bluuebunny/crossref_metadata_2025 huggingface dataset:
Anandamide initiates Ca2+ signaling via CB2 receptor linked to phospholipase C in calf pulmonary endothelial cells
Authors: Zoratti Cristina , Kipmen‐Korgun Dijle , Osibow Karin , Malli Roland , Graier Wolfgang F
Published: December 2003

The endocannabinoid anandamide has been reported to affect neuronal cells, immune cells and smooth muscle cells via either CB1 or CB2 receptors. In endothelial cells, the receptors involved in activating signal transduction are still unclear, despite the fact that anandamide is produced in this cell type.

The present study was designed to explore in detail the effect of this endocannabinoid on Ca2+ signaling in single cells of a calf pulmonary endothelial cell line.

Anandamide initiated a transient Ca2+ elevation that was prevented by the CB2 receptor antagonist SR144528, but not by the CB1 antagonist SR141716A. These data were confirmed by molecular identification of the bovine CB2 receptor in these endothelial cells by partial sequencing.

The phospholipase C inhibitor 1‐[6‐[[(17β)‐3‐methoxyestra‐1,3,5(10)‐trien‐17‐yl]amino]hexyl]‐1H‐pyrrole‐2,5dione and the inositol 1,4,5‐trisphosphate receptor antagonist 2‐aminoethoxydiphenylborate prevented Ca2+ signaling in response to anandamide.

Using an improved cameleon probe targeted to the endoplasmic reticulum (ER), fura‐2 and ratiometric‐pericam, which is targeted to the mitochondria, anandamide was found to induce Ca2+ depletion of the ER accompanied by the activation of capacitative Ca2+ entry (CCE) and a transient elevation of mitochondrial Ca2+.

These data demonstrate that anandamide stimulates the endothelial cells used in this study via CB2 receptor‐mediated activation of phospholipase C, formation of inositol 1,4,5‐trisphosphate, Ca2+ release from the ER and subsequent activation of CCE. Moreover, the cytosolic Ca2+ elevation was accompanied by a transient Ca2+ increase in the mitochondria. Thus, in addition to its actions on smooth muscle cells, anandamide also acts as a powerful stimulus for endothelial cells.

British Journal of Pharmacology (2003) 140, 1351–1362. doi:10.1038/sj.bjp.0705529
Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase
Authors: Eynott Paul R , Nath Puneeta , Leung Sum‐Yee , Adcock Ian M , Bennett Brydon L , Chung K Fan
Published: December 2003

Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N‐terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)‐1.

We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9‐cd] pyrazole‐6 (2 H)‐one), in a model of chronic allergic inflammation in the rat.

Rats sensitised to ovalbumin (OA) were exposed to OA‐aerosol every third day on six occasions and were treated with SP600125 (30 mg kg−1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T‐cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine.

SP600125 significantly reduced the number of eosinophils (P<0.05) and lymphocytes (P<0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (P<0.05) and CD2+ T‐cell (P<0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (P<0.05) and epithelial cell incorporation (P<0.05).

SP600125 did not alter bronchial hyper‐responsiveness observed after chronic allergen exposure.

Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.

British Journal of Pharmacology (2003) 140, 1373–1380. doi:10.1038/sj.bjp.0705569
ET‐1‐associated vasomotion and vasospasm in lymphatic vessels of the guinea‐pig mesentery
Authors: Zhao Jun , Van Helden Dirk F
Published: December 2003

In vitro experiments were performed to investigate the actions of endothelin‐1 (ET‐1) on vasomotion and vasospasm in guinea‐pig mesenteric lymphatics.

ET‐1 modulated lymphatic vasomotion independent of the endothelium, with lower concentrations (10 nM) increasing lymphatic vasomotion and higher concentrations (100 nM) causing vasospasm.

ET‐1‐induced increases in vasomotion were accompanied by an increase in tonic [Ca2+]i.

These actions were inhibited by the ETA receptor antagonist BQ‐123 (1 μM), the phospholipase C (PLC) inhibitor U73122 (5 μM), removal of extracellular Ca2+, chelation of intracellular Ca2+ with BAPTA/AM (10 μM), the store Ca2+‐ATPase inhibitor thapsigargin (1 μM), caffeine (10 mM) and the inositol 1,4,5‐trisphosphate (IP3) receptor blocker heparin and 2‐APB (30 μM). In contrast, the ETB receptor antagonist BQ‐788 (1 μM), ryanodine (1 & 20 μM), pertussis toxin (PTx) or Cs+ had no significant actions on vasomotion or the magnitude of increase in tonic [Ca2+]i.

ET‐1‐induced vasospasm was accompanied by a transient increase in smooth muscle [Ca2+]i followed by a sustained plateau, an action that was abolished by removal of extracellular Ca2+, but only marginally inhibited by nifedipine (1 μM).

Caffeine (10 mM), SKF 96165 (30 μM) or U73122 (5 μM) together with nifedipine (1 μM) abolished ET‐1‐induced vasospasm and increase in [Ca2+]i.

These results indicate that ET‐1 increases lymphatic vasomotion by acting on smooth muscle ETA receptors and activation of G‐protein‐PLC‐IP3 cascade, which is known to cause pacemaker Ca2+ release and resultant pacemaker potentials. High concentrations of ET‐1 cause a failure in Ca2+ homeostasis causing vasospasm, triggered by excessive Ca2+ influx primarily through store‐operated channels (SOCs) with L‐Ca2+ voltage‐operated channels (VOCs) also contributing, but to a much lesser extent.

British Journal of Pharmacology (2003) 140, 1399–1413. doi:10.1038/sj.bjp.0705573
Linkage and QTL mapping for Sus scrofa chromosome 2
Authors: Lee S. S. , Chen Y. , Moran C. , Cepica S. , Reiner G. , Bartenschlager H. , Moser G. , Geldermann H.
Published: December 2003

Sus scrofa chromosome 2 (SSC2) linkage maps were generated from three F2 families involving Meishan (M), Pietrain (P) and Wild Boar (W) crosses and the same 10 marker loci. SSC2 linkage maps were similar between families and correspond to published maps. Quantitative trait loci (QTLs) for carcass traits, daily gain and heart weight were identified on SSC2, especially in the intervals 0–20 and 80–90 cM in the M × P family, the intervals 20–50 and 125–140 cM in the W × P family, and the interval 15–70 cM in the W × M family. QTL presence and position varied among families. QTL effects explained up to 10% of F2 phenotypic variance. Pietrain QTL alleles were associated with high muscle and heart mass, high daily gain and low fat deposition and Meishan alleles with high carcass fat content. Wild Boar alleles were associated with leaner carcass but lower daily gain than Meishan alleles.
Linkage and QTL mapping forSus scrofachromosome 6
Authors: Yue G. , Stratil A. , Kopecny M. , Schröffelova D. , Schröffel J. , Hojny J. , Cepica S. , Davoli R. , Zambonelli P. , Brunsch C. , Sternstein I. , Moser G. , Bartenschlager H. , Reiner G. , Geldermann H.
Published: December 2003

Linkage maps have been constructed forSus scrofachromosome 6 (SSC6) based on 17 markers, of which 10 were used in all three F2families of Wild Boar (W), Meishan (M) and Pietrain (P) crosses. The coverage of the linkage maps of SSC6 was almost complete. All loci were ordered identically in the families, but two intervals (RYR1‐A1BG‐EAH,S0146‐S0003‐SW824) differed from published maps. Major quantitative trait loci (QTLs) for meat quality, stress resistance and carcass composition explaining up to 59% of F2phenotypic variance have been mapped in the M × P and W × P families centred on the segregatingRYR1T and C alleles. In the W × M family, which was homozygous for theRYR1 Callele, no QTL effects for meat quality and stress‐resistance, but moderate effects for carcass composition have been observed in this region. These findings indicate further loci closely linked with theRYR1or/and further alleles at theRYR1locus, involved in the variation of carcass and growth traits.
Linkage and QTL mapping for Sus scrofa chromosome 8
Authors: Beeckmann P. , Moser G. , Bartenschlager H. , Reiner G. , Geldermann H.
Published: December 2003

Linkage maps of Sus scrofa chromosome 8 (SSC8) were constructed using seven markers in three F2 families based on Meishan (M), Pietrain (P) and Wild Boar (W) crosses. The maps were similar for the pedigrees and in agreement with published maps. Most quantitative trait loci (QTLs) were found for the W × P family, while only minor QTLs were detected in the M × P and W × M families. SSC8 harbours QTLs mapped in the interval SW905 to SW933 explaining up to 6% of the F2 phenotypic variance for body conformation, carcass and growth traits. Pietrain alleles positively influenced carcass traits, with additive effects often larger than dominance effects. For food conversion ratio a large dominance QTL effect was observed in the M × P family.
Linkage and QTL mapping for Sus scrofa chromosome 10
Authors: Dragos‐Wendrich M. , Moser G. , Bartenschlager H. , Reiner G. , Geldermann H.
Published: December 2003

Linkage and QTL maps of Sus scrofa chromosome 10 (SSC10) were constructed by genotyping six microsatellite markers in three F2 families based on Wild Boar (W), Meishan (M) and Pietrain (P) crosses. The linkage maps were similar for the families and in agreement with the published maps. Quantitative Trait Loci (QTLs) were found in the M × P and W × M families, but not in the W × P family. In both these families, QTLs for the number of teats were mapped on distal SSC10. Further, QTLs in the W × M family affect the weight of head, live weight and carcass weight traits and were mapped proximally on SSC10 near SW830. The QTLs on SSC10 explained up to 6.5% of F2 phenotypic variance. QTL effects for some traits were overdominant. Except for the weight of head, Wild Boar alleles slightly increased weight traits and, unexpectedly, markedly increased teat numbers in comparison with Meishan alleles. In the M × P family, however, teat number was increased by Meishan alleles.
Linkage and QTL mapping for Sus scrofa chromosome 18
Authors: Dragos‐Wendrich M. , Stratil A. , Hojny J. , Moser G. , Bartenschlager H. , Reiner G. , Geldermann H.
Published: December 2003

Linkage and QTL maps of Sus scrofa chromosome 18 (SSC18) were generated using five markers in three F2 families based on Wild Boar (W), Pietrain (P) and Meishan (P) crosses. The linkage maps were similar for the three families and confirm the published map. Quantitative trait loci (QTLs) for meat content, fat‐to‐meat ratio, weight of liver and food conversion ratio were mapped in the W × M family. A QTL for pH value 24 h after slaughter in Musculus semimembranosus was found in the M × P family. The QTL for carcass meat content and fat‐to‐meat ratio in the W × M family were localized near the leptin gene (LEP).
Therapeutic Effects of Fig Tree Latex on Bovine Papillomatosis
Authors: Hemmatzadeh F. , Fatemi A. , Amini F.
Published: December 2003

The effects of fig tree latex in treating teat papillomatosis in cow in comparison with salicylic acid were evaluated. For this purpose, 12 cows of 1–3 years of age (average 2.25) affected by teat papillomatosis were divided into three groups. In group A, four cows were treated by fig tree (Ficus carica) latex; in group B, four cows were treated with 10% salicylic acid solution and in group C, four cows were kept as control animals receiving no treatment. Animals in each treatment group received their treatment once every 5 days.

In groups A and B, de‐epithelialization and shrinking of the warts began from the fifth day of treatment and all the warts disappeared within 30 days. However, in the control group no changes in the number of warts were observed until day 15 but thereafter a number of warts disappeared spontaneously in some of the animals. Both salicylic acid and fig tree latex were evaluated as having similar therapeutic effects in treating teat papillomatosis in cow.
Genetic Diversity at alkB Locus in Brucella abortus
Authors: Marianelli C. , La Rosa G. , Ciuchini F. , Muscillo M. , Pasquali P. , Adone R.
Published: December 2003

DNA polymorphism of the alkB gene, a DNA repair gene, was assessed by PCR on Brucella abortus biovars 1 (strains 99, S19, 45/20, RB51 and 2308), 3 (Tulya strain), 5 (B3196 strain) and 6 (870 strain). A DNA repetitive element, named IS711, was detected in all studied biovars 1 and its complete nucleotide sequence was determined. We found that the element in alkB gene, bounded by 14 bp imperfect inverted repeats (IRs), is 840 bp long and appears to duplicate a consensus target site, CTAG. Analysing its nucleotide sequence of both forward and reverse strands, more than 10 open reading frames (ORFs) were found. Two potential transposase coding regions were chosen comparing all possible ORFs with the database. Comparing IS711 elements isolated from Brucella species, including both those characterized in our work and the published ones, differences in length and in nucleotide composition were observed among Brucella species, members of the same species and within the same strain. Our results confirm the heterogeneity of IS711 elements in Brucella genus and suggest the possibility to use this element to assess gene and genome diversity and to identify new molecular markers for Brucella species.
Investigations into an Outbreak of Tuberculosis in a Flock of Sheep in Contact with Tuberculous Cattle
Authors: Malone F. E. , Wilson E. C. , Pollock J. M. , Skuce R. A.
Published: December 2003

Tuberculosis, associated with Mycobacterium bovis infection, occurs infrequently in sheep. A sheep flock, which was potentially exposed to a high level of infection from in‐contact tuberculous cattle, was examined for evidence of infection. Six sheep that had given a positive reaction to the comparative intradermal tuberculin test were examined post mortem. Tuberculous lesions were present in four of these sheep. Lesion morphology and distribution in the sheep was similar to that in cattle. M. bovis was cultured from the lesions and the isolates were strain typed by spoligotyping and variable number of tandem repeats (VNTR) typing. Tuberculin‐reacting sheep also reacted positively to an assay for in vitro release of interferon‐γ. This paper describes the first report of an outbreak of tuberculosis in sheep in either Britain or Ireland. The report describes immunology and pathology findings and, using molecular typing techniques, suggests that the sheep had been infected from in‐contact cattle.
Endophytic fungi alter relationships between diversity and ecosystem properties
Authors: Rudgers Jennifer A. , Koslow Jennifer M. , Clay Keith
Published: December 2003

Recent studies have expanded research on biodiversity by investigating whether the effects of diversity on ecosystem functioning hinge on the presence of symbiotic microorganisms. Cool‐season grasses commonly harbour endophytic fungi that can enhance plant resistance to herbivory, drought and competition. We address whether these endosymbionts modify relationships between diversity and two ecosystem properties: productivity and invasibility. We develop a graphical model that predicts endophyte infection of a grass host will weaken correlations between diversity and ecosystem properties. We then use a long‐term field experiment to test this prediction by manipulating symbiosis in tall fescue grass (Festuca arundinacea), a common and invasive species in the US. As predicted, endophyte infection reduced the strength of correlations between diversity and both primary productivity and the invasiveness of tall fescue. By altering relationships between diversity and ecosystem functioning, endophytic fungi may contribute more to the dynamics of communities than previously supposed.
Delayed treatment with melatonin enhances electrophysiological recovery following transient focal cerebral ischemia in rats
Authors: Lee E‐Jian , Wu Tian‐Shung , Lee Ming‐Yang , Chen Tsung‐Ying , Tsai Yi‐Yin , Chuang Jih‐Ing , Chang Guan‐Liang
Published: December 2003

Abstract:  Melatonin has been reported to reduce infarct volumes induced by transient middle cerebral artery (MCA) occlusion. We examined whether melatonin could improve electrophysiological and neurobehavioral recoveries in rats after 72 hr of reperfusion following 1.5 hr of MCA occlusion. Melatonin (5 mg/kg) or vehicle was given intravenously at the commencement of reperfusion. Neurobehavioral outcome was serially examined, and somatosensory evoked potentials (SSEP) were recorded prior to ischemia and at 72 hr after the onset of reperfusion. Brain infarction was assessed upon killing. Before ischemia‐reperfusion, stable SSEP waveforms were consistently recorded after individual fore‐ or hindpaw stimulation. The amplitude between the first positive (P1) and the first negative (N1) peaks and the P1 latency did not differ significantly between controls and melatonin‐treated animals. At 72 hr of reperfusion, controls had severely depressant SSEPs recorded from ischemic fore‐ and hindpaw cortical fields, and the amplitudes decreased to 36 and 35% of baselines, respectively (P < 0.001). These animals also had transcallosal electrophysiological diaschisis in the SSEPs recorded at the contralateral hindpaw cortical field (P < 0.01). Relative to controls, melatonin‐treated animals not only had significantly improved amplitudes of the SSEPs recorded from both ischemic fore‐ and hindpaw cortical fields, by 33 and 37% of baselines, respectively (P < 0.001), but also exhibited diminished transcallosal electrophysiological diaschisis following ischemia‐reperfusion. In addition, melatonin improved sensory and motor neurobehavioral outcomes by 40 and 28%, respectively (P < 0.001), and reduced cortical and striatal infarct sizes by 32 and 40%, respectively (P < 0.05). Thus, delayed intravenous administration with melatonin both enhances electrophysiological and neurobehavioral recoveries and reduces cortical and striatal infarct sizes after cerebral ischemia and reperfusion injury.
Melatonin attenuates rat carotid chemoreceptor response to hypercapnic acidosis
Authors: Tjong Yung Wui , Chen Yueping , Liong Emily C. , Ip Shing Fat , Tipoe George L. , Fung Man Lung
Published: December 2003

Abstract: Respiratory activity is under circadian modulation and the physiological mechanisms may involve the pineal secretory product, melatonin, and the carotid chemoreceptor. We hypothesized that melatonin modulates the carotid chemoreceptor response to hypercapnic acidosis. To determine whether the effect of melatonin on the chemoreceptor response to hypercapnic acidosis is mediated by melatonin receptors in the chemosensitive cells, cytosolic calcium ([Ca2+]i) was measured by spectrofluorometry in fura‐2‐loaded glomus cells dissociated from rat carotid bodies. Melatonin (0.01–10 nm) per se did not change the [Ca2+]i levels of the glomus cells but it concentration‐dependently attenuated the peak [Ca2+]i response to hypercapnic acidosis in the glomus cells. In addition, the [Ca2+]i response was attenuated by 2‐iodomelatonin, an agonist of melatonin receptors. The melatonin‐induced attenuation of the [Ca2+]i response to hypercapnic acidosis was abolished by pretreatment with an non‐selective mt1/MT2 antagonist, luzindole, and by MT2 antagonists, 4‐phenyl‐2‐propionamidotetraline or DH97. In situ hybridization study with antisense mt1 and MT2 receptor mRNA oligonucleotide probes showed an expression of mt1 and MT2 receptors in the rat carotid body. Also, melatonin attenuated the carotid afferent response to hypercapnic acidosis in single‐ or pauci‐fibers recorded from the sinus nerve in isolated carotid bodies superfused with bicarbonate‐buffer saline. Results suggest that an activation of the melatonin receptors expressed in the glomus cells of the rat carotid body reduces the chemoreceptor response to hypercapnic acidosis. This modulation may play a physiological role in the influence of the circadian rhythms on the chemoreflex.
Geochemical factors affecting leachate composition derived from soils in reclaimed lands using laboratory fresh and saline water column experiments
Authors: Suh Jeong-Yul , Brown Paul L. , Birch Gavin F.
Published: December 2003

The present study compared the geochemistry of saline and freshwater percolating through columns containing soils sampled from reclaimed land adjoining Sydney Harbour, Australia. The investigation assessed the flux of contaminants from the soil and, hence, estimated the affect of reclaimed land (using construction waste or dredged sediment) on the adjoining aquatic environment. Leachate samples were collected weekly for 22 weeks and were monitored for pH, Eh (redox potential), electrical conductivity, dissolved oxygen, major elements and heavy metals. In the early stages of the experiment (until approximately Week 12), the concentrations of the major elements in water percolating from the two columns were similar. Differing pseudo-steady-state conditions were reached in the columns after approximately 14 weeks. Sodium and Cl are weakly sorbed onto surface sites of the material in the saline column. The exchange of Na with other cations results in an increase in the aqueous concentrations of Ca, K and Mg in this column. As the parallel field concentrations are considerably higher than those measured in the column experiments, and are much higher (by orders of magnitude) than those measured in seawater, results of the fresh and saline water column tests strongly indicate that elevated concentrations of trace metals probably enter the estuary by tidal action and during periods of rainfall.
Does salinity influence the distribution of exotic willows (Salix spp.) along the Lower River Murray?
Authors: Kennedy Shaun A. , Ganf George G. , Walker Keith F.
Published: December 2003

The weeping willow Salix babylonica and crack willow S. fragilis dominate the riparian vegetation of the River Murray between Mannum and Wellington, South Australia, Australia. The presence of S. fragilis is confirmed, over-riding earlier, informal references to S. × rubens. In this region S. babylonica is represented by females and S. fragilis is represented by males. The flowering times of the two species overlap but the growing season begins earlier for the former. No evidence of hybridization was found, although this is not conclusive. Salix babylonica is most common upstream of Murray Bridge whereas S. fragilis occurs mainly downstream. A field survey in 1999 showed that estimated soil water conductivity varied between sites (median 6.0 mS cm–1) along the river, but this was not reflected in the distributions of the species. In a glasshouse experiment, cuttings of both species proved intolerant of conductivities exceeding 7 mS cm–1. In the field, foliar salt levels indicated that neither species was salt-stressed, despite growing in moderately saline soil. Also, it appears that the trees may access less saline river water in preference to that in the soil. The distributions of the two species in this region could reflect the history of planting rather than salinity tolerance.
Combining DNA expression with positional information to detect functional silencing of chromosomal regions
Authors: Hüsing Johannes , Zeschnigk Michael , Boes Tanja , Jöckel Karl-Heinz
Published: December 2003

Motivation: Loss of chromosomal material is often observed in cancer cells. In this situation the expression of genes is related to their position on the genome. Epigenetic phenomena may also silence several genes in the same region of a chromosome. While cytogenetic or other molecular genetic methods spot changes of DNA copy number, they cannot detect other causes of silencing.

Results: We propose a method that utilizes the link from expression information gained from high-density DNA microarrays to the gene locus according to current databases. Statistical methods adequate to spot conspicuous runs of non-expressed genes are introduced and compared to one another by merit of their power and robustness against false positives.

Availability: Code for the formulae can be obtained (R code) via http://www.panix.com/~derwisch/hannes/longrun
JXP4BIGI: a generalized, Java XML-based approach for biological information gathering and integration
Authors: Huang Yihua , Ni Tianyun , Zhou Lei , Su Stanley
Published: December 2003

Motivation: In the post-genomic era, biologists interested in systems biology often need to import data from public databases and construct their own system-specific or subject-oriented databases to support their complex analysis and knowledge discovery. To facilitate the analysis and data processing, customized and centralized databases are often created by extracting and integrating heterogeneous data retrieved from public databases. A generalized methodology for accessing, extracting, transforming and integrating the heterogeneous data is needed.

Results: This paper presents a new data integration approach named JXP4BIGI (Java XML Page for Biological Information Gathering and Integration). The approach provides a system-independent framework, which generalizes and streamlines the steps of accessing, extracting, transforming and integrating the data retrieved from heterogeneous data sources to build a customized data warehouse. It allows the data integrator of a biological database to define the desired bio-entities in XML templates (or Java XML pages), and use embedded extended SQL statements to extract structured, semi-structured and unstructured data from public databases. By running the templates in the JXP4BIGI framework and using a number of generalized wrappers, the required data from public databases can be efficiently extracted and integrated to construct the bio-entities in the XML format without having to hard-code the extraction logics for different data sources. The constructed XML bio-entities can then be imported into either a relational database system or a native XML database system to build a biological data warehouse.

Availability: JXP4BIGI has been integrated and tested in conjunction with the IKBAR system (http://www.ikbar.org/) in two integration efforts to collect and integrate data for about 200 human genes related to cell death from HUGO, Ensembl, and SWISS-PROT (Bairoch and Apweiler, 2000), and about 700 Drosophila genes from FlyBase (FlyBase Consortium, 2002). The integrated data has been used in comparative genomic analysis of x-ray induced cell death. Also, as explained later, JXP4BIGI is a middleware and framework to be integrated with biological database applications, and cannot run as a stand-alone software for end users. For demonstration purposes, a demonstration version is accessible at (http://www.ikbar.org/jxp4bigi/demo.html).
Algorithms for large-scale genotyping microarrays
Authors: Liu Wei-min , Di Xiaojun , Yang Geoffrey , Matsuzaki Hajime , Huang Jing , Mei Rui , Ryder Thomas B. , Webster Teresa A. , Dong Shoulian , Liu Guoying , Jones Keith W. , Kennedy Giulia C. , Kulp David
Published: December 2003

Motivation: Analysis of many thousands of single nucleotide polymorphisms (SNPs) across whole genome is crucial to efficiently map disease genes and understanding susceptibility to diseases, drug efficacy and side effects for different populations and individuals. High density oligonucleotide microarrays provide the possibility for such analysis with reasonable cost. Such analysis requires accurate, reliable methods for feature extraction, classification, statistical modeling and filtering.

Results: We propose the modified partitioning around medoids as a classification method for relative allele signals. We use the average silhouette width, separation and other quantities as quality measures for genotyping classification. We form robust statistical models based on the classification results and use these models to make genotype calls and calculate quality measures of calls. We apply our algorithms to several different genotyping microarrays. We use reference types, informative Mendelian relationship in families, and leave-one-out cross validation to verify our results. The concordance rates with the single base extension reference types are 99.36% for the SNPs on autosomes and 99.64% for the SNPs on sex chromosomes. The concordance of the leave-one-out test is over 99.5% and is 99.9% higher for AA, AB and BB cells. We also provide a method to determine the gender of a sample based on the heterozygous call rate of SNPs on the X chromosome. See http://www.affymetrix.com for further information. The microarray data will also be available from the Affymetrix web site.

Availability: The algorithms will be available commercially in the Affymetrix software package.
LOX-DB—a database on lipoxygenases
Authors: Lütteke T. , Krieg P. , Fürstenberger G. , von der Lieth C.-W.
Published: December 2003

Summary: Lipoxygenases are a family of enzymes involved in a variety of human diseases like inflammation, asthma, artherosclerosis and cancer. The lipoxygenases database (LOX-DB) aims to be a web accessible compendium of information in particular on the mammalian members of this multigene family. This resource includes molecular structures, reference data, tools for structural and computational analysis as well as links to related information maintained by others. The data can be retrieved by the use of various search options and analyzed applying publicly available visualization tools.

Availability: LOX-DB is available at http://www.dkfz-heidelberg.de/spec/lox-db/
Global snapshot of a protein interaction network—a percolation based approach
Authors: Chin Chen-Shan , Samanta Manoj Pratim
Published: December 2003

Motivation: Biologically significant information can be revealed by modeling large-scale protein interaction data using graph theory based network analysis techniques. However, the methods that are currently being used draw conclusions about the global features of the network from local connectivity data. A more systematic approach would be to define global quantities that measure (1) how strongly a protein ties with the other parts of the network and (2) how significantly an interaction contributes to the integrity of the network, and connect them with phenotype data from other sources. In this paper, we introduce such global connectivity measures and develop a stochastic algorithm based upon percolation in random graphs to compute them.

Results: We show that, in terms of global connectivities, the distribution of essential proteins is distinct from the background. This observation highlights a fundamental difference between the essential and the non-essential proteins in the network. We also find that the interaction data obtained from different experimental methods such as immunoprecipitation and two-hybrid techniques contribute differently to network integrities. Such difference between different experimental methods can provide insight into the systematic bias present among these techniques.

Supplementary information: The full list of our results can be found in the supplemental web site http://www.nas.nasa.gov/Groups/SciTech/nano/msamanta/projects/percolation/index.php
Susceptibility of non-linear systems as an approach to metabolic responses
Authors: Torralba Antonio S.
Published: December 2003

Motivation: Recent developments of several analytical techniques and fast sampling procedures are making it possible to study non-linear dynamics on an automated basis. Approaches that suggest experimental setups and fully exploit the data are needed. To prevent unreliable fits of parameters to experimental data, model-independent methods would be advantageous. One such method consists in representing the response of a system by means of a transformation or functional, of an excitation, i.e. a flux of a metabolite.

Results: A functional of unknown form can be expanded in series if its functional derivatives are known. An algorithm for calculating such generalized derivatives from impulse-perturbation experiments was developed. The only assumption was that the implicit kinetics is time-independent, i.e. the system is time-invariant. The method is illustrated on a part of fructose catabolism. A reaction network that involves 14 metabolites and 11 enzymes and includes several branches and feedback loops is considered. It is shown that the method provides good approximations to the responses of this complex system.

Availability: FUNDER is available from http://bbm1.ucm.es/torralba/funder/down/

Supplementary information:  http://bbm1.ucm.es/torralba/funder/
Assessing sequence comparison methods with the average precision criterion
Authors: Chen Zhuoran
Published: December 2003

Motivation: Comprehensive performance assessment is important for improving sequence database search methods. Sensitivity, selectivity and speed are three major yet usually conflicting evaluation criteria. The average precision (AP) measure aims to combine the sensitivity and selectivity features of a search algorithm. It can be easily visualized and extended to analyze results from a set of queries. Finally, the time–AP plot can clearly show the overall performance of different search methods.

Results: Experiments are performed based on the SCOP database. Popular sequence comparison algorithms, namely Smith–Waterman (SSEARCH), FASTA, BLAST and PSI-BLAST are evaluated. We find that (1) the low-complexity segment filtration procedure in BLAST actually harms its overall search quality; (2) AP scores of different search methods are approximately in proportion of the logarithm of search time; and (3) homologs in protein families with many members tend to be more obscure than those in small families. This measure may be helpful for developing new search algorithms and can guide researchers in selecting most suitable search methods.

Availability: Test sets and source code of this evaluation tool are available upon request.
Characterizing gene sets with FuncAssociate
Authors: Berriz Gabriel F. , King Oliver D. , Bryant Barbara , Sander Chris , Roth Frederick P.
Published: December 2003

Summary: FuncAssociate is a web-based tool to help researchers use Gene Ontology attributes to characterize large sets of genes derived from experiment. Distinguishing features of FuncAssociate include the ability to handle ranked input lists, and a Monte Carlo simulation approach that is more appropriate to determine significance than other methods, such as Bonferroni or S̆idák p-value correction. FuncAssociate currently supports 10 organisms (Vibrio cholerae, Shewanella oneidensis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Caenorhaebditis elegans, Drosophila melanogaster, Mus musculus, Rattus norvegicus and Homo sapiens).

Availability: FuncAssociate is freely accessible at http://llama.med.harvard.edu/Software.html. Source code (in Perl and C) is freely available to academic users ‘as is’.
Activation of Receptor-Mediated Angiogenesis and Signaling Pathways after VEGF Administration in Fetal Rat CNS Explants
Authors: Mani Nina , Khaibullina Alfia , Krum Janette M. , Rosenstein Jeffrey M.
Published: December 2003

The angiogenic role of vascular endothelial growth factor (VEGF) receptors, flk-1 and flt-1, and their downstream signaling pathways, MAPK/ERK and PI-3 kinase, were examined in a fetal rat cortical explant model after exposure to exogenous VEGF. Treatment with VEGF resulted in substantial neovascularization characterized by increased vascular flk-1 receptor expression, whereas flt-1 receptor protein expression was absent. The specific role of flk-1 receptors in the angiogenic process was confirmed by the addition of antisense oligonucleotides (AS-ODNs) to flk-1, which blocked angiogenesis, whereas AS-ODNs to flt-1 had no effect. These results were further supported by the finding that specific chemical inhibition of flk-1 receptors caused disruption of the angiogenic response, whereas inhibition of the flt-1 receptors had no effect. Application of either MAPK/ERK or PI-3 kinase pathway inhibitors disrupted VEGF-induced angiogenesis, thereby indicating that both signaling pathways mediate this process. Thus VEGF binding to the endothelial flk-1 receptor activates the MAPK/ERK and PI-3 kinase pathways, resulting in neoangiogenic events. Of interest is the fact that although VEGF is regarded as a vascular permeability factor, its application to nascent cortical tissue caused an increase in a key physiologic protein of the blood-brain barrier function, glucose transporter-1, suggesting that the cytokine may have a role in blood-brain barrier development.
Determination of Kinetic Rate Constants for 2-[18F]fluoro-2-deoxy-d-glucose and Partition Coefficient of Water in Conscious Macaques and Alterations in Aging or Anesthesia Examined on Parametric Images with an Anatomic Standardization Technique
Authors: Noda Akihiro , Takamatsu Hiroyuki , Minoshima Satoshi , Tsukada Hideo , Nishimura Shintaro
Published: December 2003

Kinetic rate constants for 2-[18F]fluoro-2-deoxy-d-glucose (FDG) and the tissue-blood partition coefficient of water were determined using dynamic positron emission tomography in conscious macaques, and alterations in these parameters in aging or anesthesia were also examined. The parameters were estimated on a pixel-by-pixel basis using an anatomic standardization technique; group differences were then examined on the parametric images from the young, aged, and anesthesia groups. For the conscious condition, seven young and seven aged male rhesus macaques were used; six young male rhesus macaques were used for the isoflurane anesthesia condition. H215O and FDG were used as tracers. The kinetic parameters were estimated by a nonlinear least-square fitting procedure with compartment models including terms for the cerebral blood volume (CBV) and time delay of the input function. Cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRglc) were also calculated from the estimated parameters. In the aged group, glucose phosphorylation was decreased more than glucose transport, and the occipital cortex was the most affected region where reduction in CBV, CMRglc, and CBF were also observed. In the anesthesia group, glucose transport was decreased; however, glucose phosphorylation was not affected except for the occipital pole. The occipital cortex was also the most affected region. The tissue-blood partition coefficient of water was decreased globally.
Plasmatic Level of Neuroinflammatory Markers Predict the Extent of Diffusion-Weighted Image Lesions in Hyperacute Stroke
Authors: Montaner Joan , Rovira Alex , Molina Carlos A. , Arenillas Juan F. , Ribó Marc , Chacón Pilar , Monasterio Jasone , Alvarez-Sabín José
Published: December 2003

Sixteen patients with acute middle cerebral artery stroke were studied to correlate neuroinflammatory markers with perfusion- and diffusion-weighted magnetic resonance imaging (MRI) lesion volumes (PWI and DWI). At arrival (less than 6 hours), plasmatic matrix metalloproteinase (MMP)-9, MMP-2, interleukin (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1, and tumor necrosis factor (TNF)-α were serially measured (by ELISA), and MRI was performed. In cerebral ischemia, tissue destruction seems related to matrix metalloproteinases expression because baseline MMP-9 was the only predictor of the infarct volume measured as a DWI lesion (lineal regression: b = 0.50, 0.25–0.74; P < 0.001). Moreover, the extent of hypoperfused brain area (PWI) was associated with a proinflammatory cytokine release in the next hours (TNF-α and IL-6).
Magnetic Resonance Imaging in Experimental Models of Brain Disorders
Authors: Dijkhuizen Rick M. , Nicolay Klaas
Published: December 2003

This review gives an overview of the application of magnetic resonance imaging (MRI) in experimental models of brain disorders. MRI is a noninvasive and versatile imaging modality that allows longitudinal and three-dimensional assessment of tissue morphology, metabolism, physiology, and function. MRI can be sensitized to proton density, T1, T2, susceptibility contrast, magnetization transfer, diffusion, perfusion, and flow. The combination of different MRI approaches (e.g., diffusion-weighted MRI, perfusion MRI, functional MRI, cell-specific MRI, and molecular MRI) allows in vivo multiparametric assessment of the pathophysiology, recovery mechanisms, and treatment strategies in experimental models of stroke, brain tumors, multiple sclerosis, neurodegenerative diseases, traumatic brain injury, epilepsy, and other brain disorders. This report reviews established MRI methods as well as promising developments in MRI research that have advanced and continue to improve our understanding of neurologic diseases and that are believed to contribute to the development of recovery improving strategies.
Diffusion Magnetic Resonance Imaging Study of a Rat Hippocampal Slice Model for Acute Brain Injury
Authors: Shepherd Timothy M. , Thelwall Peter E. , Blackband Stephen J. , Pike Brian R. , Hayes Ronald L. , Wirth Edward D.
Published: December 2003

Diffusion magnetic resonance imaging (MRI) provides a surrogate marker of acute brain pathology, yet few studies have resolved the evolution of water diffusion changes during the first 8 hours after acute injury, a critical period for therapeutic intervention. To characterize this early period, this study used a 17.6-T wide-bore magnet to measure multicomponent water diffusion at high b-values (7 to 8,080 s/mm2) for rat hippocampal slices at baseline and serially for 8 hours after treatment with the calcium ionophore A23187. The mean fast diffusing water fraction (Ffast) progressively decreased for slices treated with 10-μmol/L A23187 (—20.9 ± 6.3% at 8 hours). Slices treated with 50-μmol/L A23187 had significantly reduced Ffast 80 minutes earlier than slices treated with 10-μmol/L A23187 (P < 0.05), but otherwise, the two doses had equivalent effects on the diffusion properties of tissue water. Correlative histologic analysis showed dose-related selective vulnerability of hippocampal pyramidal neurons (CA1 > CA3) to pathologic swelling induced by A23187, confirming that particular intravoxel cell populations may contribute disproportionately to water diffusion changes observed by MRI after acute brain injury. These data suggest diffusion-weighted images at high b-values and the diffusion parameter Ffast may be highly sensitive correlates of cell swelling in nervous issue after acute injury.
Value leadership: the principles driving corporate value
Authors: Cohan Peter S.
Published: December 2003

Two years on from Enron, the litany of problems facing equity capitalism has been well aired. The simple reality is that the misbehaviour of a small number of rogue executives, analysts and bankers has made life much harder for the majority who are honest, hardworking and eager to enrich their shareholders, employees, customers and communities. Peter S Cohan argues that what executives need now is a way to rethink their businesses that will inspire people and revive corporate performance.
Seven habits of spectacularly unsuccessful people
Authors: Finkelstein Sydney
Published: December 2003

Creating catastrophic corporate collapse requires some truly awesome personal characteristics, argues Sydney Finkelstein. Unfortunately, they are often the very same qualities we profess to most admire and value in business leaders.
Strategically embedding CRM
Authors: Langerak Fred , Verhoef Peter C.
Published: December 2003

Scepticism and disappointment have replaced initial enthusiasm about customer relationship management (CRM). The disappointing results of CRM projects are often related to difficulties that managers encounter in embedding CRM in their strategy and organisation structure. Fred Langerak and Peter C Verhoef believe that distinguishing between strategic and tactical CRM might lead to more effective understanding and implementation of CRM.
Cryptic chromosomal rearrangement screening in 30 patients with mental retardation and dysmorphic features
Authors: Rodriguez‐Revenga L , Badenas C , Sánchez A , Mallolas J , Carrió A , Pedrinaci S , Barrionuevo JL , Milà M
Published: December 2003

Mental retardation affects 1–3% of the general population, and the genetic causes in many cases are unknown. Cytogenetically undetected chromosomal imbalances have been indicated as an explanation. Nowadays, due to the development of molecular cytogenetic techniques, it is possible to identify cryptic rearrangements involving the ends of chromosomes. We report a screening using chromosome‐specific telomere fluorescence in‐situ hybridization (FISH) probes, in a group of 30 patients with a well‐characterized phenotype including mental retardation, dysmorphic features, and a normal karyotype. Among them, two subtelomeric rearrangements have been detected and characterized. One of them is a de novo deletion of 1p36, which has been previously described as a new contiguous gene syndrome. The second is an unbalanced product of a cryptic translocation involving chromosomes 1 and 13, which results in a partial 1q trisomy and partial 13q monosomy. These findings highlight, the importance of searching for cryptic subtelomeric rearrangements in non‐syndromic mentally retarded patients.
Refining the primary open‐angle glaucoma GLC1C region on chromosome 3 by haplotype analysis
Authors: Samples JR , Kitsos G , Economou‐Petersen E , Steinkamp P , Sykes R , Rust K , Patzer C , Grigoriadou M , Aperis G , Psilas K , Petersen MB , Wirtz MK
Published: December 2003

The GLC1C locus for primary open‐angle glaucoma (POAG) is inherited as an autosomal dominant trait. This region on chromosome 3 is 11 cM long. DNA samples from members of a Greek and an American GLC1C family were obtained to determine whether additional typing of microsatellite markers in family members might narrow the region. GLC1C family members were evaluated clinically for POAG on the basis of open angles, intraocular pressures, cupping of discs, and visual fields. DNA samples from the Greek and Oregon GLC1C families were used to further refine the GLC1C region using microsatellite markers. A total of 22 affected members were identified in the two families. Common alleles for D3S3637 and D3S3612 were present in the disease haplotype from both families, suggesting that they may have a common founder. A newly diagnosed patient in the American family had a recombination in the distal portion of the GLC1C haplotype. This recombination narrows the GLC1C region from 11 to 4 cM.
The social and political control of knowledge in modern societies*
Authors: Stehr Nico
Published: December 2003

This paper is conceived as part of a line of inquiry into the reasons for controlling novel scientific knowledge, and the ways of doing so, by major social institutions within and across modern societies. The sociology of knowledge always had an interest in the social role of knowledge (power based on knowledge), its transformation and its carriers (experts, intellectuals, cognitive elites). However, the primary knowledge‐guiding interest of the sociology of knowledge traditionally has been on questions concerned with the production and not the consumption of knowledge. The emerging focus of sociology of knowledge inquiry should be with issues that may be designated as “knowledge politics”. I will first describe and delineate the notion of knowledge politics as a new field of political activity. When it comes to the utilisation of new capacities for action (that is, knowledge) knowledge politics does not have to be restrictive a priori; my focus, however, will be on efforts to anticipate the effects of new knowledge on social relations, and attempts to control its impact. Second, I will delineate some of the main reasons why knowledge politics gains prominence as a field of political activity in modern societies. I will stress, in particular, changing relations between science and society. In a third section of the paper, the distinction between knowledge and science policies will be introduced. Before concluding the discussion with a brief outlook, I will sketch some pertinent episodes that illustrate knowledge politics in action.