bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spermidine synthase is prominently expressed in the striatal patch compartment and in putative interneurones of the matrix compartment
Authors: Krauss M. , Langnaese K. , Richter K. , Brunk I. , Wieske M. , Ahnert‐Hilger G. , Veh R. W. , Laube G. 
Published: March 2006

AbstractThe ubiquitous polyamines spermidine and spermine are known as modulators of glutamate receptors and inwardly rectifying potassium channels. They are synthesized by a set of specific enzymes in which spermidine synthase is the rate‐limiting step catalysing the formation of the spermine precursor spermidine from putrescine. Spermidine and spermine were previously localized to astrocytes, probably reflecting storage rather than synthesis in these cells. In order to identify the cellular origin of spermidine and spermine synthesis in the brain, antibodies were raised against recombinant mouse spermidine synthase. As expected, strong spermidine synthase‐like immunoreactivity was obtained in regions known to express high levels of spermidine and spermine, such as the hypothalamic paraventricular and supraoptic nuclei. In the striatum, spermidine synthase was found in neurones and the neuropil of the patch compartment (striosome) as defined by expression of the µ opiate receptor. The distinct expression pattern of spermidine synthase, however, only partially overlapped with the distribution of the products spermidine and spermine in the striatum. In addition, spermidine synthase‐like immunoreactivity was seen in patch compartment‐apposed putative interneurones. These spermidine synthase‐positive neurones did not express any marker characteristic of the major striatal interneurone classes. The neuropil labelling in the patch compartment and in adjacent putative interneurones may indicate a role for polyamines in intercompartmental signalling in the striatum.
The JAK3 inhibitor WHI‐P154 prevents PDGF‐evoked process outgrowth in human neural precursor cells
Authors: Richards G. R. , Smith A. J. , Cuddon P. , Ma Q. P. , Leveridge M. , Kerby J. , Roderick H. L. , Bootman M. D. , Simpson P. B. 
Published: March 2006

AbstractThe prospect of manipulating endogenous neural stem cells to replace damaged tissue and correct functional deficits offers a novel mechanism for treating a variety of CNS disorders. The aim of this study was to investigate pathways controlling neurite outgrowth in human neural precursor cells, in particular in response to platelet‐derived growth factor (PDGF). PDGF‐AA, ‐AB and ‐BB were found to initiate calcium signalling and produce robust increases in neurite outgrowth. PDGF‐induced outgrowth of Tuj1‐positive precursors was abolished by the addition of EGTA, suggesting that calcium entry is a critical part of the signalling pathway. Wortmannin and PD098059 failed to inhibit PDGF‐induced outgrowth. Clostridium Toxin B increased the amount of PDGF‐induced neurite branching but had no effect on basal levels. In contrast, WHI‐P154, an inhibitor of Janus protein tyrosine kinase (JAK3), Hck and Syk, prevented PDGF‐induced neurite outgrowth. PDGF activates multiple signalling pathways with considerable potential for cross‐talk. This study has highlighted the complexity of the pathways leading to neurite outgrowth in human neural precursors, and provided initial evidence to suggest that calcium entry is critical in producing the morphological changes observed.
Modulated splicing‐associated gene expression in P19 cells expressing distinct acetylcholinesterase splice variants
Authors: Ben‐Ari Shani , Toiber Debra , Sas Aldema S. , Soreq Hermona , Ben‐Shaul Yoram 
Published: March 2006

AbstractAlternative splicing configurations and acetylcholinesterase (AChE) gene expression are both modified in neurons under stress. However, it is unclear if these phenomena are functionally interrelated. Using a home‐made spotted microarray focused on splicing‐associated transcripts, we tested the effects of excess 3′ splice variants of human AChE on splicing‐related gene expression in semi‐differentiated neuronal P19 cells. Of the tested transcripts, 17.3% and 20.2% showed modified expression levels (log2 of the ratio < − 0.3 or > 0.3) in transfected P19 cells overexpressing the stress‐inducible AChE‐R variant or the synaptic AChE‐S protein, respectively. Multiple transcripts encoding serine‐arginine rich (SR) and SR‐related splicing regulators were suppressed in cells expressing either of these variants, whereas the gene groups including splicing‐related helicases and transcripts involved in apoptosis displayed variant‐specific changes. Our findings are compatible with the assumption that both neuronal overexpression and alternative splicing of pre‐AChE mRNA may be causally involved in initiating global changes in neuronal alternative splicing, causing subsequent modifications in the expression patterns of numerous target genes.
Critical role of ASK1 in the 6‐hydroxydopamine‐induced apoptosis in human neuroblastoma SH‐SY5Y cells
Authors: Ouyang Mingxing , Shen Xun 
Published: March 2006

Abstract6‐Hydroxydopamine (6‐OHDA)‐induced apoptosis in dopaminergic neuronal cells is a common cell model of Parkinson's disease (PD). The role of apoptosis signal‐regulating kinase 1 (ASK1) in this model has not been well studied. We observed significant activation of ASK1, p38 and JNK, as well as apoptosis in human dopaminergic neuroblastoma SH‐SY5Y cells exposed to 6‐OHDA. Over‐expressing kinase‐dead mutant ASK1(K709M) or knock‐down of endogenous ASK1 by its small interfering RNA (siRNA) greatly suppressed activation of these kinases and apoptosis in the cells. It was found that the activation of p38 and JNK was suppressed to almost the same extent as that of ASK1 in the ASK1‐knock‐down cells, suggesting that activated ASK1 is almost totally responsible for activation of p38/JNK. It was also observed that the 6‐OHDA‐induced cell apoptosis could be effectively prevented by over‐expressing the dominant‐negative mutant of p38 or p38 inhibitor SB203580, demonstrating that activation of p38/JNK signalling is required for initiating the programmed cell death. Furthermore, suppression of the 6‐OHDA‐generated reactive oxygen species (ROS) by pre‐incubation of cells with N‐acetyl‐l‐cysteine effectively inhibited the 6‐OHDA‐induced activation of ASK1, p38 and JNK, and protected the cells from apoptosis. This study clearly shows the route from ROS generation by 6‐OHDA to initiation of p38/JNK signalling via activation of ASK1 in the studied PD model.
Big dynorphin as a putative endogenous ligand for the κ‐opioid receptor
Authors: Merg Florence , Filliol Dominique , Usynin Ivan , Bazov Igor , Bark Niklas , Hurd Yasmin L. , Yakovleva Tatjana , Kieffer Brigitte L. , Bakalkin Georgy 
Published: March 2006

AbstractThe diversity of peptide ligands for a particular receptor may provide a greater dynamic range of functional responses, while maintaining selectivity in receptor activation. Dynorphin A (Dyn A), and dynorphin B (Dyn B) are endogenous opioid peptides that activate the κ‐opioid receptor (KOR). Here, we characterized interactions of big dynorphin (Big Dyn), a 32‐amino acid prodynorphin‐derived peptide consisting of Dyn A and Dyn B, with human KOR, μ‐ (hMOR) and δ‐ (hDOR) opioid receptors and opioid receptor‐like receptor 1 (hORL1) expressed in cells transfected with respective cDNA. Big Dyn and Dyn A demonstrated roughly similar affinity for binding to hKOR that was higher than that of Dyn B. Dyn A was more selective for hKOR over hMOR, hDOR and hORL1 than Big Dyn, while Dyn B demonstrated low selectivity. In contrast, Big Dyn activated G proteins through KOR with much greater potency, efficacy and selectivity than other dynorphins. There was no correlation between the rank order of the potency for the KOR‐mediated activation of G proteins and the binding affinity of dynorphins for KOR. The rank of the selectivity for the activation of G proteins through hKOR and of the binding to this receptor also differed. Immunoreactive Big Dyn was detected using the combination of radioimmunoassay (RIA) and HPLC in the human nucleus accumbens, caudate nucleus, hippocampus and cerebrospinal fluid (CSF) with the ratio of Big Dyn and Dyn B being approximately 1 : 3. The presence in the brain implies that Big Dyn, along with other dynorphins, is processed from prodynorphin and secreted from neurons. Collectively, the high potency and efficacy and the relative abundance suggest that Big Dyn may play a role in the KOR‐mediated activation of G proteins.
Neuronal cell death caused by inhibition of intracellular cholesterol trafficking is caspase dependent and associated with activation of the mitochondrial apoptosis pathway
Authors: Huang Zhili , Hou Qingsong , Cheung Nam Sang , Li Qiu‐Tian 
Published: March 2006

AbstractAn elevated level of cholesterol in mitochondrial membranes of Niemann‐Pick disease type C1 (NPC1) mouse brains and neural cells has been found to cause mitochondrial dysfunction. In this study, we demonstrate that inhibition of intracellular cholesterol trafficking in primary neurons by class 2 amphiphiles, which mimics the major biochemical and cellular feature of NPC1, led to not only impaired mitochondrial function but also activation of the mitochondrial apoptosis pathway. In activation of this pathway both cytochrome c and Smac/Diablo were released but apoptosis‐inducing factor (AIF) was not involved. Treatment of the neurons with taurine, a caspase 9‐specific inhibitor, could prevent the amphiphile‐induced apoptotic cell death, suggesting that formation of apoptosome, followed by caspase 9 and caspase 3 activation, might play a critical role in the neuronal death pathway. Taken together, the mitochondria‐dependent death cascade induced by blocking intracellular cholesterol trafficking was caspase dependent. The findings provide clues for both understanding the molecular basis of neurodegeneration in NPC1 disease and developing therapeutic strategies for treatment of this disorder.
Mass spectrometric characterization and physiological actions of GAHKNYLRFamide, a novel FMRFamide‐like peptide from crabs of the genus Cancer
Authors: Cruz‐Bermúdez Nelson D. , Fu Qiang , Kutz‐Naber Kimberly K. , Christie Andrew E. , Li Lingjun , Marder Eve 
Published: March 2006

AbstractThe stomatogastric ganglion (STG) and the cardiac ganglion (CG) of decapod crustaceans are modulated by neuroactive substances released locally and by circulating hormones released from neuroendocrine structures including the pericardial organs (POs). Using nanoscale liquid chromatography electrospray ionization quadrupole‐time‐of‐flight tandem mass spectrometry and direct tissue matrix‐assisted laser desorption/ionization Fourier transform mass spectrometry we have identified and sequenced a novel neuropeptide, GAHKNYLRFamide (previously misassigned as KHKNYLRFamide in a study that did not employ peptide derivatization), from the POs and/or the stomatogastric nervous system (STNS) of the crabs, Cancer borealis, Cancer productus and Cancer magister. In C. borealis, exogenous application of GAHKNYLRFamide increased the burst frequency and number of spikes per burst of the isolated CG and re‐initiated bursting activity in non‐bursting ganglia, effects also elicited by the FMRFamide‐like peptides (FLPs) SDRNFLRFamide and TNRNFLRFamide. In the intact STNS (which contains the STG), exogenous application of GAHKNYLRFamide increased the frequency of the pyloric rhythm and activated the gastric mill rhythm, effects also similar to those elicited by SDRNFLRFamide and TNRNFLRFamide. FLP‐like immunoreactivity in the POs and the STNS was abolished by pre‐adsorption with the synthetic GAHKNYLRFamide. Different members of the FLP family exhibited differential degradation in the presence of extracellular peptidases. Taken collectively, the amino acid sequence of GAHKNYLRFamide, the blocking of FLP‐like immunostaining, and its physiological effects on the CG and STNS suggest that this peptide is a novel member of the FLP superfamily.
Up‐regulation of tyrosine hydroxylase gene transcription by tetradecanoylphorbol acetate is mediated by the transcription factors Ets‐like protein‐1 (Elk‐1) and Egr‐1
Authors: Stefano Luisa , Al Sarraj Jude , Rössler Oliver G. , Vinson Charles , Thiel Gerald 
Published: March 2006

AbstractTyrosine hydroxylase is the rate‐limiting enzyme in the biosynthesis of catecholamines. Expression of the tyrosine hydroxylase gene is regulated at the transcriptional level by extracellular signalling molecules, including epidermal growth factor (EGF), nerve growth factor (NGF) and glucocorticoids. We have analysed the stimulation of tyrosine hydroxylase gene transcription by the phorbol ester 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in noradrenergic locus coeruleus‐like CATH.a cells and observed a striking enhancement of the transcriptional activation potential of the ternary complex factor Ets‐like protein‐1 (Elk‐1), a key transcriptional regulator of serum response element‐driven gene transcription. Likewise, TPA strongly up‐regulated the biosynthesis of the transcription factor Egr‐1 via distal serum response elements within the Egr‐1 5′‐flanking region. Subsequently, enhancement of the transcriptional activation potential of Egr‐1 was observed. Overexpression of Egr‐1 was sufficient to activate transcription of a tyrosine hydroxylase promoter/reporter gene, corroborating the view that the tyrosine hydroxylase gene is a target gene of Egr‐1. Expression of dominant‐negative mutants of Elk‐1 or Egr‐1 impaired TPA‐induced stimulation of a tyrosine hydroxylase promoter/reporter gene transcription. In contrast, dominant‐negative mutants of the transcription factors activating transcription factor (ATF)‐2, ATF4, cAMP response element‐binding protein, c‐Jun and CCAAT/enhancer binding protein (C/EBP) did not change TPA‐induced tyrosine hydroxylase promoter activity, indicating that these proteins are not part of the TPA‐mediated signalling cascade directed towards the tyrosine hydroxylase gene.
Effects of antidepressant treatment on gene expression profile in mouse brain: cell type‐specific transcription profiling using laser microdissection and microarray analysis
Authors: Boehm C. , Newrzella D. , Herberger S. , Schramm N. , Eisenhardt G. , Schenk V. , Sonntag‐Buck V. , Sorgenfrei O. 
Published: March 2006

AbstractA gene expression study of mice treated with the tricyclic antidepressant amitriptyline was performed. To enable the detection of cell type‐specific expression changes, laser‐microdissected nucleus accumbens was analysed after 4 and 28 days of treatment. After 4 days of treatment no significantly regulated genes could be detected in this study. In contrast, 95 genes exhibited different expression levels in animals treated for 28 days with amitrityline compared with sham animals. This observation reflects the long‐term effects and adaptation processes observed in patients treated with this drug. Among the regulated genes are receptors belonging to the dopamine‐dependent signalling cascade, ion channels (mainly voltage‐dependent potassium and calcium channels) potentially involved in signalling cascades and neuropeptides. The results support the hypothesis that the therapeutic effect of this antidepressant is much more complex and not confined to a reuptake inhibition of neurotransmitters. Paradigms inducing only weak expression changes, which may be limited to certain cell types within the highly complex brain structure, can therefore be reliably investigated by applying a cell type‐specific expression profiling technique based on laser microdissection and subsequent RNA amplification followed by DNA microarray analysis.
Lipocalin‐type prostaglandin D synthase is up‐regulated in oligodendrocytes in lysosomal storage diseases and binds gangliosides
Authors: Mohri Ikuko , Taniike Masako , Okazaki Issei , Kagitani‐Shimono Kuriko , Aritake Kosuke , Kanekiyo Takahisa , Yagi Takashi , Takikita Shoichi , Kim Hyung‐Suk , Urade Yoshihiro , Suzuki Kinuko 
Published: March 2006

AbstractLipocalin‐type prostaglandin (PG) D synthase (L‐PGDS) is a dually functional protein, acting both as a PGD2‐synthesizing enzyme and as an extracellular transporter of various lipophilic small molecules. L‐PGDS is expressed in oligodendrocytes (OLs) in the central nervous system and is up‐regulated in OLs of the twitcher mouse, a model of globoid cell leukodystrophy (Krabbe's disease). We investigated whether up‐regulation of L‐PGDS is either unique to Krabbe's disease or is a more generalized phenomenon in lysosomal storage disorders (LSDs), using LSD mouse models of Tay–Sachs disease, Sandhoff disease, GM1 gangliosidosis and Niemann–Pick type C1 disease. Quantitative RT‐PCR revealed that L‐PGDS mRNA was up‐regulated in the brains of all these mouse models. In addition, strong L‐PGDS immunoreactivity was observed in OLs, but not in either astrocytes or microglia in these models. Thus, up‐regulation of L‐PGDS appears to be a common response of OLs in LSDs. Moreover, surface plasmon resonance analyses revealed that L‐PGDS binds GM1 and GM2 gangliosides, accumulated in neurons in the course of LSD, with high affinities (KD = 65 and 210 nm, respectively). This suggests that L‐PGDS may play a role in scavenging harmful lipophilic substrates in LSD.
Archaeal diversity and geochemical energy yields in a geothermal well on Vulcano Island, Italy
Authors: ROGERS K. L. , AMEND J. P. 
Published: March 2006

ABSTRACTThe archaeal diversity in a shallow geothermal well on Vulcano Island, Italy was characterized using culture‐independent 16S rDNA sequence analysis. Environmental DNA was extracted from 56 °C well water, and the 16S ribosomal RNA gene was amplified with archaea‐specific primers. Restriction fragment length polymorphism (RFLP) analysis of ∼250 clones revealed 35 unique patterns, which were sequenced and analyzed. These yielded 17 operational taxonomic units, of which 13, 3, and 1 were unique cren‐, eury‐, and korarchaeotal sequences, respectively. The majority of the crenarchaeotal phylotypes formed a novel, deeply‐branching clade that includes sequences from other hydrothermal environments, but no cultured representatives. Three phylotypes represent novel lineages in the Thermoproteales and two phylotypes represent a novel genus of Euryarchaeota. One euryarchaeotal phylotype was nearly identical (99%) to Palaeococcus helgesonii, an aerotolerant, hyperthermophilic fermenter previously isolated from the same well. To place this diverse archaeal community in the geochemical framework of this ecosystem, we calculate values of Gibbs free energy of 145 organic and inorganic redox reactions at in situ conditions. Energy yields ranged from 0 to 125 kJ per mole of electrons transferred. The most exergonic organic reactions were organic carbon oxidation with O2 (>100 kJ/mol e−), followed by oxidation with (61–93 kJ/mol e−), Fe(III) (43–60 kJ/mol e−), and S0/ (6–27 kJ/mol e−) as terminal electron acceptors. Overall, energy yields from inorganic reactions were similar to those of the organic reactions considered, but were less systematic with respect to terminal electron acceptor. The oxidation of methane coupled with Fe(III) reduction yielded the most energy (123 kJ/mol e−). However, the most exergonic inorganic reactions were predominantly O2, , or reduction. Reduction of , S0, CO2, and CO yielded significantly less energy (0–18 kJ/mol e−). Metabolisms of the cultured organisms identified in the Pozzo Istmo archaeal clone library were exergonic. However, most of the archaeal diversity remains uncultured and energetic calculations reveal an extensive suite of potential lithotrophic and heterotrophic metabolisms that could be exploited by these novel organisms.
Ethnic Differences in Birth Outcomes in England*
Authors: Dearden Lorraine , Mesnard Alice , Shaw Jonathan 
Published: March 2006

AbstractThis paper uses the Millennium Cohort Study to look at ethnic differences in birth outcomes for a cohort of English children born in 2000 and 2001. There is an increasingly large literature showing that longer gestation and higher birthweight are positively associated with cognitive and non‐cognitive outcomes later in life, so understanding sources of ethnic differences in these outcomes and identifying factors that may influence birth outcomes has a lot of potential policy interest. This paper shows that even after controlling for background characteristics in a number of ways, there still remain unexplained differences in both gestation and birthweight outcomes across broad ethnic groups. It also suggests, however, that there may be potential policy levers that could be used to narrow this ethnic gap in birth outcomes, such as reducing the proportion of underweight Asian mothers and overweight Black mothers and increasing ethnic minority attendance at antenatal classes.
UNRESOLVED ISSUES IN DIALYSIS: Revisiting the Hemodialysis Dose
Authors: Leypoldt John K. , Cheung Alfred K. 
Published: March 2006

ABSTRACTAn adequate dose of hemodialysis is currently defined by the Kidney Disease Outcomes Quality Initiative (K/DOQI) and European guidelines as a delivered single‐pool urea Kt/V (spKt/V) of 1.2 and 1.4, respectively. Results from several studies, in particular the Hemodialysis (HEMO) study, have largely supported the legitimacy of these guidelines, although they may need to be altered or amended for certain patient subgroups. This review discusses several potential changes to current guidelines based on recent clinical outcome studies. The following questions are addressed: 1) Should the dialysis dose for low molecular weight water‐soluble solutes (i.e., urea) be normalized by the body distribution volume for urea? 2) Should spKt/V or equilibrated Kt/V (eKt/V) be used for routine monitoring of the hemodialysis dose? 3) Should the dialysis dose for small solutes be dependent on gender? 4) Should the dialysis dose for middle molecules be used in clinical practice? 5) What should be the dialysis dose when using hemodialysis treatment strategies that are more frequent than thrice weekly?
UNRESOLVED ISSUES IN DIALYSIS: Revisiting the Peritoneal Dialysis Dose
Authors: Moran John , Correa‐Rotter Ricardo 
Published: March 2006

ABSTRACTThe question of the minimum dose for adequate peritoneal dialysis has been settled following the publication of two randomized controlled studies and a number of nonrandomized studies. This review summarizes these studies, concluding that these studies support a weekly total Kt/V of 1.7 as the minimum dose, with careful observation for symptoms or signs of uremia and adjustment of the clearance as indicated.
UNRESOLVED ISSUES IN DIALYSIS: Dialysis‐Related Amyloidosis: Late Finding or Hidden Epidemic?
Authors: Dember Laura M. , Jaber Bertrand L. 
Published: March 2006

ABSTRACTDialysis‐related amyloidosis is a complication of end‐stage renal disease (ESRD) that results from retention of β2‐microglobulin (β2M) and its deposition as amyloid fibrils into osteoarticular tissue. The clinical manifestations usually develop after several years of dialysis dependence and include carpal tunnel syndrome, destructive arthropathy, and bone cysts and fractures. High‐flux membranes, daily dialysis, and hemofiltration all would be expected to delay the onset of dialysis‐related amyloidosis because, to varying degrees, each increases the clearance of β2M from the plasma. Thus what is currently a late complication of ESRD might become an even later complication as dialysis practices change. The significance of histologically evident but clinically silent β2M amyloid, detectable not only in osteoarticular tissue but also in blood vessels, is unclear. Accumulating evidence that amyloidogenic proteins have direct and specific effects on cell processes irrespective of the extent of amyloid deposition raises the possibility that early, clinically silent β2M amyloid deposits have unrecognized importance.