bluuebunny/crossref_metadata_2025 huggingface dataset:
PatternLab for proteomics: a tool for differential shotgun proteomics
Authors: Carvalho Paulo C , Fischer Juliana SG , Chen Emily I , Yates John R , Barbosa Valmir C
Published: July 2008

Background

A goal of proteomics is to distinguish between states of a biological system by identifying protein expression differences. Liuet al. demonstrated a method to perform semi-relative protein quantitation in shotgun proteomics data by correlating the number of tandem mass spectra obtained for each protein, or "spectral count", with its abundance in a mixture; however, two issues have remained open: how to normalize spectral counting data and how to efficiently pinpoint differences between profiles. Moreover, Chenet al. recently showed how to increase the number of identified proteins in shotgun proteomics by analyzing samples with different MS-compatible detergents while performing proteolytic digestion. The latter introduced new challenges as seen from the data analysis perspective, since replicate readings are not acquired.

Results

To address the open issues above, we present a program termed PatternLab for proteomics. This program implements existing strategies and adds two new methods to pinpoint differences in protein profiles. The first method, ACFold, addresses experiments with less than three replicates from each state or having assays acquired by different protocols as described by Chenet al. ACFold uses a combined criterion based on expression fold changes, the AC test, and the false-discovery rate, and can supply a "bird's-eye view" of differentially expressed proteins. The other method addresses experimental designs having multiple readings from each state and is referred to as nSVM (natural support vector machine) because of its roots in evolutionary computing and in statistical learning theory. Our observations suggest that nSVM's niche comprises projects that select a minimum set of proteins for classification purposes; for example, the development of an early detection kit for a given pathology. We demonstrate the effectiveness of each method on experimental data and confront them with existing strategies.

Conclusion

PatternLab offers an easy and unified access to a variety of feature selection and normalization strategies, each having its own niche. Additionally, graphing tools are available to aid in the analysis of high throughput experimental data. PatternLab is available athttp://pcarvalho.com/patternlab.
Merging microsatellite data: enhanced methodology and software to combine genotype data for linkage and association analysis
Authors: Presson Angela P , Sobel Eric M , Pajukanta Paivi , Plaisier Christopher , Weeks Daniel E , Åberg Karolina , Papp Jeanette C
Published: July 2008

Background

Correctly merged data sets that have been independently genotyped can increase statistical power in linkage and association studies. However, alleles from microsatellite data sets genotyped with different experimental protocols or platforms cannot be accurately matched using base-pair size information alone. In a previous publication we introduced a statistical model for merging microsatellite data by matching allele frequencies between data sets. These methods are implemented in our software MicroMerge version 1 (v1). While MicroMerge v1 output can be analyzed by some genetic analysis programs, many programs can not analyze alignments that do not match alleles one-to-one between data sets. A consequence of such alignments is that codominant genotypes must often be analyzed as phenotypes. In this paper we describe several extensions that are implemented in MicroMerge version 2 (v2).

Results

Notably, MicroMerge v2 includes a new one-to-one alignment option that creates merged pedigree and locus files that can be handled by most genetic analysis software. Other features in MicroMerge v2 enhance the following aspects of control: 1) optimizing the algorithm for different merging scenarios, such as data sets with very different sample sizes or multiple data sets, 2) merging small data sets when a reliable set of allele frequencies are available, and 3) improving the quantity and 4) quality of merged data. We present results from simulated and real microsatellite genotype data sets, and conclude with an association analysis of three familial dyslipidemia (FD) study samples genotyped at different laboratories. Independent analysis of each FD data set did not yield consistent results, but analysis of the merged data sets identified strong association at locus D11S2002.

Conclusion

The MicroMerge v2 features will enable merging for a variety of genotype data sets, which in turn will facilitate meta-analyses for powering association analysis.
A comprehensive comparison of random forests and support vector machines for microarray-based cancer classification
Authors: Statnikov Alexander , Wang Lily , Aliferis Constantin F
Published: July 2008

Background

Cancer diagnosis and clinical outcome prediction are among the most important emerging applications of gene expression microarray technology with several molecular signatures on their way toward clinical deployment. Use of the most accurate classification algorithms available for microarray gene expression data is a critical ingredient in order to develop the best possible molecular signatures for patient care. As suggested by a large body of literature to date, support vector machines can be considered "best of class" algorithms for classification of such data. Recent work, however, suggests that random forest classifiers may outperform support vector machines in this domain.

Results

In the present paper we identify methodological biases of prior work comparing random forests and support vector machines and conduct a new rigorous evaluation of the two algorithms that corrects these limitations. Our experiments use 22 diagnostic and prognostic datasets and show that support vector machines outperform random forests, often by a large margin. Our data also underlines the importance of sound research design in benchmarking and comparison of bioinformatics algorithms.

Conclusion

We found that both on average and in the majority of microarray datasets, random forests are outperformed by support vector machines both in the settings when no gene selection is performed and when several popular gene selection methods are used.
Importin alpha binding and nuclear localization of PARP-2 is dependent on lysine 36, which is located within a predicted classical NLS
Authors: Haenni Sandra S , Altmeyer Matthias , Hassa Paul O , Valovka Taras , Fey Monika , Hottiger Michael O
Published: July 2008

Background

The enzymes responsible for the synthesis of poly-ADP-ribose are named poly-ADP-ribose polymerases (PARP). PARP-2 is a nuclear protein, which regulates a variety of cellular functions that are mainly controlled by protein-protein interactions. A previously described non-conventional bipartite nuclear localization sequence (NLS) lies in the amino-terminal DNA binding domain of PARP-2 between amino acids 1–69; however, this targeting sequence has not been experimentally examined or validated.

Results

Using a site-directed mutagenesis approach, we found that lysines 19 and 20, located within a previously described bipartite NLS, are not required for nuclear localization of PARP-2. In contrast, lysine 36, which is located within a predicted classical monopartite NLS, was required for PARP-2 nuclear localization. While wild type PARP-2 interacted with importin α3 and to a very weak extent with importin α1 and importin α5, the mutant PARP-2 (K36R) did not interact with importin α3, providing a molecular explanation why PARP-2 (K36R) is not targeted to the nucleus.

Conclusion

Our results provide strong evidence that lysine 36 of PARP-2 is a critical residue for proper nuclear targeting of PARP-2 and consequently for the execution of its biological functions.
Gene expression patterns of sulfur starvation in Synechocystis sp. PCC 6803
Authors: Zhang Zhigang , Pendse Ninad D , Phillips Katherine N , Cotner James B , Khodursky Arkady
Published: July 2008

Background

The unicellular cyanobacteriumSynechocystissp. PCC 6803 is a model microbe for studying biochemistry, genetics and molecular biology of photobiological processes. Importance of this bacterium in basic and applied research calls for a systematic, genome-wide description of its transcriptional regulatory capacity. Characteristic transcriptional responses to changes in the growth environment are expected to provide a scaffold for describing theSynechocystistranscriptional regulatory network as well as efficient means for functional annotation of genes in the genome.

Results

We designed, validated and usedSynechocystisgenome-wide oligonucleotide (70-mer) microarray (representing 96.7% of all chromosomal ORFs annotated at the time of the beginning of this project) to study transcriptional activity of the cyanobacterial genome in response to sulfur (S) starvation. The microarray data were verified by quantitative RT-PCR. We made five main observations: 1) Transcriptional changes upon sulfate starvation were relatively moderate, but significant and consistent with growth kinetics; 2) S acquisition genes encoding for a high-affinity sulfate transporter were significantly induced, while decreased transcription of genes for phycobilisome, photosystems I and II, cytochrome b6/f, and ATP synthase indicated reduced light-harvesting and photosynthetic activity; 3) S starvation elicited transcriptional responses associated with general growth arrest and stress; 4) A large number of genes regulated by S availability encode hypothetical proteins or proteins of unknown function; 5) Hydrogenase structural and maturation accessory genes were not identified as differentially expressed, even though increased hydrogen evolution was observed.

Conclusion

The expression profiles recorded by using this oligonucleotide-based microarray platform revealed that during transition from the condition of plentiful S to S starvation,Synechocystisundergoes coordinated transcriptional changes, including changes in gene expression whose products are involved in sensing nutrient limitations and tuning bacterial metabolism. The transcriptional profile of the nutrient starvation was dominated by a decrease in abundances of many transcripts. However, these changes were unlikely due to the across-the-board, non-specific shut down of transcription in a condition of growth arrest. Down-regulation of transcripts encoding proteins whose function depends on a cellular S status indicated that the observed repression has a specific regulatory component. The repression of certain S-related genes was paralleled by activation of genes involved in internal and external S scavenging.
Invasive pneumococcal infections among persons with and without underlying medical conditions: Implications for prevention strategies
Authors: Klemets Peter , Lyytikäinen Outi , Ruutu Petri , Ollgren Jukka , Nuorti J Pekka
Published: July 2008

Background

The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for persons aged < 65 years with chronic medical conditions. We evaluated the risk and mortality from invasive pneumococcal disease (IPD) among persons with and without the underlying medical conditions which are considered PPV23 indications.

Methods

Population-based data on all episodes of IPD (positive blood or cerebrospinal fluid culture) reported by Finnish clinical microbiology laboratories during 1995–2002 were linked to data in national health care registries and vital statistics to obtain information on the patient's preceding hospitalisations, co-morbidities, and outcome of illness.

Results

Overall, 4357 first episodes of IPD were identified in all age groups (average annual incidence, 10.6/100,000). Patients aged 18–49 and 50–64 years accounted for 1282 (29%) and 934 (21%) of IPD cases, of which 372 (29%) and 427 (46%) had a current PPV23 indication, respectively. Overall, 536 (12%) IPD patients died within one month of first positive culture. Persons aged 18–64 years accounted for 254 (47%) of all deaths (case-fatality proportion, 12%). Of those who died 117 (46%) did not have a vaccine indication. In a survival model, patients with alcohol-related diseases, non-haematological malignancies, and those aged 50–64 years were most likely to die.

Conclusion

In the general population of non-elderly adults, almost two-thirds of IPD and half of fatal cases occurred in persons without a recognised PPV23 indication. Policymakers should consider additional prevention strategies such as lowering the age of universal PPV23 vaccination and introducing routine childhood pneumococcal conjugate immunisation which could provide substantial health benefits to this population through indirect vaccine effects.
Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31)
Authors: Schlang Katharina J , Arning Larissa , Epplen Joerg T , Stemmler Susanne
Published: July 2008

Background

Mutations in the SPG4 gene (spastin) and in the SPG3A gene (atlastin) account for the majority of 'pure' autosomal dominant form of hereditary spastic paraplegia (HSP). Recently, mutations in the REEP1 gene were identified to cause autosomal dominant HSP type SPG31. The purpose of this study was to determine the prevalence of REEP1 mutations in a cohort of 162 unrelated Caucasian index patients with 'pure' HSP and a positive family history (at least two persons per family presented symptoms).

Methods

162 patients were screened for mutations by, both, DHPLC and direct sequencing.

Results

Ten mutations were identified in the REEP1 gene, these included eight novel mutations comprising small insertions/deletions causing frame shifts and subsequently premature stop codons, one nonsense mutation and one splice site mutation as well as two missense mutations. Both missense mutations and the splice site mutation were not identified in 170 control subjects.

Conclusion

In our HSP cohort we found pathogenic mutations in 4.3% of cases with autosomal dominant inheritance. Our results confirm the previously observed mutation range of 3% to 6.5%, respectively, and they widen the spectrum of REEP1 mutations.
Evaluation of high-risk Human papillomaviruses type distribution in cervical cancer in Sichuan province of China
Authors: Wu En-qi , Zhang Guo-nan , Yu Xiang-hui , Ren Yuan , Fan Ying , Wu Yong-ge , Kong Wei , Zha Xiao
Published: July 2008

Background

Infection with high-risk human papillomavirus is an important factor associated with cervical cancer, and the distribution of HPV types varies greatly worldwide. Determination of type-specific HPV prevalence constitutes an important step towards the development of vaccines for the prevention of cervical cancer.

Methods

The human papillomavirus (HPV) genotypes in 190 cervical cancer specimens taken from the Sichuan province, the most populous province of Southwest China, were detected by a combination of MY09/11 consensus primers PCR (MY09/11 PCR), type-specific primers one-step PCR (One-step TS PCR) and E6/E7 gene type-specific primers nested PCR (Nested TS PCR). The prevalence and distribution of HPV in patients with cervical cancer, especially for HPV types 16, 18, 52, 58 and 59, suspected to be most common in certain parts of China, was investigated.

Results

The HPV infection rates detected by MY09/11 PCR, One-step TS PCR and Nested TS PCR were 159 (83.7%), 145 (76.3%) and 172 (90.5%), respectively. The overall HPV prevalence was 93.2% (177/190). The positive specimens for HPV16, 18, 52, 58 and 59 detected by One-step TS-PCR were 111 (58.4%), 14 (7.4%), 6 (3.2%), 13 (6.8%) and 4 (2.1%), respectively. By Nested TS-PCR analysis, the detection rates of HPV16, 52, 58 and 59 were increased to 140 (73.7%), 30 (15.8%), 37 (19.5%) and 25 (13.2%), while only 4 (2.1%) additional specimens were found to be infected with HPV18.

Conclusion

Our data demonstrate that, besides HPV 16, which was found to be the most prevalent type, HPV types 58, 52 and 59 are more prevalent than HPV18 in women with cervical cancer in the Sichuan area of China.
Attitudes toward psychopharmacology among hospitalized patients from diverse ethno-cultural backgrounds
Authors: Thorens Gabriel , Gex-Fabry Marianne , Zullino Daniele F , Eytan Ariel
Published: July 2008

Background

Biological factors influencing individual response to drugs are being extensively studied in psychiatry. Strikingly, there are few studies addressing social and cultural differences in attitudes toward psychotropic medications. The objective of this study was to investigate ethno-culturally determined beliefs, expectations and attitudes toward medication among a sample of hospitalized psychiatric patients.

Methods

An ad hoc questionnaire was designed to assess patients' expectations, attitudes and prejudice toward medication. The study included 100 adult patients hospitalized in Geneva, Switzerland.

Results

Patients were in majority male (63%), originated from Switzerland (54%) and spoke the local language fluently (93%). They took on the average 3 different psychotropic drugs. Sixty-eight percent of patients expected side effects and 60% were ready to stop medication because of them. Thirty percent of patients expected negative personal changes with treatment and 34% thought that their mental disorder could have been treated without drugs. Thirty six percent of the sample used alternative or complementary medicines. 35% of immigrant patients believed that medication had different effects on them than on local patients. When compared with Swiss patients, they more often reported that significant others had an opinion about medication (p = 0.041) and more frequently valued information provided by other patients about treatment (p = 0.010).

Conclusion

Patients' attitudes toward medication should be investigated in clinical practice, as specific expectations and prejudice exist. Targeted interventions, especially for immigrant patients, might improve adherence.
A historically controlled, single-arm, multi-centre, prospective trial to evaluate the safety and efficacy of MonoMax® suture material for abdominal wall closure after primary midline laparotomy. ISSAAC-Trial [NCT005725079]
Authors: Fischer Lars , Baumann Petra , Hüsing Johannes , Seidlmayer Christoph , Albertsmeier Markus , Franck Annette , Luntz Steffen , Seiler Christoph M , Knaebel Hanns-Peter
Published: July 2008

Background

Several randomized controlled trials have compared different suture materials and techniques for abdominal wall closure with respect to the incidence of incisional hernias after midline laparotomy and shown that it remains, irrespective of the methods used, considerably high, ranging from 9% to 20%. The development of improved suture materials which would reduce postoperative complications may help to lower its frequency.

Design

This is a historically controlled, single-arm, multi-centre, prospective trial to evaluate the safety of MonoMax®suture material for abdominal wall closure in 150 patients with primary elective midline incisions. INSECT patients who underwent abdominal closure using Monoplus®and PDS®will serve as historical control group. The incidences of wound infections and of burst abdomen are defined as composite primary endpoints. Secondary endpoints are the frequency of incisional hernias within one year after operation and safety. To ensure adequate comparability in surgical performance and recruitment, the 4 largest centres of the INSECT-Trial will participate. After hospital discharge, the investigators will examine the enrolled patients again at 30 days and at 12 ± 1 months after surgery.

Conclusion

This historically controlled, single-arm, multi-centre, prospective ISSAAC trial aims to assess whether the use of an ultra-long-lasting absorbable monofilament suture material is safe and efficient.

Trial registration

NCT005725079
Increased cell motility and invasion upon knockdown of lipolysis stimulated lipoprotein receptor (LSR) in SW780 bladder cancer cells
Authors: Herbsleb Malene , Birkenkamp-Demtroder Karin , Thykjaer Thomas , Wiuf Carsten , Hein Anne-Mette K , Ørntoft Torben F , Dyrskjøt Lars
Published: July 2008

Background

Mechanisms underlying the malignant development in bladder cancer are still not well understood. Lipolysis stimulated lipoprotein receptor (LSR) has previously been found to be upregulated by P53. Furthermore, we have previously found LSR to be differentially expressed in bladder cancer. Here we investigated the role of LSR in bladder cancer.

Methods

A time course siRNA knock down experiment was performed to investigate the functional role of LSR in SW780 bladder cancer cells. Since LSR was previously shown to be regulated by P53, siRNA against TP53 was included in the experimental setup. We used Affymetrix GeneChips for measuring gene expression changes and we used Ingenuity Pathway Analysis to investigate the relationship among differentially expressed genes upon siRNA knockdown.

Results

By Ingenuity Pathway analysis of the microarray data from the different timepoints we identified six gene networks containing genes mainly related to the functional categories "cancer", "cell death", and "cellular movement". We determined that genes annotated to the functional category "cellular movement" including "invasion" and "cell motility" were highly significantly overrepresented. A matrigel assay showed that 24 h after transfection the invasion capacity was significantly increased 3-fold (p < 0.02) in LSR-siRNA transfected cells, and 2.7-fold (p < 0.02) in TP53-siRNA transfected cells compared to controls. After 48 h the motility capacity was significantly increased 3.5-fold (p < 0.004) in LSR-siRNA transfected cells, and 4.7-fold (p < 0.002) in TP53-siRNA transfected cells compared to controls.

Conclusion

We conclude that LSR may impair bladder cancer cells from gaining invasive properties.
Regulation of vascular endothelial growth factor expression by homeodomain-interacting protein kinase-2
Authors: Puca Rosa , Nardinocchi Lavinia , D'Orazi Gabriella
Published: July 2008

Background

Homeodomain-interacting protein kinase-2 (HIPK2) plays an essential role in restraining tumor progression as it may regulate, by itself or within multiprotein complexes, many proteins (mainly transcription factors) involved in cell growth and apoptosis. This study takes advantage of the recent finding that HIPK2 may repress the β-catenin transcription activity. Thus, we investigated whether HIPK2 overexpression may down-regulate vascular endothelial growth factor (VEGF) levels (a β-catenin target gene) and the role of β-catenin in this regulation, in order to consider HIPK2 as a tool for novel anti-tumoral therapeutical approaches.

Methods

The regulation of VEGF expression by HIPK2 was evaluated by using luciferase assay with VEGF reporter construct, after overexpression of the β-catenin transcription factor. Relative quantification of VEGF and β-catenin mRNAs were assessed by reverse-transcriptase-PCR (RT-PCR) analyses, following HIPK2 overexpression, while β-catenin protein levels were evaluated by western immunoblotting.

Results

HIPK2 overexpression in tumor cells downregulated VEGF mRNA levels and VEGF promoter activity. The VEGF downregulation was partly depending on HIPK2-mediated β-catenin regulation. Thus, HIPK2 could induce β-catenin protein degradation that was prevented by cell treatment with proteasome inhibitor MG132. The β-catenin degradation was dependent on HIPK2 catalytic activity and independent of p53 and glycogen synthase kinase 3β (GSK-3β) activities.

Conclusion

These results suggest that VEGF might be a target of HIPK2, at least in part, through regulation of β-catenin activity. These findings support the function of HIPK2 as tumor suppressor and hypothesise a role for HIPK2 as antiangiogenic tool in tumor therapy approaches.
Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis
Authors: Jin Pei , Zhang Juan , Sumariwalla Percy F , Ni Irene , Jorgensen Brett , Crawford Damian , Phillips Suzanne , Feldmann Marc , Shepard H Michael , Paleolog Ewa M
Published: July 2008

Introduction

Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturallyin vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF) – a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins – many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in anin vivomodel of arthritis.

Methods

To identify novel splice variants, we performed RT-PCR using an mRNA pool representing major human tissue types and tumors. Novel ASV were identified by alignment of each cloned sequence to its respective genomic sequence in comparison with full-length transcripts. To test whether these ASV have biologic activity, we characterized a subset of them for ligand binding, and for efficacy in an animal model of arthritis. Thein vivostudy was accomplished using adenoviruses expressing secreted ASV.

Results

We cloned 60 novel human ASV from 21 genes, encoding cell surface receptors – many of which are known to be important in the regulation of angiogenesis. The ASV were characterized by exon extension, intron retention and alternative exon utilization. Efficient expression and secretion of selected ASV – corresponding to VEGF receptor type 1, VEGF receptor type 2, VEGF receptor type 3, angiopoietin receptor Tie1, Met (receptor for hepatocyte growth factor), colony-stimulating factor 1 receptor, platelet-derived growth factor receptor beta, fibroblast growth factor receptor 1, Kit, and RAGE – was demonstrated, together with binding to their cognate ligands. Importantly, ASV derived from VEGF receptor type 1 and Tie1, and to a lesser extent from VEGF receptor type 2 and fibroblast growth factor receptor 1, reduced clinical signs of arthritisin vivo. The reduction was paralleled by decreased joint inflammation and destruction.

Conclusion

The present study shows that unique ASV derived from receptors that play key roles in angiogenesis – namely, VEGF receptor type 1 and, for the first time, Tie1 – can markedly reduce arthritis severity. More broadly, our results demonstrate that ASV are a source of novel proteins with therapeutic potential in diseases in which angiogenesis and cellular hyperplasia play a central role, such as rheumatoid arthritis.
Over-expression of Skp2 is associated with resistance to preoperative doxorubicin-based chemotherapy in primary breast cancer
Authors: Davidovich Shirly , Ben-Izhak Ofer , Shapira Ma'anit , Futerman Boris , Hershko Dan D
Published: July 2008

Introduction

Preoperative chemotherapy is often used in patients with locally advanced breast cancer. However, commonly used clinical and pathological parameters are poor predictors of response to this type of therapy. Recent studies have suggested that altered regulation of the cell cycle in cancer may be involved in resistance to chemotherapy. Over-expression of the ubiquitin ligase Skp2 results in loss of the cell cycle inhibitor p27Kip1 and is associated with poor prognosis in early breast cancer. The purpose of the present study was to examine the role of these proteins as predictors of clinical outcome and response to chemotherapy in locally advanced breast cancer.

Methods

The expression levels of Skp2 and p27Kip1 were determined by immunohistochemistry both before and after preoperative chemotherapy in 40 patients with locally advanced breast cancer. All patients were treated with cyclophosphamide/doxorubicin (adriamycin)/5-fluorouracil (CAF) and some patients received additional treatment with docetaxel. Expression data were compared with patients' clinical and pathological features, clinical outcome, and response to chemotherapy.

Results

Skp2 expression before preoperative chemotherapy was inversely related to p27Kip1 levels, tumor grade, and expression of estrogen and progesterone receptors. Both Skp2 and p27Kip1 were found to be accurate prognostic markers for disease-free and overall survival. High preoperative expression of Skp2 was associated with resistance to CAF therapy in 94% of patients (P < 0.0001) but not with resistance to docetaxel.

Conclusion

Skp2 expression may be a useful marker for predicting response to doxorubicin-based preoperative chemotherapy and clinical outcome in patients with locally advanced breast cancer.
Plastic architecture of bacterial genome revealed by comparative genomics of Photorhabdus variants
Authors: Gaudriault Sophie , Pages Sylvie , Lanois Anne , Laroui Christine , Teyssier Corinne , Jumas-Bilak Estelle , Givaudan Alain
Published: July 2008

Background

The phenotypic consequences of large genomic architecture modifications within a clonal bacterial population are rarely evaluated because of the difficulties associated with using molecular approaches in a mixed population. Bacterial variants frequently arise among Photorhabdus luminescens, a nematode-symbiotic and insect-pathogenic bacterium. We therefore studied genome plasticity within Photorhabdus variants.

Results

We used a combination of macrorestriction and DNA microarray experiments to perform a comparative genomic study of different P. luminescens TT01 variants. Prolonged culturing of TT01 strain and a genomic variant, collected from the laboratory-maintained symbiotic nematode, generated bacterial lineages composed of primary and secondary phenotypic variants and colonial variants. The primary phenotypic variants exhibit several characteristics that are absent from the secondary forms. We identify substantial plasticity of the genome architecture of some variants, mediated mainly by deletions in the 'flexible' gene pool of the TT01 reference genome and also by genomic amplification. We show that the primary or secondary phenotypic variant status is independent from global genomic architecture and that the bacterial lineages are genomic lineages. We focused on two unusual genomic changes: a deletion at a new recombination hotspot composed of long approximate repeats; and a 275 kilobase single block duplication belonging to a new class of genomic duplications.

Conclusion

Our findings demonstrate that major genomic variations occur in Photorhabdus clonal populations. The phenotypic consequences of these genomic changes are cryptic. This study provides insight into the field of bacterial genome architecture and further elucidates the role played by clonal genomic variation in bacterial genome evolution.
Intensive dysarthria therapy for older children with cerebral palsy: findings from six cases
Authors: Pennington Lindsay , Smallman Claire , Farrier Faith
Published: July 2008

Children with cerebral palsy often have speech, language and communication difficulties that affect their access to social and educational activities. Speech and language therapy to improve the intelligibility of the speech of children with cerebral palsy has long been advocated, but there is a dearth of research investigating therapy effectiveness. To begin to explore the possible effectiveness of therapy focussing on speech production, six students aged 10-18 years, were given intensive individual therapy to increase breath support for speech, maintain breath support and volume across utterances and hence maximise their background effort for speech. Intelligibility of single words and connected speech was measured immediately before and after the block of therapy and again seven weeks later. Gains in intelligibility were observed at the single word level, but not for continuous speech. Implications for therapy and future research are discussed.
Coming out of the kitchen: texts, contexts and debates
Authors: Floyd Janet
Published: July 2008

This essay revisits prevailing assumptions about the domestic kitchen. While the status of this space and even its existence as a discrete area within the home have become a maater for discussion, the work of cooking located in the kitchen remains a compelling subject within a range of popular cultural forms. We are accustomed to thinking of the kitchen as a scene of routine and ritual, but here I explore its appearances as an improvisatory and rebellious zone. Such possibilities are not necessarily the outcome of shifting practices associated with the postmodern home and its representation. On the contrary, the kitchen has long been a space, both intimate and socially significant, from which to generate arguments about gender, class and nation.
The home in the world: women, threshold designs and performative relations in contemporary Tamil Nadu, south India
Authors: Dohmen Renate
Published: July 2008

This article seeks to outline a performative reading of the Tamil version of the pan-Indian tradition of drawing threshold designs, an exclusively female practice seen as housework by the executing party. The argument put forward is that a reading of the practice in terms of a performative relation of ‘home’ and the ‘world’ as part of the Tamil cultural imaginary locates the ‘home’ not only in terms of a larger ‘local’ community but also within Tamil spatio-temporal perceptions constituting the ‘world’ at large. More generally, this performative perspective is situated in the context of the polycentric rearticulation in the visual field proposed by the emerging discipline of visual culture. It seeks to break from previous discussions informed by Eurocentric notions of art versus craft and understandings of the ‘primitive’ or ‘traditional’ as firmly located in the past and hence, in the present modern age, as characterized by a sense of loss.
A qualitative exploration of the production of Hospital Episode Statistics in a Guernsey hospital: implications for regional comparisons of UK health data
Authors: Head Rosemary F , Byrom Allyson , Ellison George T H
Published: July 2008

Hospital Episode Statistics (HES) are widely used in the UK for audit and research. This often includes comparisons between different geographical regions, but there is some doubt as to the reliability of comparisons made using these data. Previous studies have focused on the quantitative accuracy of the coding, but not the full data chain. This study is a qualitative examination of the production of HES in a small hospital in Guernsey, which is not part of the NHS. Interviews were conducted with key participants in the production of HES to determine how the data were created, and the strengths and weaknesses of this system. We found that face-to-face communication between administrative and clinical staff was felt to contribute to the accuracy of the HES codes, and that a lack of detail in the case-notes was felt to be more problematic than the accuracy of the coders themselves. These findings have implications for the comparison of HES between NHS Trusts, since the processes involved in producing the data will be different in larger hospitals with less contact between coders and clinicians. It is therefore important to bear this in mind when making comparisons between such diverse sources of HES.
Organizational determinants of boundary spanning activity in outpatient substance abuse treatment programmes
Authors: Alexander Jeffrey A , Wells Rebecca , Jiang Lan , Pollack Harold
Published: July 2008

Objectives

Substance abuse treatment programmes depend on boundary spanning to identify opportunities and threats, and represent their interests to stakeholders such as licensing entities and regulators. This study sought to identify director, client, unit and market factors associated with active director boundary spanning.

Methods

Using data from the 1995, 1999–2000 and 2005 waves of a national survey of outpatient substance abuse treatment units, generalized estimating equation regression models tested associations between predictors and five aspects of directors' self-reported boundary spanning.

Results

Directors licensed as substance abuse treatment counsellors spent more time than average consulting with other treatment providers and making presentations in the community. Older directors spent less time consulting with other treatment providers, making community presentations and liaisoning with monitoring organizations. The few associations between client unemployment and director boundary spanning were positive; the two associations between the percentage of clients who were African-American and boundary spanning were negative. Private ownership and being based in larger organizations were negatively associated with some types of boundary spanning. Perceived competition for public support was positively associated with all measures of boundary spanning.

Conclusion

Directors of treatment organizations may improve treatment practices and political leverage by directly, but selectively, interacting with key external stakeholders.
Choice Interactions and Business Strategy
Authors: Ghemawat Pankaj , Levinthal Daniel
Published: July 2008

Choice settings are strategic to the extent that they entail cross-sectional or intertemporal linkages. These same factors may impose daunting demands on decision makers. We develop a graph-theoretic generalization of the NK model of fitness landscapes to model the way in which policy choices may be more or less strategic. We use this structure to examine, through simulation, how fully articulated a strategy or set of policy choices must be to achieve a high level of performance and how feasible it is to offset past strategic mistakes through tactical adjustments (instead of alignment). Our analysis highlights the role of asymmetry in the interaction of strategic choices and in particular the degree to which choices vary in terms of being influential, dependent, or autonomous from other choices.
Associations between peer victimization, fear of future victimization and disrupted concentration on class work among junior school pupils
Authors: Boulton Michael J. , Trueman Mark , Murray Lindsay
Published: July 2008

Background. Studies have shown that peer victimization is associated with psychological maladjustment, and have implicated such maladjustment in disrupted ability to concentrate.

Aims. To investigate the levels of, and associations between, physical, verbal, and social exclusion victimization, fear of future victimization, and disrupted classroom concentration.

Sample. Participants consisted of 485 pupils aged 10–11 drawn from 11 junior schools in the UK.

Method. Peer‐ and self‐nominations of physical, verbal, and social exclusion victimization were collected in individual interviews. Self‐reports of other variables were collected either individually or in small groups.

Results. A substantial minority of pupils reported high levels of fear of future victimization and disrupted concentration on class work, and girls reported higher levels of fear of future victimization than boys. All three types of self‐reported victimization, all three types of peer‐reported victimization, and fear of all three types of future victimization predicted disrupted concentration on class work. Fear of future social exclusion moderated the association between peer‐reported social exclusion and disrupted concentration on class work.

Conclusions. In addition to tackling victimization per se, allaying pupils' fears of it happening to them in the future is called for in order to address a hitherto largely overlooked correlate, and possible source, of disrupted classroom concentration.
Muscle Protein Alterations in LGMD2I Patients With Different Mutations in the Fukutin-related Protein Gene
Authors: Yamamoto Lydia U. , Velloso Fernando J. , Lima Bruno L. , Fogaça Luciana L.Q. , de Paula Flávia , Vieira Natássia M. , Zatz Mayana , Vainzof Mariz
Published: July 2008

Fukutin-related protein (FKRP) is a protein involved in the glycosylation of cell surface molecules. Pathogenic mutations in the FKRP gene cause both the more severe congenital muscular dystrophy Type 1C and the milder Limb-Girdle Type 2I form (LGMD2I). Here we report muscle histological alterations and the analysis of 11 muscle proteins: dystrophin, four sarcoglycans, calpain 3, dysferlin, telethonin, collagen VI, α-DG, and α2-laminin, in muscle biopsies from 13 unrelated LGMD2I patients with 10 different FKRP mutations. In all, a typical dystrophic pattern was observed. In eight patients, a high frequency of rimmed vacuoles was also found. A variable degree of α2-laminin deficiency was detected in 12 patients through immunofluorescence analysis, and 10 patients presented α-DG deficiency on sarcolemmal membranes. Additionally, through Western blot analysis, deficiency of calpain 3 and dystrophin bands was found in four and two patients, respectively. All the remaining proteins showed a similar pattern to normal controls. These results suggest that, in our population of LGMD2I patients, different mutations in the FKRP gene are associated with several secondary muscle protein reductions, and the deficiencies of α2-laminin and α-DG on sections are prevalent, independently of mutation type or clinical severity.
Hydrothermal dissolution of mixed southern hardwoods
Authors: Tunc Mehmet Sefik , van Heiningen Adriaan R.P.
Published: July 2008

A hydrothermal dissolution profile of wood components cellulose, hemicelluloses, and lignin of hardwood during autohydrolysis for 100 min at temperatures from 130 to 170°C in a modified accelerated solid extraction system (Dionex ASE-100) is described. The content of cellulose, hemicelluloses, lignin, acetyl, and uronic acid groups remaining in the extracted wood were determined. The extract was analyzed for oligosaccharides and monosaccharides, lignin, acetic acid, uronic acid, furfural, and hydroxymethylfurfural. Xylo-oligomers are the predominant component in the extract at temperatures higher than 150°C. At temperatures higher than 160°C, small amounts of furfural and hydroxymethylfurfural are generated. Most of the arabinan and galactan are removed from the wood at 160°C. The xylan remaining in the wood is acetylated at the same degree as in the original wood. In the extract, the ratio of acetyl groups bound to xylo-oligosaccharides decreases with increasing temperature. The content of uronic acid groups found in the extract obtained after autohydrolysis at T≥150°C is significantly smaller than that calculated from the decrease in uronic content of the wood.
Randomized Trial of Endotracheal Tube Versus Laryngeal Mask Airway in Simulated Prehospital Pediatric Arrest
Authors: Chen Lei , Hsiao Allen L.
Published: July 2008

OBJECTIVE. Proficiency in airway management in children is difficult to acquire and maintain for prehospital providers. The laryngeal mask airway is a relatively new airway device. Its ease of use makes it an attractive potential alternative to endotracheal tubes in pediatrics. The objective of this study was to investigate whether, in simulated cardiopulmonary arrests in children, the use of laryngeal mask airway, compared with endotracheal tubes, results in shorter time to effective ventilation when performed by prehospital providers.

METHODS. A randomized, crossover study was conducted in a local paramedic training program. Fifty-two emergency medical technicians agreed to participate. After a 2-hour training session, an arrest scenario was presented to each participant by using an infant-sized human patient simulator. The participants were randomly assigned first to use 1 of the 2 devices. Time to successful ventilation was recorded. Number of attempts and results were recorded. After the airway was secured successfully, the scenario was repeated with the alternative device.

RESULTS. The mean ± SD length of time to effective ventilation was 46 seconds when using endotracheal tubes and 23 seconds when using laryngeal mask airway, with a mean difference of 23 seconds. The mean number of attempts to achieve effective ventilation was 1.27 when using endotracheal tubes and 1.1 when using laryngeal mask airway. There were 9 (17%) episodes of esophageal intubations and 14 (27%) episodes of right main-stem intubations in the endotracheal tube group, and there were 5 (9.5%) episodes of malposition in the laryngeal mask airway group.

CONCLUSIONS. In simulated pediatric arrests, the use of laryngeal mask airway, compared with endotracheal tubes, led to more rapid establishment of effective ventilation and fewer complications when performed by prehospital providers.
Testing limiting similarity in Quaternary terrestrial gastropods
Authors: Huntley John Warren , Yanes Yurena , Kowalewski Michał , Castillo Carolina , Delgado-Huertas Antonio , Ibáñez Miguel , Alonso María R. , Ortiz José E. , de Torres Trinidad
Published: July 2008

The hypothesis of limiting similarity, which postulates that morphologically and/or ecologically similar species will differ enough in shape, size, or other variables to minimize competition, has been controversial among ecologists and paleoecologists. Many studies have reported the occurrence of limiting similarity in modern environments or in time-averaged fossil deposits; however, empirical high-resolution time series demonstrating limiting similarity over longer time scales are lacking. We have integrated radiocarbon-calibrated amino acid dating techniques, stable isotope estimates, and morphometric data to test the hypothesis of limiting similarity in late Quaternary land snails from the Canary Islands over a period of 42,500 years. We tested for both ecological character displacement (two closely related species will differ in size in order to minimize competition in sympatry and these differences will be minimized in allopatry) and communitywide character displacement (overdispersion of body size among competitors in a guild). Multiple proxies of body size consistently show that two endemic congeneric pulmonate gastropod species (Theba geminataandT. arinagae) maintained a difference in size from ~42,500 B.P. through the last occurrence ofT. arinagae14,900 B.P., with a concomitant trend of a decreasing body size.Theba geminatabody size did not converge on that ofT. arinagaeand variation inT. geminatabody size did not increase significantly following the extinction ofT. arinagae; therefore, ecological character displacement and release did not occur. Community-wide character displacement was found in only one time bin over the last 42,500 years. These results suggest that limiting similarity is a transient ecological phenomenon rather than a long-term evolutionary process. This study not only demonstrates the problems inherent in biological “snapshot” studies and geological studies of time-averaged deposits to test limiting similarity adequately, but it also presents a more adequate research protocol to test the importance of interspecific competition in the history of life.