bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Regimes in Health Care: Institutions, Critical Junctures and the Logic of Escalation in England and the Netherlands
Authors: Pollitt Christopher , Harrison Stephen , Dowswell George , Jerak-Zuiderent Sonja , Bal Roland
Published: January 2010

The Netherlands and England are near neighbours whose health care systems have much in common and whose health policy communities have also usually been well aware of what is going on in the other country. Nevertheless, for the two decades from 1982, England adopted and repeatedly redeveloped performance indicator (PI) systems in the health care field while the Netherlands virtually shunned them. A broad institutional explanation for this divergence is provided by England’s majoritarian and adversarial political system that leaves governments with fewer constraints and compromises than in the more consociational Dutch system. More recently, however, a Dutch national system of health care PIs has appeared, suggesting that this explanation needs to be supplemented. This paper draws on an empirical study of PI systems in the two countries over the period from 1982 to 2007 to suggest that two further factors are at work. Established institutional patterns may be disrupted by ‘punctuations’, while technical and political factors endogenous to PI systems may exert a logic of their own.
International Comparison of Public Sector Performance: The Use of Anchoring Vignettes to adjust Self-Reported Data
Authors: Rice Nigel , Robone Silvana , Smith Peter C.
Published: January 2010

International comparison of performance has become an influential lever for change in the provision of public services. For health care, patients’ views and opinions are increasingly being recognized as legitimate means for assessing the provision of services, to stimulate quality improvements, and more recently, in evaluating system performance. This has shifted the focus of analyses towards the use of individual-level surveys of performance from the perspective of the user and raises the issue of how to compare appropriately self-reported data across institutional settings and population groups. Using data on health systems responsiveness across 17 EU countries contained within the World Health Survey, this paper outlines the issues that arise in comparative inference that relies on respondent self-reports. The problem of systematic reporting behaviour is described and illustrated together with potential solutions brought about through the use of anchoring vignettes. Our results show large differences in the rankings of country performance once adjustment for systematic country-level reporting behaviour has been undertaken compared to the ranking observed in the raw unadjusted data. The use of anchoring vignettes as a means to obtain comparability in self-reported survey instruments of performance promises to be a fundamental tool for international comparative research.
City Planning and Infrastructure: Once and Future Partners
Authors: Neuman Michael , Smith Sheri
Published: January 2010

Great cities are born of and give rise to great infrastructure. Historically, city planning has been deeply rooted in infrastructure and physical planning. One of its ontological bases has been to create urban place out of space through the intermediary of infrastructure. Currently, the links between infrastructure and city planning may be described as numerous but nonstrategic and noncomprehensive, even as the bond between infrastructure and cities remains tight. In part, this is because the planning profession has left key roles in infrastructure to other professions. This article chronicles the rises and falls in the fortunes of urban infrastructure in relation to city planning.
Historical legacy, social memory and representations of the past within a Polish community
Authors: Hewer Christopher J. , Kut Malgorzata
Published: January 2010

Shared representations of national history play a significant role in the construction of social memory and the development of a common cultural worldview. Representations of 20th-century history studied within a small Polish community in the UK with respect to their content, meaning and effect on identity produced themes of injustice, abandonment, betrayal by the West, trauma and victimization, which continue to evoke strong emotions. The simplified, subjective and selective nature of historical representations was evident in the way in which a legitimate and coherent narrative on key aspects of the past was accompanied by omissions, contradictions and a lack of clarity on other aspects of the same period. The past continues to weigh on the present for a new generation of Poles, which demonstrates that historical legacy remains a significant factor in the social psychological analysis of mind, identity, social action and international relations.
Endotoxin recognition in fish results in inflammatory cytokine secretion not gene expression
Authors: Roher Nerea , Callol Agnes , Planas Josep V. , Goetz Frederick W. , MacKenzie Simon A.
Published: January 2010

Macrophages are phagocytes that have a central role in the organization of the immune system after an infection. These cells can recognize specific molecular components of micro-organisms (pathogen-associated molecular patterns, PAMPs) via specific receptors (PRRs) and elicit specific cellular responses. In the past, the expression of immune genes in response to different PAMPs has been characterized in different fish species. However, little is known about actual cytokine release. We characterized the secretion of tumour necrosis factor (TNF)-α in primary macrophage cultures of rainbow trout (Oncorhynchus mykiss) in response to several PAMPs by Western blot and compared this to the induction of TNF-α gene expression as well as other pro-inflammatory cytokines such as interleukin (IL)-1β and IL-6 and anti-viral molecules such as INF-α and Mx protein (Mx). We show that lipopolysaccharide (LPS) and zymosan are major inducers of TNF-α secretion, which is not initially linked to the induction of TNF-α mRNA expression. The secretion of TNF-α, but intriguingly not the expression, is also stimulated by ultrapure LPS meaning that, in fish, contaminants of commercial LPS preparations are better inducers of the inflammatory response. Moreover, we have characterized the signaling pathways that are activated by different PAMPs and the link between those pathways and the final step of TNF-α secretion: TNF-α shedding by TNF-α converting enzyme (TACE/ ADAM17). For the first time, we show that, in fish macrophages, TNF-α is processed by TACE-like activity and this cleavage is dependent upon the activation of ERK, p38MAPK and JNK signaling pathways by LPS.
Analgesic effects of chemically synthesized NOD1 and NOD2 agonists in mice
Authors: Sato Tadasu , Shikama Yosuke , Shimauchi Hidetoshi , Endo Yasuo , Takada Haruhiko
Published: January 2010

Intracellular nucleotide-binding oligomerization domain (NOD)-like receptors, NOD1 and NOD2, recognize the diaminopimelic acid (DAP)-containing peptide moiety and muramyldipeptide (MDP) moiety of bacterial peptidoglycan, respectively. Muramyldipeptide has been reported to exert analgesic activity to decrease the frequency of acetic acid-induced writhing movements in mice. In this study, we demonstrated the analgesic activities of NOD1 as well as NOD2 agonists. Intravenous injection of NOD2-agonistic MDP, 6-O-stearoyl-MDP (L18-MDP), and MDP-Lys (L18) exhibited analgesic activity at 10, 50, and 2.0 µg/head, respectively, in BALB/c mice. NOD1-Agonistic FK156 (D-lactyl-L-Ala-D-Glu-meso-DAP-L-Gly) and FK565 (heptanoyl-D-Glu-meso-DAP-D-Ala) were also analgesic at 50 µg/head and 1.0 µg/head, respectively. The analgesic effect of FK565 appeared from 30 min, reached maximum activity at 8 h, and continued until 24 h. The FK565 exhibited activity by various administration routes; intravenous, intraperitoneal, intramuscular, sublingual (1.0 µg/head each), subcutaneous, intragastric (oral), intragingival (10 µg/ head each) and intracerebroventricular (0.01 µg/head). The analgesic activity of FK565 was observed even in tumor necrosis factor (TNF)-α knockout, interleukin (IL)-1α/β double knockout, and their triple knockout mice. Naloxane, a non-selective antagonist for the opioid receptor, completely inhibited the analgesic effect of FK565. These findings suggest that NOD1 and NOD2 activation induces an analgesic effect via opioid receptors in a TNF-α and IL-1α/βindependent manner.
Review: Optimal use of biologics in the management of Crohn’s disease
Authors: Panaccione Remo , Ghosh Subrata
Published: January 2010

Crohn’s disease (CD) is a chronic relapsing and remitting disorder of the gastrointestinal tract with no known cure. The inflammation that drives the disease can lead to debilitating symptoms and a number of complications that may lead to surgery. The introduction of biologic therapy a decade ago has offered a new option for patients failing conventional therapy. Over time, biologic therapy has also led to the desire to achieve treatment goals beyond the control of symptoms. In order to achieve short-term and long-term goals with these new agents, it is important to review how these therapies may be optimized for the best results.
Identification of inhibitors of Plasmodium falciparum phosphoethanolamine methyltransferase using an enzyme-coupled transmethylation assay
Authors: Bobenchik April M , Choi Jae-Yeon , Mishra Arunima , Rujan Iulian N , Hao Bing , Voelker Dennis R , Hoch Jeffrey C , Mamoun Choukri Ben
Published: January 2010

Background

The phosphoethanolamine methyltransferase, PfPMT, of the human malaria parasite Plasmodium falciparum, a member of a newly identified family of phosphoethanolamine methyltransferases (PMT) found solely in some protozoa, nematodes, frogs, and plants, is involved in the synthesis of the major membrane phospholipid, phosphatidylcholine. PMT enzymes catalyze a three-step S-adenosylmethionine-dependent methylation of the nitrogen atom of phosphoethanolamine to form phosphocholine. In P. falciparum, this activity is a limiting step in the pathway of synthesis of phosphatidylcholine from serine and plays an important role in the development, replication and survival of the parasite within human red blood cells.

Results

We have employed an enzyme-coupled methylation assay to screen for potential inhibitors of PfPMT. In addition to hexadecyltrimethylammonium, previously known to inhibit PfPMT, two compounds dodecyltrimethylammonium and amodiaquine were also found to inhibit PfPMT activity in vitro. Interestingly, PfPMT activity was not inhibited by the amodiaquine analog, chloroquine, or other aminoquinolines, amino alcohols, or histamine methyltransferase inhibitors. Using yeast as a surrogate system we found that unlike wild-type cells, yeast mutants that rely on PfPMT for survival were sensitive to amodiaquine, and their phosphatidylcholine biosynthesis was inhibited by this compound. Furthermore NMR titration studies to characterize the interaction between amoidaquine and PfPMT demonstrated a specific and concentration dependent binding of the compound to the enzyme.

Conclusion

The identification of amodiaquine as an inhibitor of PfPMT in vitro and in yeast, and the biophysical evidence for the specific interaction of the compound with the enzyme will set the stage for the development of analogs of this drug that specifically inhibit this enzyme and possibly other PMTs.
Prediction of novel miRNAs and associated target genes in Glycine max
Authors: Joshi Trupti , Yan Zhe , Libault Marc , Jeong Dong-Hoon , Park Sunhee , Green Pamela J , Sherrier D Janine , Farmer Andrew , May Greg , Meyers Blake C , Xu Dong , Stacey Gary
Published: January 2010

Background

Small non-coding RNAs (21 to 24 nucleotides) regulate a number of developmental processes in plants and animals by silencing genes using multiple mechanisms. Among these, the most conserved classes are microRNAs (miRNAs) and small interfering RNAs (siRNAs), both of which are produced by RNase III-like enzymes called Dicers. Many plant miRNAs play critical roles in nutrient homeostasis, developmental processes, abiotic stress and pathogen responses. Currently, only 70 miRNA have been identified in soybean.

Methods

We utilized Illumina's SBS sequencing technology to generate high-quality small RNA (sRNA) data from four soybean (Glycine max) tissues, including root, seed, flower, and nodules, to expand the collection of currently known soybean miRNAs. We developed a bioinformatics pipeline using in-house scripts and publicly available structure prediction tools to differentiate the authentic mature miRNA sequences from other sRNAs and short RNA fragments represented in the public sequencing data.

Results

The combined sequencing and bioinformatics analyses identified 129 miRNAs based on hairpin secondary structure features in the predicted precursors. Out of these, 42 miRNAs matched known miRNAs in soybean or other species, while 87 novel miRNAs were identified. We also predicted the putative target genes of all identified miRNAs with computational methods and verified the predicted cleavage sites in vivo for a subset of these targets using the 5' RACE method. Finally, we also studied the relationship between the abundance of miRNA and that of the respective target genes by comparison to Solexa cDNA sequencing data.

Conclusion

Our study significantly increased the number of miRNAs known to be expressed in soybean. The bioinformatics analysis provided insight on regulation patterns between the miRNAs and their predicted target genes expression. We also deposited the data in a soybean genome browser based on the UCSC Genome Browser architecture. Using the browser, we annotated the soybean data with miRNA sequences from four tissues and cDNA sequencing data. Overlaying these two datasets in the browser allows researchers to analyze the miRNA expression levels relative to that of the associated target genes. The browser can be accessed at http://digbio.missouri.edu/soybean_mirna/.
AntiBP2: improved version of antibacterial peptide prediction
Authors: Lata Sneh , Mishra Nitish K , Raghava Gajendra PS
Published: January 2010

Background

Antibacterial peptides are one of the effecter molecules of innate immune system. Over the last few decades several antibacterial peptides have successfully approved as drug by FDA, which has prompted an interest in these antibacterial peptides. In our recent study we analyzed 999 antibacterial peptides, which were collected from Antibacterial Peptide Database (APD). We have also developed methods to predict and classify these antibacterial peptides using Support Vector Machine (SVM).

Results

During analysis we observed that certain residues are preferred over other in antibacterial peptide, particularly at the N and C terminus. These observation and increased data of antibacterial peptide in APD encouraged us to again develop a new and more robust method for predicting antibacterial peptides in protein from their amino acid sequence or given peptide have antibacterial properties or not. First, the binary patterns of the 15 N terminus residues were used for predicting antibacterial peptide using SVM and achieved accuracy of 85.46% with 0.705 Mathew's Correlation Coefficient (MCC). Then we used the binary pattern of 15 C terminus residues and achieved accuracy of 85.05% with 0.701 MCC, latter on we developed prediction method by combining N & C terminus and achieved an accuracy of 91.64% with 0.831 MCC. Finally we developed SVM based model using amino acid composition of whole peptide and achieved 92.14% accuracy with MCC 0.843. In this study we used five-fold cross validation technique to develop all these models and tested the performance of these models on an independent dataset. We further classify antibacterial peptides according to their sources and achieved an overall accuracy of 98.95%. We further classify antibacterial peptides in their respective family and got a satisfactory result.

Conclusion

Among antibacterial peptides, there is preference for certain residues at N and C terminus, which helps to discriminate them from non-antibacterial peptides. Amino acid composition of antibacterial peptides helps to demarcate them from non-antibacterial peptide and their further classification in source and family. Antibp2 will be helpful in discovering efficacious antibacterial peptide, which we hope will be helpful against antibiotics resistant bacteria. We also developed user friendly web server for the biological community.
Efficient protein alignment algorithm for protein search
Authors: Lu Zaixin , Zhao Zhiyu , Fu Bin
Published: January 2010

Background

Proteins show a great variety of 3D conformations, which can be used to infer their evolutionary relationship and to classify them into more general groups; therefore protein structure alignment algorithms are very helpful for protein biologists. However, an accurate alignment algorithm itself may be insufficient for effective discovering of structural relationships among tens of thousands of proteins. Due to the exponentially increasing amount of protein structural data, a fast and accurate structure alignment tool is necessary to access protein classification and protein similarity search; however, the complexity of current alignment algorithms are usually too high to make a fully alignment-based classification and search practical.

Results

We have developed an efficient protein pairwise alignment algorithm and applied it to our protein search tool, which aligns a query protein structure in the pairwise manner with all protein structures in the Protein Data Bank (PDB) to output similar protein structures. The algorithm can align hundreds of pairs of protein structures in one second. Given a protein structure, the tool efficiently discovers similar structures from tens of thousands of structures stored in the PDB always in 2 minutes in a single machine and 20 seconds in our cluster of 6 machines. The algorithm has been fully implemented and is accessible online at our webserver, which is supported by a cluster of computers.

Conclusion

Our algorithm can work out hundreds of pairs of protein alignments in one second. Therefore, it is very suitable for protein search. Our experimental results show that it is more accurate than other well known protein search systems in finding proteins which are structurally similar at SCOP family and superfamily levels, and its speed is also competitive with those systems. In terms of the pairwise alignment performance, it is as good as some well known alignment algorithms.
Structure prediction for the helical skeletons detected from the low resolution protein density map
Authors: Al Nasr Kamal , Sun Weitao , He Jing
Published: January 2010

Background

The current advances in electron cryo-microscopy technique have made it possible to obtain protein density maps at about 6-10 Å resolution. Although it is hard to derive the protein chain directly from such a low resolution map, the location of the secondary structures such as helices and strands can be computationally detected. It has been demonstrated that such low-resolution map can be used during the protein structure prediction process to enhance the structure prediction.

Results

We have developed an approach to predict the 3-dimensional structure for the helical skeletons that can be detected from the low resolution protein density map. This approach does not require the construction of the entire chain and distinguishes the structures based on the conformation of the helices. A test with 35 low resolution density maps shows that the highest ranked structure with the correct topology can be found within the top 1% of the list ranked by the effective energy formed by the helices.

Conclusion

The results in this paper suggest that it is possible to eliminate the great majority of the bad conformations of the helices even without the construction of the entire chain of the protein. For many proteins, the effective contact energy formed by the secondary structures alone can distinguish a small set of likely structures from the pool.
Computational prediction of type III secreted proteins from gram-negative bacteria
Authors: Yang Yang , Zhao Jiayuan , Morgan Robyn L , Ma Wenbo , Jiang Tao
Published: January 2010

Background

Type III secretion system (T3SS) is a specialized protein delivery system in gram-negative bacteria that injects proteins (called effectors) directly into the eukaryotic host cytosol and facilitates bacterial infection. For many plant and animal pathogens, T3SS is indispensable for disease development. Recently, T3SS has also been found in rhizobia and plays a crucial role in the nodulation process. Although a great deal of efforts have been done to understand type III secretion, the precise mechanism underlying the secretion and translocation process has not been fully understood. In particular, defined secretion and translocation signals enabling the secretion have not been identified from the type III secreted effectors (T3SEs), which makes the identification of these important virulence factors notoriously challenging. The availability of a large number of sequenced genomes for plant and animal-associated bacteria demands the development of efficient and effective prediction methods for the identification of T3SEs using bioinformatics approaches.

Results

We have developed a machine learning method based on the N-terminal amino acid sequences to predict novel type III effectors in the plant pathogen Pseudomonas syringae and the microsymbiont rhizobia. The extracted features used in the learning model (or classifier) include amino acid composition, secondary structure and solvent accessibility information. The method achieved a precision of over 90% on P. syringae in a cross validation study. In combination with a promoter screen for the type III specific promoters, this classifier trained on the P. syringae data was applied to predict novel T3SEs from the genomic sequences of four rhizobial strains. This application resulted in 57 candidate type III secreted proteins, 17 of which are confirmed effectors.

Conclusion

Our experimental results demonstrate that the machine learning method based on N-terminal amino acid sequences combined with a promoter screen could prove to be a very effective computational approach for predicting novel type III effectors in gram-negative bacteria. Our method and data are available to the public upon request.
Virtual Screening of potential drug-like inhibitors against Lysine/DAP pathway of Mycobacterium tuberculosis
Authors: Garg Aarti , Tewari Rupinder , Raghava Gajendra PS
Published: January 2010

Background

An explosive global spreading of multidrug resistant Mycobacterium tuberculosis (Mtb) is a catastrophe, which demands an urgent need to design or develop novel/potent antitubercular agents. The Lysine/DAP biosynthetic pathway is a promising target due its specific role in cell wall and amino acid biosynthesis. Here, we report identification of potential antitubercular candidates targeting Mtb dihydrodipicolinate synthase (DHDPS) enzyme of the pathway using virtual screening protocols.

Results

In the present study, we generated three sets of drug-like molecules in order to screen potential inhibitors against Mtb drug target DHDPS. The first set of compounds was a combinatorial library, which comprised analogues of pyruvate (substrate of DHDPS). The second set of compounds consisted of pyruvate-like molecules i.e. structurally similar to pyruvate, obtained using 3D flexible similarity search against NCI and PubChem database. The third set constituted 3847 anti-infective molecules obtained from PubChem. These compounds were subjected to Lipinski's rule of drug-like five filters. Finally, three sets of drug-like compounds i.e. 4088 pyruvate analogues, 2640 pyruvate-like molecules and 1750 anti-infective molecules were docked at the active site of Mtb DHDPS (PDB code: 1XXX used in the molecular docking calculations) to select inhibitors establishing favorable interactions.

Conclusion

The above-mentioned virtual screening procedures helped in the identification of several potent candidates that possess inhibitory activity against Mtb DHDPS. Therefore, these novel scaffolds/candidates which could have the potential to inhibit Mtb DHDPS enzyme would represent promising starting points as lead compounds and certainly aid the experimental designing of antituberculars in lesser time.
NeMo: Network Module identification in Cytoscape
Authors: Rivera Corban G , Vakil Rachit , Bader Joel S
Published: January 2010

Background

As the size of the known human interactome grows, biologists increasingly rely on computational tools to identify patterns that represent protein complexes and pathways. Previous studies have shown that densely connected network components frequently correspond to community structure and functionally related modules. In this work, we present a novel method to identify densely connected and bipartite network modules based on a log odds score for shared neighbours.

Results

To evaluate the performance of our method (NeMo), we compare it to other widely used tools for community detection including kMetis, MCODE, and spectral clustering. We test these methods on a collection of synthetically constructed networks and the set of MIPS human complexes. We apply our method to the CXC chemokine pathway and find a high scoring functional module of 12 disconnected phospholipase isoforms.

Conclusion

We present a novel method that combines a unique neighbour-sharing score with hierarchical agglomerative clustering to identify diverse network communities. The approach is unique in that we identify both dense network and dense bipartite network structures in a single approach. Our results suggest that the performance of NeMo is better than or competitive with leading approaches on both real and synthetic datasets. We minimize model complexity and generalization error in the Bayesian spirit by integrating out nuisance parameters. An implementation of our method is freely available for download as a plugin to Cytoscape through our website and through Cytoscape itself.
Molecular dynamics simulation studies and in vitro site directed mutagenesis of avian beta-defensin Apl_AvBD2
Authors: Soman Soja Saghar , Sivakumar Krishnankutty Chandrika , Sreekumar Easwaran
Published: January 2010

Background

Defensins comprise a group of antimicrobial peptides, widely recognized as important elements of the innate immune system in both animals and plants. Cationicity, rather than the secondary structure, is believed to be the major factor defining the antimicrobial activity of defensins. To test this hypothesis and to improve the activity of the newly identified avian β-defensin Apl_AvBD2 by enhancing the cationicity, we performed in silico site directed mutagenesis, keeping the predicted secondary structure intact. Molecular dynamics (MD) simulation studies were done to predict the activity. Mutant proteins were made by in vitro site directed mutagenesis and recombinant protein expression, and tested for antimicrobial activity to confirm the results obtained in MD simulation analysis.

Results

MD simulation revealed subtle, but critical, structural variations between the wild type Apl_AvBD2 and the more cationic in silico mutants, which were not detected in the initial structural prediction by homology modelling. The C-terminal cationic 'claw' region, important in antimicrobial activity, which was intact in the wild type, showed changes in shape and orientation in all the mutant peptides. Mutant peptides also showed increased solvent accessible surface area and more number of hydrogen bonds with the surrounding water molecules. In functional studies, the Escherichia coli expressed, purified recombinant mutant proteins showed total loss of antimicrobial activity compared to the wild type protein.

Conclusion

The study revealed that cationicity alone is not the determining factor in the microbicidal activity of antimicrobial peptides. Factors affecting the molecular dynamics such as hydrophobicity, electrostatic interactions and the potential for oligomerization may also play fundamental roles. It points to the usefulness of MD simulation studies in successful engineering of antimicrobial peptides for improved activity and other desirable functions.
Downstream genes of Pax6 revealed by comprehensive transcriptome profiling in the developing rat hindbrain
Authors: Numayama-Tsuruta Keiko , Arai Yoko , Takahashi Masanori , Sasaki-Hoshino Makiko , Funatsu Nobuo , Nakamura Shun , Osumi Noriko
Published: January 2010

Background

The transcription factor Pax6 is essential for the development of the central nervous system and it exerts its multiple functions by regulating the expression of downstream target molecules. To screen for genes downstream of Pax6, we performed comprehensive transcriptome profiling analyses in the early hindbrain ofPax6homozygous mutant and wild-type rats using microarrays.

Results

Comparison of quadruplicate microarray experiments using two computational methods allowed us to identify differentially expressed genes that have relatively small fold changes or low expression levels. Gene ontology analyses of the differentially expressed molecules demonstrated that Pax6 is involved in various signal transduction pathways where it regulates the expression of many receptors, signaling molecules, transporters and transcription factors. The up- or down-regulation of these genes was further confirmed by quantitative RT-PCR.In situstaining ofFabp7,Dbx1, Unc5h1andCyp26b1mRNAs showed that expression of these transcripts not only overlapped with that ofPax6in the hindbrain of wild-type andPax6heterozygous mutants, but also was clearly reduced in the hindbrain of thePax6homozygous mutant. In addition, thePax6homozygous mutant hindbrain showed thatCyp26b1expression was lacked in the dorsal and ventrolateral regions of rhombomeres 5 and 6, and that the size of rhombomere 5 expanded rostrocaudally.

Conclusions

These results indicate thatUnc5h1andCyp26b1are novel candidates for target genes transactivated by Pax6. Furthermore, our results suggest the interesting possibility that Pax6 regulates anterior-posterior patterning of the hindbrain via activation of Cyp26b1, an enzyme that metabolizes retinoic acid.
A glycine receptor is involved in the organization of swimming movements in an invertebrate chordate
Authors: Nishino Atsuo , Okamura Yasushi , Piscopo Stefania , Brown Euan R
Published: January 2010

Background

Rhythmic motor patterns for locomotion in vertebrates are generated in spinal cord neural networks known as spinal Central Pattern Generators (CPGs). A key element in pattern generation is the role of glycinergic synaptic transmission by interneurons that cross the cord midline and inhibit contralaterally-located excitatory neurons. The glycinergic inhibitory drive permits alternating and precisely timed motor output during locomotion such as walking or swimming. To understand better the evolution of this system we examined the physiology of the neural network controlling swimming in an invertebrate chordate relative of vertebrates, the ascidian larva Ciona intestinalis.

Results

A reduced preparation of the larva consisting of nerve cord and motor ganglion generates alternating swimming movements. Pharmacological and genetic manipulation of glycine receptors shows that they are implicated in the control of these locomotory movements. Morphological molecular techniques and heterologous expression experiments revealed that glycine receptors are inhibitory and are present on both motoneurones and locomotory muscle while putative glycinergic interneurons were identified in the nerve cord by labeling with an anti-glycine antibody.

Conclusions

In Ciona intestinalis, glycine receptors, glycinergic transmission and putative glycinergic interneurons, have a key role in coordinating swimming movements through a simple CPG that is present in the motor ganglion and nerve cord. Thus, the strong association between glycine receptors and vertebrate locomotory networks may now be extended to include the phylum chordata. The results suggest that the basic network for 'spinal-like' locomotion is likely to have existed in the common ancestor of extant chordates some 650 M years ago.
SoyDB: a knowledge database of soybean transcription factors
Authors: Wang Zheng , Libault Marc , Joshi Trupti , Valliyodan Babu , Nguyen Henry T , Xu Dong , Stacey Gary , Cheng Jianlin
Published: January 2010

Background

Transcription factors play the crucial rule of regulating gene expression and influence almost all biological processes. Systematically identifying and annotating transcription factors can greatly aid further understanding their functions and mechanisms. In this article, we present SoyDB, a user friendly database containing comprehensive knowledge of soybean transcription factors.

Description

The soybean genome was recently sequenced by the Department of Energy-Joint Genome Institute (DOE-JGI) and is publicly available. Mining of this sequence identified 5,671 soybean genes as putative transcription factors. These genes were comprehensively annotated as an aid to the soybean research community. We developed SoyDB - a knowledge database for all the transcription factors in the soybean genome. The database contains protein sequences, predicted tertiary structures, putative DNA binding sites, domains, homologous templates in the Protein Data Bank (PDB), protein family classifications, multiple sequence alignments, consensus protein sequence motifs, web logo of each family, and web links to the soybean transcription factor database PlantTFDB, known EST sequences, and other general protein databases including Swiss-Prot, Gene Ontology, KEGG, EMBL, TAIR, InterPro, SMART, PROSITE, NCBI, and Pfam. The database can be accessed via an interactive and convenient web server, which supports full-text search, PSI-BLAST sequence search, database browsing by protein family, and automatic classification of a new protein sequence into one of 64 annotated transcription factor families by hidden Markov models.

Conclusions

A comprehensive soybean transcription factor database was constructed and made publicly accessible at http://casp.rnet.missouri.edu/soydb/.
Prevalence and risk factors for soil-transmitted helminth infection in mothers and their infants in Butajira, Ethiopia: a population based study
Authors: Belyhun Yeshambel , Medhin Girmay , Amberbir Alemayehu , Erko Berhanu , Hanlon Charlotte , Alem Atalay , Venn Andrea , Britton John , Davey Gail
Published: January 2010

Background

Soil-transmitted helminths (STHs) are widespread in underdeveloped countries. In Ethiopia, the prevalence and distribution of helminth infection varies by place and with age. We therefore investigated the prevalence of and risk factors for STH infection in mothers and their one year-old children living in Butajira town and surrounding rural areas in southern Ethiopia.

Methods

In 2005-2006, 1065 pregnant women were recruited in their third trimester of pregnancy. In 2006-2007, when children reached their first birthdays, data on the infants and their mothers were collected, including stool samples for qualitative STH analysis. Questionnaire data on various demographic, housing and lifestyle variables were available. Logistic regression analysis was employed to determine the independent risk factors for STH infection in the mothers and children.

Results

908 mothers and 905 infants provided complete data for analysis. Prevalence of any STH infection was 43.5% (95% confidence interval (CI) 40.2-46.8%) in mothers and 4.9% (95%CI 3.6-6.5%) in children. In the fully adjusted regression model, infrequent use of soap by the mother was associated with increased risk (odds ratio (OR) 1.40, 95% CI 1.04-1.88, and 1.66, 95% CI 0.92-2.99, for use at least once a week and less frequent than once a week respectively, relative to daily use; p for trend = 0.018), and urban place of residence (OR 0.45, 95% CI 0.28-0.73, p = 0.001) was associated with reduced risk of maternal STH infection. The only factor associated with STH infection in infants was household source of water, with the greatest risk in those using piped water inside the compound (OR 0.09, 95% CI 0.02-0.38 for river water, 0.20, 95% CI 0.56-0.69 for either well or stream water and 0.21, 95% CI 0.09-0.51 for piped water outside compared with piped water inside the compound, overall p = 0.002)

Conclusion

In this rural Ethiopian community with a relatively high prevalence of STH infection, we found a reduced risk of infection in relation to maternal hygiene and urban living. Daily use of soap and a safe supply of water are likely to reduce the risk of STH infection.
Predictors of short and long term outcome in patellofemoral pain syndrome: a prospective longitudinal study
Authors: Collins Natalie J , Crossley Kay M , Darnell Ross , Vicenzino Bill
Published: January 2010

Background

Patellofemoral pain syndrome (PFP) is a common musculoskeletal condition that has a tendency to become chronic and problematic in a proportion of affected individuals. The objective of this study was to identify prognostic factors that may have clinical utility in predicting poor outcome on measures of pain and function in individuals with PFP.

Methods

A prospective follow-up study was conducted of 179 participants in a randomised clinical trial. Nine baseline factors (age, gender, body mass index, arch height, duration of knee pain, worst pain visual analogue scale, Kujala Patellofemoral Score (KPS), functional index questionnaire (FIQ), step down repetitions) were investigated for their prognostic ability on outcome assessed at six, 12 and 52 weeks (worst pain, KPS and FIQ). Factors with significant univariate associations were entered into multivariate linear regression models to identify a group of factors independently associated with poor outcome.

Results

Long symptom duration was the most consistent predictor of poor outcome over 52 weeks rated on the KPS and the FIQ (β-0.07, 95% confidence interval -0.1 to -0.03, p < 0.000; and -0.02, -0.03 to -0.01, p < 0.000, respectively). Worse KPS at baseline was predictive of outcome at six, 12 and 52 weeks. Gender, body mass index and arch height were generally not associated with outcome (univariate analysis), while age, worst pain, FIQ and step downs were excluded during multivariate analyses.

Conclusions

Patients presenting with PFP of long duration who score worse on the KPS have a poorer prognosis, irrespective of age, gender and morphometry. These results suggest that strategies aimed at preventing chronicity of more severe PFP may optimise prognosis.
Characterization of the quinolone resistant determining regions in clinical isolates of pneumococci collected in Canada
Authors: Patel Samir N , Melano Roberto , McGeer Allison , Green Karen , Low Donald E
Published: January 2010

Background

The objective of this study was to examine Streptococcus pneumoniae isolates collected from a longitudinal surveillance program in order to determine their susceptibility to currently used fluoroquinolones and of the frequency and type of mutations in the quinolone-resistant determining regions (QRDRs) of their parC and gyrA genes.

Methods

The Canadian Bacterial Surveillance Network has been collecting clinical isolates of S. pneumoniae from across Canada since 1988. Broth microdilution susceptibility testing was carried out according to the Clinical and Laboratory Standards Institute guidelines. The QRDRs of the parC and gyrA genes were sequenced for all isolates with ciprofloxacin MIC ≥ 4 mg/L, and a large representative sample of isolates (N = 4,243) with MIC ≤ 2 mg/L.

Results

A total of 4,798 out of 30,111 isolates collected from 1988, and 1993 to 2007 were studied. Of those isolates that were successfully sequenced, 184 out of 1,032 with mutations in parC only, 11 out of 30 with mutations in gyrA only, and 292 out of 298 with mutations in parC and gyrA were considered resistant to ciprofloxacin (MIC ≥ 4 mg/L). The most common substitutions in the parC were at positions 137 (n = 722), 79 (n = 209), and 83 (n = 56), of which substitutions at positions 79 and 83 were associated with 4-fold increase in MIC to ciprofloxacin, whereas substitutions at position 137 had minimal effect on the ciprofloxacin MIC. A total of 400 out of 622 isolates with Lys-137 parC mutation belonged to serotypes 1, 12, 31, 7A, 9V, 9N and 9L, whereas only 49 out of 3064 isolates with no mutations belonged to these serotypes. Twenty-one out of 30 isolates with substitutions at position 81 of the gyrA gene had an increased MIC to ciprofloxacin. Finally, we found that isolates with mutations in both parC and gyrA were significantly associated with increased MIC to fluoroquinolones.

Conclusions

Not all mutations, most frequently Lys-137, found in the QRDRs of the parC gene of S. pneumoniae is associated with an increased MIC to fluoroquinolones. The high prevalence of Lys-137 appears to be due to its frequent occurrence in common serotypes.
The effect of intraoperative specimen inking on lumpectomy re-excision rates
Authors: Singh Mansher , Singh Gayatri , Hogan Kevin T , Atkins Kristen A , Schroen Anneke T
Published: January 2010

Background

Lumpectomy re-excision to obtain negative margins is common. We compare the effect of two specimen orientation approaches on lumpectomy re-excision rates.

Methods

All women undergoing lumpectomy for breast cancer by a single surgeon between 03/2007 - 02/2009 were included. Lumpectomies underwent standard inking (SI) after surgery by a pathologist from 03/2007-02/2008 while intraoperative inking (II) with direct surgeon input was done from 03/2008-02/2009. Rates of margin positivity and re-excision were compared between these methods.

Results

65 patients were evaluated, reflecting SI in 39 and II in 26 cases. Margin positivity rates of 46% [SI] vs. 23% [II] (p = 0.06) and re-excision rates of 38% [SI] vs. 19% [II] were observed. Residual disease at re-excision was found in 27% [SI] vs. 67% [II] of cases.

Conclusions

Intraoperative inking in this practice offered a simple way to reduce re-excision rates after lumpectomy and affect an improvement in quality of patient care.
Panallergens and their impact on the allergic patient
Authors: Hauser Michael , Roulias Anargyros , Ferreira Fátima , Egger Matthias
Published: January 2010

The panallergen concept encompasses families of related proteins, which are involved in general vital processes and thus, widely distributed throughout nature. Plant panallergens share highly conserved sequence regions, structure, and function. They are responsible for many IgE cross-reactions even between unrelated pollen and plant food allergen sources. Although usually considered as minor allergens, sensitization to panallergens might be problematic as it bears the risk of developing multiple sensitizations. Clinical manifestations seem to be tightly connected with geographical and exposure factors. Future population- and disease-based screenings should provide new insights on panallergens and their contribution to disease manifestations. Such information requires molecule-based diagnostics and will be valuable for developing patient-tailored prophylactic and therapeutic approaches. In this article, we focus on profilins, non-specific lipid transfer proteins, polcalcins, and Bet v 1-related proteins and discuss possible consequences of panallergen sensitization for the allergic patient. Based on their pattern of IgE cross-reactivity, which is reflected by their distribution in the plant kingdom, we propose a novel classification of panallergens into ubiquitously spread "real panallergens" (e.g. profilins) and widespread "eurallergens" (e.g. polcalcins). "Stenallergens" display more limited distribution and cross-reactivity patterns, and "monallergens" are restricted to a single allergen source.
Cancer proliferation and therapy: the Warburg effect and quantum metabolism
Authors: Demetrius Lloyd A , Coy Johannes F , Tuszynski Jack A
Published: January 2010

Background

Most cancer cells, in contrast to normal differentiated cells, rely on aerobic glycolysis instead of oxidative phosphorylation to generate metabolic energy, a phenomenon called the Warburg effect.

Model

Quantum metabolism is an analytic theory of metabolic regulation which exploits the methodology of quantum mechanics to derive allometric rules relating cellular metabolic rate and cell size. This theory explains differences in the metabolic rates of cells utilizing OxPhos and cells utilizing glycolysis. This article appeals to an analytic relation between metabolic rate and evolutionary entropy - a demographic measure of Darwinian fitness - to: (a) provide an evolutionary rationale for the Warburg effect, and (b) propose methods based on entropic principles of natural selection for regulating the incidence of OxPhos and glycolysis in cancer cells.

Conclusion

The regulatory interventions proposed on the basis of quantum metabolism have applications in therapeutic strategies to combat cancer. These procedures, based on metabolic regulation, are non-invasive, and complement the standard therapeutic methods involving radiation and chemotherapy
Spectrum of musculo-skeletal disorders in sickle cell disease in Lagos, Nigeria
Authors: Balogun Rufai A , Obalum Dike C , Giwa Suleiman O , Adekoya-Cole Thomas O , Ogo Chidiebere N , Enweluzo George O
Published: January 2010

Background

Sickle cell anemia (SCA) is a common genetic disease in Nigeria. Past studies from West Africa focused on isolated aspects of its medical and surgical presentations. To the best of our knowledge, the musculo-skeletal presentations amongst Nigerians with SCA have not been documented in a single all encompassing study. This work aims to prospectively document the musculo-skeletal disease burden among SCA patients.

Methods

In a prospective study of 318 consecutive patients with genotype-confirmed SCA at the Lagos University Teaching Hospital (LUTH), the musculo-skeletal pathologies, anatomic sites, grade of disease, age at presentation and management outcome were recorded over a one-year period. Data obtained were analyzed using Epi-Info software version 6.0. Data are presented as frequencies (%) and mean values (SD) as appropriate.

Results

The HbSS genotype occurred in 296 (93.0%), while 22 (7.0%) were HbSC. 100 (31.4%) patients with average presenting haemoglobin concentration of 8.2 g/100 ml in the study group, presented with 131 musculo-skeletal pathologies in 118 anatomic sites. Osteomyelitis 31 (31%) and septic arthritis 19 (19%) were most commonly observed in children less than 10 years. Skin ulcers and avascular necrosis (AVN) occurred predominantly in the older age groups, with frequencies of 13 (13.0%) and 26 (26.0%) respectively. 20 (71.5%) of diagnosed cases of AVN presented with radiological grade 4 disease. The lower limbs were involved in 84 (71.1%) of sites affected. Lesions involving the spine were rare 11 (0.9%). Multiple presentations occurred in 89 (28.0%) of patients; 62 (69.7%) of which were children below 10 years.

Conclusions

Musculo-skeletal complications are common features of sickle cell anaemia seen in 31.4%. Infectious aetiologies predominate with long bones and joints of lower limbs more commonly affected by osteomyelitis and septic arthritis. Healthcare providers managing SCA should be aware of the potential morbidity and mortality of these conditions to ensure early diagnosis and adequate management.