bluuebunny/crossref_metadata_2025_split 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

AbstractBackgroundA 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.ResultsTo 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.ConclusionPatternLab 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

Abstract

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

Abstract

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

Abstract

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

AbstractBackgroundThe 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.ResultsWe 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.ConclusionThe 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

AbstractBackgroundSeveral 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.DesignThis 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.ConclusionThis 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 registrationNCT005725079
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

Abstract

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

Abstract

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.