bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity and Fgf dependence of adult neural progenitors in the zebrafish telencephalon
Authors: Ganz Julia , Kaslin Jan , Hochmann Sarah , Freudenreich Dorian , Brand Michael 
Published: May 2010

AbstractAdult telencephalic neurogenesis is a conserved trait of all vertebrates studied. It has been investigated in detail in rodents, but very little is known about the composition of neurogenic niches and the cellular nature of progenitors in nonmammalian vertebrates. To understand the components of the progenitor zones in the adult zebrafish telencephalon and the link between glial characteristics and progenitor state, we examined whether canonical glial markers are colocalized with proliferation markers. In the adult zebrafish telencephalon, we identify heterogeneous progenitors that reside in two distinct glial domains. We find that the glial composition of the progenitor zone is linked to its proliferative behavior. Analyzing both fast‐cycling proliferating cells as well as slowly cycling progenitors, we find four distinct progenitor types characterized by differential expression of glial markers. Importantly, a significant proportion of progenitors do not display typical radial glia characteristics. By blocking or activating Fgf signaling by misexpression of a dominant negative Fgf‐receptor 1 or Fgf8a, respectively, we find that ventral and dorsal progenitors in the telencephalon also differ in their requirement for Fgf signaling. Together with data on the expression of Fgf signaling components in the ventricular zone of the telencephalon, this suggests that Fgf signaling directly regulates proliferation of specific subsets of adult telencephalic progenitors in vivo. Taken together our results show that adult neural progenitor cells are heterogeneous with their respect to distribution into two distinct glial domains and their dependence upon Fgf signaling as a proliferative cue in the zebrafish telencephalon. © 2010 Wiley‐Liss, Inc.
Sphingolipid rheostat alterations related to transformation can be exploited for specific induction of lysosomal cell death in murine and human glioma
Authors: Mora Rodrigo , Dokic Ivana , Kees Tim , Hüber Christian M. , Keitel Denise , Geibig Renate , Brügge Britta , Zentgraf Hanswalter , Brady Nathan R. , Régnier‐Vigouroux Anne 
Published: May 2010

AbstractThe search for cancer cell‐specific targets suffers from a lack of integrative approaches that take into account the relative contributions of several mechanisms or pathways involved in cell death. A systematic experimental and computational comparison of murine glioma cells with astrocytes, their nontransformed counterparts, identified differences in the sphingolipid (SL) rheostat linked to an increased lysosomal instability in glioma cells. In vitro and in silico analyses indicate that sphingosine metabolized in lysosomes was preferentially recycled into ceramide, the prodeath member of the rheostat, in astrocytes. In glioma cells, it preferentially was used for production of the prosurvival sphingosine‐1‐phosphate (S1P). A combination of tumor necrosis factor alpha (TNF‐α), lipopolysaccharide (LPS), and interferon gamma (IFN‐γ) strongly decreased S1P production that resulted in abnormal lysosome enlargement and cell death associated with mitochondrial dysfunction of glioma cells only. Lack of intracellular S1P in glioma cells was concomitant with protein and lipid accumulation in enlarged lysosomes, indicating a blockade in lysosome recycling, and hence a role for S1P in membrane trafficking. A pharmacological sphingosine kinase inhibitor efficiently replaced the TNF‐α, LPS, and IFN‐γ combination and killed murine and human glioma cells without affecting astrocytes. Our study provides evidence for a novel mechanism of lysosomal death dependent upon the SL rheostat that can be specifically triggered in glioma cells. It further strengthens the potential of cancer therapies based on specific ceramide pathway alterations. © 2010 Wiley‐Liss, Inc.
Mitogen‐activated protein kinase activated protein kinase 2 (MK2) participates in p38 MAPK regulated control of oligodendrocyte differentiation
Authors: Haines Jeffery D. , Fang Jun , Mushynski Walter E. , Almazan Guillermina 
Published: May 2010

AbstractThe p38 mitogen‐activated protein kinases (p38 MAPKs) are a family of kinases that regulate a number of cellular functions including cell migration, proliferation, and differentiation. We have previously reported a role for p38 MAPK in the regulation of oligodendrocyte (OLG) differentiation and Schwann cell myelination. Here, we extend our previous findings by showing that a p38 substrate, mitogen‐activated protein kinase activated protein kinase 2 (MK2) is a downstream element of the p38 signaling pathway responsible for effecting OLG differentiation. Inhibition of MK2 activity in oligodendrocyte progenitors (OLPs) using CMPD1 [4‐(2′‐fluorobiphenyl‐4‐yl)‐N‐(4‐hydroxyphenyl)‐butyramide] blocked the activation of MK2 and resulted in decreased accumulation of myelin‐differentiation markers, including myelin‐associated glycoprotein (MAG) and myelin basic protein (MBP). We corroborated these findings using a small‐interfering RNA to MK2, which decreased the myelin‐specific lipid galactosylceramide and MAG. Treatment of cultures with CMPD1 decreased the steady state levels of mRNA encoding myelin transcription factor 1 (Myt1), MAG, MBP, and Opalin, a transmembrane sialylglycoprotein expressed in oligodendrocytes. In contrast, increases were observed in the mRNA levels of OLG transcriptional repressors, including transcription factor 4 (Tcf4), Notch1, and inhibitor of differentiation 2 (Id2). Furthermore, we found that the predominantly expressed isoform of p38 in OLGs, p38α, and MK2 can form coimmunoprecipitable complexes in OLPs and OLGs. Our results demonstrate that the p38‐MK2 pathway is a component of the signaling cascade regulating OLG differentiation. © 2010 Wiley‐Liss, Inc.
Ethanol inhibits neuritogenesis induced by astrocyte muscarinic receptors
Authors: Guizzetti Marina , Moore Nadia H. , Giordano Gennaro , VanDeMark Kathryn L. , Costa Lucio G. 
Published: May 2010

AbstractIn uteroalcohol exposure can lead to fetal alcohol spectrum disorders, characterized by cognitive and behavioral deficits.In vivoandin vitrostudies have shown that ethanol alters neuronal development. We have recently shown that stimulation of M3muscarinic receptors in astrocytes increases the synthesis and release of fibronectin, laminin, and plasminogen activator inhibitor‐1, causing neurite outgrowth in hippocampal neurons. As M3muscarinic receptor signaling in astroglial cells is strongly inhibited by ethanol, we hypothesized that ethanol may also inhibit neuritogenesis in hippocampal neurons induced by carbachol‐stimulated astrocytes. In the present study, we report that the effect of carbachol‐stimulated astrocytes on hippocampal neuron neurite outgrowth was inhibited in a concentration‐dependent manner (25–100 mM) by ethanol. This effect was because of the inhibition of the release of fibronectin, laminin, and plasminogen activator inhibitor‐1. Similar effects on neuritogenesis and on the release of astrocyte extracellular proteins were observed after the incubation of astrocytes with carbachol in the presence of 1‐butanol, another short‐chain alcohol, which like ethanol is a competitive substrate for phospholipase D, but not bytert‐butanol, its analog that is not a substrate for this enzyme. This study identifies a potential novel mechanism involved in the developmental effects of ethanol mediated by the interaction of ethanol with cell signaling in astrocytes, leading to an impairment in neuron–astrocyte communication. © 2010 Wiley‐Liss, Inc.
Preclinical Assessment of Simultaneous Targeting of Epidermal Growth Factor Receptor (ERBB1) and ERBB2 as a Strategy for Cholangiocarcinoma Therapy†,‡
Authors: Zhang Zichen , Oyesanya Regina A. , Campbell Deanna J. W. , Almenara Jorge A. , DeWitt Jennifer L. , Sirica Alphonse E. 
Published: May 2010

Abstract

Overexpression of epidermal growth factor receptor (ErbB1) and/or ErbB2 has been implicated in the pathogenesis of cholangiocarcinoma, suggesting that combined ErbB1/ErbB2 targeting might serve as a target-based therapeutic strategy for this highly lethal cancer. To test this strategy, we investigated targeting with the ErbB1 inhibitor tryphostin AG1517 and the ErbB2 inhibitor tryphostin AG879, in combination and alone, as well as with the dual ErbB1/ErbB2 inhibitor lapatinib, to assess the effectiveness of simultaneous targeting of ErbB1 and ErbB2 signaling over single inhibitor treatments in suppressing cholangiocarcinoma cell growth

in vitro

and the therapeutic efficacy of lapatinib

in vivo

. Our

in vitro

studies were carried out using rat (BDEneu and C611B) and human (HuCCT1 and TFK1) cholangiocarcinoma cell lines. The efficacy of lapatinib to significantly suppress liver tumor growth was tested in an orthotopic, syngeneic rat model of intrahepatic cholangiocarcinoma progression. Our results demonstrated that simultaneous targeting of ErbB1 and ErbB2 signaling was significantly more effective in suppressing the

in vitro

growth of both rat and human cholangiocarcinoma cells than individual receptor targeting. Lapatinib was an even more potent inhibitor of cholangiocarcinoma cell growth and inducer of apoptosis than either tryphostin when tested

in vitro

against these respective cholangiocarcinoma cell lines, regardless of differences in their levels of ErbB1 or ErbB2 protein expression and/or mechanism of activation. Lapatinib treatment also produced a significant suppression of intrahepatic cholangiocarcinoma growth when administered early to rats, but was without effect in inhibiting liver tumor growth in rats with more advanced tumors.

Conclusion:

Our findings suggest that simultaneous targeting of ErbB1 and ErbB2 could be a potentially selective strategy for cholangiocarcinoma therapy, but is likely to be ineffective by itself against advanced cancer.
Role of tau protein on neocortical and hippocampal oscillatory patterns
Authors: Cantero Jose L. , Moreno‐Lopez Bernardo , Portillo Federico , Rubio Alicia , Hita‐Yañez Eva , Avila Jesus 
Published: May 2010

AbstractTau is a neuronal microtubule‐associated protein implicated in microtubules stabilization, axonal establishment and elongation during neuronal morphogenesis. Because of its elevated expression in neocortical regions and hippocampus, tau might play a role in sculpting collective neural responses underlying slow and fast brain oscillations and/or long‐range synchronization patterns between hippocampus and neocortex. To test this hypothesis, local field potentials were recorded in tau‐deficient (tau−/−) and wild‐type mice from different neocortical regions and from the hippocampus during spontaneous motor exploratory behavior. We found that tau−/− mice showed hippocampal theta slowing and reduced levels of gamma long‐range synchronization involving the frontal cortex. We hypothesize that the lack of normal phosphorylated tau during early stages of development might influence the maturation of parvalbumin interneurons affecting the spatiotemporal structure of long‐range gamma synchronization. Also, the proper functioning of gap‐junction channels might be compromised by the absence of tau in hippocampal networks. Altogether, these results provide novel insights into the functional role of tau protein in the formation of collective neural responses and emergence of neocortical‐hippocampal interactions in the mammalian brain. © 2010 Wiley‐Liss, Inc.
Preserved hippocampal novelty responses following anterior temporal‐lobe resection that impairs familiarity but spares recollection
Authors: Bowles Ben , O'Neil Edward B. , Mirsattari Seyed M. , Poppenk Jordan , Köhler Stefan 
Published: May 2010

AbstractAlthough it is well established that the integrity of the medial temporal lobe (MTL) is critical for declarative memory, the functional organization of the MTL remains a matter of intense debate. One issue that has received little consideration so far is whether the hippocampus can function normally in the presence of a lesion to perirhinal cortex that produces noticeable memory impairments. This question is intriguing as the MTL forms a hierarchical system, in which perirhinal cortex represents one of the critical nodes in the reciprocal projections between neocortical association areas and the hippocampus. Here, we used functional magnetic resonance imaging to examine whether NB, an individual who underwent surgical resection of the left anterior temporal lobe that included large aspects of perirhinal and entorhinal cortex but spared the hippocampus, exhibits intact hippocampal novelty responses to auditory sentences. Our results revealed such evidence in NB's left and right hippocampus. They complement previous behavioral work in NB, indicating that recollective processes considered to rely on hippocampal integrity are also preserved. Further analyses revealed intact novelty responses in structures that provide neuroanatomical input to the hippocampus, including remaining perirhinal cortex and surgically spared parahippocampal cortex. These findings point to viable neuroanatomical mechanisms as to how functional integrity in the hippocampus may be maintained in the face of widespread, but incomplete removal of its input structures. © 2010 Wiley‐Liss, Inc.
Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults
Authors: Yassa Michael A. , Lacy Joyce W. , Stark Shauna M. , Albert Marilyn S. , Gallagher Michela , Stark Craig E.L. 
Published: May 2010

AbstractThere is widespread evidence that memory deteriorates with aging, however the exact mechanisms that underlie these changes are not well understood. Given the growing size of the aging population, there is an imperative to study age‐related neurocognitive changes in order to better parse healthy from pathological aging. Using a behavioral paradigm that taxes pattern separation (the ability to differentiate novel yet similar information from previously learned information and thus avoid interference), we investigated age‐related neural changes in the human hippocampus using high‐resolution (1.5 mm isotropic) blood‐oxygenation level‐dependent fMRI. Recent evidence from animal studies suggests that hyperactivity in the CA3 region of the hippocampus may underlie behavioral deficits in pattern separation in aged rats. Here, we report evidence that is consistent with findings from the animal studies. We found a behavioral impairment in pattern separation in a sample of healthy older adults compared with young controls. We also found a related increase in CA3/dentate gyrus activity levels during an fMRI contrast that stresses pattern separation abilities. In a detailed analysis of behavior, we also found that the pattern of impairment was consistent with the predictions of the animal model, where larger changes in the input (greater dissimilarity) were required in order for elderly adults to successfully encode new information as distinct from previously learned information. These findings are also consistent with recent fMRI and behavioral reports in healthy aging, and further suggest that a specific functional deficit in the CA3/dentate network contributes to memory difficulties with aging. © 2010 Wiley‐Liss, Inc.
Brain‐derived neurotrophic factor val66met polymorphism and hippocampal activation during episodic encoding and retrieval tasks
Authors: Dennis Nancy A. , Cabeza Roberto , Need Anna C. , Waters‐Metenier Sheena , Goldstein David B. , LaBar Kevin S. 
Published: May 2010

AbstractBrain‐derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long‐term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype and functional activity in the hippocampus during episodic and working memory tasks in healthy young adults. Specifically, studies have found that met carriers exhibit both poorer performance and reduced neural activity within the medial temporal lobe (MTL) when performing episodic memory tasks. However, these studies have not been well replicated and have not considered the role of behavioral differences in the interpretation of neural differences. The current study sought to control for cognitive performance in investigating the role of the BDNF val66met genotype on neural activity associated with episodic memory. Across item and relational memory tests, met carriers exhibited increased MTL activation during both encoding and retrieval stages, compared to noncarriers. The results suggest that met carriers are able to recruit MTL activity to support successful memory processes, and reductions in cognitive performance observed in prior studies are not a ubiquitous effect associated with variants of the BDNF val66met genotype. © 2010 Wiley‐Liss, Inc.
Ultrastructural modifications of spine and synapse morphology by SAP97
Authors: Poglia Lorenzo , Muller Dominique , Nikonenko Irina 
Published: May 2010

AbstractSynaptic scaffolding proteins from membrane‐associated guanylate kinases (MAGUK) family are implicated in synapse formation and functioning. To better understand the role of one of the proteins of this family, SAP97, we studied with electron microscopy the effects of its overexpression on spine and synapse morphology in CA1 pyramidal neurons of rat organotypic hippocampal slice cultures. Dramatic spine enlargement induced by SAP97 overexpression was accompanied by marked morphological changes, with spines enwrapping and engulfing presynaptic terminals. The size and complexity of the PSD was also significantly increased. Similar to PSD‐95, SAP97 promoted formation of multi‐innervated spines (MIS). In addition, both MAGUK proteins induced multiple excitatory contacts on dendritic shafts suggesting a mechanism for shaft synapse formation. Formation of MIS and shaft synapses was blocked by the nitric oxide synthase (NOS) inhibitor L‐NAME. Immunochemistry revealed that overexpression of SAP97 was associated with overexpression of PSD‐95 and recruitment of nNOS to the synapse. These data provide evidence for both common and distinct structural alterations produced by overexpression of SAP97 and PSD‐95 and demonstrate strong interactions between these two proteins to regulate contact formation through nitric oxide signaling. © 2010 Wiley‐Liss, Inc.
Major ion geochemistry and nutrient behaviour in the mixing zone of the Changjiang (Yangtze) River and its tributaries in the Three Gorges Reservoir
Authors: Ran Xiangbin , Yu Zhigang , Yao Qingzheng , Chen Hongtao , Mi Tiezhu 
Published: May 2010

AbstractInorganic ions and nutrients were measured at different depths of the Xiangxi and Daninghe Rivers to explore the mixing processes of representative bays in the Three Gorges Reservoir (TGR). HCO3−and Ca2+are the dominant ions. Carbonate weathering is the most important mechanism controlling the ion water chemistry; however, important differences exist between the main channel and its tributaries. Major ion levels in the TGR bays depend on hydrological mixing. Results show that the major ions of Ca2+, Mg2+, Na+, K+, Sr2+, SO42−and Cl−show chemically conservative behaviour during transit through the bays of the TGR. This means the ions can be used as tracers in the same way that salinity is used in estuaries to explore behaviour of other non‐conservative elements and to indicate specific source waters. In contrast, nutrients are not conserved in the mixing zone. The mixing of the main channel and tributaries and biological utilization in backwater reaches were the key factor controlling nutrient distributions in Xiangxi and Daninghe Bays. Copyright © 2010 John Wiley & Sons, Ltd.
Associations of aspirin, nonsteroidal anti‐inflammatory drug and paracetamol use with PSA‐detected prostate cancer: Findings from a large, population‐based, case–control study (the ProtecT study)
Authors: Murad Ali S. , Down Liz , Davey Smith George , Donovan Jenny L. , Athene Lane Janet , Hamdy Freddie C. , Neal David E. , Martin Richard M. 
Published: May 2010

AbstractEvidence from laboratory studies suggests that chronic inflammation plays an important role in prostate cancer aetiology. This has resulted in speculation that nonsteroidal anti‐inflammatory drugs may protect against prostate cancer development. We analysed data from a cross‐sectional case–control study (ncases= 1,016; ncontrols= 5,043), nested within a UK‐wide population‐based study that used prostate specific antigen (PSA) testing for identification of asymptomatic prostate cancers, to investigate the relationship of aspirin, nonsteroidal anti‐inflammatory drug (NSAID) and paracetamol use with prostate cancer. In conditional logistic regression models accounting for stratum matching on age (5‐year age bands) and recruitment centre, use of non‐aspirin NSAIDs [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.04–1.67] or all NSAIDs (OR = 1.25; 95% CI = 1.07–1.47) were positively associated with prostate cancer. There were weaker, not conventionally statistically significant, positive associations of aspirin (OR = 1.13; 95% CI = 0.94–1.36) and paracetamol (OR = 1.20; 95% CI = 0.90–1.60) with prostate cancer. Mutual adjustment for aspirin, non‐aspirin NSAIDs or paracetamol made little difference to these results. There was no evidence of confounding by age, family history of prostate cancer, body mass index or self‐reported diabetes. Aspirin, NSAID and paracetamol use were associated with reduced serum PSA concentrations amongst controls. Our findings do not support the hypothesis that NSAIDs reduce the risk of PSA‐detected prostate cancer. Our conclusions are unlikely to be influenced by PSA detection bias because the inverse associations of aspirin, NSAID and paracetamol use with serum PSA would have attenuated (not generated) the observed positive associations.
CHI3L1 (YKL‐40) is expressed in human gliomas and regulates the invasion, growth and survival of glioma cells
Authors: Ku Bo Mi , Lee Yeon Kyung , Ryu Jinhyun , Jeong Joo Yeon , Choi Jungil , Eun Keyoung Mi , Shin Hye Young , Kim Dong Gyu , Hwang Eun Mi , Yoo Jae cheal , Park Jae‐Yong , Roh Gu Seob , Kim Hyun Joon , Cho Gyeong Jae , Choi Wan Sung , Paek Sun Ha , Kang Sang Soo 
Published: May 2010

AbstractChitinase 3‐like 1 (CHI3L1) is a secreted glycoprotein that has pleiotropic activity in aggressive cancers. In our study, we examined the expression and function of CHI3L1 in glioma cells. CHI3L1 was highly expressed in human glioma tissue, whereas its expression in normal brain tissue was very low. CHI3L1 suppression by shRNA reduced glioma cell invasion, anchorage‐independent growth and increased cell death triggered by several anticancer drugs, including cisplatin, etoposide and doxorubicin, whereas CHI3L1 overexpression had the opposite effect in glioma cells. Because the invasive nature of glioma cells plays a critical role in the high morbidity of glioma, we have further defined the role of CHI3L1 in the process of glioma invasion. Downregulation of CHI3L1 results in decreased cell–matrix adhesion and causes a marked increase in stress fiber formation and cell size with fewer cellular processes. Furthermore, the expression and activity of matrix metalloproteinase‐2 was also decreased in glioma cells in which CHI3L1 was knocked down. Taken together, these results suggest that CHI3L1 plays an important role in the regulation of malignant transformation and local invasiveness in gliomas. Thus, targeting the CHI3L1 molecule may be a potential therapeutic molecular target for gliomas.