bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of cartilage canals in endochondral and perichondral bone formation: are there similarities between these two processes?
Authors: Blumer Michael J. F. , Longato Stefano , Richter Elisabeth , Pérez Maria Teresa , Konakci Kadriye Zeynep , Fritsch Helga
Published: March 2005

We investigated the development of cartilage canals to clarify their function in the process of bone formation. Cartilage canals are tubes containing vessels that are found in the hyaline cartilage prior to the formation of a secondary ossification centre (SOC). Their exact role is still controversial and it is unclear whether they contribute to endochondral bone formation when an SOC appears. We examined the cartilage canals of the chicken femur in different developmental stages (E20, D2, 5, 7, 8, 10 and 13). To obtain a detailed picture of the cellular and molecular events within and around the canals the femur was investigated by means of three‐dimensional reconstruction, light microscopy, electron microscopy, histochemistry and immunohistochemistry [vascular endothelial growth factor (VEGF), type I and II collagen]. An SOC was visible for the first time on the last embryonic day (E20). Cartilage canals were an extension of the vascularized perichondrium and its mesenchymal stem cell layers into the hyaline cartilage. The canals formed a complex network within the epiphysis and some of them penetrated into the SOC were they ended blind. The growth of the canals into the SOC was promoted by VEGF. As the development progressed the SOC increased in size and adjacent canals were incorporated into it. The canals contained chondroclasts, which opened the lacunae of hypertrophic chondrocytes, and this was followed by invasion of mesenchymal cells into the empty lacunae and formation of an osteoid layer. In older stages this layer mineralized and increased in thickness by addition of further cells. Outside the SOC cartilage canals are surrounded by osteoid, which is formed by the process of perichondral bone formation. We conclude that cartilage canals contribute to both perichondral and endochondral bone formation and that osteoblasts have the same origin in both processes.
Thromboxane A2 Receptor‐Mediated Cell Proliferation, Survival and Gene Expression in Oligodendrocytes
Authors: Lin Xin , Ramamurthy Santosh K. , Le Breton Guy C.
Published: March 2005

Thromboxane A2 receptors (TP) were previously localized to discrete regions in the rat brain on myelinated fiber tracts and oligodendrocytes (OLGs). The present studies extended these findings and investigated the effects of TP signaling on cell proliferation, survival, and gene expression in OLG progenitor cells (OPCs) and OLGs. It was found that the TP agonist, U46619 stimulated the proliferation of OPCs and promoted the survival of mature OLGs. Examination of the early gene expression events involved in OPC proliferation, revealed that c‐fos expression was substantially increased by U46619 stimulation. Treatment of OPCs or OLGs with U46619 caused activation of the mitogen‐activated protein kinases (MAPK) ERK 1/2. In OPCs this activation was blocked by inhibition of src. However, in OLGs this phosphorylation was not only blocked by inhibition of src but also by inhibition of protein kinase C (PKC). Furthermore, U46619 was found to increase CREB phosphorylation in both OPCs and OLGs. Similar to ERK 1/2 activation, there was a divergence in the mechanism of the TP‐mediated CREB response for each cell type. Specifically, U46619 activation was attenuated by src and protein kinase A (PKA) inhibition in OPCs, whereas in OLGs this effect was blocked by inhibition of src, PKA as well as by inhibition of PKC. Collectively, these results provide the first demonstration that TP‐activated nuclear signaling events are involved in the proliferation of OPCs, the survival of mature OLGs, and the stimulation of gene expression.
Sequestration of serum response factor in the hippocampus impairs long‐term spatial memory
Authors: Dash Pramod K. , Orsi Sara A. , Moore Anthony N.
Published: March 2005

The formation of long‐term memory has been shown to require protein kinase‐mediated gene expression. One such kinase, mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAPK/ERK), can lead to the phosphorylation of serum response factor (SRF) and Elk‐1, enhancing the expression of target genes. However, a direct involvement of these transcription factors in memory storage has not been demonstrated. We have employed an oligonucleotide decoy technique to interrogate SRF and Elk‐1. Previously, it has been shown that intra‐amygdalal infusion of small double‐stranded decoy oligonucleotides for nuclear factor‐kappaB (NFkappaB) can impair long‐term memory for fear‐potentiated startle. Using this approach, we found that intra‐hippocampal infusion of NFkappaB decoy oligonucleotides also impairs long‐term spatial memory, consistent with a role for this factor in long‐term memory storage. Decoy oligonucleotides containing the binding site for SRF, as confirmed by shift‐western, did not influence memory acquisition but impaired long‐term spatial memory. Analysis of search behavior during the transfer test revealed deficits consistent with a loss of precise platform location information. In contrast, oligonucleotides with a binding site for either Elk‐1 or another target of ERK activity, SMAD3/SMAD4, did not interfere with memory formation or storage. These findings suggest that SRF‐mediated gene expression is required for long‐term spatial memory.
Alcohol‐responsive genes in the frontal cortex and nucleus accumbens of human alcoholics
Authors: Flatscher‐Bader Traute , van der Brug Marcel , Hwang John W , Gochee Peter A , Matsumoto Izuru , Niwa Shin‐ichi , Wilce Peter A
Published: March 2005

The molecular processes underlying alcohol dependence are not fully understood. Many characteristic behaviours result from neuroadaptations in the mesocorticolimbic system. In addition, alcoholism is associated with a distinct neuropathology. To elucidate the molecular basis of these features, we compared the RNA expression profile of the nucleus accumbens and prefrontal cortex of human brain from matched individual alcoholic and control cases using cDNA microarrays. Approximately 6% of genes with a marked alcohol response were common to the two brain regions. Alcohol‐responsive genes were grouped into 11 functional categories. Predominant alcohol‐responsive genes in the prefrontal cortex were those encoding DNA‐binding proteins including transcription factors and repair proteins. There was also a down‐regulation of genes encoding mitochondrial proteins, which could result in disrupted mitochondrial function and energy production leading to oxidative stress. Other alcohol‐responsive genes in the prefrontal cortex were associated with neuroprotection/apoptosis. In contrast, in the nucleus accumbens, alcohol‐responsive genes were associated with vesicle formation and regulation of cell architecture, which suggests a neuroadaptation to chronic alcohol exposure at the level of synaptic structure and function. Our data are in keeping with the previously reported alcoholism‐related pathology characteristic of the prefrontal cortex, but suggest a persistent decrease in neurotransmission and changes in plasticity in the nucleus accumbens of the alcoholic.
Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non‐tumour brain tissue
Authors: Petersen Gitte , Moesgaard Birthe , Schmid Patricia C. , Schmid Harald H. O. , Broholm Helle , Kosteljanetz Michael , Hansen Harald S.
Published: March 2005

The endogenous levels of the two cannabinoid receptor ligands 2‐arachidonoyl glycerol and anandamide, and their respective congeners, monoacyl glycerols and N‐acylethanolamines, as well as the phospholipid precursors of N‐acylethanolamines, were measured by gas chromatography‐mass spectrometry in glioblastoma (WHO grade IV) tissue and meningioma (WHO grade I) tissue and compared with human non‐tumour brain tissue. Furthermore, the metabolic turnover of N‐acylethanolamines was compared by measurements of the enzymatic activity of N‐acyltransferase, N‐acylphosphatidylethanolamine‐hydrolysing phospholipase D and fatty acid amide hydrolase in the same three types of tissue. Glioblastomas were characterized by enhanced levels of N‐acylethanolamines (eightfold, 128 ± 59 pmol/μmol lipid phosphorus) including anandamide (17‐fold, 4.6 ± 3.1pmol/μmol lipid phosphorus) and several species of N‐acylphosphatidylethanolamines (three to eightfold). This was accompanied by a more than 60% reduction in the enzyme activities of N‐acylphosphatidylethanolamine‐hydrolysing phospholipase D and fatty acid amide hydrolase. By contrast, meningiomas were characterized by a massively enhanced level of 2‐monoacyl glycerols (20‐fold, 2293 ± 361 pmol/μmol lipid phosphorus) including 2‐arachidonoyl glycerol (20‐fold, 1524 ± 361 pmol/μmol lipid phosphorus). This was accompanied by an enhanced in vitro conversion of phosphatidylcholine to monoacyl glycerol (fivefold). The enhanced level of the 2‐arachidonoyl glycerol, anandamide and other N‐acylethanolamines detected in the two types of tumour tissue may possibly act as endogenous anti‐tumour mediators by stimulation of both cannabinoid and non‐cannabinoid receptor‐mediated mechanisms.
Alterations in the solubility and intracellular localization of parkin by several familial Parkinson's disease‐linked point mutations
Authors: Wang Cheng , Tan Jeanne M. M. , Ho Michelle W. L. , Zaiden Norazean , Wong Siew Heng , Chew Constance L. C. , Eng Pei Woon , Lim Tit Meng , Dawson Ted M. , Lim Kah Leong
Published: March 2005

Mutations in the parkin gene, which encodes a ubiquitin ligase, are currently recognized as the main contributor to familial forms of Parkinson's disease (PD). A simple assumption about the effects of PD‐linked mutations in parkin is that they impair or ablate the enzyme activity. However, a number of recent studies, including ours, have indicated that many disease‐linked point mutants of parkin retain substantial catalytic activity. To understand how the plethora of mutations on parkin contribute to its dysfunction, we have conducted a systematic analysis of a significant number of parkin point mutants (22 in total), which represent the majority of parkin missense/nonsense mutations reported to date. We found that more than half of these mutations, including many located outside of the parkin RING fingers, produce alteration in the solubility of parkin which influences its detergent extraction property. This mutation‐mediated alteration in parkin solubility is also associated with its propensity to form intracellular, aggresome‐like, protein aggregates. However, they do not represent sites where parkin substrates become sequestered. As protein aggregation sequesters the functional forms away from their normal sites of action, our results suggest that alterations in parkin solubility and intracellular localization may underlie the molecular basis of the loss of function caused by several of its mutations.
Cloning and characterization of a Family C orphan G‐protein coupled receptor
Authors: Kuang Donghui , Yao Yi , Lam Janice , Tsushima Robert G. , Hampson David R.
Published: March 2005

Members of the family C receptors within the G‐protein coupled receptor superfamily include the metabotropic glutamate receptors, GABAB receptors, the calcium‐sensing receptor (CaSR), the V2R pheromone receptors, the T1R taste receptors, and a small group of uncharacterized orphan receptors. We have cloned and studied the mouse GPRC6A family C orphan receptor. The open reading frame codes for a protein with highest sequence identity to the fish 5.24 odorant receptor and the mammalian CaSR. The gene structure shows a striking resemblance to that of the CaSR. Results from RT‐PCR analyses showed that mouse GPRC6A mRNA is expressed in mouse brain, skeletal muscle, heart, lung, spleen, kidney, liver, and in the early stage mouse embryo. Immunocytochemical analysis of the cloned mouse GPRC6A cDNA expressed in human embryonic kidney 293 cells demonstrated that GPRC6A was present on the plasma membrane, as well as in the endoplasmic reticulum and nuclear envelope membranes of transfected cells. A chimeric cDNA construct in which the extracellular ligand binding domain of the fish 5.24 amino acid‐activated odorant receptor was ligated to the complementary downstream sequence of the mouse GPRC6A receptor indicated that GPRC6A is coupled to phosphoinositol turnover and release of intracellular calcium. Further studies with mouse GPRC6A expressed in Xenopus laevis ooctyes demonstrated that this receptor possesses a pharmacological profile resembling that of the fish 5.24 odorant receptor. These findings suggest that GPRC6A may function as the receptor component of a novel cellular transmitter system in mammals.
Differential phosphodiesterase expression and cytosolic Ca2+ in human CNS tumour cells and in non‐malignant and malignant cells of rat origin
Authors: Vatter Sandra , Pahlke Gudrun , Deitmer Joachim W. , Eisenbrand Gerhard
Published: March 2005

A promising attempt in the field of tumour therapy is the modulation of intracellular, proliferation‐associated signalling pathways. The role of cyclic nucleotide phosphodiesterases (PDEs), key enzymes in cAMP/cGMP signal transduction, was investigated in two human CNS tumour cell lines as well as in the rat glioblastoma cell line C6 in comparison with rat cerebellar astrocytes with the emphasis on target evaluation. We found differential PDE expression patterns in human CNS tumour cell lines as well as in CNS cells of rat origin. In human glioblastoma cells, intracellular cAMP and Ca2+ levels correlated well with the PDE expression pattern. There were, however, marked differences in PDE expression and Ca2+ kinetics between the human glioblastoma cell lines. In contrast to human epithelial tumour cells, shown earlier by us to express significantly enhanced cAMP‐specific PDE activity, this was not the case in rat glioblastoma cells compared with non‐malignant rat astrocytes. Despite different levels of PDE1 and PDE4 expression and activity, cyclic nucleotide and Ca2+ levels in non‐malignant and malignant rat CNS cells were similar. These in vitro data do not support the concept of PDE1C representing a target exploitable for drug treatment of malignant CNS tumours.
CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model
Authors: Chou Szu‐Yi , Lee Yi‐Chao , Chen Hui‐Mei , Chiang Ming‐Chang , Lai Hsing‐Lin , Chang Hao‐Hung , Wu Yi‐Chih , Sun Chung‐Nan , Chien Chen‐Li , Lin Yow‐Sien , Wang Shyi‐Chyi , Tung Yu‐Ying , Chang Chen , Chern Yijuang
Published: March 2005

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a CAG trinucleotide expansion in exon 1 of the Huntingtin (Htt) gene. We show herein that in an HD transgenic mouse model (R6/2), daily administration of CGS21680 (CGS), an A2A adenosine receptor (A2A‐R)‐selective agonist, delayed the progressive deterioration of motor performance and prevented a reduction in brain weight. 3D‐µMRI analysis revealed that CGS reversed the enlarged ventricle‐to‐brain ratio of R6/2 mice, with particular improvements in the left and right ventricles. 1H‐MRS showed that CGS significantly reduced the increased choline levels in the striatum. Immunohistochemical analyses further demonstrated that CGS reduced the size of ubiquitin‐positive neuronal intranuclear inclusions (NIIs) in the striatum of R6/2 mice and ameliorated mutant Htt aggregation in a striatal progenitor cell line overexpressing mutant Htt with expanded polyQ. Moreover, chronic CGS treatment normalized the elevated blood glucose levels and reduced the overactivation of a major metabolic sensor [5′AMP‐activated protein kinase (AMPK)] in the striatum of R6/2 mice. Since AMPK is a master switch for energy metabolism, modulation of energy dysfunction caused by the mutant Htt might contribute to the beneficial effects of CGS. Collectively, CGS is a potential drug candidate for the treatment of HD.
Selective serotonin reuptake blockade increases extracellular dopamine in noradrenaline‐rich isocortical but not prefrontal areas: dependence on serotonin‐1A receptors and independence from noradrenergic innervation
Authors: Valentini V. , Cacciapaglia F. , Frau R. , Di Chiara G.
Published: March 2005

The present study investigated the effects of two serotonin (5‐HT) uptake inhibitors, citalopram and paroxetine, and of a non‐selective noradrenaline (NA) and 5‐HT uptake blocker, imipramine, on extracellular NA and dopamine (DA) in the prefrontal cortex (PfCX), parietal cortex (ParCX) and occipital cortex (OccCX). Citalopram, the most selective 5‐HT uptake blocker, increased dialysate DA in the OccCX and ParCX but not in the PfCX and this effect was prevented in the OccCX by WAY‐100635, an antagonist of serotonin‐1A (5‐HT1A) receptors, but not by dorsal noradrenergic bundle (DNAB) lesions that reduced to unmeasurable levels basal dialysate NA but did not affect dialysate DA. Paroxetine, a less selective 5‐HT uptake inhibitor than citalopram, at the dose of 5 mg/kg, increased DA in the OccCX but not in the PfCX; however, at doses of 10 mg/kg, which increase PfCX NA, paroxetine increased DA also in this area. Imipramine increased dialysate DA and NA both in the PfCX and in the OccCX and this effect was abolished by DNAB lesions and was reduced but not abolished by WAY‐100635. Administration of doses of reboxetine and citalopram that do not increase DA release in the OccCX if given separately, markedly increased DA when combined. These results indicate that endogenous 5‐HT, raised by selective blockade of the 5‐HT carrier, can increase extracellular DA in the OccCX and in the ParCX by stimulating 5‐HT1A receptors independently from the presence of NA terminals, although blockade of 5‐HT and NA carrier can strongly interact to raise extracellular DA in this area. These observations are consistent with the existence of DA neurons separate from the NA ones contributing to extracellular DA even in NA‐rich/DA poor isocortical areas.
Stage‐ and site‐specific DNA demethylation during neural cell development from embryonic stem cells
Authors: Shimozaki Koji , Namihira Masakazu , Nakashima Kinichi , Taga Tetsuya
Published: March 2005

Activation of the transcription factor STAT3 is important for astrocyte differentiation during neural development. Demethylation of the methyl‐CpG dinucleotide in the STAT3 binding site in the promoter of the glial fibrillary acidic protein (GFAP) gene, a marker for astrocytes, was previously shown to be a crucial cue for neural progenitors to express this gene in response to astrogenic signals during brain development. In this study, we analyzed the methylation status of the STAT3 binding site in the GFAP gene promoter during neural cell development from mouse embryonic stem (ES) cells in vitro. The CpG dinucleotide in the STAT3 binding site in the GFAP gene promoter exhibited a high incidence of cytidine‐methylation in undifferentiated pluripotent ES cells. The high incidence of methylation of this particular cytidine was maintained in ES cell‐derived neuroectoderm‐like cells, but it underwent demethylation when the neural lineage cells became competent to express GFAP in response to a STAT3 activation signal. In contrast, hypermethylation of the CpG site was maintained in non‐neural cells generated from the same ES cells. Progressive demethylation of the STAT3 binding site in the GFAP gene promoter was also observed in primary embryonic neuroepithelial cells during in vitro culture, whereas non‐neural cells maintained hypermethylation of this site even after culture. Taken together, these results demonstrate that the astrocyte gene‐specific cytidine‐demethylation is programmed when neural progenitors from pluripotent cells are committed to a neural lineage that is capable of producing astrocytes.
Impaired long‐term potentiation in c‐Jun N‐terminal kinase 2‐deficient mice
Authors: Chen Ju‐Tao , Lu Da‐Hua , Chia Chern‐Pang , Ruan Di‐Yun , Sabapathy Kanaga , Xiao Zhi‐Cheng
Published: March 2005

c‐Jun N‐terminal kinases (JNKs) are thought to be involved in regulating synaptic plasticity. We therefore investigated the specific role of JNK2 in modulating long‐term potentiation (LTP) in hippocampus during development, using JNK2‐deficient mice. The morphological structure and the numbers of both NeuN, a specific neuronal marker, and GABA‐positive neurons in the hippocampal areas were similar in wild‐type and Jnk2–/– mice. Western blot analysis revealed that JNK2 expression was higher and stable at 1 and 3 months of age, but JNK1 levels were lower at 1 month of age and almost undetectable in 3‐month‐old wild‐type mice. In contrast to wild‐type mice, there was a significant increase in JNK1 expression in JNK2 mutant mice, especially at 1 month of age. Electrophysiological studies demonstrated that LTP was impaired in both the CA1 and CA3 regions in 1‐month‐old, but not in adult, Jnk2–/– mice, probably owing to decreased presynaptic neurotransmitter release. Moreover, late‐phase LTP, but not early‐phase LTP, was impaired in the Jnk2–/– adult mice, suggesting that JNK2 plays a role in transforming early LTP to late LTP. Together, the data highlight the specific role of JNK2 in hippocampal synaptic plasticity during development.
Astroglial cytoprotection by erythropoietin pre‐conditioning: implications for ischemic and degenerative CNS disorders
Authors: Diaz Zuanel , Assaraf Michael I. , Miller Wilson H. , Schipper Hyman M.
Published: March 2005

Erythropoietin (Epo) is a glycoprotein secreted by the kidney in response to hypoxia that stimulates erythropoiesis through interaction with cell surface Epo receptors. Pre‐treatment with Epo has been shown to protect neurons in models of ischemic injury. The mechanism responsible for this neuroprotection and the effects of Epo on astroglial and other non‐neuronal cell populations remain unknown. In the present study, we determined whether Epo pre‐treatment protects neonatal rat astrocytes from apoptotic cell death resulting from treatment with nitric oxide, staurosporine (STS) and arsenic trioxide and possible mechanisms mediating Epo‐related cytoprotection. Epo (5–20 U/mL) significantly attenuated multiple hallmarks of apoptotic cell death in astroglia exposed to nitric oxide and STS but not arsenic trioxide. Epo (20 U/mL) induced mild oxidative stress as shown by increases in heme oxygenase (HO)‐1 mRNA and protein expression that could be suppressed by antioxidant coadministration. Moreover, coincubation with tin‐mesoporphyrin, a competitive inhibitor of HO activity, abrogated the cytoprotective effects of Epo (20 U/mL) in the face of STS treatment. Thus, induction of the ho‐1 gene may contribute to the glioprotection accruing from high‐dose Epo exposure. Epo may augment astroglial resistance to certain chemical stressors by oxidative stress‐dependent and ‐independent mechanisms.
Histone deacetylase inhibitors decrease reelin promoter methylation in vitro
Authors: Mitchell Colin P. , Chen Ying , Kundakovic Marija , Costa Erminio , Grayson Dennis R.
Published: March 2005

We investigated the effects of agents that induce reelin mRNA expression in vitro on the methylation status of the human reelin promoter in neural progenitor cells (NT2). NT2 cells were treated with the histone deacetylase inhibitors, trichostatin A (TSA) and valproic acid (VPA), and the methylation inhibitor aza‐2′‐deoxycytidine (AZA) for various times. All three drugs reduced the methylation profile of the reelin promoter relative to untreated cells. The acetylation status of histones H3 and H4 increased following treatment with VPA and TSA at times as short as 15 min following treatment; a result consistent with the reported mode of action of these drugs. Chromatin immunoprecipitation experiments showed that these changes were accompanied by changes occurring at the level of the reelin promoter as well. Interestingly, AZA decreased reelin promoter methylation without concomittantly increasing histone acetylation. In fact, after prolonged treatments with AZA, the acetylation status of histones H3 and H4 decreased relative to untreated cells. We also observed a trend towards reduced methylated H3 after 18 h treatment with TSA and VPA. Our data indicate that while TSA and VPA act to increase histone acetylation and reduce promoter methylation, AZA acts only to decrease the amount of reelin promoter methylation.
Sp1 and Sp3 activate transcription of the human dopamine transporter gene
Authors: Wang Jun , Bannon Michael J.
Published: March 2005

The dopamine transporter is a plasma membrane protein that controls extracellular concentrations of the neurotransmitter dopamine. The physiological importance of the DAT provides the impetus for studies aimed at understanding the molecular mechanisms underlying regulation of the DAT gene. In this study, we identified a DAT‐expressing neuroblastoma cell line (SK‐N‐AS) and employed it to investigate the transcriptional regulation of the human DAT gene. Two GC boxes (located at −130 and −60, respectively, relative to the transcriptional start site) were identified as important cis‐acting elements mediating DAT promoter activity in dopaminergic SK‐N‐AS cells. Utilizing Sp‐deficient Drosophila Schneider line (SL‐2) cells, we showed that both Sp1 and Sp3 are strong activators of DAT transcriptional activity. Differential binding of Sp1 and Sp3 to the two GC boxes was demonstrated by electrophoretic mobility shift assays and super‐shift assays. Our results indicate that the Sp1 family of proteins plays an important role in controlling the expression of the dopamine transporter gene within dopaminergic neurons.
Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6‐methyl‐phenyl‐tetrahydropyridine toxicity
Authors: Conti Bruno , Sugama Shuei , Lucero Jacinta , Winsky‐Sommerer Raphaelle , Wirz Sebastian A. , Maher Pamela , Andrews Zane , Barr Alasdair M. , Morale Maria C. , Paneda Covadonga , Pemberton Janell , Gaidarova Svetlana , Behrens M. Margarita , Beal Flint , Sanna Pietro Paolo , Horvath Tamas , Bartfai Tamas
Published: March 2005

Oxidative stress is implicated in the death of dopaminergic neurons in sporadic forms of Parkinson's disease. Because oxidative stress can be modulated endogenously by uncoupling proteins (UCPs), we hypothesized that specific neuronal expression of UCP2, one member of the UCP family that is rapidly induced in the CNS following insults, could confer neuroprotection in a mouse model of Parkinson's disease. We generated transgenic mice overexpressing UCP2 in catecholaminergic neurons under the control of the tyrosine hydroxylase promoter (TH‐UCP2). In these mice, dopaminergic neurons of the substantia nigra showed a twofold elevation in UCP2 expression, elevated uncoupling of their mitochondria, and a marked reduction in indicators of oxidative stress, an effect also observed in the striatum. Upon acute exposure to 1,2,3,6‐methyl‐phenyl‐tetrahydropyridine, TH‐UCP2 mice showed neuroprotection and retention of locomotor functions. Our data suggest that UCP2 may represent a drug target for slowing the progression of Parkinson's disease.
Control of cyclin‐dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability
Authors: Wei Fan‐Yan , Tomizawa Kazuhito , Ohshima Toshio , Asada Akiko , Saito Taro , Nguyen Chan , Bibb James A. , Ishiguro Koichi , Kulkarni Ashok B. , Pant Harish C. , Mikoshiba Katsuhiko , Matsui Hideki , Hisanaga Shin‐ichi
Published: March 2005

Although the roles of cyclin‐dependent kinase 5 (Cdk5) in neurodevelopment and neurodegeneration have been studied extensively, regulation of Cdk5 activity has remained largely unexplored. We report here that glutamate, acting via NMDA or kainate receptors, can induce a transient Ca2+/calmodulin‐dependent activation of Cdk5 that results in enhanced autophosphorylation and proteasome‐dependent degradation of a Cdk5 activator p35, and thus ultimately down‐regulation of Cdk5 activity. The relevance of this regulation to synaptic plasticity was examined in hippocampal slices using theta burst stimulation. p35–/– mice exhibited a lower threshold for induction of long‐term potentiation. Thus excitatory glutamatergic neurotransmission regulates Cdk5 activity through p35 degradation, and this pathway may contribute to plasticity.
Importance of niche quality for Yellowhammer Emberiza citrinella nestling survival, development and body condition in its native and exotic ranges: the role of diet
Authors: MACLEOD CATRIONA J. , PARISH DAVID M. B. , DUNCAN RICHARD P. , MOREBY STEVE , HUBBARD STEPHEN F.
Published: March 2005

The niche hypothesis predicts that some introduced species establish and spread successfully because their new environment provides expanded niche opportunities compared with their native environments. By investigating nestling survival, growth and body condition in relation to diet composition and prey abundance, we tested the prediction that the success of Yellowhammers Emberiza citrinella in New Zealand could be explained by the availability of better quality food resources in its introduced range compared with its native range. We found that Yellowhammer nestlings in New Zealand were larger and heavier than those in Britain, but that nestling survival and body condition did not differ between countries. The preferred prey items, which had some influence on nestling development and survival, were more prevalent in the diet of nestlings in New Zealand, suggesting that nestlings in the introduced range had a superior quality diet. However, there was little evidence to support the prediction that the preferred prey were more abundant in the introduced range, implying that some other factor such as prey accessibility or adult fitness may account for the differences in diet between countries.
Pale Rock Sparrow Carpospiza brachydactyla in the Mount Lebanon range: modelling breeding habitat
Authors: KNIGHT CHRISTOPHER G. , BEALE COLIN M.
Published: March 2005

The Pale Rock Sparrow Carpospiza brachydactyla is a poorly known species with very little documentation of its breeding habitat preferences. Using detailed surveys and habitat modelling for a population in southern Lebanon's Bekaa valley, we have identified aspects of the habitat associated both temporally and spatially with breeding. Static spatial habitat modelling using three fundamentally different statistical techniques (multiple linear regression, regression trees and artificial neural networks) agreed on positive associations of breeding density with ‘pebbliness’ of ground cover and the quantity of available habitat, and a negative association with trees. Temporal associations were found between breeding and a rise in temperature and peaks in grasshopper and beetle abundance, the two main prey that we observed the birds taking. These findings are discussed in the context of Pale Rock Sparrow conservation and implications for species‐directed habitat assessment more generally.
Sex‐specific foraging behaviour in tropical boobies: does size matter?
Authors: LEWIS SUE , SCHREIBER E. A. , DAUNT FRANCIS , SCHENK GARY A. , ORR KATE , ADAMS AILEEN , WANLESS SARAH , HAMER KEITH C.
Published: March 2005

Sex differences in the foraging behaviour of adults have been observed in a number of sexually size‐dimorphic birds, and the usual inference has been that these sex‐specific differences are driven primarily by differences in body size. An alternative explanation is that foraging differences result from sex differences unrelated to size, such as sex‐specific nutritional requirements. To examine these alternative hypotheses, the foraging behaviour of parents was compared between two sympatric and congeneric species of seabird, the Brown Booby Sula leucogaster, which is highly sexually size‐dimorphic (females 38% larger) and the Red‐footed Booby S. sula, in which sex differences in body size are less marked (females 15% larger). Using temperature and depth loggers, we found that there were highly significant differences in the foraging trip durations and diving behaviour of male and female Brown Boobies. These sex differences were less marked in Red‐footed Boobies. Thus, our interspecies comparison revealed that the magnitude of the difference between the sexes matched the sexual size dimorphism of the species, providing support for the size hypothesis.
Learning styles among geography undergraduates: an international comparison
Authors: Healey Mick , Kneale Pauline , Bradbeer John ,   with other members of the INLT Learning Styles and Concepts Group
Published: March 2005

Growing diversity is focusing attention on the range of different student learning styles. This study assesses whether geographers have a predominant learning style and whether this varies between and within countries. The findings are based on over 900 geography students from 12 universities in Australia, New Zealand, the UK and the US, who completed Kolb's Learning Style Inventory (LSI). The implications for curriculum design and student learning strategies are discussed. It is suggested that departments should aim to produce balanced learners with a full range of learning capacities rather than simply matching teaching to existing learning styles.
The journey to school in Britain since the 1940s: continuity and change
Authors: Pooley Colin G , Turnbull Jean , Adams Mags
Published: March 2005

The journey to school has major significance both for families and urban environments, yet little is known in detail about the ways this has changed over the twentieth century. This study uses oral history evidence to compare decisions about the journey to school in the past and the present, and to assess the impact of these changes on the mobility experience of children. The paper argues that despite obvious increases in car use, and decreases in children travelling alone, other characteristics of the journey to school in British urban areas have changed little over the past 60 years.
Reflections on the iconography of environmental justice activism
Authors: Kurtz Hilda E
Published: March 2005

The United States environmental justice movement has grown in the last 20 years from tactical cooperation between civil rights and environmental activists on hazardous waste issues into a broad‐based movement for social change. As dozens of organizations invest resources in an environmental justice agenda, it is important to examine how such organizations portray their stance toward the goals of the larger movement in order to better understand tensions within the movement between social justice and environmental protection, diversity and commonality, and localized and broader movement agendas. This paper explores what contemporary environmental justice imagery tells us about this social movement through a critical discourse analysis of environmental justice organizations’ logos. The conceptual approach used here links a tradition of critical discourse analysis of textual materials with elements of a critical visual methodology. The paper examines how the social grievance of environmental injustice is constructed in relation to the social and natural world, and considers what these images tell us about the identities, relationships and modes of authority that constitute the contemporary environmental justice movement.
The impact of small‐scale wood harvesting on neem Azadirachta indica A. Juss stands in the coastal savanna of Ghana
Authors: Campbell Michael O’Neal
Published: March 2005

Although the introduced neem tree Azadirachta indica A. Juss is a very important energy source in the coastal savanna of Ghana, the sustainability of small‐scale wood harvesting (SSWH) has not been investigated with regard to this species. This paper assesses the sustainability of SSWH on neem stands in the coastal savanna, using a socio‐economic and ecological survey. The results show that SSWH, incorporating coppicing, stand tolerance, balanced with total bole cutting and root removal, and based on socio‐cultural supports, has created a modified yet sustainable system of SSWH. It is concluded that these systems may contribute to tree stand conservation.
Patch Testing with Egg Represents a Useful Integration to Diagnosis of Egg Allergy in Children with Atopic Dermatitis
Authors: Giusti Francesca , Seidenari Stefania
Published: March 2005

Abstract:  Our aim was to investigate atopy patch and skin prick test reactions to egg in 85 children with atopic dermatitis, and to evaluate their relevance by performing repeated open challenges with egg. Thirty‐one percent of our patients showed an eczematous response to the challenge. Positive reactions to atopy patch and skin prick tests were recorded in 37% and 19%, respectively. Atopy patch test sensitivity proved significantly higher than that of skin prick test (79.6% vs. 46.2%), whereas specificity was lower (81.4% vs. 93.2%). Our data suggest that combined skin prick and patch testing improves screening for egg allergy in affected children, identifying 92% of those who were challenge positive among our patients.
Herpetic Whitlow as a Harbinger of Pediatric HIV‐1 Infection
Authors: El Hachem M. , Bernardi S. , Giraldi L. , Diociaiuti A. , Palma P. , Castelli‐Gattinara G.
Published: March 2005

Abstract:  Herpetic whitlow applies to a primary or recurrent herpes simplex infection of the fingers. It is a rare condition in immunocompetent patients, and usually has a rapid evolution and prompt response to treatment. We report a 10‐year‐old girl referred to our department of infectious diseases with recurrent and unresponsive ulcerated and necrotic lesions of the fingers of both hands as a first sign of human immunodeficiency virus infection. Numerous instances of extensive or recurrent herpes lesions of the mouth, lips, and perianal areas have been found in the literature, but we have not found any report of periungual infection as a first manifestation of human immunodeficiency virus infection. Pediatricians and dermatologists need to be aware of this association in order to make an early diagnosis and start treatment of these patients’ disease.
X‐linked Reticulate Pigmentary Disorder with Systemic Manifestations: Report of a Third Family and Literature Review
Authors: Anderson Robert C. , Zinn Andrew R. , Kim June , Carder K. Robin
Published: March 2005

Abstract:  Three siblings, two boys and one girl, presented with pigmentary abnormalities. The brothers, ages 11 and 6 years, had diffuse reticulate macular hyperpigmentation with onset in early childhood. In addition, these boys had hypohydrosis, coarse hair with an upswept frontal hairline, failure to thrive, and chronic pulmonary disease. The older boy also had corneal dystrophy and marked photophobia. A punch biopsy specimen from the 11‐year‐old showed melanophages and necrotic keratinocytes. Stains for amyloid were negative. The sister, age 2 years, had congenital linear hyperpigmented patches involving the intertrigenous areas, but was otherwise normal. The clinical findings of these children were consistent with X‐linked reticulate pigmentary disorder with systemic manifestations. We present a summary of the clinical manifestations of this rare disorder and discuss efforts to identify the causative gene.
Vaccine‐Associated “Wild‐Type” Measles
Authors: Berggren Kelle Liermann , Tharp Michael , Boyer Kenneth M.
Published: March 2005

Abstract:  Measles is the most contagious of the childhood exanthems and is the leading cause of vaccine‐preventable deaths in children, mostly in developing countries. The prodromal stage, consisting of high fever and the triad of cough, coryza, and conjunctivitis, is followed by a caudal progressing rash over a period of 2 to 3 days. With a worldwide vaccination program in place, mortality and morbidity have decreased substantially. Receipt of the live attenuated vaccine generally causes no or only mild side effects such as a low‐grade fever and a subtle rash. We report a 1‐year‐old boy who, 10 days after vaccination, developed vaccine measles which was clinically indistinguishable from the natural disease. Vaccine virus was detected by polymerase chain reaction in the patient's nasopharyngeal secretions.
Infantile Perianal Pyramidal Protrusion: Report of a Case and Review of the Literature
Authors: Fleet Shelley L. , Davis Loretta S.
Published: March 2005

Abstract:  Infantile perianal pyramidal protrusion is an important, relatively newly recognized condition, which is thought to be under‐reported in the pediatric literature. Previous reports refer to these lesions as skin tags or skin folds. More recently, the name infantile perianal pyramidal protrusion has been suggested, based on the characteristic presentation of the lesion in prepubertal children, especially girls. Recognition of these lesions has many implications regarding proper diagnosis and management. They may easily be mistaken for condyloma accuminata or as a sign of trauma, leading to an investigation of sexual abuse. This situation may be avoided with awareness of this entity in combination with thorough history taking and a classic presentation. We present a classic presentation of infantile perianal pyramidal protrusion and further discuss this condition.
Generalized Lichen Nitidus
Authors: Al‐Mutairi Nawaf , Hassanein Ayman , Nour‐Eldin Osama , Arun Joshi
Published: March 2005

Abstract:  Lichen nitidus is a rare chronic condition of unknown etiology. Generalized lichen nitidus is even rarer. We report here a 5‐year‐old girl who had multiple, asymptomatic, discrete, 1 to 2 mm flesh‐colored, shiny, flat, papules on her face, upper limbs, and thighs with relative sparing of the trunk. Resolution of these papular lesions was followed by hyperpigmented macules in those areas. Histopathologic examination of a papular lesion revealed a localized granulomatous lymphohistiocytic infiltrate in an expanded dermal papilla with thinning of overlying epidermis and downward extension of the rete ridges at the lateral margin of the infiltrate, producing a typical “claw clutching a ball” picture, confirming our clinical diagnosis of lichen nitidus. The pigmented macules showed melanin pigmentation on histology. There was no response to oral astemizole treatment for 3 months. However, the lichen nitidus lesions resolved spontaneously without any further treatment over the next year, leaving behind a prominent pigmentary disturbance.
A Practical Approach for the Use of Oral Isotretinoin for Infantile Acne
Authors: Barnes Cheryl J. , Eichenfield Lawrence F. , Lee Jungho , Cunningham Bari B.
Published: March 2005

Abstract:  Infantile acne is a rare occurrence. It is more common in boys and predominately occurs on the cheeks in infants between the ages of 1 and 16 months. Clinically, the lesions range from comedones to inflammatory papulopustules to cysts. Successful therapies include topical tretinoin, benzoyl peroxide and topical and oral erythromycin. For more serious cases, oral isotretinoin (Accutane) has been reported to successfully treat recalcitrant infantile cystic acne. We describe two additional patients with infantile cystic acne treated successfully with oral isotretinoin. The dose of isotretinoin used ranged from 0.2 mg/kg/day to 1.5 mg/kg/day. The treatment duration varied from 5 to 14 months. Careful monthly monitoring is recommended because of the many side effects reported with isotretinoin. Practical tips for the administration of oral isotretinoin in infants are reviewed.
TOXIN PROFILE, PIGMENT COMPOSITION, AND LARGE SUBUNIT RDNA PHYLOGENETIC ANALYSIS OF AN ALEXANDRIUM MINUTUM (DINOPHYCEAE) STRAIN ISOLATED FROM THE FLEET LAGOON, UNITED KINGDOM1
Authors: Nascimento Silvia M. , Purdie Duncan A. , Lilly Emily L. , Larsen Jacob , Morris Steven
Published: March 2005

Paralytic shellfish toxins, pigment composition, and large subunit (LSU) rDNA sequence were analyzed for a clonal culture of Alexandrium minutum Halim isolated in 2000 from the coastal Fleet Lagoon, Dorset, United Kingdom. The HPLC pigment analysis revealed the presence of chl a, peridinin, and diadinoxanthin as major pigments and chl c1+c2 and c3, diatoxanthin, and β‐carotene as minor components. The toxins responsible for paralytic shellfish poisoning were analyzed by HPLC with postcolumn derivatization and fluorescence detection. The paralytic shellfish poisoning toxin profile of the Fleet Lagoon strain of A. minutum in exponential growth phase was dominated by gonyautoxin‐3 up to 54%, whereas gonyautoxin‐2 made up 10% and saxitoxin (STX) 36%. The average toxicity of the culture was 3.8 pg STX Eq·cell−1, and total toxin content varied from 5.6 fmol·cell−1 on day 1 to a maximum of 16.8 fmol·cell−1 during the early stationary phase. Sequence analysis of the LSU rDNA revealed the strain to be closely related to several European strains of A. minutum and one isolated from Australian waters, although most of these do not produce STX. The shallow Fleet Lagoon may provide a favorable environment for A. minutum to bloom, and the presence of highly potent saxitoxins in this strain indicates potential for future shellfish contamination.
A MOVING MAT: PHOTOTAXIS IN THE FILAMENTOUS GREEN ALGAE SPIROGYRA (CHLOROPHYTA, ZYGNEMATACEAE)1
Authors: Kim Gwang Hoon , Yoon Minchul , Klotchkova Tatiana A.
Published: March 2005

A blue light– (peak at 470 nm) induced photomovement was observed in the filamentous eukaryotic algae, Spirogyra spp. When Spirogyra filaments were scattered in a water chamber under a unilateral light source, they rapidly aligned toward the light source in 1 h and bound with neighboring filaments to form thicker parallel bundles of filaments. The filaments in the anterior of the bundles curved toward the light first and then those in the posterior began to roll up toward the light, forming an open‐hoop shape. The bundle of filaments then moved toward the light source by repeated rolling and stretching of filaments. When the moving bundle met other filaments, they joined and formed a bigger mat. The coordination of filaments was essential for the photomovement. The average speed of movement ranged between 7.8 and 13.2 μm·s−1. The movement was induced in irradiance level from 1 to 50 μmol photons·m−2·s−1. The filaments of Spirogyra showed random bending and stretching movement under red or far‐red light, but the bundles did not move toward the light source. There was no distinct diurnal rhythm in the photomovement of Spirogyra spp.
FERTILIZATION SUCCESS CAN DRIVE PATTERNS OF PHASE DOMINANCE IN COMPLEX LIFE HISTORIES1
Authors: Fierst Janna , TerHorst Casey , Kübler Janet E. , Dudgeon Steve
Published: March 2005

Many algal life cycles alternate between two free‐living generations. Life histories in which the two generations look identical (isomorphic) are common, particularly in the Rhodophyta. Reports of natural populations dominated by one generation of the life history have sought explanation in terms of phase‐specific differences in mortality and reproductive output, yet in many cases identification of these adaptations has been elusive or inconsistent with predictions. We hypothesized that the gametophyte‐to‐sporophyte ratio of ecologically equivalent isomorphs could result from variation in fertilization rate. We developed two models to test this hypothesis: one representing a generalized isomorphic life history and the other specific to red algae with a Polysiphonia‐type life history. Fertilization rate affected the gametophyte‐to‐sporophyte ratio, especially at low fertilization rates. In the general model, gametophytes dominated the population regardless of fertilization rate unless egg production greatly exceeded meiospore production. In the red algal model, phase dominance depended on the combination of fertilization rate and the number of carpospores produced per fertilization. The generational composition of model multiphasic algal populations results from their inherent reproductive characteristics and the dynamic environment to which fertilization and mortality rates are tied.