bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of malformations in chromosomally normal fetuses by routine ultrasound at 12 or 18 weeks of gestation—a randomised controlled trial in 39 572 pregnancies
Authors: Saltvedt S , Almström H , Kublickas M , Valentin L , Grunewald C 
Published: May 2006

Objective  To compare the antenatal detection rate of malformations in chromosomally normal fetuses between a strategy of offering one routine ultrasound examination at 12 gestational weeks (gws) and a strategy of offering one routine examination at 18 gws.Design  Randomised controlled trial.Setting  Multicentre trial including eight hospitals.Population  A total of 39 572 unselected pregnant women.Methods  Women were randomised either to one routine ultrasound scan at 12 (12–14) gws including nuchal translucency (NT) measurement or to one routine scan at 18 (15–22) gws. Anomaly screening was performed in both groups following a check‐list. A repeat scan was offered in the 12‐week scan group if the fetal anatomy could not be adequately seen at 12–14 gws or if NT was ≥3.5 mm in a fetus with normal or unknown chromosomes.Main outcome measures  Antenatal detection rate of malformed fetuses.Results  The antenatal detection rate of fetuses with a major malformation was 38% (66/176) in the 12‐week scan group and 47% (72/152) in the 18‐week scan group (P= 0.06). The corresponding figures for detection at <22 gws were 30% (53/176) and 40% (61/152) (P= 0.07). In the 12‐week scan group, 69% of fetuses with a lethal anomaly were detected at a scan at 12–14 gws.Conclusions  None of the two strategies for prenatal diagnosis is clearly superior to the other. The 12‐week strategy has the advantage that most lethal malformations will be detected at <15 gws, enabling earlier pregnancy termination. The 18‐week strategy seems to be associated with a slightly higher detection rate of major malformations, although the difference was not statistically significant.
Tomoregulin‐2 is found extensively in plaques in Alzheimer's disease brain
Authors: Siegel Donald A. , Davies Peter , Dobrenis Kostantin , Huang May 
Published: May 2006

AbstractTomoregulin (TR)2 is a transmembrane protein predominantly expressed in brain. It has a unique extracellular domain, containing epidermal growth factor‐like and follistatin‐like modules. The ectodomain is released from the cell surface, and thought to function as a neurotrophic factor and dendritogenic agent. During CNS development and in the neuronal storage disease GM2 gangliosidosis, which is characterized by ectopic dendrites, the TR2 ectodomain is present in neuronal nuclei where it may function in dendrite initiation. Data presented here demonstrate that TR2 is found extensively in Alzheimer's disease (AD) plaques. Confocal microscopy shows that TR2 is present throughout plaques. Interestingly, TR2 is absent from plaques in the presenilin‐1/amyloid precursor protein mouse model of AD. From these data, and what is known about TR2, it is hypothesized that TR2 may participate in amyloid plaque formation and contribute to the pathogenesis of AD. The human TR2 gene is located on chromosome 2q32.3, near a locus linked to Parkinson's disease. TR2 is reported to be a trophic factor for dopaminergic mesencephalic neurons.
Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress
Authors: Muqit Miratul M. K. , Abou‐Sleiman Patrick M. , Saurin Adrian T. , Harvey Kirsten , Gandhi Sonia , Deas Emma , Eaton Simon , Payne Smith Martin D. , Venner Kerrie , Matilla Antoni , Healy Daniel G. , Gilks William P. , Lees Andrew J. , Holton Janice , Revesz Tamas , Parker Peter J. , Harvey Robert J. , Wood Nicholas W. , Latchman David S. 
Published: May 2006

AbstractFollowing our identification of PTEN‐induced putative kinase 1 (PINK1) gene mutations in PARK6‐linked Parkinson's disease (PD), we have recently reported that PINK1 protein localizes to Lewy bodies (LBs) in PD brains. We have used a cellular model system of LBs, namely induction of aggresomes, to determine how a mitochondrial protein, such as PINK1, can localize to aggregates. Using specific polyclonal antibodies, we firstly demonstrated that human PINK1 was cleaved and localized to mitochondria. We demonstrated that, on proteasome inhibition with MG‐132, PINK1 and other mitochondrial proteins localized to aggresomes. Ultrastructural studies revealed that the mechanism was linked to the recruitment of intact mitochondria to the aggresome. Fractionation studies of lysates showed that PINK1 cleavage was enhanced by proteasomal stress in vitro and correlated with increased expression of the processed PINK1 protein in PD brain. These observations provide valuable insights into the mechanisms of LB formation in PD that should lead to a better understanding of PD pathogenesis.
Biochemical and biological characterization of a neuroendocrine‐associated phosphatase
Authors: Wang Jiz‐Yuh , Lin Chia‐Hua , Yang Chi‐Hwa , Tan Tse‐Hua , Chen Yi‐Rong 
Published: May 2006

AbstractThe biochemical and biological properties of a novel neuroendocrine‐associated phosphatase (NEAP) were characterized. NEAP had a sequence characteristic of a dual‐specificity phosphatase (DSP), and was preferentially expressed in neuroendocrine cells/tissues as well as in skeletal muscle and heart. Expression of NEAP was up‐regulated in nerve growth factor (NGF)‐treated, differentiated PC12 cells. NEAP was cytosolic and did not apparently have effects against extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase activated by various stimuli. Although NEAP and MAPK phosphatase (MPK)‐1 showed similar phosphatase activity towardsp‐nitro phenylphosphate (pNPP), in contrast to MKP‐1, NEAP did not dephosphorylate JNK and p38‐MAPKin vitro. Overexpression of NEAP, but not the C152S mutant, in PC12 cells suppressed NGF‐induced phosphorylation of the p85 subunit of phosphatidylinositol 3‐kinase (PI3K) and Akt activation. Overexpression of NEAP also suppressed neurite outgrowth induced by NGF and sensitized PC12 cells to cisplatin‐induced apoptosis. Suppression of NEAP by RNA interference enhanced NGF‐induced neurite outgrowth and Akt activation. Our results indicated that, unlike other DSPs, down‐regulation of conventional MAPKs was not the major function of NEAP. Furthermore, NEAP might be involved in neuronal differentiation via regulation of the PI3K/Akt signaling.
Tissue Inhibitor of Metalloproteinase‐2 (TIMP‐2) expression is regulated by multiple neural differentiation signals
Authors: Jaworski Diane M. , Pérez‐Martínez Leonor 
Published: May 2006

AbstractNeuronal differentiation requires exquisitely timed cell cycle arrest for progenitors to acquire an appropriate neuronal cell fate and is achieved by communication between soluble signals, such as growth factors and extracellular matrix molecules. Here we report that the expression of TIMP‐2, a matrix metalloproteinase inhibitor, is up‐regulated by signals that control proliferation (bFGF and EGF) and differentiation (retinoic acid and NGF) in neural progenitor and neuroblastoma cell lines. TIMP‐2 expression coincides with the appearance of neurofilament‐positive neurons, indicating that TIMP‐2 may play a role in neurogenesis. The up‐regulation of TIMP‐2 expression by proliferate signals suggests a role in the transition from proliferation to neuronal differentiation. Live labeling experiments demonstrate TIMP‐2 expression only on α3 integrin‐positive cells. Thus, TIMP‐2 function may be mediated via interaction with integrin receptor(s). We propose that TIMP‐2 represents a component of the neurogenic signaling cascade induced by mitogenic stimuli that may withdraw progenitor cells from the cell cycle permitting their terminal neuronal differentiation.
Increased calcitonin gene‐related peptide in neuroma and invading macrophages is involved in the up‐regulation of interleukin‐6 and thermal hyperalgesia in a rat model of mononeuropathy
Authors: Ma Weiya , Quirion Remi 
Published: May 2006

AbstractThe pain related peptide, calcitonin gene‐related peptide (CGRP), plays an important role in inflammatory pain and immune responses. However, its role in neuropathic pain is not established. Following nerve injury, CGRP and pro‐inflammatory interleukin‐6 (IL‐6) are increased in injured nerves. The aim of this study was to determine if CGRP in injured nerves is involved in the up‐regulation of IL‐6 and in the maintenance of neuropathic pain. Perineural injection of a neutralizing IL‐6 antiserum or CGRP receptor antagonists (CGRP8‐37 and BIBN4096BS) effectively attenuated thermal hyperalgesia 4 weeks after partial sciatic nerve ligation. Perineural CGRP antagonists also dramatically reduced IL‐6 level in injured nerves. CGRP release from injured sites was dramatically increased and CGRP immunoreactivity was localized in both neuroma and invading macrophages. CGRP receptor markers (CRLR and RAMP1) were expressed in invading macrophages. Both CGRP antagonists significantly reduced IL‐6 release from injured nerve explants. In cell cultures derived from injured nerves, CGRP concentration‐dependently increased IL‐6 release, an effect also blocked by CGRP antagonists. Taken together, these data show that increased levels of CGRP in injured neuroma and invading macrophages are involved in the up‐regulation of IL‐6 in macrophages as well as in the maintenance of neuropathic pain.
Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells
Authors: Cao Fang , Hata Ryuji , Zhu Pengxiang , Ma Yong‐Jie , Tanaka Junya , Hanakawa Yasushi , Hashimoto Koji , Niinobe Michio , Yoshikawa Kazuaki , Sakanaka Masahiro 
Published: May 2006

AbstractTo investigate the effects of suppressors of cytokine signaling 3 (SOCS3) on neural stem cell fate, stem cells were infected with an adenoviral vector expressing SOCS3. Three days later, western blot analysis and immunocytochemical analysis revealed that the protein level of MAP2 and the number of MAP2‐positive cells were significantly increased in SOCS3‐transfected cells, whereas the protein level of GFAP and the number of GFAP‐positive cells were significantly decreased. Furthermore, promoter assay revealed a significant reduction in the transcriptional level of signal transducer and activator of transcription 3 (Stat3) in the transfected cells. In addition, the mRNA levels of Notch family member (notch1) and inhibitory basic helix‐loop‐helix (bHLH) factors (hes5 and id3) were significantly up‐regulated 1 day after overexpression of SOCS3. Three days after transfection, the mRNA level of hes5 was significantly decreased, whereas that of notch1 was still up‐regulated. Moreover, all of SOCS3‐positive cells expressed Nestin protein but did not express MAP2 or GFAP proteins. These data indicate that overexpression of SOCS3 induced neurogenesis and inhibited astrogliogenesis in neural stem cells. Our data also show that SOCS3 promoted maintenance of neural stem cells.
Sodium channel β4 subunit: down‐regulation and possible involvement in neuritic degeneration in Huntington's disease transgenic mice
Authors: Oyama Fumitaka , Miyazaki Haruko , Sakamoto Naoaki , Becquet Celine , Machida Yoko , Kaneko Kumi , Uchikawa Chiharu , Suzuki Taishi , Kurosawa Masaru , Ikeda Tetsurou , Tamaoka Akira , Sakurai Takashi , Nukina Nobuyuki 
Published: May 2006

AbstractSodium channel β4 is a very recently identified auxiliary subunit of the voltage‐gated sodium channels. To find the primarily affected gene in Huntington's disease (HD) pathogenesis, we profiled HD transgenic mice using a high‐density oligonucleotide array and identified β4 as an expressed sequence tag (EST) that was significantly down‐regulated in the striatum of HD model mice and patients. Reduction in β4 started at a presymptomatic stage in HD mice, whereas other voltage‐gated ion channel subunits were decreased later. In contrast, spinal cord neurons, which generate only negligible levels of expanded polyglutamine aggregates, maintained normal levels of β4 expression even at the symptomatic stage. Overexpression of β4 induced neurite outgrowth in Neuro2a cells, and caused a thickening of dendrites and increased density of dendritic spines in hippocampal primary neurons, indicating that β4 modulates neurite outgrowth activities. These results suggest that down‐regulation of β4 may lead to abnormalities of sodium channel and neurite degeneration in the striatum of HD transgenic mice and patients with HD.
Olfactory receptors and signalling elements in the Grueneberg ganglion
Authors: Fleischer Jörg , Schwarzenbacher Karin , Besser Stefanie , Hass Nicole , Breer Heinz 
Published: May 2006

AbstractThe Grueneberg ganglion (GG) is a cluster of neurones present in the vestibule of the anterior nasal cavity. Although its function is still elusive, recent studies have shown that cells of the GG transcribe the gene encoding the olfactory marker protein (OMP) and project their axons to glomeruli of the olfactory bulb, suggesting that they may have a chemosensory function. Chemosensory responsiveness of olfactory neurones in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) is based on the expression of either odorant receptors or vomeronasal putative pheromone receptors. To scrutinize its presumptive olfactory nature, the GG was assessed for receptor expression by extensive RT–PCR analyses, leading to the identification of a distinct vomeronasal receptor which was expressed in the majority of OMP‐positive GG neurones. Along with this receptor, these cells expressed the G proteins Go and Gi, both of which are also present in sensory neurones of the vomeronasal organ. Odorant receptors were expressed by very few cells during prenatal and perinatal stages; a similar number of cells expressed adenylyl cyclase type III and Golf/s, characteristic signalling elements of the main olfactory system. The findings of the study support the notion that the GG is in fact a subunit of the complex olfactory system, comprising cells with either a VNO‐like or a MOE‐like phenotype. Moreover, expression of a vomeronasal receptor indicates that the GG might serve to detect pheromones.
Increase of proliferating oligodendroglial progenitors in the adult mouse brain upon Sonic hedgehog delivery in the lateral ventricle
Authors: Loulier Karine , Ruat Martial , Traiffort Elisabeth 
Published: May 2006

AbstractSonic hedgehog signaling is required for the maintenance of stem cell niches in the postnatal subventricular zone and the proliferation of neural progenitors in the mature hippocampus. We show here that delivery of Sonic hedgehog protein into the lateral ventricle of adult mice increases cell proliferation in the corpus callosum and cerebral cortex. In this latter area, the number of neural progenitors expressing the proteoglycan NG2 is enhanced 2 days after the injection. In both areas, mRNA up‐regulation of the transcriptional target gene Patched was observed in cells expressing the oligodendroglial transcription factor Olig1. Twenty‐six days following the adenovirus‐mediated delivery of Sonic hedgehog into the lateral ventricle, newly generated cells in the cerebral cortex and in the corpus callosum are influenced towards the initial steps of oligodendrogenesis, as indicated by a 50% increase in the number of cells expressing the oligodendroglial marker DM20. Our experiments demonstrate that the number of oligodendrocyte precursor cells in the cerebral cortex and corpus callosum can be increased upon delivery of Sonic hedgehog proteins and highlight the potential capacity of the adult brain to mobilize a pool of premyelinating cells.
Balance of purines may determine life or death of retinal ganglion cells as A3 adenosine receptors prevent loss following P2X7 receptor stimulation
Authors: Zhang Xiulan , Zhang Mei , Laties Alan M. , Mitchell Claire H. 
Published: May 2006

AbstractThe purines ATP and adenosine can act as a coordinated team of transmitters. As extracellular adenosine is frequently derived from the enzymatic dephosphorylation of released ATP, the distinct actions of the two purines can be synchronized. In retinal ganglion cells (RGCs), stimulation of the P2X7 receptor for ATP leads to increased intracellular Ca2+ and death. Here we define the contrasting effects of adenosine and identify protective actions mediated by the A3 receptor. Adenosine attenuated the rise in Ca2+ produced by the P2X7 agonist 3′‐O‐(4‐benzoylbenzoyl)ATP (BzATP). Adenosine was also neuroprotective, increasing the survival of ganglion cells exposed to BzATP. The A3 adenosine receptor agonist 2‐chloro‐N6‐(3‐iodobenzyl)‐adenosine‐5′‐N‐methyluronimide (Cl‐IB‐MECA) mimicked the inhibition of the Ca2+ rise, whereas the A3 antagonist 3‐Ethyl‐5‐benzyl‐2‐methyl‐4‐phenylethynyl‐6‐phenyl‐1,4‐(±)‐dihydropyridine‐3,5‐dicarboxylate (MRS‐1191) reduced the protective effects of adenosine. Both Cl‐IB‐MECA and a second A3 receptor agonist IB‐MECA reduced the cell loss triggered by BzATP. The actions of BzATP were mimicked by ATPγS, but not by ATP. In summary, adenosine can stop the rise in Ca2+ and cell death resulting from stimulation of the P2X7 receptor on RGCs, with the A3 adenosine receptor contributing to this protection. Hydrolysis of ATP into adenosine and perhaps inosine shifts the balance of purinergic action from that of death to the preservation of life.
Phosphorylation of dystrophin Dp71d by Ca2+/calmodulin‐dependent protein kinase II modulates the Dp71d nuclear localization in PC12 cells
Authors: Calderilla‐Barbosa Luis , Ortega Arturo , Cisneros Bulmaro 
Published: May 2006

AbstractWe have shown that the splicing isoform of Dp71 (Dp71d) localizes to the nucleus of PC12 cells, an established cell line derived from a rat pheochromocytoma; however, the mechanisms governing its nuclear localization are unknown. As protein phosphorylation modulates the nuclear import of proteins, and as Dp71d presents several potential sites for phosphorylation, we analyzed whether Dp71d is phosphorylated in PC12 cells and the role of phosphorylation on its nuclear localization. We demonstrated that Dp71d is phosphorylated under basal conditions at serine and threonine residues by endogenous protein kinases. Dp71d phosphorylation was activated by 2‐O‐tetradecanoyl phorbol 13‐acetate (TPA), but this effect was blocked by EGTA. Supporting the role of intracellular calcium on Dp71d phosphorylation, we observed that the stimulation of calcium influx by cell depolarization increased Dp71d phosphorylation, and that the calcium‐calmodulin inhibitor N‐(6‐aminohexyl)‐1‐naphthalenesulfonamide (W‐7) blocked such induction. The blocking action of bisindolylmaleimide I (Bis I), a specific inhibitor for Ca2+/diacylglicerol‐dependent protein kinase (PKC), on Dp71d phosphorylation suggested the participation of PKC in this event. In addition, transfection experiments with Ca2+/calmodulin‐dependent protein kinase II (CaMKII) expression vectors as well as the use of KN‐62, a CaMKII‐specific inhibitor, demonstrated that CaMKII is also involved in Dp71d phosphorylation. Stimulation of Dp71d phosphorylation by cell depolarization and/or the overexpression of CaMKII favored the Dp71d nuclear accumulation. Overall, our results indicate that CAMKII‐mediated Dp71d phosphorylation modulates its nuclear localization.
Mouse brains deficient in neuronal PDGF receptor‐β develop normally but are vulnerable to injury
Authors: Ishii Yoko , Oya Takeshi , Zheng Lianshun , Gao Zhiyang , Kawaguchi Makoto , Sabit Hemragul , Matsushima Takako , Tokunaga Ayano , Ishizawa Shin , Hori Etsuro , Nabeshima Yo‐ichi , Sasaoka Toshikuni , Fujimori Toshihiko , Mori Hisashi , Sasahara Masakiyo 
Published: May 2006

AbstractPlatelet‐derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are widely expressed in the mammalian CNS, though their functional significance remains unclear. The corresponding null‐knockout mutations are lethal. Here, we developed novel mutant mice in which the gene encoding the β subunit of PDGFR (PDGFR‐β) was genetically deleted in CNS neurons to elucidate the role of PDGFR‐β, particularly in the post‐natal stage. Our mutant mice reached adulthood without apparent anatomical defects. In the mutant brain, immunohistochemical analyses showed that PDGFR‐β detected in neurons and in the cells in the subventricular zone of the lateral ventricle in wild‐type mice was depleted, but PDGFR‐β detected in blood vessels remained unaffected. The cerebral damage after cryogenic injury was severely exacerbated in the mutants compared with controls. Furthermore, TdT‐mediated dUTP‐biotin nick end labeling (TUNEL)‐positive neuronal cell death and lesion formation in the cerebral hemisphere were extensively exacerbated in our mutant mice after direct injection of NMDA without altered NMDA receptor expression. Our results clearly demonstrate that PDGFR‐β expressed in neurons protects them from cryogenic injury and NMDA‐induced excitotoxicity.
GATA‐3 regulates the transcriptional activity of tyrosine hydroxylase by interacting with CREB
Authors: Hong Seok Jong , Huh Youngbuhm , Chae Han , Hong Sunghoi , Lardaro Thomas , Kim Kwang‐Soo 
Published: May 2006

AbstractThe zinc finger transcription factor GATA‐3 is a master regulator of type 2 T‐helper cell development. Interestingly, in GATA‐3–/– mice, noradrenaline (NA) deficiency is a proximal cause of embryonic lethality. However, neither the role of GATA‐3 nor its target gene(s) in the nervous system were known. Here, we report that forced expression of GATA‐3 resulted in an increased number of tyrosine hydroxylase (TH) expressing neurons in primary neural crest stem cell (NCSC) culture. We also found that GATA‐3 transactivates the promoter function of TH via specific upstream sequences, a domain of the TH promoter residing at −61 to −39 bp. Surprisingly, this domain does not contain GATA‐3 binding sites but possesses a binding motif, a cAMP response element (CRE), for the transcription factor, CREB. In addition, we found that site‐directed mutation of this CRE almost completely abolished transactivation of the TH promoter by GATA‐3. Furthermore, protein–protein interaction assays showed that GATA‐3 is able to physically interact with CREB in vitro as well as in vivo. Based on these results, we propose that GATA‐3 may regulate TH gene transcription via a novel and distinct protein–protein interaction, and directly contributes to NA phenotype specification.
Ten polymorphic microsatellite loci for the endangered Buena Vista Lake shrew (Sorex ornatus relictus)
Authors: MALDONADO JESÚS E. , LEONARD JENNIFER , MIRANDA GUSTAVO A. , ORTEGA JORGE , WAYNE ROBERT K. , AGUILERA RENATO J. 
Published: May 2006

AbstractThe ornate shrew (Sorex ornatus) is restricted to the vanishing wetlands of California, USA and Baja California, Mexico. Several subspecies of ornate shrews are considered ‘mammal species of special concern’ in California by the Department of Fish and Game, and one (Sorex ornatus relictus) has recently been listed as endangered. Populations of shrews around Buena Vista Lake have been diminished or extirpated due to habitat deterioration and human development. In order to study the patterns of genetic variation in isolated populations of Buena Vista Lake shrews, we developed 10 polymorphic microsatellite loci. There were 6–27 alleles per locus, and the loci had heterozygosity values that ranged from 20 to 80%. In addition, we screened 20 different populations of S. ornatus, eight species within two subfamilies of shrews (Soricinae and Crocidurinae), as well as in a mole (Talpidae, Neurotrichus gibbsii), to determine if these loci could be informative in other species as well.