bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison Among Some Models of Orientation Selectivity
Authors: Teich Andrew F. , Qian Ning
Published: April 2006

Several models exist for explaining primary visual cortex (V1) orientation tuning. The modified feedforward model (MFM) and the recurrent model (RM) are major examples. We have implemented these two models, at the same level of detail, alongside a few newer variations, and thoroughly compared their receptive-field structures. We found that antiphase inhibition in the MFM enhances both spatial phase information and orientation tuning, producing well-tuned simple cells. This remains true for a newer version of the MFM that incorporates untuned complex-cell inhibition. In contrast, when the recurrent connections in the RM are strong enough to produce typical V1 orientation tuning, they also eliminate spatial phase information, making the cells complex. Introducing phase specificity into the connections of the RM (as done in an original version of the RM) can make the cells phase sensitive, but the cells show an incorrect 90° peak shift of orientation tuning under opposite contrast signs. An inhibition-dominant version of the RM can generate well-tuned cells across the simple–complex spectrum, but it predicts that the net effect of cortical interactions is to suppress feedforward excitation across all orientations in simple cells. Finally, adding antiphase inhibition used in the MFM into the RM produces a most general model. We call this new model the modified recurrent model (MRM) and show that this model can also produce well-tuned cells throughout the simple–complex spectrum. Unlike the inhibition-dominant RM, the MRM is consistent with data from cat V1, suggesting that the net effect of cortical interactions is to boost simple cell responses at the preferred orientation. These results suggest that the MFM is well suited for explaining orientation tuning in simple cells, whereas the standard RM is for complex cells. The assignment of the RM to complex cells also avoids conflicts between the RM and the experiments of cortical inactivation (done on simple cells) and the spatial-frequency dependency of orientation tuning (found in simple cells). Because orientation-tuned V1 cells show a continuum of simple- to complex-cell behavior, the MRM provides the best description of V1 data.
On error formulas for approximation by sums of univariate functions
Authors: Ismailov Vugar E.
Published: April 2006

The purpose of the paper is to develop a new method for obtaining explicit formulas for the error of approximation of bivariate functions by sums of univariate functions. It should be remarked that formulas of this type have been known only for functions defined on a rectangle with sides parallel to coordinate axes. Our method, based on a maximization process over closed bolts, allows the consideration of functions defined on a hexagon or octagon with sides parallel to coordinate axes.
Large‐scale stochastic hereditary systems under Markovianstructural perturbations. Part I. Variational comparison theorems
Authors: Ladde G. S.
Published: April 2006

This three‐part series work investigates the qualitative analysis
of large‐scale stochastic hereditary systems under random
structural perturbations. The random structural perturbations are
described by a Markov chain with a finite number of states. The
first part of this three‐part series work deals with the problem
formulation and the development of mathematical tool to undertake
this investigation. In this first part, we present variational
comparison theorems for isolated subsystems of large‐scale
stochastic hereditary systems under Markovian structural
perturbations. This part lays down the basis for the study of
hierarchic systems.
Large‐scale stochastic hereditary systems under Markovianstructural perturbations. Part II. Qualitative analysis of isolatedsubsystems
Authors: Ladde G. S.
Published: April 2006

In this part of the work, the convergence and stability analysis
of isolated subsystems of stochastic hereditary systems under
random structural perturbations is investigated. The variational
comparison theorems developed in Part I are used to achieve this
goal. Under algebraic conditions on the rate coefficients,
time‐delay, and an intensity matrix associated with the Markov
chain, convergence and stability results are obtained.
Furthermore, it is shown that these properties are affected by
hereditary and random structural perturbations effects. It is
further shown that the mathematical conditions are algebraically
simple and are robust to the parametric changes. This
investigation provides a basis for drawing the conclusions about
the overall large‐scale system.
Inhibition of Akt/PKB by a COX-2 Inhibitor Induces Apoptosis in Gastric Cancer Cells
Authors: Fan Xiao Ming , Jiang Xiao Hua , Gu Qing , Ching Yick Pang , He Hua , Xia Harry H.X. , Lin Marie Chia Mi , Chan Annie O.O. , Yuen Man Fung , Kung Hsiang-Fu , Wong Benjamin Chun-Yu
Published: April 2006

Background/Aim: Inhibition of cyclooxygenase-2 has been proposed to be a potential mechanism for the chemoprevention of gastrointestinal tumors by nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer cell lines and its downstream signaling pathway. Methods: Two gastric cancer cell lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and apoptosis. The involvement of mitogen-activated protein kinase and Akt kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were studied in the AGS cell line. Results: SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor SB203580 and the dominant-negative stress-activated protein kinase/jun kinase both failed, while the constitutively active form of Akt/PKB was able to block SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of cytochrome c and activation of caspases. Conclusion: One of the pathways involved in SC-236-induced apoptosis in gastric cancer cells is through downregulation of Akt and then release of cytochrome c.
Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD
Authors: Rocnik Jennifer L. , Okabe Rachel , Yu Jin-Chen , Lee Benjamin H. , Giese Neill , Schenkein David P. , Gilliland D. Gary
Published: April 2006

Acquired mutations in the FLT3 receptor tyrosine kinase are common in acute myeloid leukemia and result in constitutive activation. The most frequent mechanism of activation is disruption of the juxtamembrane autoregulatory domain by internal tandem duplications (ITDs). FLT3-ITDs confer factor-independent growth to hematopoietic cells and induce a myeloproliferative syndrome in murine bone marrow transplant models. We and others have observed that FLT3-ITD activates STAT5 and its downstream effectors, whereas ligand-stimulated wild-type FLT3 (FLT3WT) does not. In vitro mapping of tyrosine phosphorylation sites in FLT3-ITD identified 2 candidate STAT5 docking sites within the juxtamembrane domain that are disrupted by the ITD. Tyrosine to phenylalanine substitution of residues 589 and 591 in the context of the FLT3-ITD did not affect tyrosine kinase activity, but abrogated STAT5 activation. Furthermore, FLT3-ITD–Y589/591F was incapable of inducing a myeloproliferative phenotype when transduced into primary murine bone marrow cells, whereas FLT3-ITD induced myeloproliferative disease with a median latency of 50 days. Thus, the conformational change in the FLT3 juxtamembrane domain induced by the ITD activates the kinase through dysregulation of autoinhibition and results in qualitative differences in signal transduction through STAT5 that are essential for the transforming potential of FLT3-ITD in vivo.
WFDC2 (HE4): A potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung
Authors: Bingle Lynne , Cross Simon S , High Alec S , Wallace William A , Rassl Doris , Yuan Guanglu , Hellstrom Ingegerd , Campos Michael A , Bingle Colin D
Published: April 2006

Background

The Whey Acidic Protein domain is an evolutionarily conserved motif found in a number of proteins, the best studied of which are antiproteinases involved in the innate immune defence of multiple epithelia. We recently characterised the WFDC2 gene which encodes a two WAP domain-containing protein, initially suggested as a marker for epididymis, and showed that it is highly expressed in the lung and salivary gland. The precise location of WFDC2 protein in these sites has not been described.

Methods

We used immunohistochemistry to localise WFDC2 in normal tissues of the respiratory tract, naso- and oropharynx, as well as in chronically inflamed lung from Cystic Fibrosis and a range of pulmonary carcinomas. We have complemented these studies with molecular analysis of WFDC2 gene expression in primary human lung cell cultures.

Results

WFDC2 is expressed in some epithelial cells of the upper airways as well as in mucous cells and ducts of submucosal glands. No staining was seen in peripheral lung. Intense staining is found in major salivary glands and in minor glands of the nose, sinuses, posterior tongue and tonsil. Studies with the related protein Secretory Leukocyte Protease Inhibitor (SLPI) show that although both proteins are expressed in similar tissues, the precise cellular localisation differs. Significant increases in expression and localisation of WFDC2 are seen in patients with Cystic Fibrosis. SLPI expression was greatly reduced in the same samples. In cultures of tracheobronchial epithelial cells, expression of WFDC2 and SLPI are differentially regulated during differentiation yet WFDC2 is not induced by pro-inflammatory mediators. The majority of adenocarcinomas stain with WFDC2 whilst a significant minority of squamous, small cell and large cell carcinomas exhibit focal staining. There is no clear association with tumour grade.

Conclusion

We believe that these studies support the hypothesis that WFDC2 may be a component of the innate immune defences of the lung, nasal and oral cavities and suggest that WFDC2 functions in concert with related WAP domain containing proteins in epithelial host defence. We also suggest that WFDC2 re-expression in lung carcinomas may prove to be associated with tumour type and should be studied in further detail.
Toll-like receptor-4 mediates cigarette smoke-induced cytokine production by human macrophages
Authors: Karimi Khalil , Sarir Hadi , Mortaz Esmaeil , Smit Joost J , Hosseini Hossein , De Kimpe Sjef J , Nijkamp Frans P , Folkerts Gert
Published: April 2006

Background

The major risk factor for the development of COPD is cigarette smoking. Smoking causes activation of resident cells and the recruitment of inflammatory cells into the lungs, which leads to release of pro-inflammatory cytokines, chemotactic factors, oxygen radicals and proteases. In the present study evidence is found for a new cellular mechanism that refers to a link between smoking and inflammation in lungs.

Methods

Employing human monocyte-derived macrophages, different techniques including FACS analysis, Cytometric Bead Array Assay and ELISA were achieved to evaluate the effects of CS on pro-inflammatory cytokine secretion including IL-8. Then, Toll-like receptor neutralization was performed to study the involvement of Toll-like receptor-4 in IL-8 production. Finally, signaling pathways in macrophages after exposure to CS medium were investigated performing ELISA and Western analysis.

Results

We demonstrate that especially human monocytes are sensitive to produce IL-8 upon cigarette smoke stimulation compared to lymphocytes or neutrophils. Moreover, monocyte-derived macrophages produce high amounts of the cytokine. The IL-8 production is dependent on Toll-like receptor 4 stimulation and LPS is not involved. Further research resolved the cellular mechanism by which cigarette smoke induces cytokine production in monocyte-derived macrophages. Cigarette smoke causes subsequently a concentration-dependent phosphorylation of IRAK and degradation of TRAF6. Moreover, IκBα was phosphorylated which suggests involvement of NF-κB. In addition, NFκB -inhibitor blocked cigarette smoke-induced IL-8 production.

Conclusion

These findings link cigarette smoke to inflammation and lead to new insights/therapeutic strategies in the pathogenesis of lung emphysema.
MIMAS: an innovative tool for network-based high density oligonucleotide microarray data management and annotation
Authors: Hermida Leandro , Schaad Olivier , Demougin Philippe , Descombes Patrick , Primig Michael
Published: April 2006

Background

The high-density oligonucleotide microarray (GeneChip) is an important tool for molecular biological research aiming at large-scale detection of small nucleotide polymorphisms in DNA and genome-wide analysis of mRNA concentrations. Local array data management solutions are instrumental for efficient processing of the results and for subsequent uploading of data and annotations to a global certified data repository at the EBI (ArrayExpress) or the NCBI (GeneOmnibus).

Description

To facilitate and accelerate annotation of high-throughput expression profiling experiments, the Microarray Information Management and Annotation System (MIMAS) was developed. The system is fully compliant with the Minimal Information About a Microarray Experiment (MIAME) convention. MIMAS provides life scientists with a highly flexible and focused GeneChip data storage and annotation platform essential for subsequent analysis and interpretation of experimental results with clustering and mining tools. The system software can be downloaded for academic use upon request.

Conclusion

MIMAS implements a novel concept for nation-wide GeneChip data management whereby a network of facilities is centered on one data node directly connected to the European certified public microarray data repository located at the EBI. The solution proposed may serve as a prototype approach to array data management between research institutes organized in a consortium.
Length-dependent prediction of protein intrinsic disorder
Authors: Peng Kang , Radivojac Predrag , Vucetic Slobodan , Dunker A Keith , Obradovic Zoran
Published: April 2006

Background

Due to the functional importance of intrinsically disordered proteins or protein regions, prediction of intrinsic protein disorder from amino acid sequence has become an area of active research as witnessed in the 6th experiment on Critical Assessment of Techniques for Protein Structure Prediction (CASP6). Since the initial work by Romeroet al. (Identifying disordered regions in proteins from amino acid sequences, IEEE Int. Conf. Neural Netw., 1997), our group has developed several predictors optimized for long disordered regions (>30 residues) with prediction accuracy exceeding 85%. However, these predictors are less successful on short disordered regions (≤30 residues). A probable cause is a length-dependent amino acid compositions and sequence properties of disordered regions.

Results

We proposed two new predictor models, VSL2-M1 and VSL2-M2, to address this length-dependency problem in prediction of intrinsic protein disorder. These two predictors are similar to the original VSL1 predictor used in the CASP6 experiment. In both models, two specialized predictors were first built and optimized for short (≤30 residues) and long disordered regions (>30 residues), respectively. A meta predictor was then trained to integrate the specialized predictors into the final predictor model. As the 10-fold cross-validation results showed, the VSL2 predictors achieved well-balanced prediction accuracies of 81% on both short and long disordered regions. Comparisons over the VSL2 training dataset via 10-fold cross-validation and a blind-test set of unrelated recent PDB chains indicated that VSL2 predictors were significantly more accurate than several existing predictors of intrinsic protein disorder.

Conclusion

The VSL2 predictors are applicable to disordered regions of any length and can accurately identify the short disordered regions that are often misclassified by our previous disorder predictors. The success of the VSL2 predictors further confirmed the previously observed differences in amino acid compositions and sequence properties between short and long disordered regions, and justified our approaches for modelling short and long disordered regions separately. The VSL2 predictors are freely accessible for non-commercial use athttp://www.ist.temple.edu/disprot/predictorVSL2.php
Generation of mice harbouring a conditional loss-of-function allele of Gata6
Authors: Sodhi Chhinder P , Li Jixuan , Duncan Stephen A
Published: April 2006

The zinc finger transcription factor GATA6 is believed to have important roles in the development of several organs including the liver, gastrointestinal tract and heart. However, analyses of the contribution of GATA6 toward organogenesis have been hampered becauseGata6-/-mice fail to develop beyond gastrulation due to defects in extraembryonic endoderm function. We have therefore generated a mouse line harbouring a conditional loss-of-function allele ofGata6usingCre/loxP technology.

LoxPelements were introduced into introns flanking exon 2 of theGata6gene by homologous recombination in ES cells. Mice containing this altered allele were bred to homozygosity and were found to be viable and fertile. To assess the functional integrity of theloxPsites and to confirm that we had generated aGata6loss-of-function allele, we bredGata6'floxed' mice toEIIa-Cremice in which Cre is ubiquitously expressed, and toVillin-Cremice that express Cre in the epithelial cells of the intestine. We conclude that we have generated a line of mice in which GATA6 activity can be ablated in a cell type specific manner by expression of Cre recombinase. This line of mice can be used to establish the role of GATA6 in regulating embryonic development and various aspects of mammalian physiology.
A phylogenomic profile of globins
Authors: Vinogradov Serge N , Hoogewijs David , Bailly Xavier , Arredondo-Peter Raúl , Gough Julian , Dewilde Sylvia , Moens Luc , Vanfleteren Jacques R
Published: April 2006

Background

Globins occur in all three kingdoms of life: they can be classified into single-domain globins and chimeric globins. The latter comprise the flavohemoglobins with a C-terminal FAD-binding domain and the gene-regulating globin coupled sensors, with variable C-terminal domains. The single-domain globins encompass sequences related to chimeric globins and «truncated» hemoglobins with a 2-over-2 instead of the canonical 3-over-3 α-helical fold.

Results

A census of globins in 26 archaeal, 245 bacterial and 49 eukaryote genomes was carried out. Only ~25% of archaea have globins, including globin coupled sensors, related single domain globins and 2-over-2 globins. From one to seven globins per genome were found in ~65% of the bacterial genomes: the presence and number of globins are positively correlated with genome size. Globins appear to be mostly absent in Bacteroidetes/Chlorobi, Chlamydia, Lactobacillales, Mollicutes, Rickettsiales, Pastorellales and Spirochaetes. Single domain globins occur in metazoans and flavohemoglobins are found in fungi, diplomonads and mycetozoans. Although red algae have single domain globins, including 2-over-2 globins, the green algae and ciliates have only 2-over-2 globins. Plants have symbiotic and nonsymbiotic single domain hemoglobins and 2-over-2 hemoglobins. Over 90% of eukaryotes have globins: the nematodeCaenorhabditishas the most putative globins, ~33. No globins occur in the parasitic, unicellular eukaryotes such asEncephalitozoon, Entamoeba, PlasmodiumandTrypanosoma.

Conclusion

Although Bacteria have all three types of globins, Archaeado not have flavohemoglobins and Eukaryotes lack globin coupled sensors. Since the hemoglobins in organisms other than animals are enzymes or sensors, it is likely that the evolution of an oxygen transport function accompanied the emergence of multicellular animals.
Development of a chicken 5 K microarray targeted towards immune function
Authors: Smith Jacqueline , Speed David , Hocking Paul M , Talbot Richard T , Degen Winfried GJ , Schijns Virgil EJC , Glass Elizabeth J , Burt David W
Published: April 2006

Background

The development of microarray resources for the chicken is an important step in being able to profile gene expression changes occurring in birds in response to different challenges and stimuli. The creation of an immune-related array is highly valuable in determining the host immune response in relation to infection with a wide variety of bacterial and viral diseases.

Results

Here we report the development of chicken immune-related cDNA libraries and the subsequent construction of a microarray containing 5190 elements (in duplicate). Clones on the array originate from tissues known to contain high levels of cells related to the immune system, namely Bursa, Peyers patch, thymus and spleen. Represented on the array are genes that are known to cluster with existing chicken ESTs as well as genes that are unique to our libraries. Some of these genes have no known homologies and represent novel genes in the chicken collection. A series of reference genes (ie. genes of known immune function) are also present on the array. Functional annotation data is also provided for as many of the genes on the array as is possible.

Conclusion

Six new chicken immune cDNA libraries have been created and nearly 10,000 sequences submitted to GenBank [GenBank: AM063043-AM071350; AM071520-AM072286; AM075249-AM075607]. A 5 K immune-related array has been developed from these libraries. Individual clones and arrays are available from the ARK-Genomics resource centre.
Synteny conservation between the Prunus genome and both the present and ancestral Arabidopsis genomes
Authors: Jung Sook , Main Dorrie , Staton Margaret , Cho Ilhyung , Zhebentyayeva Tatyana , Arús Pere , Abbott Albert
Published: April 2006

Background

Due to the lack of availability of large genomic sequences for peach or other Prunus species, the degree of synteny conservation between the Prunus species and Arabidopsis has not been systematically assessed. Using the recently available peach EST sequences that are anchored to Prunus genetic maps and to peach physical map, we analyzed the extent of conserved synteny between the Prunus and the Arabidopsis genomes. The reconstructed pseudo-ancestral Arabidopsis genome, existed prior to the proposed recent polyploidy event, was also utilized in our analysis to further elucidate the evolutionary relationship.

Results

We analyzed the synteny conservation between the Prunus and the Arabidopsis genomes by comparing 475 peach ESTs that are anchored to Prunus genetic maps and their Arabidopsis homologs detected by sequence similarity. Microsyntenic regions were detected between all five Arabidopsis chromosomes and seven of the eight linkage groups of the Prunus reference map. An additional 1097 peach ESTs that are anchored to 431 BAC contigs of the peach physical map and their Arabidopsis homologs were also analyzed. Microsyntenic regions were detected in 77 BAC contigs. The syntenic regions from both data sets were short and contained only a couple of conserved gene pairs. The synteny between peach and Arabidopsis was fragmentary; all the Prunus linkage groups containing syntenic regions matched to more than two different Arabidopsis chromosomes, and most BAC contigs with multiple conserved syntenic regions corresponded to multiple Arabidopsis chromosomes. Using the same peach EST datasets and their Arabidopsis homologs, we also detected conserved syntenic regions in the pseudo-ancestral Arabidopsis genome. In many cases, the gene order and content of peach regions was more conserved in the ancestral genome than in the present Arabidopsis region. Statistical significance of each syntenic group was calculated using simulated Arabidopsis genome.

Conclusion

We report here the result of the first extensive analysis of the conserved microsynteny using DNA sequences across the Prunus genome and their Arabidopsis homologs. Our study also illustrates that both the ancestral and present Arabidopsis genomes can provide a useful resource for marker saturation and candidate gene search, as well as elucidating evolutionary relationships between species.
Cloning and expression analysis of two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp, Ctenopharyngodon idellus
Authors: Law Sheran HW , Wu Rudolf SS , Ng Patrick KS , Yu Richard MK , Kong Richard YC
Published: April 2006

Background

Hypoxia-inducible factors (HIFs) are involved in adaptive and survival responses to hypoxic stress in mammals. In fish, very little is known about the functions of HIFs.

Results

We have cloned and characterized two distinct HIF-alpha cDNAs – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp. The deduced gcHIF-1alpha protein is highly similar to the HIF-1alphas (57–68%) from various vertebrate species, while gcHIF-4alpha is a novel isoform, and shows an equivalent degree of amino acid identity (41–47%) to the HIF-1alpha, HIF-2alpha and HIF-3alpha proteins so far described. Parsimony analysis indicated that gcHIF-4alpha is most closely related to the HIF-3alpha proteins. Northern blot analysis showed that mRNA levels of gcHIF-1alpha and gcHIF-4alpha differ substantially under normoxic and hypoxic conditions, while Western blot studies demonstrated that the endogenous protein levels for both gcHIF-1alpha and gcHIF-4alpha are similarly responsive to hypoxia. Our findings suggest that both gcHIF-1alpha and gcHIF-4alpha are differentially regulated at the transcriptional and translational levels. HRE-luciferase reporter assays show that both proteins function as transcription activators and play distinct roles in modulating the hypoxic response in grass carp.

Conclusion

There are at least two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – in the hypoxia-tolerant grass carp, which are differentially expressed and regulated in different fish organs in response to hypoxic stress. Overall, the results suggest that unique molecular mechanisms operate through these two HIF-alpha isoforms, which underpin the hypoxic response in the hypoxia-tolerant grass carp.
Convulsant bicuculline modifies CNS muscarinic receptor affinity
Authors: Schneider Patricia G , Rodríguez de Lores Arnaiz Georgina
Published: April 2006

Background

Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP), a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB) to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC), known to antagonize the GABA-A postsynaptic receptor subtype.

Results

We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg) and convulsant (7.5 mg/kg) doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity.

Conclusion

Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process itself. Findings support the notion that the muscarinic receptors play a major role in experimental epilepsy and provide a new example of differential neuronal plasticity.
Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats
Authors: Booze Rosemarie M , Wallace David R , Silvers Janelle M , Strupp Barbara J , Snow Diane M , Mactutus Charles F
Published: April 2006

Background

Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α2-adrenergic receptor (α2-AR) density in adolescent (35-days-old) rats, using [3H]RX821002 (5 nM).

Results

Sex-specific alterations of α2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α2-AR in parietal cortex.

Conclusion

These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine.
ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-β and constitutively active receptor induced gene expression
Authors: Lux Andreas , Salway Fiona , Dressman Holly K , Kröner-Lux Gabriele , Hafner Mathias , Day Philip JR , Marchuk Douglas A , Garland John
Published: April 2006

Background

TGF-β1 is an important angiogenic factor involved in the different aspects of angiogenesis and vessel maintenance. TGF-β signalling is mediated by the TβRII/ALK5 receptor complex activating the Smad2/Smad3 pathway. In endothelial cells TGF-β utilizes a second type I receptor, ALK1, activating the Smad1/Smad5 pathway. Consequently, a perturbance of ALK1, ALK5 or TβRII activity leads to vascular defects. Mutations inALK1cause the vascular disorder hereditary hemorrhagic telangiectasia (HHT).

Methods

The identification of ALK1 and not ALK5 regulated genes in endothelial cells, might help to better understand the development of HHT. Therefore, the human microvascular endothelial cell line HMEC-1 was infected with a recombinant constitutively active ALK1 adenovirus, and gene expression was studied by using gene arrays and quantitative real-time PCR analysis.

Results

After 24 hours, 34 genes were identified to be up-regulated by ALK1 signalling. Analysing ALK1 regulated gene expression after 4 hours revealed 13 genes to be up- and 2 to be down-regulated. Several of these genes, includingIL-8,ET-1,ID1,HPTPηandTEAD4are reported to be involved in angiogenesis. Evaluation of ALK1 regulated gene expression in different human endothelial cell types was not in complete agreement. Further on, disparity between constitutively active ALK1 and TGF-β1 induced gene expression in HMEC-1 cells and primary HUVECs was observed.

Conclusion

Gene array analysis identified 49 genes to be regulated by ALK1 signalling and at least 14 genes are reported to be involved in angiogenesis. There was substantial agreement between the gene array and quantitative real-time PCR data. The angiogenesis related genes might be potential HHT modifier genes. In addition, the results suggest endothelial cell type specific ALK1 and TGF-β signalling.
Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of aseptic meningitis
Authors: Lee Bonita E , Chawla Rupesh , Langley Joanne M , Forgie Sarah E , Al-Hosni Mohammed , Baerg Krista , Husain Entesar , Strong James , Robinson Joan L , Allen Upton , Law Barbara J , Dobson Simon , Davies H Dele
Published: April 2006

Background

The seasonality, clinical and radiographic features and outcome of aseptic meningitis have been described for regional outbreaks but data from a wider geographic area is necessary to delineate the epidemiology of this condition.

Methods

A retrospective chart review was completed of children presenting with aseptic meningitis to eight Canadian pediatric hospitals over a two-year period.

Results

There were 233 cases of proven enteroviral (EV) meningitis, 495 cases of clinical aseptic meningitis and 74 cases of possible aseptic meningitis with most cases occurring July to October. Headache, vomiting, meningismus and photophobia were more common in children ≥ 5 years of age, while rash, diarrhea and cough were more common in children < 5 years of age. Pleocytosis was absent in 22.3% of children < 30 days of age with proven EV meningitis. Enterovirus was isolated in cerebrospinal fluid (CSF) from 154 of 389 patients (39.6%) who had viral culture performed, and a nucleic acid amplification test for enterovirus was positive in CSF from 81 of 149 patients (54.3%). Imaging of the head by computerized tomography or magnetic resonance imaging was completed in 96 cases (19.7%) and 24 had abnormal findings that were possibly related to meningitis while none had changes that were definitely related to meningitis. There was minimal morbidity and there were no deaths.

Conclusion

The clinical presentation of aseptic meningitis varies with the age of the child. Absence of CSF pleocytosis is common in infants < 30 days of age. Enterovirus is the predominant isolate, but no etiologic agent is identified in the majority of cases of aseptic meningitis in Canadian children.
Detection of Norovirus genogroup I and II by multiplex real-time RT- PCR using a 3'-minor groove binder-DNA probe
Authors: Hoehne Marina , Schreier Eckart
Published: April 2006

Background

Due to an increasing number of norovirus infections in the last years rapid, specific, and sensitive diagnostic tools are needed. Reverse transcriptase-polymerase chain reactions (RT-PCR) have become the methods of choice. To minimize the working time and the risk of carryover contamination during the multi-step procedure of PCR the multiplex real-time RT-PCR for the simultaneous detection of genogroup I (GI) and II (GII) offers advantages for the handling of large amounts of clinical specimens.

Methods

We have developed and evaluated a multiplex one-tube RT-PCR using a combination of optimized GI and GII specific primers located in the junction between ORF1 and ORF2 of the norovirus genome. For the detection of GI samples, a 3'- minor groove binder-DNA probe (GI-MGB-probe) were designed and used for the multiplex real-time PCR.

Results

Comparable results to those of our in-house nested PCR and monoplex real-time-PCR were only obtained using the GI specific MGB-probe. The MGB-probe forms extremely stable duplexes with single-stranded DNA targets, which enabled us to design a shorter probe (length 15 nucleotides) hybridizing to a more conserved part of the GI sequences. 97 % of 100 previously norovirus positive specimens (tested by nested PCR and/or monoplex real-time PCR) were detected by the multiplex real-time PCR. A broad dynamic range from 2 × 10^1 to 2 × 10^7 genomic equivalents per assay using plasmid DNA standards for GI and GII were obtained and viral loads between 2.5 × 10^2 and 2 × 10^12 copies per ml stool suspension were detected.

Conclusion

The one-tube multiplex RT real-time PCR using a minor groove binder -DNA probe for GI is a fast, specific, sensitive and cost-effective tool for the detection of norovirus infections in both mass outbreaks and sporadic cases and may have also applications in food and environmental testing.
GAIA: An easy-to-use web-based application for interaction analysis of case-control data
Authors: Macgregor Stuart , Khan Imtiaz A
Published: April 2006

Background

The advent of cheap, large scale genotyping has led to widespread adoption of genetic association mapping as the tool of choice in the search for loci underlying susceptibility to common complex disease. Whilst simple single locus analysis is relatively trivial to conduct, this is not true of more complex analysis such as those involving interactions between loci. The importance of testing for interactions between loci in association analysis has been highlighted in a number of recent high profile publications.

Results

Genetic Association Interaction Analysis (GAIA) is a web-based application for testing for statistical interactions between loci. It is based upon the widely used case-control study design for genetic association analysis and is designed so that non-specialists may routinely apply tests for interaction. GAIA allows simple testing of both additive and additive plus dominance interaction models and includes permutation testing to appropriately correct for multiple testing. The application will find use both in candidate gene based studies and in genome-wide association studies. For large scale studies GAIA includes a screening approach which prioritizes loci (based on the significance of main effects at one or both loci) for further interaction analysis.

Conclusion

GAIA is available at http://www.bbu.cf.ac.uk/html/research/biostats.htm
WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study
Authors: Netinatsunthorn Wirote , Hanprasertpong Jitti , Dechsukhum Chavaboon , Leetanaporn Roengsak , Geater Alan
Published: April 2006

Background

WT1 is a tumor suppressor gene responsible for Wilms' tumor. WT1 reactivity is limited to ovarian serous carcinomas. Recent studies have shown that WT1 plays an important role in the progression of disease and indicates a poorer prognosis of human malignancies such as acute myeloid leukemia and breast cancer. The aims of this study were to determine the survival and recurrence-free survival of women with advanced serous epithelial ovarian carcinoma in relation to WT1 gene expression.

Methods

The study accrued women over an 18-year period, from 1987–2004. During the study period, 163 patients were diagnosed with advanced serous epithelial ovarian carcinoma and had undergone complete post-operative chemotherapy, but the final study group comprised 99 patients. The records of these women were reviewed and the paraffin-embedded tissue of these women stained with WT1 immunostaining. Survival analysis was performed using Kaplan-Meier and Cox regression methods.

Results

Fifty patients showed WT1 staining and forty-nine did not. Five-year survival of non-staining and staining groups were 39.4% and 10.7% (p < 0.00005); five-year recurrence-free survival of these groups were 29.8% and ≤ 7.5% (p < 0.00005), respectively. For survival the HR of WT1 staining, adjusted for residual tumor and chemotherapy response, was 1.98 (95% CI 1.28–3.79), and for recurrence-free survival the HR was 3.36 (95% CI 1.60–7.03). The HR for recurrence-free survival was not confounded by any other variables.

Conclusion

This study suggests that expression of WT1 gene may be indicative of an unfavorable prognosis in patients with advanced serous epithelial ovarian carcinoma.
Incidence rates and management of urinary tract infections among children in Dutch general practice: results from a nation-wide registration study
Authors: Kwok Wing-Yee , de Kwaadsteniet Marjolein CE , Harmsen Mirjam , van Suijlekom-Smit Lisette WA , Schellevis François G , van der Wouden Johannes C
Published: April 2006

Background

We aimed to investigate incidence rates of urinary tract infections in Dutch general practice and their association with gender, season and urbanisation level, and to analyse prescription and referral in case of urinary tract infections.

Method

During one calendar year, 195 general practitioners in 104 practices in the Netherlands registered all their patient contacts. This study was performed by the Netherlands Institute for Health Services Research (NIVEL) in 2001. Of 82,053 children aged 0 to 18 years, the following variables were collected: number of episodes per patient, number of contacts per episode, month of the year in which the diagnosis of urinary tract infection was made, age, gender, urbanisation level, drug prescription and referral.

Results

The overall incidence rate was 19 episodes per 1000 person years. The incidence rate in girls was 8 times as high as in boys. The incidence rate in smaller cities and rural areas was 2 times as high as in the three largest cities. Throughout the year, incidence rates varied with a decrease in summertime for children at the age of 0 to 12 years. Of the prescriptions, 66% were in accordance with current guidelines, but only 18% of the children who had an indication were actually referred.

Conclusion

This study shows that incidence rates of urinary tract infections are not only related to gender and season, but also to urbanisation. General practitioners in the Netherlands frequently do not follow the clinical guidelines for urinary tract infections, especially with respect to referral.
Cross-sectional and longitudinal construct validity of two rotator cuff disease-specific outcome measures
Authors: Razmjou Helen , Bean Andrea , van Osnabrugge Varda , MacDermid Joy C , Holtby Richard
Published: April 2006

Background

Disease-specific Quality Of Life (QOL) measures are devised to assess the impact of a specific disease across a spectrum of important domains of life. The purpose of this study was to examine the cross-sectional and longitudinal construct validity (sensitivity to change) of two rotator cuff disease-specific measures, the Rotator Cuff-Quality Of Life (RC-QOL) and the Western Ontario Rotator Cuff (WORC) index, in relation to one another and to other joint and limb specific measures in the same population of the patients suffering from rotator cuff pathology.

Methods

Participants enrolled were consecutive patients who received physical therapy for management of impingement syndrome or received treatment following rotator cuff repair, acromioplasty or decompression surgeries. All subjects received physical therapy treatment and completed four outcome measures at 3 single points (initial, interim, and final). Cross-sectional convergent validity was assessed at each of the 3 time-points by correlating the WORC and RC-QOL's scores to each other and to two alternative scales; a joint-specific scale, the American Shoulder and Elbow Surgeons (ASES) standardized shoulder assessment form and a limb-specific measure, the Upper Extremity Functional Index (UEFI). Non-parametric statistics (Spearman's rho and Wilcoxon-Mann-Whitney tests) examined the construct validity. The standardized response mean (SRM) was used to examine sensitivity to change.

Results

Forty-one participants entered the study and their scores were compared at 3 cross sectional single points. The correlation coefficients among the 4 measures varied from 0.60 to 0.91. Correlation between corresponding domains of the WORC and RC-QOL varied from 0.45 to 0.85. The known group validity was not significantly different among individual sub-scores and total scores. The final SRMs were (1.42), (1.43), (1.44), and (1.54) for the ASES, RCQOL, WORC, and UEFI respectively.

Conclusion

The WORC and RC-QOL exhibit similar cross-sectional convergent validity in patients suffering from rotator cuff pathology. The sensitivity to change was very close among all scores, with the UEFI having the highest sensitivity. Further research is needed to examine the extent to which each physical or emotional domain contributes to prognostic or therapeutic decision-making.
Display of a thermostable lipase on the surface of a solvent-resistant bacterium, Pseudomonas putida GM730, and its applications in whole-cell biocatalysis
Authors: Jung Heung-Chae , Kwon Seok-Joon , Pan Jae-Gu
Published: April 2006

Background

Whole-cell biocatalysis in organic solvents has been widely applied to industrial bioprocesses. In two-phase water-solvent processes, substrate conversion yields and volumetric productivities can be limited by the toxicity of solvents to host cells and by the low mass transfer rates of the substrates from the solvent phase to the whole-cell biocatalysts in water.

Results

To solve the problem of solvent toxicity, we immobilized a thermostable lipase (TliA) fromPseudomonas fluorescenson the cell surface of a solvent-resistant bacterium,Pseudomonas putidaGM730. Surface immobilization of enzymes eliminates the mass-transfer limitation imposed by the cell wall and membranes. TliA was successfully immobilized on the surface ofP. putidacells using the ice-nucleation protein (INP) anchoring motif fromPseudomonas syrinage. The surface location was confirmed by flow cytometry, protease accessibility and whole-cell enzyme activity using a membrane-impermeable substrate. Three hundred and fifty units of whole-cell hydrolytic activity per gram dry cell mass were obtained when the enzyme was immobilized with a shorter INP anchoring motif (INPNC). The surface-immobilized TliA retained full enzyme activity in a two-phase water-isooctane reaction system after incubation at 37°C for 12 h, while the activity of the free form enzyme decreased to 65% of its initial value. Whole cells presenting immobilized TliA were shown to catalyze three representative lipase reactions: hydrolysis of olive oil, synthesis of triacylglycerol and chiral resolution.

Conclusion

In vivosurface immobilization of enzymes on solvent-resistant bacteria was demonstrated, and appears to be useful for a variety of whole-cell bioconversions in the presence of organic solvents.
Primary aneurysmal bone cyst of coronoid process
Authors: Goyal Amit , Tyagi Isha , Syal Rajan , Agrawal Tanu , Jain Manoj
Published: April 2006

Background

Aneurysmal bone cysts are relatively uncommon in the facial skeleton. These usually affect the mandible but origin from the coronoid process is even rarer. To the best of our knowledge, this is the first reported case of a coronoid process aneurysmal bone cyst presenting as temporal fossa swelling.

Case presentation

A 17 year old boy presented with a progressively increasing swelling in the left temporal region developed over the previous 8 months. An expansile lytic cystic lesion originating from the coronoid process of the left mandible and extending into the infratemporal and temporal fossa regions was found on CT scan. It was removed by a superior approach to the infratemporal fossa.

Conclusion

Aneurysmal bone cyst of the coronoid process can attain enormous dimensions until the temporal region is also involved. A superior approach to the infratemporal fossa is a reasonable approach for such cases, providing wide exposure and access to all parts of the lesion and ensuring better control and complete excision.