bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grid cells and theta as oscillatory interference: Theory and predictions
Authors: Burgess Neil 
Published: November 2008

AbstractThe oscillatory interference model [Burgess et al. (2007) Hippocampus 17:801–802] of grid cell firing is reviewed as an algorithmic level description of path integration and as an implementation level description of grid cells and their inputs. New analyses concern the relationships between the variables in the model and the theta rhythm, running speed, and the intrinsic firing frequencies of grid cells. New simulations concern the implementation of velocity‐controlled oscillators (VCOs) with different preferred directions in different neurons. To summarize the model, the distance traveled along a specific direction is encoded by the phase of a VCO relative to a baseline frequency. Each VCO is an intrinsic membrane potential oscillation whose frequency increases from baseline as a result of depolarization by synaptic input from speed modulated head‐direction cells. Grid cell firing is driven by the VCOs whose preferred directions match the current direction of motion. VCOs are phase‐reset by location‐specific input from place cells to prevent accumulation of error. The baseline frequency is identified with the local average of VCO frequencies, while EEG theta frequency is identified with the global average VCO frequency and comprises two components: the frequency at zero speed and a linear response to running speed. Quantitative predictions are given for the inter‐relationships between a grid cell's intrinsic firing frequency and grid scale, the two components of theta frequency, and the running speed of the animal. Qualitative predictions are given for the properties of the VCOs, and the relationship between environmental novelty, the two components of theta, grid scale and place cell remapping. © 2008 Wiley‐Liss, Inc.
Grid cells: The position code, neural network models of activity, and the problem of learning
Authors: Welinder Peter E. , Burak Yoram , Fiete Ila R. 
Published: November 2008

AbstractWe review progress on the modeling and theoretical fronts in the quest to unravel the computational properties of the grid cell code and to explain the mechanisms underlying grid cell dynamics. The goals of the review are to outline a coherent framework for understanding the dynamics of grid cells and their representation of space; to critically present and draw contrasts between recurrent network models of grid cells based on continuous attractor dynamics and independent‐neuron models based on temporal interference; and to suggest open questions for experiment and theory. © 2008 Wiley‐Liss, Inc.
The emergence of grid cells: Intelligent design or just adaptation?
Authors: Kropff Emilio , Treves Alessandro 
Published: November 2008

AbstractIndividual medial entorhinal cortex (mEC) ‘grid’ cells provide a representation of space that appears to be essentially invariant across environments, modulo simple transformations, in contrast to multiple, rapidly acquired hippocampal maps; it may therefore be established gradually during rodent development. We explore with a simplified mathematical model the possibility that the self‐organization of multiple grid fields into a triangular grid pattern may be a single‐cell process, driven by firing rate adaptation and slowly varying spatial inputs. A simple analytical derivation indicates that triangular grids are favored asymptotic states of the self‐organizing system, and computer simulations confirm that such states are indeed reached during a model learning process, provided it is sufficiently slow to effectively average out fluctuations. The interactions among local ensembles of grid units serve solely to stabilize a common grid orientation. Spatial information, in the real mEC network, may be provided by any combination of feedforward cortical afferents and feedback hippocampal projections from place cells, since either input alone is likely sufficient to yield grid fields. © 2008 Wiley‐Liss, Inc.
The effect of cantharidins on leukemic stem cells
Authors: Dorn David C. , Kou Cynthia A. , Png Kim J. , Moore Malcolm A.S. 
Published: November 2008

AbstractTo identify an agent with specific activity against leukemic stem cells (LSCs), we evaluated compounds that targeted hepatic leukemia factor (HLF), a gene implicated in hematopoietic stem cell (HSCs) regulation, that we found overexpressed in LSCs. Cantharidin, a natural toxin from blister beetles, used as medicinal agent since antiquity, has been described to modulate theHLFcompetitorNFIL3and is under clinical evaluation as an antitumor and antimetastatic agent. The molecule is not a substrate for multidrug resistant pumps and does not cause myelosuppression, and therefore it represents a promising compound for selective ablation of LSCs. Cantharidin and norcantharidin, a derivative with reduced toxicity, decreased HLF protein levels and induced apoptosis in the AML cell line MV4‐11 by modulating the expression of several molecules that govern survival pathway, including HLF, SLUG, NFIL3 and c‐myc, thereby inducing p53 and the mitochondrial caspase cascade.In vitro, cantharidin readily targeted primary AML stem and progenitor cells in contrast to conventional chemotherapeutic agents, such as Ara‐C and daunorubicin, that mainly targeted more differentiated leukemic cells.In vitrothe compound did not exhibit a therapeutic window, being equally toxic to normal HSCs and LSCs.In vivocantharidin did not produce myelosuppression. Because of dose‐limiting toxicityin vivo, neither cantharidin nor norcantharidin proved therapeutical benefit in AML xenograft models as a single agent. However, its potentin vitroLSC activity and pathway targeting may still be exploited clinically with a new generation of cantharidin derivatives or formulations and with appropriate drug combinations. © 2008 Wiley‐Liss, Inc.
Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivovia cyclooxygenase‐2 and apoptotic pathways
Authors: Hao Yubin , Xie Tianpei , Korotcov Alexandru , Zhou Yanfei , Pang Xiaowu , Shan Liang , Ji Hongguang , Sridhar Rajagopalan , Wang Paul , Califano Joseph , Gu Xinbin 
Published: November 2008

AbstractOverexpression of cyclooxygenase‐2 (COX‐2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a nonsteroidal anti‐inflammatory drug, which inhibits COX‐2 but not COX‐1. This selective COX‐2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long‐term chemoprevention and therapy. Salvianolic acid B (Sal‐B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal‐B inhibits HNSCC growth. Sal‐B was isolated from S. miltiorrhiza Bge by solvent extraction followed by 2 chromatographic steps. Pharmacological activity of Sal‐B was assessed in HNSCC and other cell lines by estimating COX‐2 expression, cell viability and caspase‐dependent apoptosis. Sal‐B inhibited growth of HNSCC JHU‐022 and JHU‐013 cells with IC50 of 18 and 50 μM, respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal‐B (80 mg/kg/day) or celecoxib (5 mg/kg/day) for 25 days to investigate in vivo effects of the COX‐2 inhibitors. Tumor volumes in Sal‐B treated group were significantly lower than those in celecoxib treated or untreated control groups (p < 0.05). Sal‐B inhibited COX‐2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal‐B also caused dose‐dependent inhibition of prostaglandin E2 synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal‐B shows promise as a COX‐2 targeted anticancer agent for HNSCC prevention and treatment. © 2008 Wiley‐Liss, Inc.
Inhibition of prostaglandin synthesis and actions by genistein in human prostate cancer cells and by soy isoflavones in prostate cancer patients
Authors: Swami Srilatha , Krishnan Aruna V. , Moreno Jacqueline , Bhattacharyya Rumi S. , Gardner Christopher , Brooks James D. , Peehl Donna M. , Feldman David 
Published: November 2008

AbstractSoy and its constituent isoflavone genistein inhibit the development and progression of prostate cancer (PCa). Our study in both cultured cells and PCa patients reveals a novel pathway for the actions of genistein, namely the inhibition of the synthesis and biological actions of prostaglandins (PGs), known stimulators of PCa growth. In the cell culture experiments, genistein decreased cyclooxygenase‐2 (COX‐2) mRNA and protein expression in both human PCa cell lines (LNCaP and PC‐3) and primary prostate epithelial cells and increased 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH) mRNA levels in primary prostate cells. As a result genistein significantly reduced the secretion of PGE2 by these cells. EP4 and FP PG receptor mRNA were also reduced by genistein, providing an additional mechanism for the suppression of PG biological effects. Further, the growth stimulatory effects of both exogenous PGs and endogenous PGs derived from precursor arachidonic acid were attenuated by genistein. We also performed a pilot randomised double blind clinical study in which placebo or soy isoflavone supplements were given to PCa patients in the neo‐adjuvant setting for 2 weeks before prostatectomy. Gene expression changes were measured in the prostatectomy specimens. In PCa patients ingesting isoflavones, we observed significant decreases in prostate COX‐2 mRNA and increases in p21 mRNA. There were significant correlations between COX‐2 mRNA suppression, p21 mRNA stimulation and serum isoflavone levels. We propose that the inhibition of the PG pathway contributes to the beneficial effect of soy isoflavones in PCa chemoprevention and/or treatment. © 2008 Wiley‐Liss, Inc.
DNA adduct formation and induction of micronuclei and mutations in B6C3F1/Tk mice treated neonatally with acrylamide or glycidamide
Authors: Von Tungeln Linda S. , Churchwell Mona I. , Doerge Daniel R. , Shaddock Joseph G. , McGarrity Lynda J. , Heflich Robert H. , Gamboa da Costa Gonçalo , Marques M. Matilde , Beland Frederick A. 
Published: November 2008

AbstractAcrylamide, a food contaminant, is carcinogenic in experimental animals, with both genotoxic and nongenotoxic pathways being proposed. To obtain information regarding mechanisms of acrylamide tumorigenesis, we compared the extent of DNA adduct formation and induction of micronuclei and mutations in mice treated neonatally with acrylamide and its electrophilic metabolite glycidamide. Male and female B6C3F1/Tk mice were treated intraperitoneally on postnatal days (PNDs) 1, 8 and 15 or PNDs 1–8 with 0.14 or 0.70 mmol acrylamide or glycidamide per kg body weight per day. One day after the final dose, B6C3F1/Tk+/+ mice were killed to measure DNA adduct levels and peripheral blood micronuclei. Three weeks after the last treatment, B6C3F1/Tk+/− mice were killed to assess the Hprt and Tk mutant frequencies in spleen lymphocytes. The levels of N7‐(2‐carbamoyl‐2‐hydroxyethyl)guanine, the major glycidamide‐DNA adduct, decreased in the order 0.70 mmol glycidamide > 0.70 mmol acrylamide > 0.14 mmol glycidamide ∼ 0.14 mmol acrylamide. Only glycidamide increased the frequency of micronucleated reticulocytes and normochromatic erythrocytes. In mice treated on PNDs 1, 8 and 15, the Hprt mutant frequency was increased by 0.70 mmol glycidamide. In mice dosed on PNDs 1–8, 0.70 mmol glycidamide caused extensive mortality; each of the other treatments increased the Tk mutant frequency, whereas acrylamide increased the Hprt mutant frequency. These data suggest that the mutagenic response in neonatal mice treated on PNDs 1, 8 and 15 is due to glycidamide, whereas mutations resulting from dosing on PNDs 1–8 are due to another mechanism. © 2008 Wiley‐Liss, Inc.
Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor‐1 in colon cancer liver metastases
Authors: Illemann Martin , Bird Nigel , Majeed Ali , Lærum Ole D. , Lund Leif R. , Danø Keld , Nielsen Boye Schnack 
Published: November 2008

AbstractMetastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase‐type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor‐1 (PAI‐1). To compare the expression patterns of uPA, uPAR and PAI‐1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI‐1 in primarily stromal cells at the invasive front. In 5 of the 14 liver metastases, we found intense expression of uPAR, uPA‐mRNA and PAI‐1 in primarily stromal cells at the metastases periphery, and in an expression pattern similar to that found in the primary tumours. In the remaining 9 liver metastases, uPAR and uPA‐mRNA were only seen associated with the presence of necrosis within the liver metastases. In addition, PAI‐1‐immunoreactivity was in all liver metastases seen in hepatocytes at the metastases periphery. Interestingly, the former 5 liver metastases positive for uPAR, uPA mRNA and PAI‐1 at the metastasis periphery all had a predominantly desmoplastic reaction, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI‐1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings may have implication for the treatment of patients with metastatic disease. © 2008 Wiley‐Liss, Inc.
Hepatocarcinogenesis in mice with a conditional knockout of the hepatocyte growth factor receptor c‐Met
Authors: Marx‐Stoelting Philip , Borowiak Malgorzata , Knorpp Thomas , Birchmeier Carmen , Buchmann Albrecht , Schwarz Michael 
Published: November 2008

AbstractThe receptor for the hepatocyte growth factor/scatter factor (HGF/SF), c‐Met, plays a role in tumour promotion, progression and metastasis. In this study, we analysed chemically induced hepatocarcinogenesis in mice lacking a functional HGF receptor in their liver. Control and c‐Met deficient mice were injected with a single dose of N‐nitrosodiethylamine (DEN, 90 μg/g b.wt.) at 6 weeks of age and mice were subsequently kept on a phenobarbital (PB) containing diet (0.05%) for 35 weeks or on control diet. At the end of the experiment, the carcinogenic response in liver of the animals was monitored. Conditional c‐met knockout (KO) mice showed a higher prevalence of macroscopically visible liver tumours and of glutamine synthetase positive and glucose‐6‐phosphatase deficient lesions in liver. Tumour promotion by PB led to significant increases in the number of preneoplastic and neoplastic lesions in liver of both wild‐type and c‐met knockout mice, with only minor differences in response. Our results indicate that a defect in c‐Met‐mediated signaling increases chemically induced tumour initiation in liver but does not significantly affect PB‐mediated tumour promotion. © 2008 Wiley‐Liss, Inc.
Pharmacogenomics and analogues of the antitumour agent N6‐isopentenyladenosine
Authors: Colombo Francesca , Falvella F. Stefania , De Cecco Loris , Tortoreto Monica , Pratesi Graziella , Ciuffreda Pierangela , Ottria Roberta , Santaniello Enzo , Cicatiello Luigi , Weisz Alessandro , Dragani Tommaso A. 
Published: November 2008

AbstractN6‐isopentenyladenosine (i6A), a member of the cytokinin family of plant hormones, has potent in vitro antitumour activity in different types of human epithelial cancer cell lines. Gene expression profile analysis of i6A‐treated cells revealed induction of genes (e.g., PPP1R15A, DNAJB9, DDIT3, and HBP1) involved in the negative regulation of cell cycle progression and reportedly up‐regulated during cell cycle arrest in stress conditions. Of 6 i6A analogues synthesized, only the 1 with a saturated double bond of the isopentenyl side chain had in vitro antitumour activity, although weaker than that of i6A, suggesting that i6A biological activity is highly linked to its structure. In vivo analysis of i6A and the active analogue revealed no significant inhibition of cancer cell growth in mice by either reagent. Thus, although i6A may inhibit cell proliferation by regulating the cell cycle, further studies are needed to identify active analogues potentially useful in vivo. © 2008 Wiley‐Liss, Inc.
Murine osteosarcoma primary tumour growth and metastatic progression is maintained after marked suppression of serum insulin‐like growth factor I
Authors: Hong Sung‐Hyeok , Briggs Joseph , Newman Rachel , Hoffman Karen , Mendoza Arnulfo , LeRoith Derek , Helman Lee , Yakar Shoshana , Khanna Chand 
Published: November 2008

AbstractThe insulin‐like growth factor I (IGF‐I) signaling pathway has been shown to play an important role in several aspects of cancer biology, including metastasis. The aim of this study was to define the contribution of serum (endocrine) and local (tumour microenvironment) IGF‐I on osteosarcoma tumour growth and metastasis, a cancer that is known to be dependent on the IGF‐I axis. To test this hypothesis, we evaluated the primary tumour growth and metastatic progression of K7M2 murine osteosarcoma cells injected to a genetically engineered mouse [liver‐specific IGF‐I deficient (LID)] in which serum IGF‐I levels are reduced by 75%, while maintaining expression of IGF‐I in normal tissues. We first demonstrated that IGF‐I in the tumour and the tumour‐microenvironment were maintained in the LID mice. Within this designed model, there was no difference in primary tumour growth or in pulmonary metastasis in LID mice compared to control mice. Furthermore, there was no difference in the number or localization of single metastatic cells immediately after their arrival in the lungs of LID mice and control mice, as analysed by single cell video microscopy. Collectively, these data suggest that marked reduction in serum IGF‐I is not sufficient to slow the progression of either primary or metastatic models of osteosarcoma. © 2008 Wiley‐Liss, Inc.
Hydraulic calculation of mechanically arranged drainage lines with vertical bends
Authors: Gurklys Vidmantas , Rimkus Alfonsas , S̆aulys Valentinas 
Published: November 2008

AbstractThe mechanical opening of drainage trenches cannot ensure constant drain line slopes. Therefore vertical bends in the pipelines are being formed. Air accumulates in these bends. Consequently the conductivity of collector drains reduces. The air is carried out by the water flow. However significant air volumes are not removed until the beginning of the dry season. Particularly unfavourable conditions for drainage operation are created when the slope of the collector drains is undulating. For the hydraulic calculation of drain parameters, an estimation of air volumes accumulated in drainage systems at the control time has to be performed. The calculation of the air moving process is necessary during the entire snow melting period. The special hydraulic calculation method is needed for this purpose. The creation and applying of this method is described in the article. Copyright © 2008 John Wiley & Sons, Ltd.
Roscovitine up‐regulates p53 protein and induces apoptosis in human HeLaS3 cervix carcinoma cells
Authors: Węsierska‐Gądek Józefa , Wandl Stefanie , Kramer Matthias P. , Pickem Christian , Kryštof Vladimir , Hajek Susanne B. 
Published: November 2008

AbstractExposure of human HeLaS3 cervix carcinoma cells to high doses of conventional cytostatic drugs, e.g. cisplatin (CP) strongly inhibits their proliferation. However, most cytostatic agents are genotoxic and may generate a secondary malignancy. Therefore, therapeutic strategy using alternative, not cytotoxic drugs would be beneficial. Inhibition of cyclin‐dependent kinases (CDKs) by pharmacological inhibitors became recently a promising therapeutic option. Roscovitine (ROSC), a selective CDK inhibitor, efficiently targets human malignant cells. ROSC induces cell cycle arrest and apoptosis in human MCF‐7 breast cancer cells. ROSC also activates p53 protein. Activation of p53 tumor suppressor protein is essential for induction of apoptosis in MCF‐7 cells. Considering the fact that in HeLaS3 cells wt p53 is inactivated by the action of HPV‐encoded E6 oncoprotein, we addressed the question whether ROSC would be able to reactivate p53 protein in them. Their exposure to ROSC for 24 h induced cell cycle arrest at G2/M and reduced the number of viable cells. Unlike CP, ROSC in the used doses did not induce DNA damage and was not directly cytotoxic. Despite lack of detectable DNA lesions, ROSC activated wt p53 protein. The increase of p53 levels was attributable to the ROSC‐mediated protein stabilization. Further analyses revealed that ROSC induced site‐specific phosphorylation of p53 protein at Ser46. After longer exposure, ROSC induced apoptosis in HeLaS3 cells. These results indicate that therapy of HeLaS3 cells by ROSC could offer an advantage over that by CP due to its increased selectivity and markedly reduced risk of generation of a secondary cancer. J. Cell. Biochem. 105: 1161–1171, 2008. © 2008 Wiley‐Liss, Inc.
Estrogenic control of mitochondrial function and biogenesis
Authors: Klinge Carolyn M. 
Published: November 2008

AbstractEstrogens have cell‐specific effects on a variety of physiological endpoints including regulation of mitochondrial biogenesis and activity. Estrogens regulate gene transcription by the classical genomic mechanism of binding to estrogen receptors α and β (ERα and ERβ) as well as the more recently described nongenomic pathways involving plasma membrane‐associated ERs that activate intracellular protein kinase‐mediated phosphorylation signaling cascades. Here I will review the rapid and longer‐term effects of estrogen on mitochondrial function. The identification of ERα and ERβ within mitochondria of various cells and tissues is discussed with a model of estrogen regulation of the transcription of nuclear respiratory factor‐1 (NRF‐1, NRF1). NRF‐1 subsequently promotes transcription of mitochondrial transcription factor Tfam (mtDNA maintenance factor, also called mtTFA) and then Tfam targets mtDNA‐encoded genes. The nuclear effects of estrogens on gene expression directly controlling mitochondrial biogenesis, oxygen consumption, mtDNA transcription, and apoptosis are reviewed. Overall, we are just beginning to evaluate the many direct and indirect effects of estrogens on mitochondrial activities. J. Cell. Biochem. 105: 1342–1351, 2008. © 2008 Wiley‐Liss, Inc.