bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flow‐induced enhancement of vasoconstriction and blockade of endothelium‐derived hyperpolarizing factor (EDHF) by ascorbate in the rat mesentery
Authors: Stirrat A , Nelli S , Dowell F J , Martin W 
Published: October 2007

Background and purpose:We previously reported that ascorbate inhibits flow‐ and agonist‐induced, EDHF‐mediated vasodilatation in the bovine ciliary circulation. This study examined whether ascorbate had similar actions in the rat mesenteric vasculature.Experimental approach:The effects of ascorbate were examined both in rat second order mesenteric arterial rings suspended in a static wire myograph and the rat mesentery perfused at different rates of flow.Key results:Ascorbate (50 μM) had no effect on U46619‐induced tone or acetylcholine‐induced, EDHF‐mediated vasodilatation in either rings of mesenteric artery or the perfused mesentery at rates of flow below 10 ml min−1. At higher rates of flow, ascorbate produced two distinct effects in the rat mesentery: a rapid and maintained enhancement of vasoconstrictor tone and a slow (max at 3 h) inhibition of acetylcholine‐induced, EDHF‐mediated vasodilatation. The enhancement of vasoconstrictor tone appeared to be due to inhibition of flow‐induced EDHF‐like activity, since it was endothelium‐dependent, but could be elicited during blockade of nitric oxide synthase and cyclooxygenase. Despite this, the classical inhibitors of EDHF, apamin and charybdotoxin, failed to affect the ascorbate‐induced enhancement of tone, although they inhibited acetylcholine‐induced vasodilatation.Conclusions and implications:Ascorbate inhibits both flow‐ and agonist‐induced EDHF in the rat mesentery. The strikingly different timecourses of these two effects, together with their differential sensitivity to apamin and charybdotoxin, suggest that the flow‐ and agonist‐induced EDHFs in the rat mesenteric vasculature may either be different entities or operate by different mechanisms.British Journal of Pharmacology (2008) 153, 1162–1168; doi:10.1038/sj.bjp.0707499; published online 8 October 2007
Phosphatase and tensin homologue deleted on chromosome ten (PTEN) as a molecular target in lung epithelial wound repair
Authors: Lai J‐P , Dalton J T , Knoell D L 
Published: October 2007

Background and purpose:Epithelial injury contributes to lung pathogenesis. Our work and that of others have identified the phosphoinositide‐3 kinase (PI3K)/Akt pathway as a vital component of survival in lung epithelia. Therefore, we hypothesized that pharmacological inhibition of PTEN, a major suppressor of this pathway, would enhance wound closure and restore lung epithelial monolayer integrity following injury.Experimental approach:We evaluated the ability of two bisperoxovanadium derivatives, bpV(phen) and bpV(pic), in differentiated primary human airway epithelia and BEAS2B cultures for their ability to inhibit PTEN, activate the PI3K/Akt pathway and restore epithelial monolayer integrity following mechanical injury.Key results:BpV(phen) and bpV(pic) induced Akt phosphorylation in primary and BEAS2B cells in a dose and time dependent manner. Minimal toxicity was observed as measured by lactate dehydrogenase (LDH) release. To verify that Akt phosphorylation is specifically induced by PTEN inhibition, the PTEN positive cell line, DU145, and two PTEN negative cell lines, LNCaP and PC3, were examined. PTEN positive cells demonstrated a dose responsive increase in Akt phosphorylation whereas PTEN negative cells showed no response indicating that bpV(phen) directly suppresses PTEN without affecting auxiliary pathways. Next, we observed that exposure to either compound resulted in accelerated wound closure following mechanical injury. Similar effects were observed after transfection with a dominant negative isoform of PTEN and PTEN specific siRNA.Conclusions and implications:From these studies, we conclude that PTEN is a valid target for future studies directed at restoring epithelial barrier function after lung injury.British Journal of Pharmacology (2007) 152, 1172–1184; doi:10.1038/sj.bjp.0707501; published online 8 October 2007
Next Generation of Self-Management Education: Web-based Bipolar Disorder Program
Authors: Proudfoot Judith , Parker Gordon , Hyett Matthew , Manicavasagar Vijaya , Smith Meg , Grdovic Sue , Greenfield Leah 
Published: October 2007

Objective: Education and self-management training assist patients with bipolar disorder to take control of their condition and to reduce disability, but the timeliness and availability of the education are important. A free Web-based bipolar education program has been recently developed to provide accessible evidence-based information for patients, carers and health professionals. The present paper describes the nine-module program, reports usage data and user profiles, and overviews the aims and methodology of a randomized controlled trial to measure its impact. Methods: Customized Web reports were developed to measure usage of the Web-based program, and to profile its users on a month-by-month basis. Data on the percentage of completers of each module were also collected. A randomized controlled trial evaluating the program in people with newly diagnosed bipolar disorder was also commenced. Results: More than 8000 visitors used the online program in its first 6 months. Users were predominantly female, of a broad cross-section of ages, 43.5% with bipolar disorder, and with the remainder describing themselves as health professionals, carers/family/friends of a person with bipolar disorder or members of the general public. The majority (76%) completed the sessions they commenced. Conclusions: The Web-based education program is attracting a steady stream of users and is exhibiting good completion rates. This preliminary support for the program's utility requires validation from our randomized controlled trial before definite conclusions can be drawn.
Maternal Mental Health and Child Behaviour Problems at 2 Years: Findings from the Pacific Islands Families Study
Authors: Gao Wanzhen , Paterson Janis , Abbott Max , Carter Sarnia , Iusitini Leon 
Published: October 2007

Objective: The present study investigated associations between the timing and persistence of maternal psychological disorder and child behaviour problems in a cohort of Pacific 2-year-old children in New Zealand. Method: Mothers of a cohort of 1398 Pacific infants born in South Auckland, New Zealand were interviewed when their children were 6 weeks, 12 and 24 months of age. Within the context of a wider interview, data regarding maternal mental health were obtained at these times and maternal reports of child behaviour were gathered when the children were 2 years old. Results: Prevalence rates for internalizing problems were significantly higher in children of mothers who had self-reported symptoms of psychological disorder (11.9% in no symptoms, 27.8% in early symptoms of postnatal depression, 21.1% in late symptoms of psychological disorder and 42.9% in persistent or recurrent symptoms). The adjusted odds ratio (OR) of a child having internalizing problems was 1.38 (95% confidence interval (CI): 0.79–2.43) in those of mothers reporting early symptoms of postnatal depression, 1.45 (95%CI: 0.85–2.49) in late symptoms of psychological disorder, and 2.93 (95%CI: 1.54–5.57) in persistent or recurrent symptoms relative to the no symptoms group. For externalizing problems, the effects of maternal psychological disorder were not significant. Conclusions: Maternal persistent or recurrent symptoms of psychological disorder may contribute to the behaviour problems of children as young as 2 years old. However, the timing of disorder, whether it is infant or toddler exposure, does not appear to be as crucial. Improved understanding of the associations between maternal psychological disorder and early child behaviour problems may help maternal and child health professionals design appropriate and effective screening and intervention programs to help Pacific mothers and children.
Trial of Interpersonal Counselling after Major Physical Trauma
Authors: Holmes Alex , Hodgins Gene , Adey Sarah , Menzel Shelly , Danne Peter , Kossmann Thomas , Judd Fiona 
Published: October 2007

Objective: The purpose of the present study was to determine if interpersonal counselling (IPC) was effective in reducing psychological morbidity after major physical trauma. Methods: One hundred and seventeen subjects were recruited from two major trauma centres and randomized to treatment as usual or IPC in the first 3 months following trauma. Measures of depressive, anxiety and post-traumatic symptoms were taken at baseline, 3 months and 6 months. The Structured Clinical Interview for DSM IV diagnoses was conducted at baseline and at 6 months to assess for psychiatric disorder. Results: Fifty-eight patients completed the study. Only half the patients randomized to IPC completed the therapy. At 6 months the level of depressive, anxiety and post-traumatic symptoms and the prevalence of psychiatric disorder did not differ significantly between the intervention and treatment-as-usual groups. Subjects with a past history of major depression who received IPC had significantly higher levels of depressive symptoms at 6 months. Conclusion: IPC was not effective as a universal intervention to reduce psychiatric morbidity after major physical trauma and may increase morbidity in vulnerable individuals. Patient dropout is likely to be a major problem in universal multi-session preventative interventions.
Increased Anterior Cingulate Cortex Volume in Bipolar I Disorder
Authors: Javadapour Ali , Malhi Gin S. , Ivanovski Belinda , Chen Xiaohua , Wen Wei , Sachdev Perminder 
Published: October 2007

Objective: Functional neuroimaging studies have implicated the anterior cingulate cortex (ACC) in the pathophysiology of bipolar disorder (BD), but findings from volumetric studies have been less consistent, therefore the purpose of the present study was to further investigate the existence of volumetric abnormalities in the ACC cortex of individuals with BD. In addition to methodological inconsistencies many previous studies have been lacking robustness clinically with respect to characterizing bipolar patients and comparison subjects. Hence, the present study matched the groups closely across a number of demographic parameters. Methods: Using magnetic resonance imaging, ACC volumes of 24 bipolar patients were compared to 24 gender-, age-, and education-matched control subjects, and these findings were further investigated in relation to both illness and treatment factors. Results: A significantly larger (26%) right ACC in bipolar patients than control subjects was seen, and this difference was not associated with a history of psychosis, familiality, or lithium treatment, after controlling for potential confounds. Patients reporting fewer affective episodes did, however, have significantly larger ACC volumes than controls, suggesting ACC volumetric changes early in the course of BD. Conclusions: An increase in the size of the ACC may have important implications for the neurobiology of BD. It is suggested that attempts to control affective instability during the early stages of the illness necessitates greater ACC mediation via its role in conflict resolution and hence this is reflected in the increased size of the ACC early in the course of the illness.
Impact of Co-Occurring Substance use on 6 Month Outcomes for Young People Seeking Mental Health Treatment
Authors: Baker Kathryn D. , Lubman Dan I. , Cosgrave Elizabeth M. , Killackey Eoin J. , Pan Yuen Hok , Hides Leanne , Baksheev Gennady N. , Buckby Joe A. , Yung Alison R. 
Published: October 2007

Objective: Co-occurring substance use and mental health disorders are highly prevalent among young people attending services, yet few studies have examined the effect of such comorbidity among those referred for treatment. The aim of the current study was to examine the impact of co-occurring substance use disorders (SUDs) on 6 month outcomes for young people seeking mental health treatment. Method: One hundred and six young people (aged 15–24 years) with a non-psychotic DSM-IV Axis I disorder were assessed following referral to a specialist youth public mental health service. Participants were given a structured interview, as well as questionnaires assessing drug use, psychopathology, psychosocial functioning and self-esteem at baseline and 6 month follow up. Results: At baseline, 23 participants met criteria for a co-occurring SUD and 83 had a non-psychotic Axis I disorder. Both the non-SUD and the co-occurring SUD groups had high levels of psychopathology, serious impairments in functioning and moderate levels of suicidal ideation, although those with co-occurring SUD had significantly poorer levels of functioning. At 6 month follow up the co-occurring SUD group continued to experience substantial problems with symptoms and functioning whereas the non-SUD group had significant improvement in both of these domains. Conclusions: The present findings are consistent with studies examining the impact of co-occurring substance use and mental health issues across different treatment settings, and reinforce recommendations that young people with co-occurring disorders require more intensive and integrated interventions. The present findings also highlight the need for routine assessment and management of substance use issues within youth mental health settings.
Delusions Incorporating Cannabis use in Dually Diagnosed Patients with a Primary Psychotic Disorder
Authors: Flanders Sarah E. 
Published: October 2007

Objective: To describe and discuss the implications for treatment of 3 cases of dually diagnosed patients with a primary psychotic disorder who have developed persisting, cannabis-oriented delusional systems. Method: Psychiatric assessment and daily observation on an acute inpatient psychiatric unit. Results: Abstinence appears to be particularly difficult to attain for a patient with psychosis who hold delusional beliefs that cannabis is a conduit for supernormal experiences with positive affective content, grandiose themes and a sense of enhanced self-efficacy. Conclusion: This phenomenon poses special challenges in the treatment of dual diagnosis patients. Modifications to existing CBT protocols for the treatment of substance abuse in psychosis might be useful in such patients.
Improved BLAST searches using longer words for protein seeding
Authors: Shiryev Sergey A. , Papadopoulos Jason S. , Schäffer Alejandro A. , Agarwala Richa 
Published: October 2007

AbstractMotivation: The blastp and tblastn modules of BLAST are widely used methods for searching protein queries against protein and nucleotide databases, respectively. One heuristic used in BLAST is to consider only database sequences that contain a high-scoring match of length at most 5 to the query. We implemented the capability to use words of length 6 or 7. We demonstrate an improved trade-off between running time and retrieval accuracy, controlled by the score threshold used for short word matches. For example, the running time can be reduced by 20-30% while achieving ROC (receiver operator characteristic) scores similar to those obtained with current default parameters.Availability: The option to use long words is in the NCBI C and C++ toolkit code for BLAST, starting with version 2.2.16 of blastall. A Linux executable used to produce the results herein is available at: ftp://ftp.ncbi.nlm.nih.gov/pub/agarwala/protein_longwordsContact: richa@helix.nih.gov
Four-Body Scoring Function for Mutagenesis
Authors: Deutsch Chris , Krishnamoorthy Bala 
Published: October 2007

AbstractMotivation: There is a need for an efficient and accurate computational method to identify the effects of single- and multiple-residue mutations on the stability and reactivity of proteins. Such a method should ideally be consistent and yet applicable in a widespread manner, i.e. it should be applied to various proteins under the same parameter settings, and have good predictive power for all of them.Results: We develop a Delaunay tessellation-based four-body scoring function to predict the effects of single- and multiple-residue mutations on the stability and reactivity of proteins. We test our scoring function on sets of single-point mutations used by several previous studies. We also assemble a new, diverse set of 237 single- and multiple-residue mutations, from over 24 different publications. The four-body scoring function correctly predicted the changes to the stability of 169 out of 210 mutants (80.5%), and the changes to the reactivity of 17 out of 27 mutants (63%). For the mutants that had the changes in stability/reactivity quantified (using reaction rates, temperatures, etc.), an average Spearman rank correlation coefficient of 0.67 was achieved with the four-body scores. We also develop an efficient method for screening huge numbers of mutants of a protein, called combinatorial mutagenesis. In one study, 64 million mutants of a cold-shock nucleus binding domain protein 1CSQ, with six of its residues being changed to all possible (20) amino acids, were screened within a few hours on a PC, and all five stabilizing mutants reported were correctly identified as stabilizing by combinatorial mutagenesis.Availability: All lists of mutants scored, and executables of programs developed as part of this study are available from this web page: http://www.wsu.edu/~kbala/Mutate.htmlContact: kbala@wsu.edu or bkrishna@math.wsu.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Extracting three-way gene interactions from microarray data
Authors: Zhang Jiexin , Ji Yuan , Zhang Li 
Published: October 2007

AbstractMotivation: It is an important and difficult task to extract gene network information from high-throughput genomic data. A common approach is to cluster genes using pairwise correlation as a distance metric. However, pairwise correlation is clearly too simplistic to describe the complex relationships among real genes since co-expression relationships are often restricted to a specific set of biological conditions/processes. In this study, we described a three-way gene interaction model that captures the dynamic nature of co-expression relationship between a gene pair through the introduction of a controller gene.Results: We surveyed 0.4 billion possible three-way interactions among 1000 genes in a microarray dataset containing 678 human cancer samples. To test the reproducibility and statistical significance of our results, we randomly split the samples into a training set and a testing set. We found that the gene triplets with the strongest interactions (i.e. with the smallest P-values from appropriate statistical tests) in the training set also had the strongest interactions in the testing set. A distinctive pattern of three-way interaction emerged from these gene triplets: depending on the third gene being expressed or not, the remaining two genes can be either co-expressed or mutually exclusive (i.e. expression of either one of them would repress the other). Such three-way interactions can exist without apparent pairwise correlations. The identified three-way interactions may constitute candidates for further experimentation using techniques such as RNA interference, so that novel gene network or pathways could be identified.Contact: lzhangli@mdanderson.orgSupplementary information: http://odin.mdacc.tmc.edu/~zhangli/ThreeWay
Evaluation and integration of 49 genome-wide experiments and the prediction of previously unknown obesity-related genes
Authors: English Sangeeta B. , Butte Atul J. 
Published: October 2007

AbstractMotivation: Genome-wide experiments only rarely show resounding success in yielding genes associated with complex polygenic disorders. We evaluate 49 obesity-related genome-wide experiments with publicly available findings including microarray, genetics, proteomics and gene knock-down from human, mouse, rat and worm, in terms of their ability to rediscover a comprehensive set of genes previously found to be causally associated or having variants associated with obesity.Results: Individual experiments show poor predictive ability for rediscovering known obesity-associated genes. We show that intersecting the results of experiments significantly improves the sensitivity, specificity and precision of the prediction of obesity-associated genes. We create an integrative model that statistically significantly outperforms all 49 individual genome-wide experiments. We find that genes known to be associated with obesity are significantly implicated in more obesity-related experiments and use this to provide a list of genes that we predict to have the highest likelihood of association for obesity. The approach described here can include any number and type of genome-wide experiments and might be useful for other complex polygenic disorders as well.Contact: abutte@stanford.eduSupplementary information: Available online and at http://buttelab.stanford.edu/doku.php?id=public:obesityintegration
Biclustering as a method for RNA local multiple sequence alignment
Authors: Wang Shu , Gutell Robin R. , Miranker Daniel P. 
Published: October 2007

AbstractMotivations: Biclustering is a clustering method that simultaneously clusters both the domain and range of a relation. A challenge in multiple sequence alignment (MSA) is that the alignment of sequences is often intended to reveal groups of conserved functional subsequences. Simultaneously, the grouping of the sequences can impact the alignment; precisely the kind of dual situation biclustering is intended to address.Results: We define a representation of the MSA problem enabling the application of biclustering algorithms. We develop a computer program for local MSA, BlockMSA, that combines biclustering with divide-and-conquer. BlockMSA simultaneously finds groups of similar sequences and locally aligns subsequences within them. Further alignment is accomplished by dividing both the set of sequences and their contents. The net result is both a multiple sequence alignment and a hierarchical clustering of the sequences.BlockMSA was tested on the subsets of the BRAliBase 2.1 benchmark suite that display high variability and on an extension to that suite to larger problem sizes. Also, alignments were evaluated of two large datasets of current biological interest, T box sequences and Group IC1 Introns. The results were compared with alignments computed by ClustalW, MAFFT, MUCLE and PROBCONS alignment programs using Sum of Pairs (SPS) and Consensus Count.Results for the benchmark suite are sensitive to problem size. On problems of 15 or greater sequences, BlockMSA is consistently the best. On none of the problems in the test suite are there appreciable differences in scores among BlockMSA, MAFFT and PROBCONS. On the T box sequences, BlockMSA does the most faithful job of reproducing known annotations. MAFFT and PROBCONS do not. On the Intron sequences, BlockMSA, MAFFT and MUSCLE are comparable at identifying conserved regions.Availability: BlockMSA is implemented in Java. Source code and supplementary datasets are available at http://aug.csres.utexas.edu/msa/Contact: shuwang2006@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online.