bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of COX‐2 and reactive gliosis by P2Y receptors in rat cortical astrocytes is dependent on ERK1/2 but independent of calcium signalling
Authors: Brambilla Roberta , Neary Joseph T. , Cattabeni Flaminio , Cottini Lorenzo , D'Ippolito Gianluca , Schiller Paul C. , Abbracchio Maria P. 
Published: March 2003

AbstractThe present study has been aimed at characterizing the ATP/P2 receptor (and transductional pathways) responsible for the morphological changes induced in vitro by αβmethyleneATP on rat astrocytes obtained from cerebral cortex, a brain area highly involved in neurodegenerative diseases. Exposure of cells to this purine analogue resulted in elongation of cellular processes, an event reproducing in vitro a major hallmark of in vivo reactive gliosis. αβmethyleneATP‐induced gliosis was prevented by the P2X/P2Y blocker pyridoxalphosphate‐6‐azophenyl‐2′‐4′‐disulfonic acid, but not by the selective P2X antagonist 2′,3′‐O‐(2,4,6‐trinitrophenyl)‐ATP, ruling out a role for ligand‐gated P2X receptors. Conversely, the Gi/Go protein inactivator pertussis toxin completely prevented αβmethyleneATP‐induced effects. No effects were induced by αβmethyleneATP on intracellular calcium concentrations. RT‐PCR and western blot analysis showed that αβmethyleneATP–induced gliosis involves up‐regulation of cyclooxygenase‐2 (but not lipooxygenase). Also this effect was fully prevented by pyridoxalphosphate‐6‐azophenyl‐2′‐4′‐disulfonic acid. Experiments with inhibitors of mitogen‐activated protein kinases (MAPK) suggest that extracellular signal regulated protein kinases (ERK)1/2 mediate both cyclooxygenase‐2 induction and the associated in vitro gliosis. These findings suggest that purine‐induced gliosis involves the activation of a calcium‐independent G‐protein‐coupled P2Y receptor linked to ERK1/2 and cyclooxygenase‐2. Based on the involvement of cyclooxygenase‐2 and inflammation in neurodegenerative diseases, these findings open up new avenues in the identification of novel biological targets for the pharmacological manipulation of neurodegeneration.
Regional differences in processing of locally translated prohormone in peptidergic neurons of Aplysia californica
Authors: Lee Wenjau , Jones Andrea M. , Ono Joyce K. , Wayne Nancy L. 
Published: March 2003

AbstractEarlier work showed that cell bodies and neurites of the peptidergic bag cell neurons of Aplysia californica contain mRNA for egg‐laying hormone. The purpose of the present study was to determine if egg‐laying hormone synthesis and prohormone processing is similar in the pleurovisceral connective nerves (containing neurites of bag cell neurons) and the bag cell neuron clusters (containing both cell bodies and neurites of bag cell neurons). Initial experiments confirmed by RT‐PCR and sequencing that egg‐laying hormone mRNA was present in the pleurovisceral connective nerves. To investigate possible regional differences in translation of mRNA and prohormone processing, clusters were separated from connective nerves and newly synthesized egg‐laying hormone‐immunoreactive proteins were analyzed. Results showed that synthesis and processing of prohormone occurred in both the clusters and isolated connective nerves; however, the relative abundance of prohormone, processing intermediates, and egg‐laying hormone was different. Pulse‐chase experiments showed that prohormone was processed more slowly in the connective nerves than in the clusters. These results show that mRNA in isolated neural processes of neuroendocrine cells can be translated, and that the cellular machinery for protein synthesis is present, but processing of the ELH prohormone is significantly compromised.
Correlation of local changes in extracellular oxygen and pH that accompany dopaminergic terminal activity in the rat caudate–putamen
Authors: Venton B. Jill , Michael Darren J. , Wightman R. Mark 
Published: March 2003

AbstractTerminal activity causes an increase in local cerebral blood flow that can be quantified by measuring the accompanying increase in tissue oxygen. Alkaline pH changes can also follow neuronal activation. The purpose of these studies was to determine whether these changes in extracellular oxygen and pH correlate. Fast‐scan cyclic voltammetry was used to detect changes in dopamine, pH and oxygen levels simultaneously in the caudate–putamen after electrical stimulation of the substantia nigra in anesthetized rats. The biphasic increases in oxygen and pH followed similar time courses, and were delayed a few seconds from the immediate release and uptake of dopamine. The changes following administration of neurotransmitter receptor antagonists as well as agents that modulate blood flow were identical for oxygen and pH. Two distinct mechanisms were identified that give rise to the oxygen and pH changes: blood vessel dilatation caused by nitric oxide synthesis after muscarinic receptor activation and adenosine receptor activation. We conclude that changes in blood flow accompanying terminal activity cause alkaline pH shifts by the rapid removal of carbon dioxide, a component of the extracellular brain buffering system.
Tethering the N‐terminus of the prion protein compromises the cellular response to oxidative stress
Authors: Zeng Fanning , Watt Nicole T. , Walmsley Adrian R. , Hooper Nigel M. 
Published: March 2003

AbstractThe role of the N‐terminal half of the prion protein (PrPC) in normal cellular function and pathology remains enigmatic. To investigate the biological role of the N‐terminus of PrP, we examined the cellular properties of a construct of murine PrP, PrP‐DA, in which the N‐terminus is tethered to the membrane by an uncleaved signal peptide and which retains the glycosyl‐phosphatidylinositol anchor. Human neuroblastoma SH‐SY5Y cells expressing PrP‐DA were more susceptible to hydrogen peroxide and copper induced toxicity than wtPrP expressing cells. The PrP‐DA expressing cells had an increased level of intracellular free radicals and reduced levels of superoxide dismutase and glutathione peroxidase as compared to the wtPrP expressing cells. The membrane topology, cell surface location, lipid raft localisation, intracellular trafficking and copper‐mediated endocytosis of PrP‐DA were not significantly different from wtPrP. However, cells expressing PrP‐DA accumulated an N‐terminal fragment that was resistant to proteinase K. The data presented here are consistent with the N‐terminal region of PrPC having a role in the cellular response to oxidative stress, and that tethering this region of the protein to the membrane compromises this function through the accumulation of a protease‐resistant N‐terminal fragment, similar to that seen in some forms of human prion disease.
The role of phosphatidylinositol 3‐kinase in neural cell adhesion molecule‐mediated neuronal differentiation and survival
Authors: Ditlevsen Dorte K. , Køhler Lene B. , Pedersen Martin V. , Risell Michael , Kolkova Kateryna , Meyer Morten , Berezin Vladimir , Bock Elisabeth 
Published: March 2003

AbstractThe neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras‐mitogen activated protein kinase (MAPK) pathway and an increase in intracellular Ca2+ levels. Stimulation of neurones with the synthetic NCAM‐ligand, C3, induces neurite outgrowth through signalling pathways similar to the pathways activated through physiological, homophilic NCAM‐stimulation. We present here data indicating that phosphatidylinositol 3‐kinase (PI3K) is required for NCAM‐mediated neurite outgrowth from PC12‐E2 cells and from cerebellar and dopaminergic neurones in primary culture, and that the thr/ser kinase Akt/protein kinase B (PKB) is phosphorylated downstream of PI3K after stimulation with C3. Moreover, we present data indicating a survival‐promoting effect of NCAM‐stimulation by C3 on cerebellar and dopaminergic neurones induced to undergo apoptosis. This protective effect of C3 included an inhibition of both DNA‐fragmentation and caspase‐3 activation. The survival‐promoting effect of NCAM‐stimulation was also shown to be dependent on PI3K.
Cholesterol is necessary both for the toxic effect of Aβ peptides on vascular smooth muscle cells and for Aβ binding to vascular smooth muscle cell membranes
Authors: Subasinghe Supundi , Unabia Sharon , Barrow Colin J. , Mok Su San , Aguilar Marie‐Isabel , Small David H. 
Published: March 2003

AbstractAccumulation of beta amyloid (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease. Aβ can bind to membrane lipids and this binding may have detrimental effects on cell function. In this study, surface plasmon resonance technology was used to study Aβ binding to membranes. Aβ peptides bound to synthetic lipid mixtures and to an intact plasma membrane preparation isolated from vascular smooth muscle cells. Aβ peptides were also toxic to vascular smooth muscle cells. There was a good correlation between the toxic effect of Aβ peptides and their membrane binding. ‘Ageing’ the Aβ peptides by incubation for 5 days increased the proportion of oligomeric species, and also increased toxicity and the amount of binding to lipids. The toxicities of various Aβ analogs correlated with their lipid binding. Significantly, binding was influenced by the concentration of cholesterol in the lipid mixture. Reduction of cholesterol in vascular smooth muscle cells not only reduced the binding of Aβ to purified plasma membrane preparations but also reduced Aβ toxicity. The results support the view that Aβ toxicity is a direct consequence of binding to lipids in the membrane. Reduction of membrane cholesterol using cholesterol‐lowering drugs may be of therapeutic benefit because it reduces Aβ‐membrane binding.
Effects of phosphatidylserine on p38 mitogen activated protein kinase, cyclic AMP responding element binding protein and nuclear factor‐κB activation in resting and activated microglial cells
Authors: Ajmone‐Cat M. A. , De Simone R. , Nicolini A. , Minghetti L. 
Published: March 2003

AbstractIn the last few years, the interaction between phosphatidylserine (PS), a phospholipid that becomes permanently exposed on the external cell surface in the early phases of apoptosis, and its specific receptor (PtdSerR) has emerged as a crucial event for the engulfing of apoptotic cells and for preventing the acquisition of pro‐inflammatory functions by peripheral macrophages. Recently, we demonstrated that PtdSerR is expressed in microglial cultures purified from neonatal rat brain, and that PS‐liposomes, used to mimic apoptotic cells, strongly reduce the lipopolysaccharide (LPS)‐induced release of inflammatory mediators. Here, we show that in resting microglia, PS‐liposomes induce cyclic AMP responding element binding protein (CREB) phosphorylation but do not activate nuclear factor‐κB (NF‐κB) and p38 mitogen‐activated protein kinase (p38), in line with the non‐inflammatory consequences of the recognition and removal of apoptotic cells by macrophages. In LPS‐activated microglia, PS‐liposomes did not affect NF‐κB activation but inhibited the phosphorylation of p38 and delayed that of CREB. To our knowledge, this is the first biochemical evidence of the molecular signaling evoked by PS/PtdSerR interaction possibly related to repression of pro‐inflammatory activities in microglial cells.
Expanding the association between the APOE gene and the risk of Alzheimer's disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription
Authors: Laws Simon M. , Hone Eugene , Gandy Sam , Martins Ralph N. 
Published: March 2003

AbstractAlzheimer's disease (AD) is the most commonly diagnosed form of dementia in the elderly. Predominantly this disease is sporadic in nature with only a small percentage of patients exhibiting a familial trait. Early‐onset AD may be explained by single gene defects; however, most AD cases are late onset (> 65 years) and, although there is no known definite cause for this form of the disease, there are several known risk factors. Of these, the ε4 allele of the apolipoprotein E (apoE) gene (APOE) is a major risk factor. The ε4 allele of APOE is one of three (ɛ2 ɛ3 and ɛ4) common alleles generated by cysteine/arginine substitutions at two polymorphic sites. The possession of the ɛ4 allele is recognized as the most common identifiable genetic risk factor for late‐onset AD across most populations. Unlike the pathogenic mutations in the amyloid precursor or those in the presenilins, APOEɛ4 alleles increase the risk for AD but do not guarantee disease, even when present in homozygosity. In addition to the cysteine/arginine polymorphisms at the ɛ2/ɛ3/ɛ4 locus, polymorphisms within the proximal promoter of the APOE gene may lead to increased apoE levels by altering transcription of the APOE gene. Here we review the genetic and biochemical evidence supporting the hypothesis that regulation of apoE protein levels may contribute to the risk of AD, distinct from the well known polymorphisms at the ɛ2/ɛ3/ɛ4 locus.
Activation of mitochondrial ATP‐sensitive potassium channels increases cell viability against rotenone‐induced cell death
Authors: Tai Kwok‐Keung , McCrossan Zoe A. , Abbott Geoffrey W. 
Published: March 2003

AbstractWe recently showed that activation of ATP‐sensitive potassium (KATP) channels in PC12 cells induces protection against the neurotoxic effect of rotenone, a mitochondrial complex I inhibitor. In this study, we sought to determine the locus of the KATP channels that mediate this protection in PC12 cells. We found that pretreatment of PC12 cells with diazoxide, a mitochondrial KATP channel selective opener, dose‐dependently increases cell viability against rotenone‐induced cell death as indicated in trypan blue exclusion assays. The protective effect of this preconditioning is attenuated by 5‐hydroxydecanoic acid (5‐HD), a selective mitochondrial KATP channel antagonist but not in the presence of HMR‐1098, a selective plasma membrane KATP potassium channel antagonist. In contrast, P‐1075, a selective plasma membrane KATP channel opener, does not induce protection. Using specific antibodies against SUR1 and Kir6.1, we detected immunoreactive proteins of apparent molecular masses 155 and 50 kDa, corresponding to those previously reported for SUR1 and Kir6.1, respectively, in the mitochondria‐enriched fraction of PC12 cells. In addition, whole cell patch‐clamp studies revealed that inward currents in PC12 cells are insensitive to P‐1075, HMR‐1098, glibenclamide and diazoxide, indicating that functional plasma membrane KATP channels are negligible. Taken together, our results demonstrate for the first time that activation of mitochondrial KATP channels elicits protection against rotenone‐induced cell death.
Swedish general practitioners’ awareness of elderly patients at risk of or actually suffering from elder abuse
Authors: Saveman Britt‐Inger , Sandvide Åsa 
Published: March 2003

Swedish general practitioners’ awareness of elderly patients at risk of or actually suffering from elder abuse The aim of this study was to describe the awareness among Swedish general practitioners (GPs) of elderly patients at risk of or suffering from abuse during a 12‐month period. A questionnaire was sent to 110 GPs working in one regional health care district in Sweden, and 59% answered and returned the questionnaire. Seventy‐seven per cent of the GPs reported having one patient at risk of abuse and or neglect, and 25% were aware of patients who were subjected to verified or suspected elder abuse. Risk situations commonly involved patients with dementia, carers with problems of their own or who felt angry about the burden of caring, or paid carers who were unable to meet the needs of the elderly person. There were GPs who had contact with colleagues, district nurses and others, as well as those who had few or no contacts at all. It is important to take seriously the large number of GPs who have elderly patients in situations where there is a risk of abuse or neglect. If elder abuse is not primarily a medical problem – it is essential that there should be a clearly identified authority to which GPs can refer cases.
Breast cancer and experiences of social support
Authors: Landmark B. T. , Strandmark M. , Wahl A. 
Published: March 2003

Breast cancer and experiences of social support. In‐depth interviews of 10 women with newly diagnosed breast cancerThe present study aimed to describe how 10 Norwegian women with newly diagnosed breast cancer experienced living with the disease. A qualitative method based on principles in Grounded Theory was used. Data were collected through in‐depth interviews. This paper explores the experience of social support as it evolves in women's relationships with others. Social support contains emotional, practical and informative dimensions. Here relationships are called interactions. Interaction can be divided into two groups. Interactions with close relatives and others the women know and have contact with. Interactions with organizations and institution staff. These interactions consist of social support and lack of social support. Health professionals can assist women and their families in this life‐threatening situation, by increasing their awareness of social support issues.
A theoretical extension of the concept of energy through an empirical study
Authors: Lerdal Anners 
Published: March 2003

A theoretical extension of the concept of energy through an empirical study This paper extends the concept of energy as a multifaceted concept of the experience of energy and proposes a theoretical model regarding the understanding of the experience of energy. The hybrid model of concept development (Schwartz‐Barcott and Kim, 2000) was used in a qualitative empirical study with a sample of athletes and chronically ill individuals. The concept of energy presented is a global concept and can be placed within the much‐discussed concept of fatigue. Focusing on energy implicates a resource approach to individuals experiencing fatigue. A theoretical model for the experience of energy emerging from this study includes the subconcepts of the feeling of energy, perceived energy capacity, energy management, and performance of activities. Two sets of strategies within the concept of energy management are identified as energy economizing and energy generating. This article explores the potential of the concept of energy in describing fatigue as a health problem. Implications for clinical practice and further theoretical development are suggested.
Characterization of microsatellite loci in chinook salmon (Oncorhynchus tshawytscha) and cross‐species amplification in other salmonids
Authors: Williamson Kevin S. , Cordes Jan F. , May Bernie 
Published: March 2003

AbstractPrevious studies of population genetic structure of fall‐run chinook salmon (Oncorhynchus tshawytscha) in California’s Central Valley have either not focused on or have been unable to resolve intertributary differences within the San Joaquin River basin. The authors describe the isolation, the polymerase chain reaction conditions, and characterize the cross‐species amplification of 17 microsatellite loci in six species of salmonids. Fourteen of these loci are polymorphic in fall‐run chinook from the San Joaquin River drainage. These results indicate the potential utility of microsatellite markers developed for one species, for both congenerics and species within a closely related genus.
Characterization of 22 microsatellites loci from the endangered Houbara bustard (Chlamydotis undulata undulata)
Authors: Chbel Faiza , Broderick Damien , Idaghdour Youssef , Korrida Amal , Mccormick Paul 
Published: March 2003

AbstractHere we present a new set of 22 microsatellite loci isolated from Chlamydotis undulata undulata, an endangered Houbara bustard found across North Africa. The number of alleles per locus ranged from one to nine, and heterozygosities ranged from 0.167 to 0.944. Total exclusionary probabilities using these loci for the first and the second parent were 0.992932 and 0.999915, respectively. Successful cross‐amplification was observed in eight other Otididae species (12–22 of the 22 loci). These microsatellite markers are powerful tools for genetic identification, paternity assignment and population genetic studies.
Characterization of 16 microsatellite marker loci in the Maasai giraffe (Giraffa camelopardalis tippelskirchi)
Authors: Huebinger Ryan M. , Pierson Donna J. , De Maar Thomas W. , Brown David M. , Brenneman Rick A. , Louis Edward E. 
Published: March 2003

AbstractSixteen polymorphic microsatellite markers with an average allele size of k = 4.3 are identified from a genomic plasmid library constructed for giraffe (Giraffa camelopardalis ssp.). Primer sequences and marker data are reported in tabular form. The markers were screened in a population of 25 Maasai giraffe (G. c. tippelskirchi) collected near the Athi River, Kenya. The average observed heterozygosity for each marker was 0.36 with an average expected heterozygosity of 0.535. Hardy–Weinberg deviations are reported from this population, which is suspected to be inbred. The markers will be used to screen the captive giraffe population for subspecific or hybrid classification.
Isolation and characterization of microsatellite loci from a threatened rattlesnake (New Mexico Ridge‐nosed Rattlesnake, Crotalus willardi obscurus)
Authors: Holycross A. T. , Douglas M. E. , Higbee J. R. , Bogden R. H. 
Published: March 2003

AbstractSix novel microsatellite loci are identified from genomic DNA of the threatened New Mexico Ridge‐nosed Rattlesnake (Crotalus willardi obscurus). Data from the Animas Mountains (New Mexico) population demonstrate these loci: (i) are highly variable with 5–24 alleles per locus, expected heterozygosities between 0.35 and 0.92, and observed heterozygosities between 0.32 and 0.91; (ii) are sufficiently variable for assigning parentage with total exclusionary power for the first parent of 0.96, and 0.99 for the second parent; and (iii) amplify similar size fragments in other rattlesnakes (C. atrox, C. lutosus, C. scutulatus, and C. tigris).
Isolation of microsatellite loci in the Florida Scrub‐Jay Aphelocoma coerulescens
Authors: Stenzler L. M. , Fitzpatrick J. W. 
Published: March 2003

AbstractThe Florida Scrub‐Jay (Aphelocoma coerulescens), a habitat specialist listed as Threatened by the U.S. Fish and Wildlife Service, exhibits extremely limited natal dispersal. We hypothesize that this behaviour results in a correlation of genetic and geographical distance. To test this, we are sampling intensively along the north–south orientated Lake Wales Ridge of central Florida. We describe the isolation and characterization of 31 microsatellite loci developed to determine the minimum distance at which genetic structure can be detected, and to test for isolation by distance. There are 3–15 alleles per locus, with expected heterozygosities from 0.16 to 0.86.
Isolation of polymorphic microsatellites in the stemless thistle (Cirsium acaule) and their utility in other Cirsium species
Authors: Jump Alistair S. , Dawson Deborah A. , James Celia M. , Woodward F. Ian. , Burke Terry 
Published: March 2003

AbstractThe genus Cirsium includes species with both widespread and restricted geographical distributions, several of which are serious weeds. Nine polymorphic microsatellite loci were isolated from the stemless thistle Cirsium acaule. Eight were polymorphic in C. acaule, six in C. arvense and seven in C. heterophyllum. One locus monomorphic in C. acaule showed polymorphism in C. heterophyllum. The mean number of alleles per locus was 4.1 in C. acaule, 6.2 in C. arvense and 2.9 in C. heterophyllum. These nine loci were also amplified in C. eriophorum and C. vulgare, suggesting that these markers may be of use throughout the genus.