bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine D3 receptor stimulation promotes the proliferation of cells derived from the post‐natal subventricular zone
Authors: Coronas V. , Bantubungi K. , Fombonne J. , Krantic S. , Schiffmann S. N. , Roger M. 
Published: December 2004

AbstractIn the adult mammalian brain, neural stem cells persist in the subventricular zone (SVZ) where dopamine D3 receptors are expressed. Here, we demonstrate that addition of 1 µm apomorphine increases cell numbers in post‐natal SVZ cell cultures. This effect was prevented by a co‐treatment with haloperidol, sulpiride or U‐99194A, a D3‐preferring antagonist, and mimicked by the dopamine D3 receptor selective agonist 7‐hydroxy‐dipropylaminotetralin (7‐OH‐DPAT). EC50 values were 4.04 ± 1.54 nm for apomorphine and 0.63 ± 0.13 nm for 7‐OH‐DPAT, which fits the pharmacological profile of the D3 receptor. D3 receptors were detected in SVZ cells by RT‐PCR and immunocytochemistry. D3 receptors were expressed in numerous β‐III tubulin immunopositive cells. The fraction of apoptotic nuclei remained unchanged following apomorphine treatment, thus ruling out any possible effect on cell survival. In contrast, proliferation was increased as both the proportion of nuclei incorporating bromo‐deoxyuridine and the expression of the cell division marker cyclin D1 were enhanced. These findings provide support for a regulatory role of dopamine over cellular dynamics in post‐natal SVZ.
Distinct promoters regulate tissue‐specific and differential expression of kallikrein 6 in CNS demyelinating disease
Authors: Christophi G. P. , Isackson P. J. , Blaber S. , Blaber M. , Rodriguez M. , Scarisbrick I. A. 
Published: December 2004

AbstractKallikrein 6 is a serine protease expressed abundantly in normal adult human and rodent CNS, and therein is regulated by injury. In the case of CNS demyelinating disease, K6 expression in CNS occurs additionally in perivascular and parenchymal inflammatory cells suggesting a role in pathogenesis. Herein we describe two unique transcripts that occur within the human and mouse K6 genes that differ in their 5′‐untranslated regions. These transcripts have identical translation initiation sites in exon 3, are expressed in a tissue‐specific fashion and are differentially regulated in response to CNS injury. While the human and mouse 5′‐transcripts differ in sequence they are identical in genomic organization and tissue‐specific expression. The most 5′‐transcript, designated transcript 1, includes exon 1–7, and was detectable in all CNS regions, but not in any non‐CNS tissues examined (spleen, thymus, liver, kidney, pancreas, submandibular gland and peripheral nerve). In contrast, transcript 2 lacks exon 1, but contains a unique sequence at the 5′‐end of exon 2, designated exon 2A. Transcript 2 was expressed both in CNS and in each peripheral tissue. In a murine model of human CNS demyelinating inflammatory disease induced by Theiler's picornovirus, mouse K6 transcript 1 was up‐regulated in brain and spinal cord at acute and more chronic phases of CNS inflammation and demyelination, while overall transcript 2 expression was not significantly altered. However, in isolated splenocyte cultures, transcript 2 was up‐regulated two‐fold by cellular activation. Tissue‐specific expression patterns and differential regulation in CNS disease indicates that each K6 5′‐transcript is probably regulated by unique promoter elements and may serve as a molecular target to treat inflammatory demyelinating disease.
The response of synaptophysin and microtubule‐associated protein 1 to restraint stress in rat hippocampus and its modulation by venlafaxine
Authors: Xu Haiyun , He Jue , Richardson J. Steven , Li Xin‐Min 
Published: December 2004

AbstractAs part of our continuing study of neural plasticity in rat hippocampus, we examined two structural proteins involved in neuronal plasticity, synaptophysin (SYP) and microtubule‐associated protein 1 (MAP1) for their response to repeated restraint stress and modulation of such response by the antidepressant drug venlafaxine. This drug has the pharmacological action of inhibiting the reuptake of serotonin and norepinephrine in nerve terminals. We subjected the rats to restraint stress for 4 h per day for three days, and then injected the animals intraperitoneally (i.p.) with vehicle or 5 mg/kg/day of venlafaxine for various time periods. In all, eight groups of 10 rats each were used. The expression of these two proteins in hippocampal tissue of the rats was examined by means of western blot and immunohistochemical staining techniques. We found that restraint stress decreased the expression of SYP in the rat hippocampus by 50% (p < 0.01), and increased the expression of MAP1 by 60% (p < 0.01). SYP returned to the pre‐stress levels in three weeks and MAP1 in two weeks. In animals treated with venlafaxine post‐stress, SYP returned to pre‐stress levels after 2 weeks and MAP1 after 1 week. These findings enhance our understanding of the compromise of the hippocampus by stressful assaults, and may be relevant to the action of venlafaxine in the treatment of patients with major depression, a mental disease thought to be related to the mal‐adaptation of subjects to environmental stressors.
Interaction of human and mouse Aβ peptides
Authors: Fung Justin , Frost David , Chakrabartty Avijit , McLaurin JoAnne 
Published: December 2004

AbstractTransgenic mice over‐expressing mutant human amyloid precursor protein have become an important tool for research on Alzheimer's disease (AD) and, in particular, for therapeutic screening. Many models have reported formation of amyloid plaques with age as is detected in AD. However, the plaques generated in transgenic mice are more soluble than human plaques. Differences in solubility may occur for a number of reasons; one proposal is the presence of murine Aβ peptides within the CNS milieu. Here, we report the interaction of human and murine Aβ peptides, Aβ40 and Aβ42, utilizing a fluorescence assay to monitor formation of mixed pre‐fibrillar aggregates, electron microscopy to examine morphological characteristics and detergent solubility to monitor stability. Our results demonstrate that interspecies Aβ aggregates and fibres are readily formed and are more stable than homogenous human fibres. Furthermore, these results suggest that the presence of endogenous murine Aβ in human APP transgenic mice does not account for the increased solubility of plaques.
Effects of neonatal ventral hippocampal lesion in rats on stress‐induced acetylcholine release in the prefrontal cortex
Authors: Laplante François , Stevenson Carl W. , Gratton Alain , Srivastava Lalit K. , Quirion Rémi 
Published: December 2004

AbstractExcitotoxic neonatal ventral hippocampus (NVH) lesions in rats result in characteristic post‐pubertal hyper‐responsiveness to stress and cognitive abnormalities analogous to those described in schizophrenia and suggestive of alterations in dopamine (DA) neurotransmission. Converging lines of evidence also point to dysfunctions in the cortical cholinergic system in neuropsychiatric disorders. In previous studies, we observed alterations in dopaminergic modulation of acetylcholine (Ach) release in the prefrontal cortex (PFC) in post‐pubertal NVH‐lesioned rats. These two neurotransmitter systems are involved in the stress response as PFC release of DA and Ach is enhanced in response to some stressful stimuli. As adult NVH‐lesioned rats are behaviorally more reactive to stress, we investigated the effects of NVH lesions on tail‐pinch stress‐induced Ach and DA release in the PFC. Using in vivo microdialysis, we observed that tail‐pinch stress resulted in significantly greater increases in prefrontal cortical Ach release in post‐pubertal NVH‐lesioned rats (220% baseline) compared with sham‐operated controls (135% baseline). Systemic administration of the D1‐like receptor antagonist SCH 23390 (0.5 mg/kg i.p.) or the D2‐like receptor antagonist haloperidol (0.2 mg/kg i.p.), as well as intra‐PFC administration of the D2‐like antagonist sulpiride (100 µm), reduced stress‐induced Ach release in PFC of adult NVH‐lesioned rats. By contrast, intra‐PFC administration of SCH 23390 (100 µm) failed to affect stress‐induced Ach release in PFC of NVH‐lesioned rats. Interestingly, using in vivo voltammetry, stress‐induced stimulation of PFC DA release was found to be attenuated in adult NVH‐lesioned rats. Taken together, these data suggest developmentally specific reorganization of prefrontal cortical cholinergic innervation notably regarding its regulation by DA neurotransmission.
Calcitonin gene‐related peptide regulates gene transcription in primary afferent neurons
Authors: Anderson L. E. , Seybold V. S. 
Published: December 2004

AbstractAlthough primary afferent neurons express receptors for calcitonin gene‐related peptide (CGRP), understanding of the cellular effects of these receptors is limited. We determined that CGRP receptors regulate gene transcription in primary afferent neurons through a cyclic AMP (cAMP)‐dependent pathway. CGRP increased cAMP in neonatal dorsal root ganglion (DRG) neurons in a concentration‐dependent manner that was blocked by the receptor antagonist CGRP8‐37. The response to CGRP also occurred in adult DRG cells. In contrast, CGRP did not alter the concentration of free intracellular calcium in neonatal or adult DRG neurons. Immunohistochemical data showed that one downstream effect of the cAMP signaling pathway was phosphorylation of cAMP response element binding (CREB) protein, suggesting that CGRP regulates gene expression. This interpretation was supported by evidence that CGRP increased CRE‐dependent gene transcription in neurons transiently transfected with a CRE‐luciferase DNA reporter construct. The effect of CGRP on gene transcription was inhibited by H89, myristoylated‐protein kinase A inhibitor14−22‐amide and U0126, indicating that protein kinase A and mitogen‐activated protein kinase/extracellular receptor kinase kinase are enzymes that mediate effects of CGRP on gene transcription. Therefore, CGRP receptors may regulate expression of proteins by primary afferent neurons during development and in response to tissue‐damaging stimuli.
RAPID COMMUNICATION: Blockade of nociceptin/orphanin FQ transmission in rat substantia nigra reverses haloperidol‐induced akinesia and normalizes nigral glutamate release
Authors: Marti Matteo , Mela Flora , Guerrini Remo , Calò Girolamo , Bianchi Clementina , Morari Michele 
Published: December 2004

AbstractWe recently showed that pharmacological blockade of nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors located in the substantia nigra stimulates the nigrostriatal dopaminergic pathway and motor behavior (Marti et al. J. Neurosci. 2004, 24, 6659–6666). To investigate whether such motor‐stimulating action was dependent on functional dopaminergic transmission, the selective NOP receptor peptide antagonist [Nphe1,Arg14,Lys15]N/OFQ‐NH2 (UFP‐101) was microinjected into the substantia nigra reticulata of rats made cataleptic by systemic haloperidol administration. UFP‐101 reduced haloperidol‐induced akinesia as measured by immobility time in the bar test. UFP‐101 also induced contralateral turning in cataleptic rats. To investigate the mechanisms involved in the anti‐akinetic action of UFP‐101, nigral glutamate release was monitored by microdialysis technique. The anti‐akinetic action of UFP‐101 correlated with normalization of nigral glutamate release, previously elevated by haloperidol injection. We conclude that endogenous N/OFQ in the substantia nigra sustains akinesia generated by impaired DA transmission and subthalamic nucleus overactivation. NOP receptor antagonists may be beneficial in the symptomatic therapy of parkinsonism, via normalization of subthalamonigral glutamatergic transmission.
Botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates
Authors: Bade Steffen , Rummel Andreas , Reisinger Clemens , Karnath Tino , Ahnert‐Hilger Gudrun , Bigalke Hans , Binz Thomas 
Published: December 2004

AbstractMulti‐domain bacterial protein toxins are being explored as potential carriers for targeted delivery of biomolecules. Previous approaches employing isolated receptor binding subunits disallow entry into the cytosol. Strategies in which catalytic domains are replaced with cargo molecules are presumably inefficient due to co‐operation of domains during the endosomal translocation step. Here, we characterize a novel transport vehicle in which cargo proteins are attached to the amino terminus of the full‐length botulinum neurotoxin type D (BoNT/D). The intrinsic enzymatic activity of the neurotoxin allowed quantification of the efficacy of cargo delivery to the cytosol. Dihydrofolate reductase and BoNT type A (BoNT/A) light chain (LC) were efficiently conveyed into the cytosol, whereas attachment of firefly luciferase or green fluorescent protein drastically reduced the toxicity. Luciferase and BoNT/A LC retained their catalytic activity as evidenced by luciferin conversion or SNAP‐25 hydrolysis in the cytosol of synaptosomes, respectively. Conformationally stabilized dihydrofolate reductase as cargo considerably decreased the toxicity indicative for the requirement of partial unfolding of cargo protein and catalytic domain as prerequisite for efficient translocation across the endosomal membrane. Thus, enzymatically inactive clostridial neurotoxins may serve as effective, safe carriers for delivering proteins in functionally active form to the cytosol of neurones.
STAT6 transcription factor binding sites with mismatches within the canonical 5′‐TTC…GAA‐3′ motif involved in regulation of δ‐ and µ‐opioid receptors
Authors: Börner Christine , Wöltje Michael , Höllt Volker , Kraus Jürgen 
Published: December 2004

AbstractOpioid receptors are expressed in neuronal and immune cells and regulated in response to immunological processes. Herein, we demonstrate up‐regulation of the δ‐opioid receptor gene by interleukin‐4 in immune cells (primary T and polymorphonuclear leukocytes, Jurkat E6 T cells), and in NG 108–15 neuronal cells. We identified an interleukin‐4‐responsive element at nt −671 on the murine gene promoter, to which the transcription factor STAT6 binds, as shown by reporter gene analysis and STAT6/DNA interaction studies in living cells with transcription factor decoy oligonucleotides. STAT6 normally binds to palindromic DNA motifs with a 5′‐TTC…GAA‐3′ core. Notably, the δ‐opioid receptor STAT6 site (5′‐TTC…GGA‐3′) is an imperfect palindrome with a mismatch within this core sequence. A systematic analysis of possible mismatch 5′‐TTC…GAA‐3′ motifs revealed that STAT6 also binds to the sequence 5′‐TTA…GAA‐3′. This motif occurs as a polymorphism in the human µ‐opioid receptor gene (Kraus et al. 2001 J. Biol. Chem 276, 43901–43908). We show that this mutated element has a significantly reduced STAT6 binding activity which correlates to its reduced interleukin (IL)‐4 inducibility. In contrast, the non‐canonical STAT6 site of the δ‐opioid receptor binds STAT6 with similar high activity as a perfectly palindromic STAT6 site and is strongly inducible by IL‐4.
Expression and regulation of cyclooxygenase‐2 in normal and neoplastic canine keratinocytes
Authors: Pronovost N. , Suter M. M. , Mueller E. , Sirois J. , Doré M. 
Published: December 2004

AbstractSquamous cell carcinoma (SCC) is one of the most common cancers in dogs, yet relatively little is known about the molecular events involved in its development. Increasing evidence implicates cyclooxygenase‐2 (COX‐2) in the pathogenesis of various cancers in humans and animals. COX‐2 overexpression has recently been demonstrated in canine SCCs. The objective of our study was to characterize the expression and regulation of COX‐2 in normal and neoplastic canine keratinocytes (CKs) to provide anin vitrosystem to investigate the implication of COX‐2 in SCC oncogenesis in dogs. Cell lines derived from normal CKs and neoplastic CKs (SCCs) were cultured in the absence or presence of agonists, and immunoblots, immunocytochemistry, radioimmunoassays and a cell proliferation assay were used to characterize COX‐2 expression and action. Results showed that neoplastic keratinocytes had a higher basal COX‐2 expression than normal keratinocytes. In both cell lines, stimulation with the tumour promoter phorbol 12‐myristate 13‐acetate induced a time‐dependent increase in COX‐2 protein, with COX‐2 induction being stronger in cancerous SCC than in normal CK cells. Moreover, SCC cells produced significantly more PGE2than CK cells, under both baseline and stimulated conditions (P < 0.05). NS‐398, a selective COX‐2 inhibitor, inhibited prostaglandin (PG)E2synthesis and decreased proliferation of CK and SCC cells (P < 0.05). Collectively, our results indicate that the canine neoplastic keratinocyte SCC cell line expresses more COX‐2 and produces more PGE2than the normal keratinocyte CK cell line, thus providing anin vitrosystem to study the molecular basis of elevated COX‐2 expression in SCCs in dogs.
Short‐Term Indwelling Catheters (A Systematic Review): Evidence for a Primarily Nursing Decision
Authors: Brosnahan Jane Elizabeth , Kent Bridie 
Published: December 2004

ABSTRACT Program Overview: Urinary tract infection is the most common infection acquired by patients in hospital. The major associated cause is the presence of indwelling urinary catheters. A variety of specialised urethral catheters have been specifically designed to reduce the risk of infection. These include antiseptic impregnated catheters and antibiotic impregnated catheters. Catheter choice or selection is primarily a nursing decision, and nurses also take a leading role in decision‐making regarding catheters purchased for hospitals. Methods: A systematic review (including metanalyses) was completed with the Cochrane Incontinence Review Group. Eighteen studies met the inclusion criteria: antiseptic impregnated catheters versus standard catheters, which included silver oxide (n = 3 trials) and silver alloy (n = 8 trials), antibiotic impregnated catheters versus standard catheters (n = 1 trial), and comparisons of different types of standard catheters (n = 6 trials). Results: Silver oxide catheters were not found to prevent bacteriuria in short‐term catheterised hospitalised adults (RR 0.87, 95% CI 0.68 to 1.13). Silver alloy catheters were found to significantly reduce the incidence of asymptomatic bacteriuria (RR 0.36, 95% CI 0.25 to 0.52.) in hospitalised adults catheterised for less than 1 week. At greater than 1‐week catheterization, the risk of asymptomatic bacteriuria was still reduced with the use of silver alloy catheters (RR 0.67, 95% CI 0.50 to 0.90). The risk of symptomatic urinary tract infection was also found to be reduced with the use of silver alloy catheters (RR 0.60, 95% CI 0.50 to 0.73). Silver alloy indwelling catheters appear to reduce the risk of catheter‐acquired urinary tract infection in hospitalised adults catheterised short term. Cost‐benefit analyses indicate that compensation for increased cost of silver alloy catheters would come from the reduction in the cost of catheter‐acquired urinary tract infection. Conclusions: This review provides not only nurses and nurse managers, but also other health professionals with evidence of effectiveness to influence catheter choice.
Identification of Barriers and Facilitators to Utilizing Research in Nursing Practice
Authors: Micevski Vaska , Sarkissian Sonia , Byrne Julie , Smirnis Jill 
Published: December 2004

ABSTRACT Background: Despite a growing body of literature, utilization of nursing research remains relatively low even within academic health care institutions. Objective: The purpose of this study was to (1) investigate barriers for utilization of research in nursing practice in multiple nursing roles (staff nurses and nursing leadership) within an academic health care setting, and (2) identify strategies that may influence nurses' perceptions to utilizing research in nursing practice. Design: This study was a prospective, descriptive, cross‐sectional study. Population, Sample, Setting: The subjects were 181 nurses employed at a tertiary care hospital in Southern Ontario, Canada. Methods: A self‐administered questionnaire identifying demographics, and perceptions of barriers and facilitators to utilizing nursing research in practice was sent to 640 nurses. Results were entered into an SPSS database, and descriptive statistics were used for data analysis. Ethical considerations included approval from the Institutional Ethics Review Board. Findings: Twenty‐eight percentage of the invited participants responded to the questionnaire. The subjects identified four particular barriers that affected their utilization of research in practice to a great extent: awareness of the research (33%), lack of time to read the research (39%), feeling that the nurse does not have the authority to change practice procedures (41%), and insufficient time on the job to implement new ideas (49%). Conclusions: Results from this study suggest that a strategic approach to enhancing utilization of nursing research in practice is essential. Organized activities enhance nurses' awareness of research in their field, and developing processes for nurses to participate in practice change is very important. In addition, providing time for nurses to read and implement research will have a positive impact on the utilization of nursing research in practice.
Specialized Persister Cells and the Mechanism of Multidrug Tolerance in
Escherichia coli
Authors: Keren Iris , Shah Devang , Spoering Amy , Kaldalu Niilo , Lewis Kim 
Published: December 2004

ABSTRACT

Bacterial populations produce persisters, cells that neither grow nor die in the presence of bactericidal agents, and thus exhibit multidrug tolerance (MDT). The mechanisms of MDT and the nature of persisters have remained elusive. Our previous research has shown that persisters are largely responsible for the recalcitrance of biofilm infections. A general method for isolating persisters was developed, based on lysis of regular cells by ampicillin. A gene expression profile of persisters contained toxin-antitoxin (TA) modules and other genes that can block important cellular functions such as translation. Bactericidal antibiotics kill cells by corrupting the target function (for example, aminoglycosides interrupt translation, producing toxic peptides). We reasoned that inhibition of translation will lead to a shutdown of cellular functions, preventing antibiotics from corrupting their targets, giving rise to MDT persister cells. Overproduction of the RelE toxin, an inhibitor of translation, caused a sharp increase in persisters. Functional expression of a putative HipA toxin also increased persisters, while deletion of the
hipBA
module caused a sharp decrease in persisters in both stationary and biofilm populations. HipA is thus the first validated persister-MDT gene. We suggest that random fluctuation in the levels of MDT proteins leads to the formation of rare persister cells. The function of these specialized dormant cells is to ensure the survival of the population in the presence of lethal factors.