bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural circuits subserving the retrieval of stems and grammatical features in regular and irregular verbs
Authors: de Diego Balaguer Ruth , Rodríguez‐Fornells Antoni , Rotte Michael , Bahlmann Jörg , Heinze Hans‐Jochen , Münte Thomas F. 
Published: March 2006

AbstractMany languages, including English and Spanish, feature regular (dance → danced) and irregular (catch → caught) inflectional systems. According to psycholinguistic theories, regular and irregular inflections are instantiated either by a single or by two specialized mechanisms. Those theories differ in their assumptions concerning the underlying information necessary for the processing of regular verbs. Whereas single mechanism accounts have stated an increased involvement of phonological processing for regular verbs, dual accounts emphasize the prominence of grammatical information. Using event‐related functional magnetic resonance imaging, we sought to delineate the brain areas involved in the generation of complex verb forms in Spanish. This language has the advantage of isolating specific differences in the regular–irregular contrasts in terms of the number of stems associated with a verb while controlling for compositionality (regular and irregular verbs apply suffixes to be inflected). The present study showed that areas related to grammatical processing are active for both types of verbs (left opercular inferior frontal gyrus). In addition, major differences between regular and irregular verbs were also observed. Several areas of the prefrontal cortex were selectively active for irregular production, presumably reflecting their role in lexical retrieval (bilateral inferior frontal area and dorsolateral prefrontal cortex). Regular verbs, however, showed increased activation in areas related to grammatical processing (anterior superior temporal gyrus/insular cortex) and in the left hippocampus, the latter possibly related to a greater implication of the phonological loop necessary for the reutilization of the same stem shared across all forms in regular verbs. Hum Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.
Cortisol responses of healthy volunteers undergoing magnetic resonance imaging
Authors: Tessner Kevin D. , Walker Elaine F. , Hochman Karen , Hamann Stephan 
Published: March 2006

AbstractSelf‐reported anxiety is associated with various medical procedures, including structural and functional magnetic resonance imaging (MRI). The present study tested the hypothesis that MRI scanning would be associated with elevated cortisol levels in participants with no prior scanning experience. Baseline and post‐scan cortisol levels, as well as measures of state and trait anxiety, were obtained from scanner‐naive (n = 6) and scanner‐experienced (n = 8) research participants. The anxiety scores and cortisol responses of the scanner‐naive and scanner‐experienced participants were compared. Subjects novel to MRI were no more anxious before the scan than were subjects familiar with the MRI examination, but the scanner‐naive subjects manifested heightened post‐scan cortisol secretion when compared to their pre‐scan level and when compared to the scanner‐experienced participants. The results are consistent with the hypothesis that the scanning environment can induce cortisol elevations and are congruent with the well‐established effects of acute stressors on activity of the hypothalamic‐pituitary‐adrenal (HPA) axis. The implications for neuroimaging studies are discussed. Hum Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.
Valuing avoided morbidity using meta‐regression analysis: what can health status measures and QALYs tell us about WTP?
Authors: Van Houtven George , Powers John , Jessup Amber , Yang Jui‐Chen 
Published: March 2006

AbstractMany economists argue that willingness‐to‐pay (WTP) measures are most appropriate for assessing the welfare effects of health changes. Nevertheless, the health evaluation literature is still dominated by studies estimating nonmonetary health status measures (HSMs), which are often used to assess changes in quality‐adjusted life years (QALYs). Using meta‐regression analysis, this paper combines results from both WTP and HSM studies applied to acute morbidity, and it tests whether a systematic relationship exists between HSM and WTP estimates. We analyze over 230 WTP estimates from 17 different studies and find evidence that QALY‐based estimates of illness severity – as measured by the Quality of Well‐Being (QWB) Scale – are significant factors in explaining variation in WTP, as are changes in the duration of illness and the average income and age of the study populations. In addition, we test and reject the assumption of a constant WTP per QALY gain. We also demonstrate how the estimated meta‐regression equations can serve as benefit transfer functions for policy analysis. By specifying the change in duration and severity of the acute illness and the characteristics of the affected population, we apply the regression functions to predict average WTP per case avoided. Copyright © 2006 John Wiley & Sons, Ltd.
The course of etoposide‐induced apoptosis in Jurkat cells lacking p53 and Bax
Authors: Karpinich Natalie O. , Tafani Marco , Schneider Timothy , Russo Matteo A. , Farber John L. 
Published: March 2006

AbstractJurkat T‐lymphocytes lack p53 and Bax but contain p73 and Bid and are killed by etoposide (ETO). With ETO c‐abl is phosphorylated and phosphorylated p73 increased. Translocation of full‐length Bid to mitochondria follows, with induction of the mitochondrial permeability transition (MPT) and release of cytochrome c into the cytosol. Pronounced swelling of mitochondria was evident ultrastructurally, and the MPT inhibitor cyclosporin A prevented the release of cytochrome c. Overexpression of Bcl‐2 prevented the translocation of Bid, the release of cytochrome c, and cell death. The pan‐caspase inhibitor ZVAD‐FMK prevented the cell killing, but not the initial release of cytochrome c. An accumulation of tBid occurred at later times in association with Bid degradation. A sequence is proposed that couples DNA damage to Bid translocation via activation of c‐abl and p73. Bid translocation induces the MPT, the event that causes release of cytochrome c, activation of caspases, and cell death. © 2006 Wiley‐Liss, Inc.
The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF‐κB pathway
Authors: Miranda Claudia , Roccato Emanuela , Raho Giovanna , Pagliardini Sonia , Pierotti Marco A. , Greco Angela 
Published: March 2006

AbstractTRK‐fused gene (TFG) was first identified as a partner of NTRK1 in generating the thyroid TRK‐T3 oncogene, and is also involved in oncogenic rearrangements with ALK in anaplastic lymphoma and NOR1 in mixoid chondrosarcoma. The TFG physiological role is still unknown, but the presence of a number of motifs involved in protein interactions suggests that it may function by associating with other proteins. We have recently demonstrated that TFG associates and regulates the activity of the tyrosine phosphatase SHP‐1. In this study by yeast two‐hybrid screening we identified NEMO and TANK, two proteins modulating the NF‐κB pathway, as novel TFG‐interacting proteins. These interactions were further characterized in vitro and in vivo. We provide evidence that TFG and NEMO may be part of the same high molecular weight complex. TFG enhances the effect of TNF‐α, TANK, TNF receptor‐associated factor (TRAF)2, and TRAF6 in inducing NF‐κB activity. We suggest that TFG is a novel member of the NF‐κB pathway. © 2006 Wiley‐Liss, Inc.
Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells
Authors: Nagasawa Kunihiko , Chiba Hideki , Fujita Hiroki , Kojima Takashi , Saito Tsuyoshi , Endo Toshiaki , Sawada Norimasa 
Published: March 2006

AbstractGap‐junction plaques are often observed with tight‐junction strands of vascular endothelial cells but the molecular interaction and functional relationships between these two junctions remain obscure. We herein show that gap‐junction proteins connexin40 (Cx40) and Cx43 are colocalized and coprecipitated with tight‐junction molecules occludin, claudin‐5, and ZO‐1 in porcine blood–brain barrier (BBB) endothelial cells. Gap junction blockers 18β‐glycyrrhetinic acid (18β‐GA) and oleamide (OA) did not influence expression of Cx40, Cx43, occludin, claudin‐5, junctional adhesion molecule (JAM)‐A, JAM‐B, JAM‐C, or ZO‐1, or their subcellular localization in the porcine BBB endothelial cells. In contrast, these gap‐junction blocking agents inhibited the barrier function of tight junctions in cells, determined by measurement of transendothelial electrical resistance and paracellular flux of mannitol and inulin. 18β‐GA also significantly reduced the barrier property in rat lung endothelial (RLE) cells expressing doxycycline‐induced claudin‐1, but did not change the interaction between Cx43 and either claudin‐1 or ZO‐1, nor their expression levels or subcellular distribution. These findings suggest that Cx40‐ and/or Cx43‐based gap junctions might be required to maintain the endothelial barrier function without altering the expression and localization of the tight‐junction components analyzed. © 2006 Wiley‐Liss, Inc.
Adjudin‐mediated junction restructuring in the seminiferous epithelium leads to displacement of soluble guanylate cyclase from adherens junctions
Authors: Sarkar Oli , Xia Weiliang , Mruk Dolores D. 
Published: March 2006

AbstractA plethora of evidence supports the role of cyclic nucleotides in junction restructuring. For instance, studies have shown cGMP to be a key regulator of junction assembly and disassembly in different in vitro and in vivo systems. In this study, we examine the role of soluble guanylate cyclase (sGC) in junction restructuring in the seminiferous epithelium of the rat testis. First, the interaction of soluble guanylate cyclase β1 (sGCβ1; sGC is a heterodimer comprised of an α and a β subunit) with proteins that constitute adherens and tight junctions in the testis was demonstrated. By immunoprecipitation, sGCβ1 was found to associate with occludin, JAM‐A, and ZO‐1, as well as with cadherin, catenin, nectin, afadin, ponsin, and espin, suggestive of its role in cell junction dynamics. These results were corroborated in part by immunohistochemistry experiments, which revealed that the localization of sGCβ1 was largely restricted to the site of the apical and basal ectoplasmic specialization. Next, the role of sGC in junction dynamics was addressed by using an in vivo model of junction restructuring. Administration of Adjudin—a chemical entity known to specifically perturb adhesion between Sertoli and germ cells (i.e., round and elongate(ing) spermatids and most spermatocytes)—resulted in a ∼1.5‐fold increase in sGCβ1, coinciding with the loss of germ cells from the epithelium. More importantly, the ability of sGCβ1 to associate with cadherin increased approximately three‐fold during Adjudin‐mediated restructuring of Sertoli–germ cell junctions, whereas its interaction with tight junction proteins (i.e., occludin and ZO‐1) decreased. Taken collectively, these results suggest that sGC participates in the remodeling of cell junctions during spermatogenesis. © 2006 Wiley‐Liss, Inc.
Elevated Golgi pH in breast and colorectal cancer cells correlates with the expression of oncofetal carbohydrate T‐antigen
Authors: Rivinoja Antti , Kokkonen Nina , Kellokumpu Ilmo , Kellokumpu Sakari 
Published: March 2006

AbstractAltered glycosylation has turned out to be a universal feature of cancer cells, and in many cases, to correlate with altered expression or localization of relevant glycosyltransferases. However, no such correlation exists between observed enzymatic changes and the expression of the oncofetal Thomsen‐Friedenreich (T)‐antigen, a core 1 (Gal‐β1 → 3‐GalNAc‐ser/thr) carbohydrate structure. Here we report that T‐antigen expression, instead, correlates with elevated Golgi pH in cancer cells. Firstly, using a Golgi‐targeted green fluorescent protein (GT‐EGFP) as a probe, we show that the medial/trans‐Golgi pH (pHG) in a high proportion of breast (MCF‐7) and colorectal (HT‐29, SW‐48) cancer cells is significantly more alkaline (pHG ≥ 6.75) than that of control cells (pHG 5.9–6.5). The pH gradient between the cytoplasm and the Golgi lumen is also markedly reduced in MCF‐7 cells, suggesting a Golgi acidification defect. Secondly, we show that T‐antigen expression is highly sensitive to changes in Golgi pH, as only a 0.2 pH unit increase was sufficient to increase T‐antigen expression in control cells. Thirdly, we found that T‐antigen expressing MCF‐7 cells have 0.3 pH units more alkaline Golgi pH than non‐expressing MCF‐7 cells. Fourthly, in all cell types examined, we observed significant correlation between the number of T‐antigen expressing cells and cells with a markedly elevated Golgi pH (pHG ≥ 6.75). Consistent with these observations in cultured cells, cells in solid tumors also heterogenously expressed the T‐antigen. Thus, elevated Golgi pH appears to be directly linked to T‐antigen expression in cancer cells, but it may also act as a more general factor for altered glycosylation in cancer by affecting the distribution of Golgi‐localized glycosyltransferases. © 2006 Wiley‐Liss, Inc.
1,25 dihydroxyvitamin‐D3 modulates JAK–STAT pathway in IL‐12/IFNγ axis leading to Th1 response in experimental allergic encephalomyelitis
Authors: Muthian Gladson , Raikwar Himanshu P. , Rajasingh Johnson , Bright John J. 
Published: March 2006

AbstractExperimental allergic encephalomyelitis (EAE) is a Th1 cell‐mediated autoimmune disease model of multiple sclerosis (MS). Vitamin D deficiency is commonly observed in MS patients and vitamin D supplements reduce the clinical symptoms of EAE and MS. Earlier studies have shown that in vivo treatment with vitamin D analogs ameliorates EAE in association with the inhibition of IL‐12 production and Th1 differentiation. The mechanisms in the regulation of Th1 response by vitamin D in EAE/MS are, however, not known. We show that in vivo treatment of C57BL/6 and SJL/J mice (i.p.) with 100 ng of 1,25 dihydroxyvitamin D3, on every other day from Day 0–30, ameliorates EAE in association with the inhibition of IL‐12 production and neural antigen‐specific Th1 response. In vitro treatment with 1,25(OH)2D3 inhibited IFNγ‐induced tyrosine phosphorylation of STAT1, without affecting JAK2, in EOC‐20 microglial cells. Treatment of activated T cells with 1,25(OH)2D3 also inhibited the IL‐12‐induced tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 in association with a decrease in T cell proliferation in vitro. These findings highlight the fact that vitamin D modulates JAK‐STAT signaling pathway in IL‐12/IFNγ axis leading to Th1 differentiation and further suggest its use in the treatment of MS and other Th1 cell‐mediated autoimmune diseases. © 2006 Wiley‐Liss, Inc.
Mitochondrial ligand inhibits store‐operated calcium influx and COX‐2 production in human microglia
Authors: Hong Seok H. , Choi Hyun B. , Kim Seung U. , McLarnon James G. 
Published: March 2006

AbstractWe used calcium sensitive fluorescence microscopy to investigate the actions of PK11195, a ligand for the mitochondrial peripheral benzodiazepine receptor (PBR), to modulate Ca2+ influx through store‐operated channels (SOC) in human microglia. PK11195 effectively blocked SOC‐mediated Ca2+ influx induced by platelet‐activating factor (PAF) in a dose‐dependent manner (IC50 of 9 μM). A prolonged SOC‐mediated Ca2+ entry was also induced using the sarcoplasmic endoreticulum Ca2+‐ATPase (SERCA) inhibitor cyclopiazonic acid (CPA) to deplete intracellular endoplasmic reticulum (ER) stores; a single concentration of PK11195 (at 20 μM) reduced SOC‐mediated Ca2+ influx by 78%. RT‐PCR and immunocytochemical analysis results showed PK11195 also inhibited the expression and production of cyclooxygenase‐2 (COX‐2) triggered by PAF stimulation. These results suggest that activation of the PBR in mitochondria is linked to reduced entry of Ca2+ through plasmalemmal SOC and subsequent modulation of cellular functions in human microglia. © 2006 Wiley‐Liss, Inc.
Fos‐enkephalin signaling in the rat medial vestibular nucleus facilitates vestibular compensation
Authors: Kitahara Tadashi , Kaneko Takeshi , Horii Arata , Fukushima Munehisa , Kizawa‐Okumura Kaoru , Takeda Noriaki , Kubo Takeshi 
Published: March 2006

AbstractIn the present study, we first observed up‐regulation in preproenkephalin (PPE)‐like immunoreactivity (‐LIR), a precursor of Met‐ and Leu‐enkephalin, in the rat ipsilateral medial vestibular nucleus (ipsi‐MVN) after unilateral labyrinthectomy (UL). By means of double‐staining immunohistochemistry with PPE and Fos, a putative regulator of PPE gene expression, we revealed that some of these PPE‐LIR neurons were also Fos immunopositive. The time course of decay of these double‐stained neurons was quite parallel to that of UL‐induced behavioral deficits. This suggests that these double‐labeled neurons could have something to do with development of vestibular compensation. We next examined correlation between Fos and PPE expression in the ipsi‐MVN by means of a 15‐min pre‐UL application of antisense oligonucleotide probes against c‐fos mRNA into the ipsi‐MVN. Gel shift assay and Western blotting revealed that elimination of Fos expression significantly reduced both AP‐1 DNA binding activity and PPE expression in the ipsi‐MVN after UL. C‐fos antisense study also revealed that depression of Fos‐PPE signaling in the ipsi‐MVN caused significantly more severe behavioral deficits during vestibular compensation. Furthermore, studies with PPE antisense and naloxone, an opioid receptor antagonist, demonstrated that specific depression of enkephalinergic effects in the ipsi‐MVN significantly delayed vestibular compensation. All these findings suggest that, immediately after UL, Fos induced in some of the ipsi‐MVN neurons could regulate consequent PPE expression via the AP‐1 activation and facilitate the restoration of balance between bilateral MVN activities via the opioid receptor activation, resulting in progress of vestibular compensation. © 2006 Wiley‐Liss, Inc.
Functional properties of neurons derived from fetal mouse neurospheres are compatible with those of neuronal precursors in vivo
Authors: Pagani Francesca , Lauro Clotilde , Fucile Sergio , Catalano Myriam , Limatola Cristina , Eusebi Fabrizio , Grassi Francesca 
Published: March 2006

AbstractNeural stem cells can be propagated in culture as neurospheres, yielding neurons and glial cells upon differentiation. Although the neurosphere model is widely used, the functional properties of the neurosphere‐derived neurons have been only partially characterized, and it is unclear whether repeated passaging alters their functional properties. In this study, we analyzed voltage‐ and transmitter‐gated responses in neuron‐like cells obtained by differentiating fetal mouse neurospheres at increasing passages in culture. We report that neurons fire overshooting action potentials in response to depolarizing currents up to passage 10 but loose this capability at later passages, as the density of voltage‐gated Na+ and K+ currents decreases. In contrast, the immunoreactivity for the neuronal marker β‐tubulin remains unaltered up to passage 21, indicating that this marker is not representative of cell function. In almost all neurons, γ‐aminobutyric acid (GABA) evoked bicuculline‐sensitive whole‐cell currents, resulting from the activation of GABAA receptors, which appeared to be excitatory, insofar as the reversal potential of GABA‐gated current was about −50 mV. Much smaller currents were elicited by the glutamatergic agonist AMPA, and only occasional responses to glycine were detected. In these functional aspects, neurosphere‐derived neurons are similar to immature neurons differentiating in vivo. Therefore, at least for a limited number of passages in vitro, neurospheres provide an adequate model of in vivo neurogenesis. © 2006 Wiley‐Liss, Inc.
CCL5 evokes calcium signals in microglia through a kinase‐, phosphoinositide‐, and nucleotide‐dependent mechanism
Authors: Shideman C.R. , Hu S. , Peterson P.K. , Thayer S.A. 
Published: March 2006

AbstractMicroglia, the resident macrophages of the CNS, are responsible for the innate immune response in the brain and participate in the pathogenesis of certain neurodegenerative disorders. Chemokines initiate activation and migration of microglia. The β‐chemokine CCL5 induces an elevation in intracellular calcium concentration ([Ca2+]i) in human microglia. Here, we examined the signal transduction pathway linking activation of chemokine receptor CCR5 to an elevation in [Ca2+]i in cultured microglia by using pharmacological approaches in combination with Fura‐2‐based digital imaging. The CCL5‐induced response required Janus kinase (Jak) activity and the stimulation of an inhibitory G protein. Multiple downstream signaling pathways were involved, including phosphatidylinositol 3‐kinase (PI3K), Bruton's tyrosine kinase (Btk), and phospholipase C (PLC)‐mediated release of Ca2+ from inositol 1,4,5‐trisphosphate (IP3)‐sensitive stores. Activation of both the kinase and the lipase pathways was required for eliciting the Ca2+ response. However, the majority of the [Ca2+]i increase was derived from sources activated by NAD metabolites. Cyclic ADP‐ribose (cADPR) evoked Ca2+ release from intracellular stores, and ADPR evoked Ca2+ influx via a nimodipine‐sensitive channel. Thus, a multistep cascade couples CCR5 activation to Ca2+ increases in human microglia. Because changes in [Ca2+]i affect chemotaxis, secretion, and gene expression, pharmacologic modulation of this pathway may alter inflammatory and degenerative processes in the CNS. © 2006 Wiley‐Liss, Inc.
Neudesin, a secreted factor, promotes neural cell proliferation and neuronal differentiation in mouse neural precursor cells
Authors: Kimura Ikuo , Konishi Morichika , Miyake Ayumi , Fujimoto Masafumi , Itoh Nobuyuki 
Published: March 2006

AbstractNeudesin encodes a secreted signal with neurotrophic activity in neurons. Most neurotrophic factors are involved in neural cell proliferation and/or differentiation. However, the role of neudesin in neural development remains to be elucidated. We examined the expression of neudesin in mouse embryonic cerebral cortex and cultured mouse neural precursor cells and its roles in neural development. Neudesin was expressed in the embryonic cerebral cortex early in development. Its expression was observed mainly in the preplate, where mostly postmitotic neural cells existed. Because neudesin mRNA was expressed in the neural precursor cells before the appearance of neurons, the roles of neudesin in neural development were examined by using the precursor cells. Neudesin significantly promoted neuronal differentiation and overrode the undifferentiated state of the neural precursor cells sustained by fibroblast growth factor 2 (FGF2). In contrast, it inhibited the differentiation of astrocytes. In addition, neudesin transiently promoted neural cell proliferation early in the developmental process. The effect on cell proliferation was distinct from that of FGF2, a self‐renewal‐promoting factor for neural precursor cells. The differentiation was mediated though activation of the protein kinase A (PKA) and phosphatidylinositol‐3 kinase (PI‐3K) pathways. In contrast, the proliferation was mediated through the mitogen‐activated protein kinase and PKA pathways. The expression profile and activity indicate that neudesin plays unique roles in neural development. The present findings have revealed new potential roles of neudesin in neural cell proliferation and neuronal differentiation. © 2006 Wiley‐Liss, Inc.