bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial haplotypes and the New Zealand origin of clonal EuropeanPotamopyrgus, an invasive aquatic snail
Authors: STÄDLER T. , FRYE M. , NEIMAN M. , LIVELY C. M. 
Published: June 2005

AbstractThe small aquatic snailPotamopyrgus antipodarumis an important invading species in Europe, Australia and North America. European populations are generally believed to derive from accidental introductions from New Zealand, probably dating back to the mid‐19th century. We have employed mitochondrial DNA sequences to test the proposed New Zealand origin of EuropeanPotamopyrgus, and to learn more about its genealogical history. Using a 481‐bp region of the 16S ribosomal RNA gene, we identified 17 distinct haplotypes among 65 snails from New Zealand. In marked contrast, only two haplotypes were found across all European samples, which cover a large geographical area. Importantly, these two haplotypes are shared with snails from the North Island of New Zealand. Due to sampling limitations we cannot rule out a South Island origin for one of the haplotypes, but our results clearly demonstrate the New Zealand origin of European populations. The marked divergence among the two European haplotypes implies the successful colonization by two distinct mitochondrial lineages, which is consistent with previous data based on nuclear markers.
Relationships between specific serum IgE, cytokines and polymorphisms in the IL‐4, IL‐4Rα in patients with penicillins allergy
Authors: Qiao H.‐L. , Yang J. , Zhang Y.‐W. 
Published: June 2005

Background:  Excessive production of interleukin (IL)‐4, IL‐13 and interferon (IFN)‐γ is thought to be important in the development of allergic disease and atopy. Several investigators have linked the IL‐4 and IL‐4R genes to allergic disease and atopy. The aim of this study is to further explore the mechanism of penicillins allergy and evaluate the possible role of the IL‐4 C‐589T and IL‐4RαQ576R polymorphisms in modulating the allergic responses to penicillins.Methods:  Radioallergosorbent test (RAST) was used to detect eight kinds of specific immunoglobulin E (IgE) to penicillins in serum. Serum levels of IL‐4, IL‐13 and IFN‐γ were measured by using enzyme‐linked immunosorbent assay (ELISA). The IL‐4 C‐589T and IL‐4RαQ576R polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP).Results:  Compared with control subjects, there were significantly higher levels of IL‐4, IL‐13 and IFN‐γ in allergic patients with positive specific IgE (P < 0.01), and the lower levels of IL‐4 and IFN‐γ were observed in allergic patients with negative specific IgE (P < 0.05). We found a growing trend of IL‐4 and IL‐13 levels with the kind increasing of positive specific IgE, and even there were significant correlations between the three kinds of cytokines and many kinds of specific IgE (P < 0.05). The IL‐4Rα*Q576 allele was significantly increased in patients with penicillins allergy compared with control subjects (P < 0.01). Furthermore, the allele was strongly associated with increased serum‐specific benzylpenicilloyl (BPO)‐, phenoxomethylpenicillanyl (PVA)‐ or ampicillanyl (APA)‐IgE levels in patients with positive specific IgE (P < 0.05).Conclusions:  These data suggest that IL‐4, IL‐13 and IFN‐γ play an important roles in penicillins allergy. The IL‐4RαQ576R polymorphism may involve in the development of penicillins allergy, and through modulating specific serum IgE levels.
Recombinant Mycobacterium bovis BCG producing IL‐18 reduces IL‐5 production and bronchoalveolar eosinophilia induced by an allergic reaction
Authors: Biet F. , Duez C. , Kremer L. , Marquillies P. , Amniai L. , Tonnel A.‐B. , Locht C. , Pestel J. 
Published: June 2005

Background:  Allergic reactions occur through the exacerbated induction of a Th2 cell type expression profile and can be prevented by agents favoring a Th1 profile. Bacillus Calmette‐Guérin (BCG) is able to induce high IFN‐γ levels and has been shown to decrease experimentally induced allergy. The induction of IFN‐γ is mediated by interleukin (IL)‐12 known to be secreted upon mycobacterial infections and can be enhanced by IL‐18 acting in synergy with IL‐12.Objective:  We evaluated the ability of a recombinant BCG strain producing IL‐18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)‐dependent allergic reaction.Methods:  Mice were injected intraperitoneally or intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received OVA together with 5 × 106 colony forming units of either rBCG or nonrecombinant BCG.Results:  A time‐course analysis of OVA‐specific immunoglobulin (Ig)E, IgG1 and IgG2a levels indicated no significant difference between the three groups of mice. However, following in vitro stimulation with OVA, lymph node cells from rBCG‐treated mice produced less IL‐5 and more IFN‐γ than those of mice injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge, a strong reduction of bronchoalveolar eosinophilia was found in the rBCG‐injected mice compared to the nontreated or nonrecombinant BCG‐treated groups.Conclusion:  These results indicate that the production of IL‐18 by rBCG may enhance the immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in particular, decrease airway eosinophilia.
A new tool to evaluate the impact of chronic urticaria on quality of life: chronic urticaria quality of life questionnaire (CU‐Q2oL)
Authors: Baiardini I. , Pasquali M. , Braido F. , Fumagalli F. , Guerra L. , Compalati E. , Braga M. , Lombardi C. , Fassio O. , Canonica G. W. 
Published: June 2005

Background:  Health‐related quality of Life in patients with chronic urticaria is evaluated by mean of generic instruments or questionnaire designed for skin diseases. No disease‐specific tool is now available for the assessment of chronic urticaria impact from patients’ viewpoint.Objective:  The aim of our study is to develop and validate a new questionnaire specifically designed for the assessment of quality of life in chronic urticaria (Chronic Urticaria Quality of Life Questionnaire – CU‐Q2oL)Methods:  In the development phase of CU‐Q2oL an initial list of items of 37 items was compiled and given to 80 patients with chronic urticaria; the 23 most significant items were selected and converted into questions evaluating the answers on a Likert scale of five steps. The validation procedure involved 125 patients (86 F and 39 M) (age 42.17 ± 9.24 years).Results:  Following a statistical analysis, CU‐Q2oL showed a six‐dimensional structure and good levels of internal consistency for the extracted factors: Pruritus (0.79), Swelling (0.65), Impact on life activities (0.83), Sleep problems (0.77), Looks (0.83) and Limits (0.74). In stable conditions CU‐Q2oL showed a good reliability, ranged between 0.64 and 0.92. Responsiveness to clinical changes was accomplished.Discussion:  These results provide evidence that CU‐Q2oL has specificity enough for being a valid tool for detecting the relative burden of CU on subjective wellbeing, and for obtaining a global evaluation both of CU impact and of treatments, taking into account the patient's point of view. The CU‐Q2oL was easily and quickly filled up and well accepted by the patients.
Age‐Dependent Changes in the Calcium Sensitivity of Striatal Mitochondria in Mouse Models of Huntington's Disease
Authors: Brustovetsky N. , LaFrance R. , Purl K. J. , Brustovetsky T. , Keene C. D. , Low W. C. , Dubinsky J. M. 
Published: June 2005

AbstractStriatal and cortical mitochondria from knock‐in and transgenic mutant huntingtin mice were examined for their sensitivity to calcium induction of the permeability transition, a cause of mitochondrial depolarization and ATP loss. The permeability transition has been suggested to contribute to cell death in Huntington's Disease. Mitochondria were examined from slowly progressing knock‐in mouse models with different length polyglutarnine expansions (Q20, Q50, Q92, Q111) and from the rapidly progressing transgenic R6/2 mice overexpressing exon I of human huntingtin with more than 110 polyglutamines. As previously observed in rats, striatal mitochondria from background strain CD1 and C57BL/6 control mice were more sensitive to calcium than cortical mitochondria. Between 5 and 12 months in knock‐in Q92 mice and between 8 and 12 weeks in knock‐in Q111 mice, striatal mitochondria developed resistance, becoming equally sensitive to calcium as cortical mitochondria, while those from Q50 mice were unchanged. Cortical mitochondrial calcium sensitivity did not change. In R6/2 mice striatal and cortical mitochondria were equally resistant to Ca2+while striatal mitochondria from littermate controls were more susceptible. No increases in calcium sensitivity were observed in the mitochondria from Huntington's Disease (HD) mice compared to controls. Neither motor abnormalities, nor expression of cyclophilin D corresponded to the changes in mitochondrial sensitivity. Polyglutamine expansions in huntingtin produced an early increased resistance to calcium in striatal mitochondria suggesting mitochondria undergo compensatory changes in calcium sensitivity in response to the many cellular changes wrought by polyglutamine expansion.
Myt1 family recruits histone deacetylase to regulate neural transcription
Authors: Romm Elena , Nielsen Joseph A. , Kim Jin G. , Hudson Lynn D. 
Published: June 2005

AbstractThe myelin transcription factor 1 (Myt1) gene family is comprised of three zinc finger genes [Myt1, Myt1L (Myt1‐Like) and NZF3] of the structurally unique CCHHC class that are expressed predominantly in the developing CNS. To understand the mechanism by which this family regulates neural differentiation, we searched for interaction partners. In both yeast and a mammalian two‐hybrid system, Myt1 and Myt1L interacted with Sin3B, a protein that mediates transcriptional repression by binding to histone deacetylases (HDACs). Myt1–Sin3B complexes were co‐immunoprecipitated from transfected mammalian cells and included HDAC1 and HDAC2. Myt1 and Myt1L could partner with all three Sin3B isoforms, the long form (Sin3BLF) that includes the HDAC‐binding domain, and the two short forms (Sin3BSF293 and Sin3BSF302) that lack this domain and may consequently antagonize Sin3BLF/HDAC‐mediated co‐repression. Myt1 or Myt1L interactions with the HDAC‐binding form of Sin3B conferred repression on a heterologous promoter. Oligodendrocytes were shown to express transcripts encoding each of the Sin3B isoforms. We present a model in which the Myt1 family of zinc finger proteins, when bound to a neural promoter, can recruit Sin3B. Depending on the relative availability of Sin3B isoforms, the Myt1 gene family may favor the silencing of genes during neural development.
Implication of cyclin‐dependent kinase 5 in the development of psychological dependence on and behavioral sensitization to morphine
Authors: Narita Minoru , Shibasaki Masahiro , Nagumo Yasuyuki , Narita Michiko , Yajima Yoshinori , Suzuki Tsutomu 
Published: June 2005

AbstractIn the present study, we investigated the role of cyclin‐dependent kinase 5 (cdk5) in the brain dynamics changed by repeated in vivo treatment with morphine. The level of phosphorylated‐cdk5 was significantly increased in the cingulate cortex of mice showing the morphine‐induced rewarding effect. Under these conditions, roscovitine, a cdk5 inhibitor, given intracerebroventricularly (i.c.v.) caused a dose‐dependent and significant inhibition of the morphine‐induced rewarding effect. In addition, the dose–response effect of the morphine‐induced rewarding effect was dramatically attenuated in cdk5 heterozygous (+/–) knockout mice. Furthermore, the development of behavioral sensitization by intermittent administration of morphine was virtually abolished in cdk5 (+/–) mice. These findings suggest that the induction and/or activation of cdk5 are implicated in the development of psychological dependence on morphine.
Transcriptional regulation of tyrosine hydroxylase by estrogen: opposite effects with estrogen receptors α and β and interactions with cyclic AMP
Authors: Maharjan Shreekrishna , Serova Lidia , Sabban Esther L. 
Published: June 2005

AbstractReported effects of estrogen administration on tyrosine hydroxylase (TH) gene expression are confusing. Therefore, we studied the mechanism of regulation of TH transcription by estrogen with different estradiol receptor (ER) subtypes. PC12 cells, transiently co‐transfected with expression vector for ERα or ERβ, and luciferase gene under control of the TH promoter, were treated with 17 β‐estradiol (E2). E2 doubled luciferase activity with ERα; however, it was decreased with ERβ. Mapping the TH promoter showed that the putative half estrogen response element (ERE) motif at − 675, as well as the activation protein 1 motif at − 205, were not required for response to E2 with either ER. The specificity protein 1/early growth response gene 1 (Egr 1) motif was required for the E2‐elicited response with ERβ, but not with ERα. Deletion of the cyclic AMP/Ca2+ response element (CRE/CaRE) nearly abolished E2‐triggered responses with either ER. Further analysis revealed an imperfect canonical putative ERE overlapping with CRE/CaRE and Nurr1 response element. Oligonucleotides spanning this ERE displayed binding to ER, Cyclic AMP Response Element Binding Protein (CREB) and other proteins. Moreover, E2 attenuated the increase in TH transcription seen with cyclic AMP analogs. Thus, TH is transcriptionally regulated by estradiol in opposite directions depending on ER subtype. The overlapping ERE and CRE/CaRE may integrate interactions elicited by various regulators of TH transcription including cAMP and estrogens.
Novel regulation of Na+, K+‐ATPase by Src tyrosine kinases in cortical neurons
Authors: Wang Xue Qing , Yu Shan Ping 
Published: June 2005

AbstractThe Na+, K+‐ATPase or Na+, K+‐pump plays a critical role in ion homeostasis and many cellular events. The Na+, K+‐pump activity is regulated by serine/threonine phosphorylation, the role of tyrosine kinases in the regulation, however, is obscure. We now present novel evidence showing that tyrosine phosphorylation activates the Na+, K+‐pump in cortical neurons. The electrogenic activity of the Na+, K+‐pump was measured using whole‐cell voltage clamp. A tonic activity was revealed by an inward current induced by the specific inhibitor ouabain or strophanthidin; an outward current due to activation of the pump was triggered by raising extracellular K+. The inward and outward currents were attenuated by the tyrosine kinase inhibitor genistein, herbimycin A, or lavendustin A, while blocking tyrosine phosphatases increased the pump current. Down‐regulation of the pump current was also seen with the Src inhibitor PP1 and intracellularly applied anti‐Lyn or anti‐Yes antibody. Consistently, intracellular application of Lyn kinase up‐regulated the pump current. Immunoprecipitation and western blotting showed tyrosine phosphorylation and a direct interaction between Lyn and the α3 subunit of the Na+, K+‐pump. The tyrosine phosphorylation of the α3 subunit was reduced by serum deprivation. These data suggest that the Na+, K+‐ATPase activity in central neurons is regulated by specific Src tyrosine kinases via a protein‐protein mechanism and may play a role in apoptosis.
Activation of the IκB kinase complex is sufficient for neuronal differentiation of PC12 cells
Authors: Azoitei Ninel , Wirth Thomas , Baumann Bernd 
Published: June 2005

AbstractWe examined the role of the IκB kinase complex in nerve growth factor (NGF)‐induced neuronal differentiation of PC12 cells. We showed that neurite outgrowth is accompanied by an activation of the IKK complex and a delayed elevation of NF‐κB‐dependent transcription. Ectopic expression of a constitutively active form of IKK2 but not of IKK1 promoted neurite outgrowth in the absence of NGF. In addition, increased expression of Bcl‐2 and Bcl‐xL and resistance to apoptosis upon serum withdrawal were found. The IKK2‐driven neurite outgrowth was not blocked by MEK1/2 and PI3K inhibitors but was repressed by the SN50 peptide suggesting that NF‐κB activation is critical for this differentiation process. Transdominant mutants of IκBα (32/36‐SS/AA) and IKK1 only marginally reduced NGF‐driven neuritogenesis. However, a dominant negative mutant of IKK2 or an IκBα protein lacking the complete N‐terminus was able to repress neuritogenesis. We also detected tyrosine phosphorylation of IκBα during differentiation. Consequently, PC12 cells expressing mutant IκBα (Y42F) show an impaired neuritogenesis. Furthermore, PC12 cells ectopically expressing p65 show almost no signs of neurite outgrowth which is, however, found to some extent in c‐Rel‐expressing cells. Our data suggest that NGF‐induced PC12 differentiation includes activation of IKK2 which may promote the release of c‐Rel‐containing dimers.
Cyclo‐oxygenase‐1 and ‐2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of N‐methyl‐d‐aspartate receptors in rat hippocampus
Authors: Pepicelli Olimpia , Fedele Ernesto , Berardi Maria , Raiteri Maurizio , Levi Giulio , Greco Anita , Ajmone‐Cat Maria Antonietta , Minghetti Luisa 
Published: June 2005

AbstractUsing intracerebral microdialysis, we reported previously that acute in vivo activation of NMDA glutamate receptors triggers rapid and transient releases of prostaglandin E2 (PGE2) and F2‐isoprostane 15‐F2t‐IsoP in the hippocampus of freely moving rats. The formation of the two metabolites – produced through cyclo‐oxygenase (COX) enzymatic activity and free radical‐mediated peroxidation of arachidonic acid (AA), respectively, – was prevented by the specific NMDA antagonist MK‐801, and was largely dependent on COX‐2 activity. Here, we demonstrate that besides COX‐2, which is the prominent COX isoform in the brain and particularly in the hippocampus, the constitutive isoform, COX‐1 also contributes to prostaglandin (PG) synthesis and oxidative damage following in vivo acute activation of hippocampal NMDA glutamate receptors. The relative contribution of the two isoforms is dynamically regulated, as the COX‐2 selective inhibitor NS398 immediately prevented PGE2 and 15‐F2t‐IsoP formation during the application of NMDA, whereas the COX‐1 selective inhibitor SC560 was effective only 1 h after agonist infusion. Our data suggest that, although COX‐2 is the prominent isoform, COX‐1 activity may significantly contribute to excitotoxicity, particularly when considering the amount of lipid peroxidation associated with its catalytic cycle. We suggest that both isoforms should be considered as possible therapeutic targets to prevent brain damage caused by excitotoxicity.
Altered membrane NTPase activity in Lesch–Nyhan disease fibroblasts: comparison with HPRT knockout mice and HPRT‐deficient cell lines
Authors: Pinto Cibele S. , Jinnah Hyder A. , Shirley Thomas L. , Nyhan William L. , Seifert Roland 
Published: June 2005

AbstractLesch–Nyhan disease (LND) is a rare disorder caused by a defect of an enzyme in the purine salvage pathway, hypoxanthine phosphoribosyl transferase (HPRT). It is still unknown how the metabolic defect translates into the complex neuropsychiatric phenotype characterized by self‐injurious behavior, dystonia and mental retardation. There are abnormalities in purine and pyrimidine nucleotide content in HPRT‐deficient cells. We hypothesized that altered nucleotide concentrations in HPRT deficiency change G‐protein‐mediated signal transduction. Therefore, our original study aim was to examine the high‐affinity GTPase activity of G‐proteins in membranes from primary human skin and immortalized mouse skin fibroblasts, rat B103 neuroblastoma cells and mouse Neuro‐2a neuroblastoma cells. Unexpectedly, in membranes from human fibroblasts, B103‐ and Neuro‐2a cells, Vmax of low‐affinity nucleoside 5′‐triphosphatase (NTPase) activities was decreased up to 7‐fold in HPRT deficiency. In contrast, in membranes from mouse fibroblasts, HPRT deficiency increased NTPase activity up to 4‐fold. The various systems analyzed differed from each other in terms of Km values for NTPs, absolute Vmax values and Ki values for nucleoside 5′‐[β,γ‐imido]triphosphates. Our data show that altered membrane NTPase activity is a biochemical hallmark of HPRT deficiency, but species and cell‐type differences have to be considered. Thus, future studies on biochemical changes in LND should be conducted in parallel in several HPRT‐deficient systems.
Aspirin prevention of NMDA‐induced neuronal death by direct protein kinase Cζ inhibition
Authors: Crisanti P. , Leon A. , Lim D. M. , Omri B. 
Published: June 2005

AbstractAspirin has been shown to protect against glutamate neurotoxicity via the nuclear factor κB pathway. Some studies have implicated the atypical protein kinase C (PKC) zeta (ζ) isoform in cell protection, but the mechanism involved remains unclear. We show here that aspirin exerts at least some of its effects through PKCζ, decreasing the NMDA‐induced activation, cleavage and nuclear translocation of this molecule. Aspirin (acetylsalicylic acid) directly inhibited the protein kinase activity of PKCζ, whereas salicylic acid did not. This direct effect of aspirin on purified human PKCζ is consistent with PKCζ inhibition preventing the NMDA‐induced death of cortical neurones. Caspase‐3 inhibition blocked the cleavage and nuclear translocation of PKCζ, whereas caspase‐1‐inhibition did not. Thus, PKCζ (protein kinase Mζ) regulates nuclear events essential for the initiation of the apoptotic pathway. Aspirin protects cells against NMDA‐induced apoptosis by means of a novel mechanism targeting PKCζ, a key molecule in inflammatory responses and neurodegeneration.
Characterization of serotonin 5‐HT2Creceptor signaling to extracellular signal‐regulated kinases 1 and 2
Authors: Werry Tim D. , Gregory Karen J. , Sexton Patrick M. , Christopoulos Arthur 
Published: June 2005

AbstractSerotonin 5‐HT2Creceptors (5‐HT2CRs) are almost exclusively expressed in the CNS, and implicated in disorders such as obesity, depression, and schizophrenia. The present study investigated the mechanisms governing the coupling of the 5‐HT2CR to the extracellular signal‐regulated kinases (ERKs) 1/2, using a Chinese hamster ovary (CHO) cell line stably expressing the receptor at levels comparable to those found in the brain. Using the non‐RNA‐edited isoform of the 5‐HT2CR, constitutive ERK1/2 phosphorylation was observed and found to be modulated by full, partial and inverse agonists. Interestingly, agonist‐directed trafficking of receptor stimulus was also observed when comparing effects on phosphoinositide accumulation and intracellular Ca2+elevation to ERK1/2 phosphorylation, whereby the agonists, [±]‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI) and quipazine, showed reversal of efficacy between the phosphoinositide/Ca2+pathways, on the one hand, and the ERK1/2 pathway on the other. Subsequent molecular characterization found that 5‐HT‐stimulated ERK1/2 phosphorylation in this cellular background requires phospholipase D, protein kinase C, and activation of the Raf/MEK/ERK module, but is independent of both receptor‐ and non‐receptor tyrosine kinases, phospholipase C, phosphoinositide 3‐kinase, and endocytosis. Our findings underscore the potential for exploiting pathway‐selective receptor states in the differential modulation of signaling pathways that play prominent roles in normal and abnormal neuronal signaling.