells.

Conclusions
PGRMC1 phosphorylation may be involved in the clinical differences that underpin breast tumors of differing ER status.
The Nithsdale Schizophrenia Surveys. VIII: Do Relatives Want Family Intervention – And Does It Help?
Authors: McCreadie R. G. , Phillips K. , Harvey J. A. , Waldron G. , Stewart M. , Baird D. 
Published: October 2008

Sixty-three relatives of 52 schizophrenics living at home were offered a package of treatments by professionals working in an everyday NHS setting: educational seminars, relatives' groups, and family meetings. Thirty-two relatives refused intervention. Of the 31 relatives who agreed, 14 attended neither the educational seminars nor the relatives' groups. Seventeen relatives had a mean of ten treatment sessions, but there was little change in their level of expressed emotion after intervention. The number of patients who relapsed was the same in the 18 months before and after intervention, although the total number of relapses fell after intervention.British Journal of Psychiatry (1991), 158, 110–113
The Worcester Development Project
Authors: Turner Richard , Roberts Glenn 
Published: October 2008

“The philosophy of Community Care has resulted in the closure of several mental hospitals in this country. The ethos of the Worcester Development Project saw the closure of St Wulstan's and Powick Hospitals, and their replacement by a community-based service. This paper briefly describes the outcome of a three-year retrospective study completed in 1988 following the closure of both hospitals. The findings provide a comparison of the two hospitals, including details of the destination of all the patients. It is suggested that the term ‘hospital replacement’ might be preferable to ‘hospital closure’.”“The Worcester Development Project began in 1968 when the Department of Health and Social Security brought together the Worcester and Kidderminster Hospital Management Committee and the County Council in a co-ordinated joint planning venture. Powick Hospital was chosen as the location for testing the hypothesis that closing a mental hospital and replacing it with general hospital psychiatric units, supported by a variety of community facilities, would provide a more economical and better service. This paper describes the outcome of this unique opportunity to study the problems involved in closing a mental hospital and its replacement with other facilities.”
Identity Diffusion Presenting as Multiple Personality Disorder in a Female Psychopath
Authors: Bruce-Jones William , Coid Jeremy 
Published: October 2008

A female psychopath presented multiple forms of psychopathology, including features of ‘multiple personality disorder’. It is proposed that a diagnosis of borderline personality disorder, or the psychodynamic features of borderline personality organisation, should be the exclusion criteria for this condition.British Journal of Psychiatry (1992), 160, 541–544
Do Benzodiazepines Interfere with the Action of Electroconvulsive Therapy?
Authors: Cohen Samuel I. , Lawton Claire 
Published: October 2008

A 67-year-old anxious and depressed woman was withdrawn from a long-term course of a benzodiazepine and soon after was given ECT. This proved ineffective, but ECT given some months later was successful. It is suggested that the chronic administration of the benzodiazepine may have induced changes in the brain that interfered with ECT.British Journal of Psychiatry (1992), 160, 545–546
The Effect of Anticonvulsants on Cognitive Functioning Following a Probable Encephalitic Illness
Authors: Goldstein L. H. , Patel V. , Aspinall P. , Lishman W. A. 
Published: October 2008

A 54-year-old man developed an acute encephalitic illness and subsequently suffered from marked memory difficulties. Considerable improvement with anticonvulsant therapy was demonstrated using a ward-based observation programme and serial neuropsychological assessments. The case report highlights the prominent role played by epileptic activity in determining the severity of the patient's amnesia.British Journal of Psychiatry (1992), 160, 546–549
Chronic Superior Mesenteric Artery Syndrome in Anorexia Nervosa
Authors: Elbadaway Mostafa H. 
Published: October 2008

An 18-year-old woman presented with SMAS: an additional diagnosis of anorexia nervosa was later made. Both conditions should be considered when an adolescent presents with weight loss and vomiting.British Journal of Psychiatry (1992), 160, 552–554
A Cross-cultural Study of Suicide Among the Elderly in Singapore
Authors: Kua Ee Heok , Ko Soo Meng 
Published: October 2008

In the general population of Singapore the mean annual suicide rate over 1985–88 was highest in the Indians (20.4 per 100 000), followed by Chinese (15.8 per 100 000), and the Malays (2.4 per 100 000). However, in the elderly population (65 years and over) the rate was highest in the Chinese (61.2 per 100 000) with Indians second (30.5 per 100 000), and Malays still the lowest (3.2 per 100 000). Among elderly Chinese, women had a higher suicide rate than men.British Journal of Psychiatry (1992), 160, 558–559
Fluoxetine and Suicidal Behaviour
Authors: Power A. C. , Cowen P. J. 
Published: October 2008

“In the practical decisions of life it will scarcely ever be possible to go through all the arguments in favour of or against one possible decision, and one will therefore always have to act on insufficient evidence” Werner Heisenberg (1962).The development of selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs) has added a new dimension to the pharmacotherapy of depression. Their lack of sedative and anticholinergic effects together with relative safety in overdose, has led some authors to suggest that the older tricyclic antidepressants (TCAs) should not now be considered a first-line treatment (Montgomery, 1988). However, since a report by Teicheret al(1990) of suicidal preoccupation associated with fluoxetine treatment, there has been both intense media interest and animated correspondence in clinical and scientific journals (O'Donnell, 1991).
‘Pick's Disease’–101 Years on Still There, But in Need of Reform
Authors: Baldwin Bob , Förstl Hans 
Published: October 2008

On 23 April 1892, Arnold Pick reported the case of AH, who died aged 71 years following a two-year history of progressive ‘feeble-mindedness', outbursts of rage, fits and, in the later stages, severe aphasia (Pick, 1892). The post-mortem showed cerebral atrophy, particularly affecting the left temporal lobe. Pick went on to describe further cases of circumscribed atrophy affecting the temporal lobe (Pick, 1901, 1904), and parietal and frontal lobes (Pick, 1906). Although he believed the focal pathology represented a local emphasis of ‘senile cortical atrophy’, he wanted to show that a localised form of cerebral atrophy could nevertheless cause specific symptoms:“… thereby bringing neuropathology and psychiatry into closer union … so that the latter may be brought nearer to medical understanding.”
Tourette's Syndrome and Right Hemisphere Dysfunction
Authors: Lanser J. B. K. , Van Santen W. H. C. , Jennekens-Schinkel A. , Roos R. A. C. 
Published: October 2008

Poor performances of patients with Tourette's syndrome (TS) on tests requiring visual-perceptual abilities had led previous authors to the suggestion of right hemisphere involvement. We have compared the results of neuropsychological examination of 16 children with TS, with those of 16 children with a lesion of the right hemisphere. No evidence was found of a dysfunction of the right hemisphere in TS.British Journal of Psychiatry (1993), 163, 116–118
Long-Term, High-Dose Disulfiram in the Treatment of Alcohol Abuse
Authors: Brewer Colin 
Published: October 2008

A patient who had experienced most of the standard methods of managing alcohol abuse found that during 11 years of treatment, the most consistently effective intervention has been the taking of disulfiram under family supervision. He has received 600 mg daily almost continuously for over six years without side-effects. Smaller doses do not have an adequate deterrent effect.British Journal of Psychiatry (1993), 163, 687–689
Cognitive Therapy
Authors: Scott Jan 
Published: October 2008

SummaryThe scientific approach advocated in CBT has increased its credibility with more biologically orientated therapists (who have remained sceptical of other psychodynamic models), making the approach acceptable to a broad group of psychiatrists. There is a rich clinical literature describing the techniques and applications of CBT in a wide variety of settings. The acquisition of a selection of the above texts offers a useful starting point, and scanning of major British and American psychiatry and psychology journals is likely to turn up at least one important paper every few months. Those with a commitment to research would benefit from subscribing to the journal Cognitive Therapy and Research.CBT does not aim to be a panacea for every disorder, and cognitive therapists are critical of its overzealous use by inadequately trained or poorly informed therapists. To practise effectively, the therapist needs a coherent cognitive model of the problem being treated and, as such, must explore the theoretical background literature and critically evaluate the data from process and outcome research. Hopefully, this ‘scientist-practitioner’ approach, tracing the emergence and development of the theory and principles of the model underpinning the therapy, means that cognitive therapists practise what they preach.
Reason and Emotion in Psychotherapy: Albert Ellis
Authors: Dryden Windy , Bond Frank W. 
Published: October 2008

SummaryTo summarise then, in 1962 RET displayed important features still current. These include the inter-relatedness of cognitive, emotive and behavioural processes, the important role that cognition plays in psychological problems, its humanistic view of the self, and the futility and dangers of self-rating. The emphasis on perpetuation rather than acquisition processes of emotional disturbance holds good now as it did then, and the core view of therapeutic change is essentially the same now as it was in 1962, despite further, more recent elaborations.Significant change has occurred in RET since 1962 that updates several of Ellis' original ideas. These include the distinction between interpretations (or inferences) and evaluations, the primary of musts in accounting for psychological disturbance, the clear distinction between healthy and unhealthy negative emotions and the greater role according to force and energy in the change process. In addition, a greater emphasis is placed on biological aspects of emotional disturbance now than 30 years ago. Finally, a greater range of cognitive, imaginal, emotive and behavioural methods are found in current RET literature than in Reason and Emotion in Psychotherapy, where Ellis restricts himself to illustrating a few cognitive and behavioural techniques.RET, then, has grown and developed over the past 30 years. In large part, this reflects the theory's flexibility and the competent people who have worked to make RET one of the most viable and widely used cognitive-behaviour therapies.
Creativity and Psychopathology a Study of 291 World-Famous Men
Authors: Post Felix 
Published: October 2008

BackgroundThis investigation sought to determine the prevalences of various psychopathologies in outstandingly creative individuals, and to test a hypothesis that the high prevalence of mental abnormalities reported in prominent living creative persons would not be found in those who had achieved and retained world status.MethodThe family background, physical health, personality, psychosexuality and mental health of 291 famous men in science, thought, politics, and art were investigated. The membership of the six series of scientists and inventors, thinkers and scholars, statesmen and national leaders, painters and sculptors, composers, and of novelists and playwrights was determined by the availability of sufficiently adequate biographies. Extracted data were transformed into diagnoses in accordance with DSM–III–R criteria, when appropriate.ResultsAll excelled not only by virtue of their abilities and originality, but also of their drive, perseverance, industry, and meticulousness. With a few exceptions, these men were emotionally warm, with a gift for friendship and sociability. Most had unusual personality characteristics and, in addition, minor ‘neurotic’ abnormalities were probably more common than in the general population. Severe personality deviations were unduly frequent only in the case of visual artists and writers. Functional psychoses were probably less frequent than psychiatric epidemiology would suggest, and they were entirely restricted to the affective varieties. Among other functional disorders, only depressive conditions, alcoholism, and, less reliably, psychosexual problems were more prevalent than expected in some professional categories, but strikingly so in writers.ConclusionsSimilar findings have been reported for living artists and writers, and this suggests that certain pathological personality characteristics, as well as tendencies towards depression and alcoholism, are causally linked to some kinds of valuable creativity.