bluuebunny/crossref_metadata_2025_split huggingface dataset:
GIMS: an integrated data storage and analysis environment for genomic and functional data
Authors: Cornell Michael , Paton Norman W. , Hedeler Cornelia , Kirby Paul , Delneri Daniela , Hayes Andrew , Oliver Stephen G. 
Published: November 2003

AbstractEffective analyses in functional genomics require access to many kinds of biological data. For example, the analysis of upregulated genes in a microarray experiment might be aided by information concerning protein interactions or proteins' cellular locations. However, such information is often stored in different formats at different sites, in ways that may not be amenable to integrated analysis. The Genome Information Management System (GIMS) is an object database that integrates genomic data with data on the transcriptome, protein–protein interactions, metabolic pathways and annotations, such as gene ontology terms and identifiers. The resulting system supports the running of analyses over this integrated data resource, and provides comprehensive facilities for handling and interrelating the results of these analyses. GIMS has been used to store Saccharomyces cerevisiae data, and we demonstrate how the integrated storage of diverse types of data can be beneficial for analysis, using combinations of complex queries. As an example, we describe how GIMS has been used to analyse a collection of aryl alcohol dehydrogenase gene deletion mutants. The GIMS database can be accessed remotely using a Java application that can be downloaded from http://img.cs.man.ac.uk/gims. Copyright © 2003 John Wiley & Sons, Ltd.
High rates of pregnancy among vocational school students: results of audio computer‐assisted self‐interview survey in Chiang Rai, Thailand
Authors: Manopaiboon Chomnad , Kilmarx Peter H. , van Griensven Frits , Chaikummao Supaporn , Jeeyapant Supaporn , Limpakarnjanarat Khanchit , Uthaiworavit Wat 
Published: November 2003

AbstractUnplanned pregnancy among young people can lead to adverse social, psychological, and health outcomes, particularly when it results in abortion. In 1999, we examined the prevalence of and factors associated with pregnancy and abortion among 1725 consenting vocational school students in northern Thailand. Results from an audio computer‐assisted self‐interview showed that 48% of the male and 43% of the female students reported ever having had sexual intercourse. Among those who had had intercourse, 27% of the women and 17% of the men said they or their partner had ever been pregnant. Among the last reported pregnancies that resulted in delivery or abortion, 95% were aborted. Age, current contraceptive use, early initiation of sexual intercourse (⩽16 years), alcohol and drug use, and sexual coercion were associated with self or partner pregnancy. The high rates of pregnancy and abortion in this population indicate the need for better sexual health education and access to effective contraceptive methods.
Stress, coping, and behavioural problems among rural and urban adolescents
Authors: Elgar Frank J , Arlett Christine , Groves Renee 
Published: November 2003

AbstractRural/urban differences were studied in self‐reported stress (life events, daily hassles and conflict), coping and behavioural problems in a community sample of adolescents. Despite challenging socioeconomic conditions in rural areas, levels of stress and ways of coping were similar in rural and urban adolescents. However, urban males reported more conflict and externalizing behaviours than females and rural males. Stress, coping, and behavioural problems were interrelated but approach coping did not moderate the influence of stress on psychological functioning. Results suggest that adolescents may utilize many coping strategies that serve little benefit in terms of behavioural outcomes.
At the feet of the dinosaurs: the early history and radiation of lizards
Authors: EVANS SUSAN E. 
Published: November 2003

ABSTRACTLizards, snakes and amphisbaenians together constitute the Squamata, the largest and most diverse group of living reptiles. Despite their current success, the early squamate fossil record is extremely patchy. The last major survey of squamate palaeontology and evolution was published 20 years ago. Since then, there have been changes in systematic theory and methodology, as well as a steady trickle of new fossil finds. This review examines our current understanding of the first 150 million years of squamate evolution in the light of the new data and changing ideas. Contrary to previous reports, no squamate fossils are currently documented before the Jurasis. Nonetheless, indirect evidence predicts that squamates had evolved by at least the middle Triassic, and diversified into existing major lineages before the end of this period. There is thus a major gap in the squamate record at a time when key morphological features were evolving. With the exception of fragmentary remains from Africa and India, Jurassic squamates are known only from localities in northern continents (Laurasia). The situation improves in the Early Cretaceous, but the southern (Gondwanan) record remains extremely poor. This constrains palaeobiogeographic discussion and makes it difficult to predict centres of origin for major squamate clades on the basis of fossil evidence alone. Preliminary mapping of morphological characters onto a consensus tree demonstrates stages in the sequence of acquisition for some characters of the skull and postcranial skeleton, but many crucial stages – most notably those relating to the acquisition of squamate skull kinesis – remain unclear.
Parasitic exploitation as an engine of diversity
Authors: SUMMERS KYLE , McKEON SEA , SELLARS JON , KEUSENKOTHEN MARK , MORRIS JAMES , GLOECKNER DAVID , PRESSLEY COREY , PRICE BLAKE , SNOW HOLLY 
Published: November 2003

ABSTRACTParasitic exploitation occurs within and between a wide variety of taxa in a plethora of diverse contexts. Theoretical and empirical analyses indicate that parasitic exploitation can generate substantial genetic and phenotypic polymorphism within species. Under some circumstances, parasitic exploitation may also be an important factor causing reproductive isolation and promoting speciation. Here we review research relevant to the relationship between parasitic exploitation, within species‐polymorphism, and speciation in some of the major arenas in which such exploitation has been studied. This includes research on the vertebrate major histocompatibility loci, plant –pathogen interactions, the evolution of sexual reproduction, intragenomic conflict, sexual conflict, kin mimicry and social parasitism, tropical forest diversity and the evolution of language. We conclude by discussing some of the issues raised by comparing the effect of parasitic exploitation on polymorphism and speciation in different contexts.
The radiation of the Cape flora, southern Africa
Authors: LINDER H. P. 
Published: November 2003

ABSTRACTThe flora of the south‐western tip of southern Africa, the Cape flora, with some 9000 species in an area of 90 000 km2 is much more speciose than can be expected from its area or latitude, and is comparable to that expected from the most diverse equatorial areas. The endemism of almost 70%, on the other hand, is comparable to that found on islands. This high endemism is accounted for by the ecological and geographical isolation of the Cape Floristic Region, but explanations for the high species richness are not so easily found. The high species richness is accentuated when its taxonomic distribution is investigated: almost half of the total species richness of the area is accounted for by 33‘Cape floral clades'. These are clades which may have initially diversified in the region, and of which at least half the species are still found in the Cape Floristic Region. Such a high contribution by a very small number of clades is typical of island floras, not of mainland floras. The start of the radiation of these clades has been dated by molecular clock techniques to between 18 million years ago (Mya)(Pelargonium) and 8 Mya (Phylica), but only six radiations have been dated to date. The fossil evidence for the dating of the radiation is shown to be largely speculative. The Cenozoic environmental history of southern Africa is reviewed in search of possible triggers for the radiations, climatic changes emerge as the most likely candidate. Due to a very poor fossil record, the climatic history has to be inferred from larger scale patterns, these suggest large‐scale fluctuations between summer wet (Palaeocene, Early Miocene)and summer dry climates (Oligocene, Middle Miocene to present). The massive speciation in the Cape flora might be accounted for by the diverse limitations to gene flow (dissected landscapes, pollinator specialisation, long flowering times allowing much phenological specialisation), as well as a richly complex environment providing a diversity of selective forces (geographically variable climate, much altitude variation, different soil types, rocky terrain providing many micro‐niches, and regular fires providing both intermediate disturbances, as well as different ways of surviving the fires). However, much of this is based on correlation, and there is a great need for (a)experimental testing of the proposed speciation mechanisms, (b)more molecular clock estimates of the age and pattern of the radiations, and (c)more fossil evidence bearing on the past climates.
Understanding genetic regulatory networks
Authors: Kauffman Stuart 
Published: November 2003

Random Boolean networks (RBM) were introduced about 35 years ago as first crude models of genetic regulatory networks. RBNs are comprised of N on–off genes, connected by a randomly assigned regulatory wiring diagram where each gene has K inputs, and each gene is controlled by a randomly assigned Boolean function. This procedure samples at random from the ensemble of all possible NK Boolean networks. The central ideas are to study the typical, or generic properties of this ensemble, and see 1) whether characteristic differences appear as K and biases in Boolean functions are introducted, and 2) whether a subclass of this ensemble has properties matching real cells.Such networks behave in an ordered or a chaotic regime, with a phase transition, ‘the edge
of chaos’ between the two regimes. Networks with continuous variables exhibit the same two regimes. Substantial evidence suggests that real cells are in the ordered regime. A key concept is that of an attractor. This is a reentrant trajectory of states of the network, called a state cycle. The central biological interpretation is that cell types are attractors. A number of properties differentiate the ordered and chaotic regimes. These include the size and number of attractors, the existence in the ordered regime of a percolating ‘sea’ of genes frozen in the on or off state, with a remainder of isolated twinkling islands of genes, a power law distribution of avalanches of gene activity changes following perturbation to a single gene in the ordered regime versus a similar power law distribution plus a spike of enormous avalanches of gene changes in the chaotic regime, and the existence of branching pathway of ‘differentiation’ between attractors induced by perturbations in the ordered regime.Noise is serious issue, since noise disrupts attractors. But numerical evidence suggests that attractors can be made very stable to noise, and meanwhile, metaplasias may be a biological manifestation of noise. As we learn more about the wiring diagram and constraints on rules controlling real genes, we can build refined ensembles reflecting these properties, study the generic properties of the refined ensembles, and hope to gain insight into the dynamics of real cells.
Extracellular ATP and adenosine induce cell apoptosis of human hepatoma Li‐7A cells via the A3 adenosine receptor
Authors: Wen Long T , Knowles Aileen F 
Published: November 2003

Extracellular ATP is a potent signaling molecule that modulates a myriad of cellular functions through the activation of P2 purinergic receptors and is cytotoxic to a variety of cells at higher concentrations. The mechanism of ATP‐elicited cytotoxicity is not fully understood. In this study, we investigated the effect of extracellular ATP on the human hepatoma Li‐7A cells.
We observed a time‐ and dose‐dependent growth inhibition of Li‐7A cells by ATP, which is accompanied by an increase in the active form of caspase‐3 as well as increased cleavage of its substrate, poly (ADP‐ribose) polymerase. The cytotoxic effect of extracellular ATP was not mediated by the P2X7 receptor, since (1) the effect was not abolished by the P2X7 receptor antagonists oxidized ATP and KN‐62, and (2) extracellular ADP, AMP, and adenosine were also cytotoxic.
We found that ATP and ADP were degraded to adenosine by Li‐7A cells and that treatment of Li‐7A cells by adenosine resulted in growth inhibition and caspase‐3 activation, indicating that adenosine is the apoptotic agent. Using adenosine receptor agonists and antagonists, as well as inhibitors of adenosine transport and deamination, we showed that the cytotoxic effect of adenosine is specifically mediated by the A3 receptor even though transcripts of A1, A2A, A2B, and a splice variant of the P2X7 receptors were detected in Li‐7A cells by RT–PCR.
Cytotoxicity caused by exogenous ATP and adenosine was completely abolished by the caspase‐3 inhibitor Z‐DEVD‐FMK, demonstrating the central role of caspase‐3 in apoptosis of Li‐7A cells.

British Journal of Pharmacology (2003) 140, 1009–1018. doi:10.1038/sj.bjp.0705523
Methyridine (2‐[2‐methoxyethyl]‐pyridine]) and levamisole activate different ACh receptor subtypes in nematode parasites: a new lead for levamisole‐resistance
Authors: Martin Richard J , Bai Guangxing , Clark Cheryl L , Robertson Alan P 
Published: November 2003

The development of resistance to all chemotherapeutic agents increases and needs to be addressed. We are interested in resistance in parasitic nematodes to the anthelmintic levamisole. During studies on methyridine, we found that it gave us a new insight into pharmacological changes associated with levamisole resistance. Initially, electrophysiological investigation using a two‐micropipette current‐clamp recording technique revealed that methyridine acts as a cholinergic agonist on nematode muscle receptors (Ascaris suum). Methyridine (>30 μM) produced reversible concentration‐dependent depolarizations and increases in input conductance. Mecamylamine (30 μM) and paraherquamide (0.3 μM) produced reversible antagonism of the depolarization and conductance responses to methyridine. These observations suggest that methyridine, like acetylcholine and levamisole, gates ion channels on the muscle of parasitic nematodes.
The antagonistic effects of dihydro‐β‐erythroidine and paraherquamide on methyridine‐induced contractions of A. suum muscle flaps were then examined to determine if methyridine showed subtype selectivity for N‐subtype (nicotine‐sensitive) or L‐subtype (levamisole‐sensitive) acetylcholine receptors. Dihydro‐β‐erythroidine weakly antagonized the effects of methyridine (but had no effect on levamisole responses). The antagonism of methyridine (pA2, 5.9) and nicotine (pA2, 6.1) by paraherquamide was similar, but was less than the antagonism of levamisole (pA2, 7.0). The antagonist profiles suggested that methyridine has a selective action on the N‐subtype rather than on the L‐subtype.
A novel use for a larval inhibition migration assay was made using L3 larvae of Oesophagostomum dentatum. Inhibitory effects of nicotine, levamisole, pyrantel and methyridine on the migration of larvae of levamisole‐sensitive (SENS) and levamisole‐resistant (LEV‐R) isolates were tested at different concentrations. Levamisole and pyrantel (putative L‐subtype‐selective agonists) concentration–response plots were displaced to the right in LEV‐R isolates. Nicotine (an N‐subtype‐selective agonist) and methyridine produced little shift in concentration–response plots in the LEV‐R isolates. Resistance dose ratios were used to calculate the relative selectivity, ρL, for the L‐type receptor (levamisole ρL=1.0; pyrantel ρL=0.93; methyridine ρL=0.17; nicotine ρL=0.06). These observations reveal an N‐subtype‐selective action of methyridine and suggest that levamisole resistance may be associated with a loss of the L‐subtype, but not the N‐subtype receptors. The pharmacology of methyridine suggests an approach for the treatment of levamisole‐resistant parasites.

British Journal of Pharmacology (2003) 140, 1068–1076. doi:10.1038/sj.bjp.0705528
The CB1/VR1 agonist arvanil induces apoptosis through an FADD/caspase‐8‐dependent pathway
Authors: Sancho Rocío , De La Vega Laureano , Appendino Giovanni , Di Marzo Vincenzo , Macho Antonio , Muñoz Eduardo 
Published: November 2003

Arvanil (N‐arachidonoylvanillamine), a nonpungent capsaicin–anandamide hybrid molecule, has been shown to exert biological activities through VR1/CB1‐dependent and ‐independent pathways. We have found that arvanil induces dose‐dependent apoptosis in the lymphoid Jurkat T‐cell line, but not in peripheral blood T lymphocytes. Apoptosis was assessed by DNA fragmentation through cell cycle and TUNEL analyses.
Arvanil‐induced apoptosis was initiated independently of any specific phase of the cell cycle, and it was inhibited by specific caspase‐8 and ‐3 inhibitors and by the activation of protein kinase C. In addition, kinetic analysis by Western blots and fluorimetry showed that arvanil rapidly activates caspase‐8, ‐7 and ‐3, and induces PARP cleavage.
The arvanil‐mediated apoptotic response was greatly inhibited in the Jurkat‐FADDDN cell line, which constitutively expresses a negative dominant form of the adapter molecule Fas‐associated death domain (FADD). This cell line does not undergo apoptosis in response to Fas (CD95) stimulation.
Using a cytofluorimetric approach, we have found that arvanil induced the production of reactive oxygen species (ROS) in both Jurkat‐FADD+ and Jurkat‐FADDDN cell lines. However, ROS accumulation only plays a residual role in arvanil‐induced apoptosis.
These results demonstrate that arvanil‐induced apoptosis is essentially mediated through a mechanism that is typical of type II cells, and implicates the death‐inducing signalling complex and the activation of caspase‐8. This arvanil‐apoptotic activity is TRPV1 and CB‐independent, and can be of importance for the development of potential anti‐inflammatory and antitumoral drugs.

British Journal of Pharmacology (2003) 140, 1035–1044. doi:10.1038/sj.bjp.0705532
Effects of endomorphin on substantia gelatinosa neurons in rat spinal cord slices
Authors: Wu Su‐Ying , Ohtubo Yoshitaka , Brailoiu G Cristina , Dun Nae J 
Published: November 2003

Whole‐cell patch recordings were made from substantia gelatinosa (SG) neurons in transverse lumbar spinal cord slices of 15‐ to 30‐day‐old rats.
Endomorphin 1 (EM‐1) or EM‐2 (10 μM) hyperpolarized or induced an outward current in 26 of the 66 SG neurons. The I–V relationship showed that the peptide activates an inwardly rectifying K+ current.
EM‐1 or EM‐2 (0.3–10 μM) suppressed short‐latency excitatory postsynaptic currents (EPSCs) and long‐latency inhibitory postsynaptic currents (IPSCs) in nearly all SG neurons tested or short‐latency IPSCs in six of the 10 SG neurons. [Met5] enkephalin or [D‐Ala2, N‐Me‐Phe4, Gly5‐ol]‐enkephalin (DAMGO) (1–10 μM) depressed EPSCs and IPSCs. EM‐1 or EM‐2 depressed synaptic responses without causing a significant change in holding currents or inward currents induced by glutamate.
Glutamate also evoked a short‐latency outward current in five SG neurons or a biphasic current in two neurons; the outward current was blocked by tetrodotoxin (TTX, 0.3 μM) or bicuculline (10 μM). EM‐1 or DAMGO (1 or 5 μM) attenuated the glutamate‐evoked outward or biphasic currents in four of the seven SG neurons.
EM‐1 (1 μM) reduced the frequency, but not the amplitude of miniature EPSCs or miniature IPSCs.
Naloxone (1 μM) or the selective μ‐opioid receptor antagonist β‐funaltrexamine (β‐FNA, 25 μM) antagonized the action of EM; EM‐induced hyperpolarizations persisted in the presence of the κ‐opioid receptor antagonist (nor‐binaltorphimine dihydrochloride, 1 μM) and/or σ‐opioid receptor antagonist (naltrindole hydrochloride, 1 μM).
It may be concluded that EM acting on μ‐opioid receptors hyperpolarizes a population of SG neurons by activating an inwardly rectifying K+ current, and attenuates excitatory and inhibitory synaptic currents evoked in a population of SG neurons, probably by a presynaptic site of action.

British Journal of Pharmacology (2003) 140, 1088–1096. doi:10.1038/sj.bjp.0705534
Functional evidence that ATP or a related purine is an inhibitory NANC neurotransmitter in the mouse jejunum: study on the identity of P2X and P2Y purinoceptors involved
Authors: De Man Joris G , De Winter Benedicte Y , Seerden Tom C , De Schepper Heiko U , Herman Arnold G , Pelckmans Paul A 
Published: November 2003

Conflicting views exist on whether ATP is a neurotransmitter in the enteric nervous system. We investigated the role of ATP in enteric transmission in circular muscle strips of the mouse jejunum.
On PGF2α‐precontracted muscle strips and in the presence of atropine and guanethidine, electrical field stimulation (EFS, 1–8 Hz) of nonadrenergic noncholinergic (NANC) nerves induced transient relaxations that were abolished by the nerve‐conductance blocker tetrodotoxin. The NO synthase blocker L‐nitroarginine (L‐NOARG) partially inhibited the NANC relaxations to EFS, but fast‐twitch relaxations to EFS were still observed in the presence of L‐NOARG.
In the presence of L‐NOARG, ATP, the P2X receptor agonist αβMeATP and the P2Y receptor agonist ADPβS relaxed jejunal muscle strips. Tetrodotoxin did not affect the relaxation to ATP and ADPβS, but inhibited that to αβMeATP.
The L‐NOARG‐resistant NANC relaxations to EFS were almost abolished by apamin, a blocker of small‐conductance Ca2+ activated K+ channels, and by suramin and PPADS, blockers of P2 purinoceptors. Relaxations to ATP were almost abolished by apamin and suramin but not affected by PPADS.
Desensitisation of αβMeATP‐sensitive P2X receptors, the P2X receptor blocker Evans blue and the P2X1,2,3 receptor blocker NF 279 inhibited the L‐NOARG‐resistant NANC relaxations to EFS and that to αβMeATP without affecting the relaxation to ADPβS. Brilliant blue G, a P2X2,5,7 receptor blocker, did not affect the relaxations to EFS.
Desensitisation of P2Y receptors and MRS 2179, a P2Y1 receptor blocker, virtually abolished the L‐NOARG‐resistant NANC relaxations to EFS and the relaxation to ADPβS without affecting the relaxation to αβMeATP.
Dipyridamole, an adenosine uptake inhibitor, or theophylline and 8‐phenyltheophylline, blockers of P1 and A1 purinoceptors, respectively, did not affect the purinergic NANC relaxations to EFS.
Our results suggest that ATP or a related purine acts as an inhibitory NANC neurotransmitter in the mouse jejunum, activating P2 but not P1 purinoceptors. Relaxations to the purinergic NANC neurotransmitter mainly involve P2Y receptors of the P2Y1 subtype that are located postjunctionally. Purinergic NANC neurotransmission also involves P2X receptors, most likely of the P2X1 and P2X3 subtype, located pre‐ and/or postjunctionally.

British Journal of Pharmacology (2003) 140, 1108–1116. doi:10.1038/sj.bjp.0705536