bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Percutaneous Endoscopic Feeding Tube Placement in Obese Patients
Authors: Wiggins Travis F. , Garrow Donald A. , DeLegge Mark H.
Published: December 2009

Background:

Percutaneous endoscopic feeding tube placement is generally safe and effective for establishing enteral access. In certain subpopulations, such as obese patients, substantial data are limited. This study evaluates the success rate and potential for late complications with placement of feeding tubes in obese patients.

Methods:

The Medical University of South Carolina endoscopy database was queried for adult patients with a body mass index ≥30 kg/m2 who had undergone percutaneous endoscopic gastrostomy, percutaneous endoscopic gastrojejunostomy, and direct percutaneous jejunostomy placement procedures between the years 2000 and 2006.

Results:

Sixty‐seven subjects met the inclusion criteria. Percutaneous endoscopic feeding tube placement was successful in 60 of 67 individuals (89.6%) with an average procedure time of 15.5 minutes (range, 5–70 minutes). Postplacement complications occurred in 26 of 59 subjects (44.1%) and included peristomal pain (8.5%), cellulitis (8.5%), inadvertent removal (6.8%), peritubular leak (6.8%), nausea (3.4%), and hemoperitoneum (3.4%). In multivariable logistic regression analysis, weight >250 pounds (>113 kg) predicted a significantly increased likelihood of complications (adjusted odds ratio = 3.86; 95% confidence interval, 1.02–14.57). Other covariates did not significantly affect the complication rate.

Conclusions:

Percutaneous enteral access device placement in obese patients is generally safe, and a body mass index ≥30 kg/m2 alone should not be a procedural contraindication. Adherence to safe enteral access placement techniques and close periprocedure follow‐up should occur in obese patients, especially those weighing >250 pounds (>113 kg). More research is needed to fully evaluate the efficacy of enteral access in this population.
Is There Still a Role for Peripheral Parenteral Nutrition?
Authors: Gura Kathleen M.
Published: December 2009

Peripheral parenteral nutrition (PPN) is often viewed as the stepchild of parenteral nutrition (PN) infused via a central venous catheter. Anecdotal reports suggest that there has been increased interest in PPN in the United States and even more so in Europe because of improvements in catheter design and infusion technology, both of which have the potential to decrease complications such as infusion phlebitis. PPN, like PN via a central venous catheter, contains dextrose, amino acids, electrolytes, vitamins, and minerals, but in more limited capacity. One of the perceived benefits of PPN is the relative ease in establishing peripheral access, which may prevent delays in establishing nutrition support. PPN is intended for short‐term use or supplementation. In most instances, it is used to maintain a previously well‐nourished, nonhypermetabolic patient or to serve as a bridge to centrally administered infusions or enteral feedings until more suitable nutrition can be provided. In some cases, inappropriate use may result in infusion phlebitis or inadequate nutrient intake. Conflicting recommendations from various organizations further complicate and confuse prescribers. The intent of this review is to discuss PPN and the challenges its use presents to the practitioner.
Physical and Chemical Stability of Iron Sucrose in Parenteral Nutrition
Authors: MacKay Mark , Rusho William , Jackson Daniel , McMillin Gwendolyn , Winther Brian
Published: December 2009

Introduction:

Current literature supports iron dextran as the only iron preparation compatible with parenteral nutrition (PN). Iron sucrose has been used for iron replacement therapy because of its lower rate of adverse events. The purpose of this study is to determine the physical and chemical stability of iron sucrose in PN.

Methods:

Physical and chemical stability of iron sucrose in nonlipid PN solutions (PN 1 for neonates and PN 2 for patients weighing >20 kg) is tested over time in triplicate. Physical stability is determined by visually inspecting each PN solution for particulate matter and by filtering and analyzing each aliquot quantitatively for crystal precipitates. Chemical stability is confirmed if the iron concentrations by mass spectrometry remain within United States Pharmacopeia (USP) standards.

Results:

Visual clarity is maintained in all PN solutions at hours 0 through 4. PN solution 1 remains clear for hours 8 through 24, whereas PN solution 2 shows an increase in particulate matter by 8 hours. All PN solutions 2 are considered visually incompatible by hour 24. Physical stability of iron sucrose for PN solutions 1 and 2 from hours 0 to 4 is within the USP guidelines for crystalline particulate matter. At hour 24, only solution 1 remains within USP guidelines. Chemical stability data indicate that iron concentrations are maintained throughout the 24‐hour time period.

Conclusion:

The physical stability of iron sucrose in PN is time and concentration dependent. Concentrations >0.25 mg/dL showed increasing particulate and should not be added to PN. However, iron sucrose is chemically stable in PN solutions.
Badder than “Just a Bunch of SPEDs”: Alternative Schooling and Student Resistance to Special Education Rhetoric
Authors: Becker Sarah
Published: December 2009

This study of a Northeastern alternative high school examines the salience of two discourses—one focused on students who have problems, the other on students who are problems—in the alternative schooling process. At Cromwell Alternative North (CAN), teachers and staff promoted a view of students as youth with “special needs.” In the students’ social world, having “special needs” was not awarded status like being a troublemaker was. Students at CAN therefore had to manage both discourses in their daily interaction with teachers and peers. Some students accepted special needs rhetoric, some rejected it. Most attempted to manage it creatively, being a problem in the eyes of peers and having problems in the eyes of teachers. Code switching between the two discourses, however, was not something all students could do. A handful of students—“shining stars”—managed both “SPED,” slang for special education students, and “bad” discourses to achieve the greatest social and academic successes at CAN.
Between Poverty and a Lifestyle: The Leisure Activities of Homeless People in Las Vegas
Authors: Borchard Kurt
Published: December 2009

Housed people judge homeless people, and in particular their leisure activities, as indicators of whether that person has chosen a “homeless lifestyle” and therefore deserves homelessness. To achieve a more complex understanding of contemporary homelessness, the author conducted ethnographic fieldwork over ten months in Las Vegas, Nevada, interviewing and participant observing dozens of homeless men and women, including observations of their leisure activities and “free time.” The author argues that homeless people’s pursuit of leisure activities helps explain the popularity of both Las Vegas as a destination for homeless people and why it is a difficult place for homeless people to end their poverty. A consideration of homeless people’s lifestyles in such a postmodern tourist environment also shows how such environments both sustain homeless people and produce homelessness.
An Examination of Entrepreneurial Orientation, Environmental Scanning, and Market Strategies of Nonprofit and For-Profit Nursing Home Administrators
Authors: Davis Jullet A. , Marino Louis D. , Aaron Joshua R. , Tolbert Carl L.
Published: December 2009

This study explores differences in entrepreneurial orientation (EO) by profit status. In addition to EO, other survey questions sought to determine how firms scanned the external market for information and the firm’s view of external market volatility. The sample, collected in 2004, consisted of 134 nursing home administrators located in the state of Florida. The data were analyzed using generalized linear model. The results show that there was no significant difference in the EO between nonprofits and for-profits but that nonprofits were significantly more likely to engage in environmental scanning activities such as gathering information from trade magazines and suppliers and that they remained abreast of economic and technological trends more than their for-profit counterparts. Given the demands of the external market, nonprofits may find that developing strategies to better compete with for-profit firms is vital.
The Chinese Family Assessment Instrument (C-FAI)
Authors: Shek Daniel T. L. , Ma Cecilia M. S.
Published: December 2009

Objective: This paper examines the dimensionality and factorial invariance of the Chinese Family Assessment Instrument (C-FAI) using multigroup confirmatory factor analyses (MCFAs). Method: A total of 3,649 students responded to the C-FAI in a community survey. Results: Results showed that there are five dimensions of the C-FAI (communication, mutuality, conflict and harmony, parental concern, parental control), which are subsumed under two higher order factors (family interaction and parenting). Evidence of factorial invariance in terms of configuration, first-order factor loadings, second-order factor loadings, intercepts of measured variable, and intercepts of first-order latent factor, was found. Conclusions: The C-FAI is an objective measure of Chinese family functioning with high factorial validity. It can be used in family practice contexts of Chinese families.
Medical, Personal, and Social Forms of Uncertainty Across the Transplantation Trajectory
Authors: Martin Summer Carnett , Stone Anne M. , Scott Allison M. , Brashers Dale E.
Published: December 2009

We designed this study to identify sources of uncertainty across the transplantation trajectory. We interviewed 38 transplant patients, who reported medical, personal, and social forms of uncertainty. Prior to transplantation, they reported uncertainty related to insufficient information about diagnosis, complex decisions about transplantation, unknown/unknowable organ availability, unclear expectations about medical procedures/outcomes, ambiguity in meaning of life, complex role and identity challenges, unclear financial consequences, questioning from others, and unclear relational implications. They reported that uncertainty experienced after transplantation was related to complex medication regimens, unpredictable future health/prognosis, complex role and identity challenges, unclear financial consequences, possible stigmatizing reactions, unclear relational implications, and complex interactions with the deceased donor’s family. These findings lay the groundwork for additional research on uncertainty management for transplant patients, and suggest that health care professionals and supportive others cannot apply a one-size-fits-all solution when aiding in uncertainty management.
Concurrent Validity of the Psychopathic Personality Inventory With Offender and Community Samples
Authors: Malterer Melanie B. , Lilienfeld Scott O. , Neumann Craig S. , Newman Joseph P.
Published: December 2009

The Psychopathy Checklist—Revised (PCL-R) is a frequently used and well-validated measure of psychopathy but is relatively time-intensive and expensive to administer. The Psychopathic Personality Inventory (PPI) is a self-report measure that provides a less time-intensive and less expensive method for identifying psychopathic individuals. Using three independent samples and two different versions of the PCL (i.e., PCL-R, PCL:SV), the authors evaluated the extent to which the PPI and PCL overlap in their measurement of the psychopathy construct. Across three studies, PPI total and Factor 2 scores correlated moderately to strongly with PCL total and Factor 2 scores. Results for PPI and PCL Factor 1 scores were less positive. These findings raise important questions concerning the integration of results obtained using alternative psychopathy assessments.
The Context(s) of Precaution: Ideological and Instrumental Appeals to the Precautionary Principle
Authors: Moreno Carolina , Todt Oliver , Luján José Luis
Published: December 2009

This article contributes to the clarification of the concept of precaution and its function in social debate. The authors compare the uses of precaution in science and technology—related conflicts (as indicated by an analysis of media reports on precaution) with data from a survey on precaution and the role of science in decision making. While the survey data confirm the existence of opposing “idealized” or “ideological” conceptualizations of the role of science in regulatory decisions, the analyzed media reports show an added degree of complexity on the level of social dynamics. The media analysis identifies an instrumental use of the concept of precaution in social debate, which is independent of “ideological” positions on precaution, and serves as a way of empowerment for social actors critical of scientific-technological proposals, allowing them to counterbalance information asymmetries.
Through the Looking Glass: Our Autoethnographic Journey Through Research Mind-Fields
Authors: McMillan Sally , Price Margaret A.
Published: December 2009

Two curriculum professors team taught naturalistic inquiry in an education college where research is the domain of a “service” department. Within the seminar, participants were challenged and transformed. Within the college, pillars of traditional research cracked. Conflicting streams of criticism, support, and imposition emerged, as grievances were filed and emails were requisitioned. Legalized bullying abounded. However, students continued to request their classes, and traditional pillars continue to crack. This article explores core questions such as the following: Who has the right to teach research? What constitutes legitimate research? What roles do narrative and imposition play in knowing and being known? Using a performative format, with Lewis Carroll’s Alice’s Adventures in Wonderland & Through the Looking-Glass as literary and methodological tools, the authors attempt to include readers in their arduous and sometimes comical journeys through the academic adolescence of Wonderland and back again through the looking glass.
Coming Out and Going Home: A Family Ethnography
Authors: Tillmann Lisa M.
Published: December 2009

The author, a heterosexual woman, and Gordon Bernstein, a gay man, have been friends and research collaborators since 1995. In 2004, the author accompanied Gordon on a trip to his hometown of Philadelphia to conduct fieldwork and interview family members. This project ethnographically explored personal and relational opportunities and challenges associated with coming out in a family system defined by avoidant communication, hegemonic masculinity, and terminal illness.
Segregation, Immigration, and Latino Participation in Ethnic Politics
Authors: Rocha Rene R. , Espino Rodolfo
Published: December 2009

This article examines the way in which racial/ethnic context influences Latino support for ethnic political causes. Welch et al. argue that feelings of solidarity within the African American community intensify as the size of the African American population in an individual’s residential environment increases. We extend this hypothesis to Latinos, while also considering how other scholars have hypothesized different structural patterns of residence among Latinos to influence their political behavior. We also consider how higher levels of in-group heterogeneity within the Latino community might complicate this relationship. These hypotheses are tested using data from the 1999 Harvard/ Kaiser/Washington Post National Survey of Latinos.We find that higher levels of segregation between Anglos and Latinos dampen the positive relationship between Latino group size and participation in ethnic political causes.
SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations
Authors: Nowak Daniel , Ogawa Seishi , Müschen Markus , Kato Motohiro , Kawamata Norihiko , Meixel Antonie , Nowak Verena , Kim Han S. , Kang Sharon , Paquette Ronald , Chang Mi-Sook , Thoennissen Nils H. , Mossner Max , Hofmann Wolf-Karsten , Kohlmann Alexander , Weiss Tamara , Haferlach Torsten , Haferlach Claudia , Koeffler H. Phillip
Published: December 2009

To elucidate whether tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia is associated with characteristic genomic alterations, we analyzed DNA samples from 45 TKI-resistant chronic myeloid leukemia patients with 250K single nucleotide polymorphism arrays. From 20 patients, matched serial samples of pretreatment and TKI resistance time points were available. Eleven of the 45 TKI-resistant patients had mutations of BCR-ABL1, including 2 T315I mutations. Besides known TKI resistance-associated genomic lesions, such as duplication of the BCR-ABL1 gene (n = 8) and trisomy 8 (n = 3), recurrent submicroscopic alterations, including acquired uniparental disomy, were detectable on chromosomes 1, 8, 9, 17, 19, and 22. On chromosome 22, newly acquired and recurrent deletions of the IGLC1 locus were detected in 3 patients, who had previously presented with lymphoid or myeloid blast crisis. This may support a hypothesis of TKI-induced selection of subclones differentiating into immature B-cell progenitors as a mechanism of disease progression and evasion of TKI sensitivity.
Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice
Authors: Song Zhangfa , Wang Jianwei , Guachalla Luis Miguel , Terszowski Grzegorz , Rodewald Hans-Reimer , Ju Zhenyu , Rudolph K. Lenhard
Published: December 2009

There is growing evidence that telomere dysfunction can contribute to human aging. Telomere dysfunction limits lymphopoiesis in aging telomerase knockout (mTerc−/−) mice primarily by the induction of stem cell–extrinsic alterations. The relative contribution of alterations in the stem cell niche and the systemic environment to the impairment of lymphopoiesis in response to telomere dysfunction is currently unknown. This study reveals a minor impact of stem cell–intrinsic defects on the impairment of B and T lymphopoiesis in response to telomere dysfunction. The impairment in B and T lymphopoiesis in aging telomere-dysfunctional mice was mainly due to alterations of the systemic environment. Telomere dysfunction had no significant cell-autonomous effects impairing the function of thymic or bone marrow niches in supporting B and T lymphopoiesis. Moreover, age-related alterations in the cellular composition of the thymic epithelium in telomere-dysfunctional mice were rescued by transplantation of the thymus into a wild-type environment; these rejuvenated thymi supported normal T lymphopoiesis in recipient mice. Together, these data place alterations in the systemic environment on top of the hierarchy of events limiting lymphopoiesis in response to telomere dysfunction.
An efficient algorithm to compute marginal posterior genotype probabilities for every member of a pedigree with loops
Authors: Totir Liviu R , Fernando Rohan L , Abraham Joseph
Published: December 2009

Background

Marginal posterior genotype probabilities need to be computed for genetic analyses such as geneticcounseling in humans and selective breeding in animal and plant species.

Methods

In this paper, we describe a peeling based, deterministic, exact algorithm to compute efficiently genotype probabilities for every member of a pedigree with loops without recourse to junction-tree methods from graph theory. The efficiency in computing the likelihood by peeling comes from storing intermediate results in multidimensional tables called cutsets. Computing marginal genotype probabilities for individual i requires recomputing the likelihood for each of the possible genotypes of individual i. This can be done efficiently by storing intermediate results in two types of cutsets called anterior and posterior cutsets and reusing these intermediate results to compute the likelihood.

Examples

A small example is used to illustrate the theoretical concepts discussed in this paper, and marginal genotype probabilities are computed at a monogenic disease locus for every member in a real cattle pedigree.
Modulation of p53 binding to MDM2: computational studies reveal important roles of Tyr100
Authors: Dastidar Shubhra Ghosh , Lane David P , Verma Chandra S
Published: December 2009

Background

The tumor suppressor protein p53 is regulated by the ubiquitin ligase MDM2 which down-regulates p53. In tumours with overexpressed MDM2, the p53-MDM2 interaction can be interrupted by a peptide or small molecule to stabilize p53 as a therapeutic strategy. Structural and biochemical/mutagenesis data show that p53 has 3 hydrophobic residues F19, W23 and L26 that embed into the ligand binding pocket of MDM2 which is highly plastic in nature and can modulate its size to accommodate a variety of ligands. This binding pocket is primarily dependent on the orientation of a particular residue, Y100. We have studied the role of the dynamics of Y100 in p53 recognition.

Results

Molecular dynamics simulations show that the Y100 side chain can be in "open" or "closed" states with only the former enabling complex formation. When both p53 and MDM2 are in near native conformations, complex formation is rapid and is driven by the formation of a hydrogen bond between W23 of p53 and L54 of MDM2 or by the embedding of F19 of p53 into MDM2. The transition of Y100 from "closed" to "open" can increase the size of the binding site. Interconversions between these two states can be induced by the N-terminal region of MDM2 or by the conformations of the p53 peptides.

Conclusion

Molecular dynamics simulations have revealed how the binding of p53 to MDM2 is modulated by the conformational mobility of Y100 which is the gatekeeper residue in MDM2. The mobility of this residue can be modulated by the conformations of p53 and the Nterminal lid region of MDM2.
BIOADI: a machine learning approach to identifying abbreviations and definitions in biological literature
Authors: Kuo Cheng-Ju , Ling Maurice HT , Lin Kuan-Ting , Hsu Chun-Nan
Published: December 2009

Background

To automatically process large quantities of biological literature for knowledge discovery and information curation, text mining tools are becoming essential. Abbreviation recognition is related to NER and can be considered as a pair recognition task of a terminology and its corresponding abbreviation from free text. The successful identification of abbreviation and its corresponding definition is not only a prerequisite to index terms of text databases to produce articles of related interests, but also a building block to improve existing gene mention tagging and gene normalization tools.

Results

Our approach to abbreviation recognition (AR) is based on machine-learning, which exploits a novel set of rich features to learn rules from training data. Tested on the AB3P corpus, our system demonstrated a F-score of 89.90% with 95.86% precision at 84.64% recall, higher than the result achieved by the existing best AR performance system. We also annotated a new corpus of 1200 PubMed abstracts which was derived from BioCreative II gene normalization corpus. On our annotated corpus, our system achieved a F-score of 86.20% with 93.52% precision at 79.95% recall, which also outperforms all tested systems.

Conclusion

By applying our system to extract all short form-long form pairs from all available PubMed abstracts, we have constructed BIOADI. Mining BIOADI reveals many interesting trends of bio-medical research. Besides, we also provide an off-line AR software in the download section on http://bioagent.iis.sinica.edu.tw/BIOADI/.
Toward reconstructing the evolution of advanced moths and butterflies (Lepidoptera: Ditrysia): an initial molecular study
Authors: Regier Jerome C , Zwick Andreas , Cummings Michael P , Kawahara Akito Y , Cho Soowon , Weller Susan , Roe Amanda , Baixeras Joaquin , Brown John W , Parr Cynthia , Davis Donald R , Epstein Marc , Hallwachs Winifred , Hausmann Axel , Janzen Daniel H , Kitching Ian J , Solis M Alma , Yen Shen-Horn , Bazinet Adam L , Mitter Charles
Published: December 2009

Background

In the mega-diverse insect order Lepidoptera (butterflies and moths; 165,000 described species), deeper relationships are little understood within the clade Ditrysia, to which 98% of the species belong. To begin addressing this problem, we tested the ability of five protein-coding nuclear genes (6.7 kb total), and character subsets therein, to resolve relationships among 123 species representing 27 (of 33) superfamilies and 55 (of 100) families of Ditrysia under maximum likelihood analysis.

Results

Our trees show broad concordance with previous morphological hypotheses of ditrysian phylogeny, although most relationships among superfamilies are weakly supported. There are also notable surprises, such as a consistently closer relationship of Pyraloidea than of butterflies to most Macrolepidoptera. Monophyly is significantly rejected by one or more character sets for the putative clades Macrolepidoptera as currently defined (P< 0.05) and Macrolepidoptera excluding Noctuoidea and Bombycoidea sensu lato (P≤ 0.005), and nearly so for the superfamily Drepanoidea as currently defined (P< 0.08). Superfamilies are typically recovered or nearly so, but usually without strong support. Relationships within superfamilies and families, however, are often robustly resolved. We provide some of the first strong molecular evidence on deeper splits within Pyraloidea, Tortricoidea, Geometroidea, Noctuoidea and others.

Separate analyses of mostly synonymous versus non-synonymous character sets revealed notable differences (though not strong conflict), including a marked influence of compositional heterogeneity on apparent signal in the third codon position (nt3). As available model partitioning methods cannot correct for this variation, we assessed overall phylogeny resolution through separate examination of trees from each character set. Exploration of "tree space" with GARLI, using grid computing, showed that hundreds of searches are typically needed to find the best-feasible phylogeny estimate for these data.

Conclusion

Our results (a) corroborate the broad outlines of the current working phylogenetic hypothesis for Ditrysia, (b) demonstrate that some prominent features of that hypothesis, including the position of the butterflies, need revision, and (c) resolve the majority of family and subfamily relationships within superfamilies as thus far sampled. Much further gene and taxon sampling will be needed, however, to strongly resolve individual deeper nodes.
MitoVariome: a variome database of human mitochondrial DNA
Authors: Lee Yong Seok , Kim Woo-Yeon , Ji Mihyun , Kim Ji Han , Bhak Jong
Published: December 2009

Background

Mitochondrial sequence variation provides critical information for studying human evolution and variation. Mitochondrial DNA provides information on the origin of humans, and plays a substantial role in forensics, degenerative diseases, cancers, and aging process. Typically, human mitochondrial DNA has various features such as HVSI, HVSII, single-nucleotide polymorphism (SNP), restriction enzyme sites, and short tandem repeat (STR).

Results

We present a variome database (MitoVariome) of human mitochondrial DNA sequences. Queries against MitoVariome can be made using accession numbers or haplogroup/continent. Query results are presented not only in text but also in HTML tables to report extensive mitochondrial sequence variation information. The variation information includes repeat pattern, restriction enzyme site polymorphism, short tandem repeat, disease information as well as single nucleotide polymorphism. It also provides a graphical interface as Gbrowse displaying all variations at a glance. The web interface also provides the tool for assigning haplogroup based on the haplogroup-diagnostic system with complete human mitochondrial SNP position list and for retrieving sequences that users query against by using accession numbers.

Conclusion

MitoVariome is a freely accessible web application and database that enables human mitochondrial genome researchers to study genetic variation in mitochondrial genome with textual and graphical views accompanied by assignment function of haplogrouping if users submit their own data. Hence, the MitoVariome containing many kinds of variation features in the human mitochondrial genome will be useful for understanding mitochondrial variations of each individual, haplogroup, or geographical location to elucidate the history of human evolution.
Improving gene expression similarity measurement using pathway-based analytic dimension
Authors: Keum Changwon , Woo Jung Hoon , Oh Won Seok , Park Sue-Nie , No Kyoung Tai
Published: December 2009

Background

Gene expression similarity measuring methods were developed and applied to search rapidly growing public microarray databases. However, current expression similarity measuring methods need to be improved to accurately measure similarity between gene expression profiles from different platforms or different experiments.

Results

We devised new gene expression similarity measuring method based on pathway information. In short, newly devised method measure similarity between gene expression profiles after converting them into pathway based expression profiles. To evaluate pathway based gene expression similarity measuring method, we conducted cell type classification test. Pathway based similarity measuring method shows higher classification accuracy. Especially, pathway based methods outperform at most 50% and 10% over conventional gene expression similarity method when search databases are limited to cross-platform profiles and cross-experiment profiles.

Conclusion

The pathway based gene expression similarity measuring method outperforms commonly used similarity measuring methods. Considering the fact that public microarray database is consist of gene expression profiles of various experiments with various type of platform, pathway based gene expression similarity measuring method could be successfully applied for searching large public microarray databases.
BOAT: Basic Oligonucleotide Alignment Tool
Authors: Zhao Shu-Qi , Wang Jun , Zhang Li , Li Jiong-Tang , Gu Xiaocheng , Gao Ge , Wei Liping
Published: December 2009

Background

Next-generation DNA sequencing technologies generate tens of millions of sequencing reads in one run. These technologies are now widely used in biology research such as in genome-wide identification of polymorphisms, transcription factor binding sites, methylation states, and transcript expression profiles. Mapping the sequencing reads to reference genomes efficiently and effectively is one of the most critical analysis tasks. Although several tools have been developed, their performance suffers when both multiple substitutions and insertions/deletions (indels) occur together.

Results

We report a new algorithm, Basic Oligonucleotide Alignment Tool (BOAT) that can accurately and efficiently map sequencing reads back to the reference genome. BOAT can handle several substitutions and indels simultaneously, a useful feature for identifying SNPs and other genomic structural variations in functional genomic studies. For better handling of low-quality reads, BOAT supports a "3'-end Trimming Mode" to build local optimized alignment for sequencing reads, further improving sensitivity. BOAT calculates an E-value for each hit as a quality assessment and provides customizable post-mapping filters for further mapping quality control.

Conclusion

Evaluations on both real and simulation datasets suggest that BOAT is capable of mapping large volumes of short reads to reference sequences with better sensitivity and lower memory requirement than other currently existing algorithms. The source code and pre-compiled binary packages of BOAT are publicly available for download at http://boat.cbi.pku.edu.cn under GNU Public License (GPL). BOAT can be a useful new tool for functional genomics studies.
MitoInteractome: Mitochondrial protein interactome database, and its application in 'aging network' analysis
Authors: Reja Rohit , Venkatakrishnan AJ , Lee Jungwoo , Kim Byoung-Chul , Ryu Jea-Woon , Gong Sungsam , Bhak Jong , Park Daeui
Published: December 2009

Background

Mitochondria play a vital role in the energy production and apoptotic process of eukaryotic cells. Proteins in the mitochondria are encoded by nuclear and mitochondrial genes. Owing to a large increase in the number of identified mitochondrial protein sequences and completed mitochondrial genomes, it has become necessary to provide a web-based database of mitochondrial protein information.

Results

We present 'MitoInteractome', a consolidated web-based portal containing a wealth of information on predicted protein-protein interactions, physico-chemical properties, polymorphism, and diseases related to the mitochondrial proteome. MitoInteractome contains 6,549 protein sequences which were extracted from the following databases: SwissProt, MitoP, MitoProteome, HPRD and Gene Ontology database. The first general mitochondrial interactome has been constructed based on the concept of 'homologous interaction' using PSIMAP (Protein Structural Interactome MAP) and PEIMAP (Protein Experimental Interactome MAP). Using the above mentioned methods, protein-protein interactions were predicted for 74 species. The mitochondrial protein interaction data of humans was used to construct a network for the aging process. Analysis of the 'aging network' gave us vital insights into the interactions among proteins that influence the aging process.

Conclusion

MitoInteractome is a comprehensive database that would (1) aid in increasing our understanding of the molecular functions and interaction networks of mitochondrial proteins, (2) help in identifying new target proteins for experimental research using predicted protein-protein interaction information, and (3) help in identifying biomarkers for diagnosis and new molecular targets for drug development related to mitochondria. MitoInteractome is available at http://mitointeractome.kobic.kr/.
Prediction of avian influenza A binding preference to human receptor using conformational analysis of receptor bound to hemagglutinin
Authors: Jongkon Nipa , Mokmak Wanwimon , Chuakheaw Daungmanee , Shaw Philip J , Tongsima Sissades , Sangma Chak
Published: December 2009

Background

It is known that the highly pathogenic avian influenza A virus H5N1 binds strongly and with high specificity to the avian-type receptor by its hemagglutinin surface protein. This specificity is normally a barrier to viral transmission from birds to humans. However, strains may emerge with mutated hemagglutinin, potentially changing the receptor binding preference from avian to human-type. This hypothesis has been proven correct, since viral isolates from Vietnam and Thailand have been found which have increased selectivity toward the human cell receptor. The change in binding preference is due to mutation, which can be computationally modelled. The aim of this study is to further explore whether computational simulation could be used as a prediction tool for host type selectivity in emerging variants.

Results

Molecular dynamics simulation was employed to study the interactions between receptor models and hemagglutinin proteins from H5N1 strains A/Duck/Singapore/3/97, mutated A/Duck/Singapore/3/97 (Q222L, G224S, Q222L/G224S), A/Thailand/1(KAN-1)/2004, and mutated A/Thailand/1(KAN-1)/2004 (L129V/A134V). The avian receptor was represented by Siaα(2,3)Gal substructure and human receptor by Siaα(2,6)Gal. The glycoside binding conformation was monitored throughout the simulations since high selectivity toward a particular host occurs when the sialoside bound with the near-optimized conformation.

Conclusion

The simulation results showed all hemagglutinin proteins used the same set of amino acid residues to bind with the glycoside; however, some mutations alter linkage preferences. Preference toward human-type receptors is associated with a positive torsion angle, while avian-type receptor preference is associated with a negative torsion angle. According to the conformation analysis of the bound receptors, we could predict the relative selectivity in accordance with in vitro experimental data when disaccharides receptor analogs were used.
Phylogenetic reconstruction using secondary structures and sequence motifs of ITS2 rDNA of Paragonimus westermani (Kerbert, 1878) Braun, 1899 (Digenea: Paragonimidae) and related species
Authors: Prasad Pramod Kumar , Tandon Veena , Biswal Devendra Kumar , Goswami Lalit Mohan , Chatterjee Anupam
Published: December 2009

Background

Most phylogenetic studies using current methods have focused on primary DNA sequence information. However, RNA secondary structures are particularly useful in systematics because they include characteristics that give "morphological" information, not found in the primary sequence. In several mountainous regions of Northeastern India, foci of Paragonimus (lung fluke) infection reportedly involve species that are known to prevail in neighbouring countries. The present study was undertaken to demonstrate the sequence analysis of the ribosomal DNA (ITS2) of the infective (metacercarial) stage of the lung fluke collected from the edible crab hosts that are abundant in a mountain stream of the area (Miao, Changlang District in Arunachal Pradesh) and to construct its phylogeny. Using the approach of molecular morphometrics that is based on ITS2 secondary structure homologies, phylogenetic relationships of the various isolates of Paragonimus species that are prevalent in the neighbouring Near-eastern countries have been discussed.

Results

Initially, ten predicted RNA secondary structures were reconstructed and the topology based only on the predicted RNA secondary structure of the ITS2 region resolved most relationships among the species studied. We obtained three similar topologies for seven species of the genus Paragonimus on the basis of traditional primary sequence analysis using MEGA and a Bayesian analysis of the combined data. The latter approach allowed us to include both primary sequence and RNA molecular morphometrics; each data partition was allowed to have a different evolution rate. Paragonimus westermani was found to group with P. siamensis of Thailand; this was best supported by both the molecular morphometrics and combined analyses. P. heterotremus, P. proliferus, P. skrjabini, P. bangkokensis and P. harinasutai formed a separate clade in the molecular phylogenies, and were reciprocally monophyletic with respect to other species. ITS2 sequence motifs allowed an accurate in-silico distinction of lung flukes.

Conclusion

Data indicate that ITS2 motifs (≤ 50 bp in size) can be considered a promising tool for trematode species identification. RNA secondary structure analysis could be a valuable tool for distinguishing new species and completing Paragonimus systematics, more so because ITS2 secondary structure contains more information than the usual primary sequence alignment.
PDbase: a database of Parkinson's Disease-related genes and genetic variation using substantia nigra ESTs
Authors: Yang Jin Ok , Kim Woo-Yeon , Jeong So-Young , Oh Jung-Hwa , Jho Sungwoong , Bhak Jong , Kim Nam-Soon
Published: December 2009

Background

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, clinically characterized by impaired motor function. Since the etiology of PD is diverse and complex, many researchers have created PD-related research resources. However, resources for brain and PD studies are still lacking. Therefore, we have constructed a database of PD-related gene and genetic variations using the substantia nigra (SN) in PD and normal tissues. In addition, we integrated PD-related information from several resources.

Results

We collected the 6,130 SN expressed sequenced tags (ESTs) from brain SN normal tissues and PD patients SN tissues using full-cDNA library and normalized cDNA library construction methods from our previous study. The SN ESTs were clustered in 2,951 unigene clusters and assigned in 2,678 genes. We then found up-regulated 57 genes and down-regulated 48 genes by comparing normal and PD SN ESTs frequencies with over 0.9 cut-off probability of differential expression based on the Audic and Claverie method. In addition, we integrated disease-related information from public resources. To examine the characteristics of these PD-related genes, we analyzed alternative splicing events, single nucleotide polymorphism (SNP) markers located in the gene regions, repeat elements, gene regulation elements, and pathways and protein-protein interaction networks.

Conclusion

We constructed the PDbase database to capture the PD-related gene, genetic variation, and functional elements. This database contains 2,698 PD-related genes through ESTs discovered from human normal and PD patients SN tissues, and through integrating several public resources. PDbase provides the mitochondrion proteins, microRNA gene regulation elements, single nucleotide polymorphisms (SNPs) markers within PD-related gene structures, repeat elements, and pathways and networks with protein-protein interaction information. The PDbase information can aid in understanding the causation of PD. It is available at http://bioportal.kobic.re.kr/PDbase/. Supplementary data is available at http://bioportal.kobic.re.kr/PDbase/suppl.jsp
RExPrimer: an integrated primer designing tool increases PCR effectiveness by avoiding 3' SNP-in-primer and mis-priming from structural variation
Authors: Piriyapongsa Jittima , Ngamphiw Chumpol , Assawamakin Anunchai , Wangkumhang Pongsakorn , Suwannasri Payiarat , Ruangrit Uttapong , Agavatpanitch Gallissara , Tongsima Sissades
Published: December 2009

Background

Polymerase chain reaction (PCR) is very useful in many areas of molecular biology research. It is commonly observed that PCR success is critically dependent on design of an effective primer pair. Current tools for primer design do not adequately address the problem of PCR failure due to mis-priming on target-related sequences and structural variations in the genome.

Methods

We have developed an integrated graphical web-based application for primer design, called RExPrimer, which was written in Python language. The software uses Primer3 as the primer designing core algorithm. Locally stored sequence information and genomic variant information were hosted on MySQLv5.0 and were incorporated into RExPrimer.

Results

RExPrimer provides many functionalities for improved PCR primer design. Several databases, namely annotated human SNP databases, insertion/deletion (indel) polymorphisms database, pseudogene database, and structural genomic variation databases were integrated into RExPrimer, enabling an effective without-leaving-the-website validation of the resulting primers. By incorporating these databases, the primers reported by RExPrimer avoid mis-priming to related sequences (e.g. pseudogene, segmental duplication) as well as possible PCR failure because of structural polymorphisms (SNP, indel, and copy number variation (CNV)). To prevent mismatching caused by unexpected SNPs in the designed primers, in particular the 3' end (SNP-in-Primer), several SNP databases covering the broad range of population-specific SNP information are utilized to report SNPs present in the primer sequences. Population-specific SNP information also helps customize primer design for a specific population. Furthermore, RExPrimer offers a graphical user-friendly interface through the use of scalable vector graphic image that intuitively presents resulting primers along with the corresponding gene structure. In this study, we demonstrated the program effectiveness in successfully generating primers for strong homologous sequences.

Conclusion

The improvements for primer design incorporated into RExPrimer were demonstrated to be effective in designing primers for challenging PCR experiments. Integration of SNP and structural variation databases allows for robust primer design for a variety of PCR applications, irrespective of the sequence complexity in the region of interest. This software is freely available at http://www4a.biotec.or.th/rexprimer.
Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of Human
Authors: Venkatachalam Gireedhar , Kumar Alan Prem , Yue Loo Ser , Pervaiz Shazib , Clement Marie Veronique , Sakharkar Meena Kishore
Published: December 2009

Background

Activation of PPARs has been reported to inhibit the proliferation of malignant cells from different lineages. They are involved in transcription regulation of genes upon activation by a ligand. The binding of PPARs to the promoter sequence either represses or activates the gene. Hence, PPARs represent promising targets for cancer treatment because of their anti-proliferative and pro-apoptotic activities. Here we computationally identified PPAR binding regions in NHE1 and MnSOD. We further validated the predictions in vitro.

Results

Our results computationally predicted the presence of 2 PPRE motifs in NHE1 and 3 PPRE motifs in MnSOD. We experimentally confirmed the true motifs and their regulation by PPAR.

Conclusion

Our results suggest that both NHE1 and MnSOD have PPRE binding motif in their upstream/promoter region and hence are regulated by PPAR upon ligand binding.
A multi-factor model for caspase degradome prediction
Authors: Wee Lawrence JK , Tong Joo Chuan , Tan Tin Wee , Ranganathan Shoba
Published: December 2009

Background

Caspases belong to a class of cysteine proteases which function as critical effectors in cellular processes such as apoptosis and inflammation by cleaving substrates immediately after unique tetrapeptide sites. With hundreds of reported substrates and many more expected to be discovered, the elucidation of the caspase degradome will be an important milestone in the study of these proteases in human health and disease. Several computational methods for predicting caspase cleavage sites have been developed recently for identifying potential substrates. However, as most of these methods are based primarily on the detection of the tetrapeptide cleavage sites - a factor necessary but not sufficient for predicting in vivo substrate cleavage - prediction outcomes will inevitably include many false positives.

Results

In this paper, we show that structural factors such as the presence of disorder and solvent exposure in the vicinity of the cleavage site are important and can be used to enhance results from cleavage site prediction. We constructed a two-step model incorporating cleavage site prediction and these factors to predict caspase substrates. Sequences are first predicted for cleavage sites using CASVM or GraBCas. Predicted cleavage sites are then scored, ranked and filtered against a cut-off based on their propensities for locating in disordered and solvent exposed regions. Using an independent dataset of caspase substrates, the model was shown to achieve greater positive predictive values compared to CASVM or GraBCas alone, and was able to reduce the false positives pool by up to 13% and 53% respectively while retaining all true positives. We applied our prediction model on the family of receptor tyrosine kinases (RTKs) and highlighted several members as potential caspase targets. The results suggest that RTKs may be generally regulated by caspase cleavage and in some cases, promote the induction of apoptotic cell death - a function distinct from their role as transducers of survival and growth signals.

Conclusion

As a step towards the prediction of in vivo caspase substrates, we have developed an accurate method incorporating cleavage site prediction and structural factors. The multi-factor model augments existing methods and complements experimental efforts to define the caspase degradome on the systems-wide basis.