bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Smart Bubbles’: Selective Targeting of Ultrasound Contrast Agents
Authors: Martin Matthew J.
Published: January 2009

Targeted ultrasound contrast agents, or targeted ‘microbubbles’ are produced by conjugation of specific ligands into the bubble membrane targeting receptor sequences expressed on surfaces of interest in the body. This allows microbubbles to be retained at pathological sites in the vasculature even under physiological flow conditions. Targeted microbubbles have great potential for diagnostic imaging of inflammation, thrombosis and angiogenesis, including the imaging of transplant rejection, deep vein thrombosis and early tumour growth. Increasingly, the application of targeted bubbles for therapeutic means is also being investigated, including microbubble-enhanced sonothrombolysis of clots and targeted drug and gene delivery. Targeted ultrasound agents could be used in future for the early diagnosis of disease states such as atherosclerosis, thrombosis and organ transplant rejection. The possibility of combining the bubbles site-specific imaging applications with their potential role as therapeutic vectors makes targeted microbubbles a very promising area of research.
A Case of Antibiotic-Resistant Dorsal Hand Purulent Tenosynovitis Diagnosed by Ultrasound Post Liver Transplant
Authors: Vidili G. , Galletti S. , Piscaglia F. , Leoni S. , Borghi A. , Salvatore V. , Bolondi L.
Published: January 2009

Tenosynovitis is an inflammation of the synovial sheath surrounding a tendon. This may be caused by a variety of etiological factors. Here we describe the case of a 40 year old diabetic patient who two months after liver transplantation developed left-hand purulent tenosynovitis. Tenosynovitis was diagnosed using ultrasound, found to be caused by cryptococcus neoformans, and successfully treated using antifungal therapy combined with ultrasound follow-up.
The Ultrasound of Intravenous Drug Abuse in the Groin - Vascular and Non-vascular Complications: A Pictorial Review
Authors: Hacking Linda , West Nicky
Published: January 2009

Intravenous drug abuse is a common social and medical problem. Incidence is estimated at 9·9 per 100 000 for England. In the ultrasound department, a common referral is for ‘IVDA QDVT’ (intravenous drug abuser, query deep vein thrombosis).

Deep vein thrombosis (DVT) is a common complication of intravenous injection of drugs via the groin, but ultrasonically can present with a variety of different acute and chronic features, including complications. The groin should also be examined for other vascular and non-vascular complications. Non-vascular complications include cellulitis, sinus track formation, abscess and lymphadenitis. Vascular complications include arterial occlusion, arteriovenous fistula, pseudo-aneurysm, acute and chronic DVT, venous stenosis and complex collateral formation. The sonographer should also be aware of distant complications including endocarditis, septic pulmonary emboli and retroperitoneal extension of groin abscess.

This is an increasing diagnostic problem. The sonographer should be aware of the range of pathologies both locally and systemically and be prepared to examine the veins, arteries and soft tissues, extending the examination above the groin and using imaging modalities if findings are atypical. If necessary, the radiologist should be involved at an early stage.
Conservative Management of Multiple Ovarian Pregnancy
Authors: Moustafa Magdy M. R. , Burnham Anabelle
Published: January 2009

Ovarian ectopic pregnancy is a rare variant of ectopic implantation, which is seldom diagnosed before surgery. Here we describe a 24 year old woman who was diagnosed by ultrasound as having a multiple ovarian pregnancy. Since her symptoms were mild, the b-hCG was falling, and the serum progesterone level was suggestive of failed pregnancy, she was treated conservatively. This case may be the first report of multiple ovarian pregnancy diagnosed with ultrasound and managed conservatively.
Development and Application of an Experimental Abdominal Aortic Aneurysm Model
Authors: Baker Philip E. , Ramnarine Kumar V.
Published: January 2009

A realistic phantom model of the abdominal aortic aneurysm (AAA) is required for experimental studies of the behaviour and nature of AAA and to validate computational models of wall stress and rupture. This study was part of an MSc project which aimed to develop a suitable elastic AAA phantom. A latex AAA phantom was constructed and used in an in vitro flow model to study whether ultrasound measurements of the maximum diameter, distension and distensibility are predictors of AAA rupture. A multigate Doppler system was found to be capable of providing suitable distension measurements, but measurement of the maximum diameter was more reliable using B-mode imaging. Further work is required to help overcome the limitations of the phantom in accounting for a range of mechanical and geometrical properties, and the pathophysiological remodelling process of real AAAs.
Non-abdominal Non-thoracic Ultrasound in Cats and Dogs: Small Parts in Small Animals
Authors: Barrett E. L.
Published: January 2009

Ultrasound is widely used in small animal veterinary medicine for the investigation of cardiac disease and abdominal disorders. However, non-abdominal non-thoracic ultrasound in dogs and cats currently has a much more minor role in routine diagnostic work-ups. This article, based on a presentation given to the annual BMUS meeting in 2007, aims to provide some insight into the use of diagnostic ultrasound in evaluating the small parts of small patients.
Interpreting Echoes: Why Bats Are Better Than US
Authors: Long Chloe V
Published: January 2009

Ultrasound has been utilised by medical professionals for the past 50 years as a tool to investigate living tissue non-invasively. There have been great technological advances to increase the effectiveness of the equipment used to image with ultrasonography, but there may still be important lessons to learn from animals that similarly employ ultrasound to assess their environment, such as bats. Despite most species having good eyesight, bats are widely recognised for having a finely-tuned ability to both emit ultrasonic pulses and interpret the resulting echoes from both moving and stationary targets with pin-point accuracy. They achieve target detection, localisation and classification using a variety of methods to enhance the information extracted from the echoes of their emitted ultrasonic pulses. This paper outlines the principles of the echolocation employed by bats and provides a comparison with the features used for medical ultrasonography, highlighting the differences that allow bats to remain ahead of the field.
CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance
Authors: Kurtz Josef , Raval Forum , Vallot Casey , Der Jayden , Sykes Megan
Published: January 2009

Although the inhibitory receptor CTLA-4 (CD152) has been implicated in peripheral CD4 T-cell tolerance, its mechanism of action remains poorly defined. We analyzed mechanisms of CD4 cell tolerance in a model of tolerance induction involving establishment of mixed hematopoietic chimerism in recipients of fully MHC-mismatched allogeneic bone marrow cells with anti-CD154 mAb. Animals lacking CD80 and CD86 failed to achieve chimerism. We detected no T cell–intrinsic requirement for CD28 for chimerism induction. However, a CD4 T cell–intrinsic signal through CTLA-4 was shown to be essential within the first 48 hours of exposure to alloantigen for the establishment of tolerance and mixed chimerism. This signal must be provided by a recipient CD80/86+ non–T-cell population. Donor CD80/86 expression was insufficient to achieve tolerance. Together, our findings demonstrate a surprising role for interactions of CTLA-4 expressed by alloreactive peripheral CD4 T cells with CD80/86 on recipient antigen-presenting cells (APCs) in the induction of early tolerance, suggesting a 3-cell tolerance model involving directly alloreactive CD4 cells, donor antigen-expressing bone marrow cells, and recipient antigen-presenting cells. This tolerance is independent of regulatory T cells and culminates in the deletion of directly alloreactive CD4 T cells.
CBFβ is critical for AML1-ETO and TEL-AML1 activity
Authors: Roudaia Liya , Cheney Matthew D. , Manuylova Ekaterina , Chen Wei , Morrow Michelle , Park Sangho , Lee Chung-Tsai , Kaur Prabhjot , Williams Owen , Bushweller John H. , Speck Nancy A.
Published: January 2009

AML1-ETO and TEL-AML1 are chimeric proteins resulting from the t(8;21)(q22;q22) in acute myeloid leukemia, and the t(12;21)(p13;q22) in pre-B-cell leukemia, respectively. The Runt domain of AML1 in both proteins mediates DNA binding and heterodimerization with the core binding factor β (CBFβ) subunit. To determine whether CBFβ is required for AML1-ETO and TEL-AML1 activity, we introduced amino acid substitutions into the Runt domain that disrupt heterodimerization with CBFβ but not DNA binding. We show that CBFβ contributes to AML1-ETO's inhibition of granulocyte differentiation, is essential for its ability to enhance the clonogenic potential of primary mouse bone marrow cells, and is indispensable for its cooperativity with the activated receptor tyrosine kinase TEL-PDGFβR in generating acute myeloid leukemia in mice. Similarly, CBFβ is essential for TEL-AML1's ability to promote self-renewal of B cell precursors in vitro. These studies validate the Runt domain/CBFβ interaction as a therapeutic target in core binding factor leukemias.
Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I2analogues
Authors: Hung C-H. , Chu Y-T. , Suen J-L. , Lee M-S. , Chang H-W. , Lo Y-C. , Jong Y-J.
Published: January 2009

Plasmacytoid dendritic cells (pDCs) are critical in controlling adaptive immunity, but the mechanisms governing cytokine expression remain incompletely defined. Analogues of prostaglandin (PG)I2, such as iloprost, can modulate functions of myeloid dendritic cells, but their involvement in the regulation of human pDCs remains unknown. To this end, the regulatory role of PGI2analogues on cytokine expression in pDCs was investigated.

Circulating pDCs were magnetically sorted with BDCA-4 cell isolation kits from human peripheral blood mononuclear cells and treated with varying concentrations of iloprost with or without the addition of Toll-like receptor agonists, or an I prostanoid (IP) receptor antagonist, CAY10449. The levels of tumour necrosis factor (TNF)-α, interferon (IFN)-α and interleukin (IL)-10 were measured by ELISA.

Iloprost induced IL-10 expression, but suppressed CpG oligodeoxynucleotide- (or imiquimod-) induced TNF-α and IFN-α production in pDCs. This effect was reversed by the addition of CAY10449. Forskolin, a cyclic adenosine monophosphate activator, conferred a similar modulating effect to that noted in iloprost-treated pDCs, although a higher concentration of forskolin was required to exert the same effect.

Iloprost enhanced interleukin-10 and suppressed Toll-like receptor-mediated tumour necrosis factor-α and interferon-α production of human plasmacytoid dendritic cellsviathe I prostanoid receptor and, in part, the cyclic adenosine monophosphate pathway.
Nonpharmacological smoking cessation interventions in clinical practice
Authors: Cornuz J. , Willi C.
Published: January 2009

Doctors and other healthcare professionals are in a unique position to advise smokers to quit by their ability to integrate the various aspects of an effective counselling. The present review provides an overview of nonpharmacological interventions for smokers presenting in a clinical setting. Strategies used for smoking cessation counselling differ according to the patient's readiness to quit. For smokers who do not intend to quit smoking, physicians should inform and sensitise about tobacco use and cessation. For smokers who are dissonant, physicians should use motivational strategies, such as discussing barriers to cessation and their solutions. For smokers ready to quit, the physician should show strong support and help set a cessation date. Physician counselling for smoking cessation is among the most cost-effective clinical interventions.
Nitric oxide gas phase release in human small airway epithelial cells
Authors: Jiang Jingjing , Malavia Nikita , Suresh Vinod , George Steven C
Published: January 2009

Background

Asthma is a chronic airway inflammatory disease characterized by an imbalance in both Th1 and Th2 cytokines. Exhaled nitric oxide (NO) is elevated in asthma, and is a potentially useful non-invasive marker of airway inflammation. However, the origin and underlying mechanisms of intersubject variability of exhaled NO are not yet fully understood. We have previously described NO gas phase release from normal human bronchial epithelial cells (NHBEs, tracheal origin). However, smaller airways are the major site of morbidity in asthma. We hypothesized that IL-13 or cytomix (IL-1β, TNF-α, and IFN-γ) stimulation of differentiated small airway epithelial cells (SAECs, generation 10–12) and A549 cells (model cell line of alveolar type II cells) in culture would enhance NO gas phase release.

Methods

Confluent monolayers of SAECs and A549 cells were cultured in Transwell plates and SAECs were allowed to differentiate into ciliated and mucus producing cells at an air-liquid interface. The cells were then stimulated with IL-13 (10 ng/mL) or cytomix (10 ng/mL for each cytokine). Gas phase NO release in the headspace air over the cells was measured for 48 hours using a chemiluminescence analyzer.

Results

In contrast to our previous result in NHBE, baseline NO release from SAECs and A549 is negligible. However, NO release is significantly increased by cytomix (0.51 ± 0.18 and 0.29 ± 0.20 pl.s-1.cm-2, respectively) reaching a peak at approximately 10 hours. iNOS protein expression increases in a consistent pattern both temporally and in magnitude. In contrast, IL-13 only modestly increases NO release in SAECs reaching a peak (0.06 ± 0.03 pl.s-1.cm-2) more slowly (30 to 48 hours), and does not alter NO release in A549 cells.

Conclusion

We conclude that the airway epithelium is a probable source of NO in the exhaled breath, and intersubject variability may be due, in part, to variability in the type (Th1 vs Th2) and location (large vs small airway) of inflammation.
STAMP: Extensions to the STADEN sequence analysis package for high throughput interactive microsatellite marker design
Authors: Kraemer Lars , Beszteri Bánk , Gäbler-Schwarz Steffi , Held Christoph , Leese Florian , Mayer Christoph , Pöhlmann Kevin , Frickenhaus Stephan
Published: January 2009

Background

Microsatellites (MSs) are DNA markers with high analytical power, which are widely used in population genetics, genetic mapping, and forensic studies. Currently available software solutions for high-throughput MS design (i) have shortcomings in detecting and distinguishing imperfect and perfect MSs, (ii) lack often necessary interactive design steps, and (iii) do not allow for the development of primers for multiplex amplifications. We present a set of new tools implemented as extensions to the STADEN package, which provides the backbone functionality for flexible sequence analysis workflows. The possibility to assemble overlapping reads into unique contigs (provided by the base functionality of the STADEN package) is important to avoid developing redundant markers, a feature missing from most other similar tools.

Results

Our extensions to the STADEN package provide the following functionality to facilitate microsatellite (and also minisatellite) marker design: The new modules (i) integrate the state-of-the-art tandem repeat detection and analysis software PHOBOS into workflows, (ii) provide two separate repeat detection steps – with different search criteria – one for masking repetitive regions during assembly of sequencing reads and the other for designing repeat-flanking primers for MS candidate loci, (iii) incorporate the widely used primer design program PRIMER 3 into STADEN workflows, enabling the interactive design and visualization of flanking primers for microsatellites, and (iv) provide the functionality to find optimal locus- and primer pair combinations for multiplex primer design. Furthermore, our extensions include a module for storing analysis results in an SQLite database, providing a transparent solution for data access from within as well as from outside of the STADEN Package.

Conclusion

The STADEN package is enhanced by our modules into a highly flexible, high-throughput, interactive tool for conventional and multiplex microsatellite marker design. It gives the user detailed control over the workflow, enabling flexible combinations of manual and automated analysis steps. The software is available under the OpenBSD License [1, 2]. The high efficiency of our automated marker design workflow has been confirmed in three microsatellite development projects.
ModuleDigger: an itemset mining framework for the detection of cis-regulatory modules
Authors: Sun Hong , De Bie Tijl , Storms Valerie , Fu Qiang , Dhollander Thomas , Lemmens Karen , Verstuyf Annemieke , De Moor Bart , Marchal Kathleen
Published: January 2009

Background

The detection of cis-regulatory modules (CRMs) that mediate transcriptional responses in eukaryotes remains a key challenge in the postgenomic era. A CRM is characterized by a set of co-occurring transcription factor binding sites (TFBS). In silico methods have been developed to search for CRMs by determining the combination of TFBS that are statistically overrepresented in a certain geneset. Most of these methods solve this combinatorial problem by relying on computational intensive optimization methods. As a result their usage is limited to finding CRMs in small datasets (containing a few genes only) and using binding sites for a restricted number of transcription factors (TFs) out of which the optimal module will be selected.

Results

We present an itemset mining based strategy for computationally detecting cis-regulatory modules (CRMs) in a set of genes. We tested our method by applying it on a large benchmark data set, derived from a ChIP-Chip analysis and compared its performance with other well known cis-regulatory module detection tools.

Conclusion

We show that by exploiting the computational efficiency of an itemset mining approach and combining it with a well-designed statistical scoring scheme, we were able to prioritize the biologically valid CRMs in a large set of coregulated genes using binding sites for a large number of potential TFs as input.
Co-evolution positions and rules for antigenic variants of human influenza A/H3N2 viruses
Authors: Huang Jhang-Wei , King Chwan-Chuen , Yang Jinn-Moon
Published: January 2009

Background

In pandemic and epidemic forms, avian and human influenza viruses often cause significant damage to human society and economics. Gradually accumulated mutations on hemagglutinin (HA) cause immunologically distinct circulating strains, which lead to the antigenic drift (named as antigenic variants). The "antigenic variants" often requires a new vaccine to be formulated before each annual epidemic. Mapping the genetic evolution to the antigenic drift of influenza viruses is an emergent issue to public health and vaccine development

Results

We developed a method for identifying antigenic critical amino acid positions, rules, and co-mutated positions for antigenic variants. The information gain (IG) and the entropy are used to measure the score of an amino acid position on hemagglutinin (HA) for discriminating between antigenic variants and similar viruses. A position with high IG and entropy implied that this position is highly correlated to an antigenic drift. Nineteen positions with high IG and high genetic diversity are identified as antigenic critical positions on the HA proteins. Most of these antigenic critical positions are located on five epitopes or on the surface based on the HA structure. Based on IG values and entropies of these 19 positions on the HA, the decision tree was applied to create a rule-based model and to identify rules for predicting antigenic variants of a given two HA sequences which are often a vaccine strain and a circulating strain. The predicting accuracies of this model on two sets, which consist of a training set (181 hemagglutination inhibition (HI) assays) and an independent test set (31,878 HI assays), are 91.2% and 96.2% respectively.

Conclusion

Our method is able to identify critical positions, rules, and co-mutated positions on HA for predicting the antigenic variants. The information gains and the entropies of HA positions provide insight to the antigenic drift and co-evolution positions for influenza seasons. We believe that our method is robust and is potential useful for studying influenza virus evolution and vaccine development.
Predicting disordered regions in proteins using the profiles of amino acid indices
Authors: Han Pengfei , Zhang Xiuzhen , Feng Zhi-Ping
Published: January 2009

Background

Intrinsically unstructured or disordered proteins are common and functionally important. Prediction of disordered regions in proteins can provide useful information for understanding protein function and for high-throughput determination of protein structures.

Results

In this paper, algorithms are presented to predict long and short disordered regions in proteins, namely the long disordered region prediction algorithm DRaai-L and the short disordered region prediction algorithm DRaai-S. These algorithms are developed based on the Random Forest machine learning model and the profiles of amino acid indices representing various physiochemical and biochemical properties of the 20 amino acids.

Conclusion

Experiments on DisProt3.6 and CASP7 demonstrate that some sets of the amino acid indices have strong association with the ordered and disordered status of residues. Our algorithms based on the profiles of these amino acid indices as input features to predict disordered regions in proteins outperform that based on amino acid composition and reduced amino acid composition, and also outperform many existing algorithms. Our studies suggest that the profiles of amino acid indices combined with the Random Forest learning model is an important complementary method for pinpointing disordered regions in proteins.
Towards comprehensive structural motif mining for better fold annotation in the "twilight zone" of sequence dissimilarity
Authors: Jia Yi , Huan Jun , Buhr Vincent , Zhang Jintao , Carayannopoulos Leonidas N
Published: January 2009

Background

Automatic identification of structure fingerprints from a group of diverse protein structures is challenging, especially for proteins whose divergent amino acid sequences may fall into the "twilight-" or "midnight-" zones where pair-wise sequence identities to known sequences fall below 25% and sequence-based functional annotations often fail.

Results

Here we report a novel graph database mining method and demonstrate its application to protein structure pattern identification and structure classification. The biologic motivation of our study is to recognize common structure patterns in "immunoevasins", proteins mediating virus evasion of host immune defense. Our experimental study, using both viral and non-viral proteins, demonstrates the efficiency and efficacy of the proposed method.

Conclusion

We present a theoretic framework, offer a practical software implementation for incorporating prior domain knowledge, such as substitution matrices as studied here, and devise an efficient algorithm to identify approximate matched frequent subgraphs. By doing so, we significantly expanded the analytical power of sophisticated data mining algorithms in dealing with large volume of complicated and noisy protein structure data. And without loss of generality, choice of appropriate compatibility matrices allows our method to be easily employed in domains where subgraph labels have some uncertainty.
A computational analysis of SARS cysteine proteinase-octapeptide substrate interaction: implication for structure and active site binding mechanism
Authors: Phakthanakanok Krongsakda , Ratanakhanokchai Khanok , Kyu Khin Lay , Sompornpisut Pornthep , Watts Aaron , Pinitglang Surapong
Published: January 2009

Background

SARS coronavirus main proteinase (SARS CoVMpro) is an important enzyme for the replication of Severe Acute Respiratory Syndrome virus. The active site region of SARS CoVMpro is divided into 8 subsites. Understanding the binding mode of SARS CoVMpro with a specific substrate is useful and contributes to structural-based drug design. The purpose of this research is to investigate the binding mode between the SARS CoVMpro and two octapeptides, especially in the region of the S3 subsite, through a molecular docking and molecular dynamics (MD) simulation approach.

Results

The one turn α-helix chain (residues 47–54) of the SARS CoVMpro was directly involved in the induced-fit model of the enzyme-substrate complex. The S3 subsite of the enzyme had a negatively charged region due to the presence of Glu47. During MD simulations, Glu47 of the enzyme was shown to play a key role in electrostatic bonding with the P3Lys of the octapeptide.

Conclusion

MD simulations were carried out on the SARS CoVMpro-octapeptide complex. The hypothesis proposed that Glu47 of SARS CoVMpro is an important residue in the S3 subsite and is involved in binding with P3Lys of the octapeptide.
Quality assessment of tandem mass spectra using support vector machine (SVM)
Authors: Zou An-Min , Wu Fang-Xiang , Ding Jia-Rui , Poirier Guy G
Published: January 2009

Background

Tandem mass spectrometry has become particularly useful for the rapid identification and characterization of protein components of complex biological mixtures. Powerful database search methods have been developed for the peptide identification, such as SEQUEST and MASCOT, which are implemented by comparing the mass spectra obtained from unknown proteins or peptides with theoretically predicted spectra derived from protein databases. However, the majority of spectra generated from a mass spectrometry experiment are of too poor quality to be interpreted while some of spectra with high quality cannot be interpreted by one method but perhaps by others. Hence a filtering algorithm that removes those spectra with poor quality prior to the database search is appealing.

Results

This paper proposes a support vector machine (SVM) based approach to assess the quality of tandem mass spectra. Each mass spectrum is mapping into the 16 proposed features to describe its quality. Based the results from SEQUEST, four SVM classifiers with the input of the 16 features are trained and tested on ISB data and TOV data, respectively. The superior performance of the proposed SVM classifiers is illustrated both by the comparison with the existing classifiers and by the validation in terms of MASCOT search results.

Conclusion

The proposed method can be employed to effectively remove the poor quality spectra before the spectral searching, and also to find the more peptides or post-translational peptides from spectra with high quality using different search engines or de novo method.
Comparative analysis of the JAK/STAT signaling through erythropoietin receptor and thrombopoietin receptor using a systems approach
Authors: Won Hong-Hee , Park Inho , Lee Eunjung , Kim Jong-Won , Lee Doheon
Published: January 2009

Background

The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway is one of the most important targets for myeloproliferative disorder (MPD). Although several efforts toward modeling the pathway using systems biology have been successful, the pathway was not fully investigated in regard to understanding pathological context and to model receptor kinetics and mutation effects.

Results

We have performed modeling and simulation studies of the JAK/STAT pathway, including the kinetics of two associated receptors (the erythropoietin receptor and thrombopoietin receptor) with the wild type and a recently reported mutation (JAK2V617F) of the JAK2 protein.

Conclusion

We found that the different kinetics of those two receptors might be important factors that affect the sensitivity of JAK/STAT signaling to the mutation effect. In addition, our simulation results support clinically observed pathological differences between the two subtypes of MPD with respect to the JAK2V617F mutation.
Extract interaction detection methods from the biological literature
Authors: Wang Hongning , Huang Minlie , Zhu Xiaoyan
Published: January 2009

Background

Considerable efforts have been made to extract protein-protein interactions from the biological literature, but little work has been done on the extraction of interaction detection methods. It is crucial to annotate the detection methods in the literature, since different detection methods shed different degrees of reliability on the reported interactions. However, the diversity of method mentions in the literature makes the automatic extraction quite challenging.

Results

In this article, we develop a generative topic model, the Correlated Method-Word model (CMW model) to extract the detection methods from the literature. In the CMW model, we formulate the correlation between the different methods and related words in a probabilistic framework in order to infer the potential methods from the given document. By applying the model on a corpus of 5319 full text documents annotated by the MINT and IntAct databases, we observe promising results, which outperform the best result reported in the BioCreative II challenge evaluation.

Conclusion

From the promising experiment results, we can see that the CMW model overcomes the issues caused by the diversity in the method mentions and properly captures the in-depth correlations between the detection methods and related words. The performance outperforming the baseline methods confirms that the dependence assumptions of the model are reasonable and the model is competent for the practical processing.
Maximum independent sets of commuting and noninterfering inversions
Authors: Swenson Krister M , To Yokuki , Tang Jijun , Moret Bernard ME
Published: January 2009

Background

Given three signed permutations, an inversion median is a fourth permutation that minimizes the sum of the pairwise inversion distances between it and the three others. This problem is NP-hard as well as hard to approximate. Yet median-based approaches to phylogenetic reconstruction have been shown to be among the most accurate, especially in the presence of long branches. Most existing approaches have used heuristics that attempt to find a longest sequence of inversions from one of the three permutations that, at each step in the sequence, moves closer to the other two permutations; yet very little is known about the quality of solutions returned by such approaches.

Results

Recently, Arndt and Tang took a step towards finding longer such sequences by using sets of commuting inversions. In this paper, we formalize the problem of finding such sequences of inversions with what we call signatures and provide algorithms to find maximum cardinality sets of commuting and noninterfering inversions.

Conclusion

Our results offer a framework in which to study the inversion median problem, faster algorithms to obtain good medians, and an approach to study characteristic events along an evolutionary path.
Identifying disease associations via genome-wide association studies
Authors: Huang Wenhui , Wang Pengyuan , Liu Zhen , Zhang Liqing
Published: January 2009

Background

Genome-wide association studies prove to be a powerful approach to identify the genetic basis of different human diseases. We studied the relationship between seven diseases characterized in a previous genome-wide association study by the Wellcome Trust Case Control Consortium. Instead of doing a horizontal association of SNPs to diseases, we did a vertical analysis of disease associations by comparing the genetic similarities of diseases. Our analysis was carried out at four levels – the nucleotide level (SNPs), the gene level, the protein level (through protein-protein interaction network), and the phenotype level.

Results

Our results show that Crohn's disease, rheumatoid arthritis, and type 1 diabetes share evidence of genetic associations at all levels of analysis, offering strong molecular support for the current grouping of the diseases. On the other hand, coronary artery disease, hypertension, and type 2 diabetes, despite being considered as a natural group with potential aetiological overlap, do not show any evidence of shared genetic basis at all levels.

Conclusion

Our study is a first attempt on mining of GWA data to examine genetic associations between different diseases. The positive result is apparently not a coincidence and hence demonstrates the promising use of our approach.
Triplet supertree heuristics for the tree of life
Authors: Lin Harris T , Burleigh J Gordon , Eulenstein Oliver
Published: January 2009

Background

There is much interest in developing fast and accurate supertree methods to infer the tree of life. Supertree methods combine smaller input trees with overlapping sets of taxa to make a comprehensive phylogenetic tree that contains all of the taxa in the input trees. The intrinsically hard triplet supertree problem takes a collection of input species trees and seeks a species tree (supertree) that maximizes the number of triplet subtrees that it shares with the input trees. However, the utility of this supertree problem has been limited by a lack of efficient and effective heuristics.

Results

We introduce fast hill-climbing heuristics for the triplet supertree problem that perform a step-wise search of the tree space, where each step is guided by an exact solution to an instance of a local search problem. To realize time efficient heuristics we designed the first nontrivial algorithms for two standard search problems, which greatly improve on the time complexity to the best known (naïve) solutions by a factor ofnandn2(the number of taxa in the supertree). These algorithms enable large-scale supertree analyses based on the triplet supertree problem that were previously not possible. We implemented hill-climbing heuristics that are based on our new algorithms, and in analyses of two published supertree data sets, we demonstrate that our new heuristics outperform other standard supertree methods in maximizing the number of triplets shared with the input trees.

Conclusion

With our new heuristics, the triplet supertree problem is now computationally more tractable for large-scale supertree analyses, and it provides a potentially more accurate alternative to existing supertree methods.
Sequence mining and transcript profiling to explore cyst nematode parasitism
Authors: Elling Axel A , Mitreva Makedonka , Gai Xiaowu , Martin John , Recknor Justin , Davis Eric L , Hussey Richard S , Nettleton Dan , McCarter James P , Baum Thomas J
Published: January 2009

Background

Cyst nematodes are devastating plant parasites that become sedentary within plant roots and induce the transformation of normal plant cells into elaborate feeding cells with the help of secreted effectors, the parasitism proteins. These proteins are the translation products of parasitism genes and are secreted molecular tools that allow cyst nematodes to infect plants.

Results

We present here the expression patterns of all previously described parasitism genes of the soybean cyst nematode,Heterodera glycines, in all major life stages except the adult male. These insights were gained by analyzing our gene expression dataset from experiments using the Affymetrix Soybean Genome Array GeneChip, which contains probeset sequences for 6,860 genes derived from preparasitic and parasiticH. glycineslife stages. Targeting the identification of additionalH. glycinesparasitism-associated genes, we isolated 633 genes encoding secretory proteins using algorithms to predict secretory signal peptides. Furthermore, because some of the knownH. glycinesparasitism proteins have strongest similarity to proteins of plants and microbes, we searched for predicted protein sequences that showed their highest similarities to plant or microbial proteins and identified 156H. glycinesgenes, some of which also contained a signal peptide. Analyses of the expression profiles of these genes allowed the formulation of hypotheses about potential roles in parasitism. This is the first study combining sequence analyses of a substantial EST dataset with microarray expression data of all major life stages (except adult males) for the identification and characterization of putative parasitism-associated proteins in any parasitic nematode.

Conclusion

We have established an expression atlas for all knownH. glycinesparasitism genes. Furthermore, in an effort to identify additionalH. glycinesgenes with putative functions in parasitism, we have reduced the currently known 6,860H. glycinesgenes to a pool of 788 most promising candidate genes (including known parasitism genes) and documented their expression profiles. Using our approach to pre-select genes likely involved in parasitism now allows detailed functional analyses in a manner not feasible for larger numbers of genes. The generation of the candidate pool described here is an important enabling advance because it will significantly facilitate the unraveling of fascinating plant-animal interactions and deliver knowledge that can be transferred to other pathogen-host systems. Ultimately, the exploration of true parasitism genes verified from the gene pool delineated here will identify weaknesses in the nematode life cycle that can be exploited by novel anti-nematode efforts.
Development of a multi-locus sequence typing scheme for Laribacter hongkongensis, a novel bacterium associated with freshwater fish-borne gastroenteritis and traveler's diarrhea
Authors: Woo Patrick CY , Teng Jade LL , Tsang Alan KL , Tse Herman , Tsang Vivien YM , Chan King-Man , Lee Edwin KY , Chan Jim KH , Ma Shirley SL , Tam Dorothy MW , Chung Liliane MW , Lau Susanna KP , Yuen Kwok-Yung
Published: January 2009

Background

Laribacter hongkongensis is a newly discovered, facultative anaerobic, Gram-negative, motile, sea gull-shaped rod associated with freshwater fish borne gastroenteritis and traveler's diarrhea. A highly reproducible and discriminative typing system is essential for better understanding of the epidemiology of L. hongkongensis. In this study, a multilocus sequence typing (MLST) system was developed for L. hongkongensis. The system was used to characterize 146 L. hongkongensis isolates, including 39 from humans and 107 from fish.

Results

Fragments (362 to 504 bp) of seven housekeeping genes were amplified and sequenced. Among the 3068 bp of the seven loci, 332 polymorphic sites were observed. The median number of alleles at each locus was 34 [range 22 (ilvC) to 45 (thiC)]. All seven genes showed very low d

n
/d

s
ratios of < 0.04, indicating that no strong positive selective pressure is present. A total of 97 different sequence types (STs) were assigned to the 146 isolates, with 80 STs identified only once. The overall discriminatory power was 0.9861. eBURST grouped the isolates into 12 lineages, with six groups containing only isolates from fish and three groups only isolates from humans. Standardized index of association (I

S

A
) measurement showed significant linkage disequilibrium in isolates from both humans and fish. The I

S

A
for the isolates from humans and fish were 0.270 and 0.636, indicating the isolates from fish were more clonal than the isolates from humans. Only one interconnected network (acnB) was detected in the split graphs. The P-value (P = 0) of sum of the squares of condensed fragments in Sawyer's test showed evidence of intragenic recombination in the rho, acnB and thiC loci, but the P-value (P = 1) of maximum condensed fragment in these gene loci did not show evidence of intragenic recombination. Congruence analysis showed that all the pairwise comparisons of the 7 MLST loci were incongruent, indicating that recombination played a substantial role in the evolution of L. hongkongensis. A website for L. hongkongensis MLST was set up and can be accessed at http://mlstdb.hku.hk:14206/MLST_index.html.

Conclusion

A highly reproducible and discriminative MLST system was developed for L. hongkongensis.
Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis
Authors: Le Thuc T , Huff Terry B , Cheng Ji-Xin
Published: January 2009

Background

Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development.

Methods

Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments.

Results

CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells.

Conclusion

Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis.
Ab initio and template-based prediction of multi-class distance maps by two-dimensional recursive neural networks
Authors: Walsh Ian , Baù Davide , Martin Alberto JM , Mooney Catherine , Vullo Alessandro , Pollastri Gianluca
Published: January 2009

Background

Prediction of protein structures from their sequences is still one of the open grand challenges of computational biology. Some approaches to protein structure prediction, especially ab initio ones, rely to some extent on the prediction of residue contact maps. Residue contact map predictions have been assessed at the CASP competition for several years now. Although it has been shown that exact contact maps generally yield correct three-dimensional structures, this is true only at a relatively low resolution (3–4 Å from the native structure). Another known weakness of contact maps is that they are generally predicted ab initio, that is not exploiting information about potential homologues of known structure.

Results

We introduce a new class of distance restraints for protein structures: multi-class distance maps. We show that C
α
trace reconstructions based on 4-class native maps are significantly better than those from residue contact maps. We then build two predictors of 4-class maps based on recursive neural networks: one ab initio, or relying on the sequence and on evolutionary information; one template-based, or in which homology information to known structures is provided as a further input. We show that virtually any level of sequence similarity to structural templates (down to less than 10%) yields more accurate 4-class maps than the ab initio predictor. We show that template-based predictions by recursive neural networks are consistently better than the best template and than a number of combinations of the best available templates. We also extract binary residue contact maps at an 8 Å threshold (as per CASP assessment) from the 4-class predictors and show that the template-based version is also more accurate than the best template and consistently better than the ab initio one, down to very low levels of sequence identity to structural templates. Furthermore, we test both ab-initio and template-based 8 Å predictions on the CASP7 targets using a pre-CASP7 PDB, and find that both predictors are state-of-the-art, with the template-based one far outperforming the best CASP7 systems if templates with sequence identity to the query of 10% or better are available. Although this is not the main focus of this paper we also report on reconstructions of C
α
traces based on both ab initio and template-based 4-class map predictions, showing that the latter are generally more accurate even when homology is dubious.

Conclusion

Accurate predictions of multi-class maps may provide valuable constraints for improved ab initio and template-based prediction of protein structures, naturally incorporate multiple templates, and yield state-of-the-art binary maps. Predictions of protein structures and 8 Å contact maps based on the multi-class distance map predictors described in this paper are freely available to academic users at the url http://distill.ucd.ie/.
Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to prioritize host targets for antiviral drug screening
Authors: Schneider Konstantin , Krömer Jens Olaf , Wittmann Christoph , Alves-Rodrigues Isabel , Meyerhans Andreas , Diez Juana , Heinzle Elmar
Published: January 2009

Background

The cellular proteins Pat1p, Lsm1p, and Dhh1p are required for the replication of some positive-strand viruses and therefore are potential targets for new antiviral drugs. To prioritize host targets for antiviral drug screening a comparative metabolome analysis in Saccharomyces cerevisiae reference strain BY4742 Matα his3Δ1 leu2Δ0 lys2Δ0 ura3Δ0 and deletion strains pat1Δ, lsm1Δ and dhh1Δ was performed.

Results

GC/MS analysis permitted the quantification of 47 polar metabolites and the identification of 41 of them. Metabolites with significant variation between the strains were identified using partial least squares to latent structures discriminate analysis (PLS-DA). The analysis revealed least differences of pat1Δ to the reference strain as characterized by Euclidian distance of normalized peak areas. The growth rate and specific production rates of ethanol and glycerol were also most similar with this strain.

Conclusion

From these results we hypothesize that the human analog of yeast Pat1p is most likely the best drug target candidate.