bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgenic inactivation of acetylcholinesterase impairs homeostasis in mouse hippocampal granule cells
Authors: Cohen J.E. , Zimmerman G. , Melamed‐Book N. , Friedman A. , Dori A. , Soreq H. 
Published: October 2007

AbstractIn the adult murine hippocampus, dentate gyrus (DG), neurogenesis and neural cell death are thought to affect learning and memory in incompletely understood mechanism(s). Because cholinergic neurotransmission influences both of these functions, we hypothesized that cholinergic signaling, affected by acetylcholinesterase (AChE) activity, expression level, and alternative splicing, may provide a link between these processes. To challenge this hypothesis, we compared DG neurogenesis in transgenic mice overexpressing engineered “synaptic” AChE‐S, incapable of acetylcholine (ACh) hydrolysis (TgSin) with strain‐matched controls. In control mice, we observed increasing AChE gene expression with progressing neurogenesis. This involved dividing DG neurons expressing proliferating cell nuclear antigen (PCNA) and Tuj1‐positive committed neurons compared with neighboring cells. However, TgSin hippocampi with lower hydrolytic AChE activity showed more PCNA‐labeled cells than controls. In contrast, TgS mice overexpressing catalytically active AChE‐S, with higher than control levels of AChE hydrolytic activity, presented elevated cell labeling by both bromodeoxyuridine and caspase‐3, reflecting facilitated survival of newly born neurons as well as increased neural apoptosis. In comparison, overexpression of the stress‐induced “readthrough” AChE‐R variant in TgR mice resulted in higher hydrolytic activities but unchanged neurogenesis and apoptosis parameters, while all strains presented similar granule cell layer areas, cell density, and neuron numbers. Importantly, this homeostasis was maintained at a cognitive cost: in the hippocampal‐dependent socially transmitted food preference task, TgS and TgSin mice showed impaired acquisition and retention, respectively. Our findings suggest that replacement of AChE‐S with AChE‐R serves to maintain DG homeostasis and associated cognitive tasks, highlighting the role of cholinergic signaling in adult hippocampal neurogenesis and functioning. © 2007 Wiley‐Liss, Inc.
Neurolymphomatosis—diagnosis and assessment of treatment response by FDG PET‐CT
Authors: Lin M , Kilanowska J , Taper J , Chu J 
Published: October 2007

AbstractNeurolymphomatosis (NL) is lymphomatous infiltration of peripheral nerves, and is an uncommon manifestation of non‐Hodgkin's lymphoma (NHL). Although nerve biopsy is the main method for histological diagnosis, a blind nerve biopsy may not be diagnostic. While CT and MRI have been used to detect NL, recent reports demonstrated the benefit of integrated positron emission tomography (PET) using F18‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) combined with computed tomography (CT). We described the utility of FDG PET‐CT in this uncommon subgroup of NHL where it can assist in establishing the diagnosis, the potential to guide sites for biopsy and in the assessment of response to therapy. Copyright © 2007 John Wiley & Sons, Ltd.
Self reported sleep quality and cognitive performance in ecstasy users
Authors: Montgomery Catharine , Fisk John E. , Wareing Michelle , Murphy Philip 
Published: October 2007

AbstractObjectivesResearch suggests that ecstasy users exhibit psychobiological changes relative to nonusers such as altered sleep patterns and cognitive deficits. In turn, it has been suggested that sleep quality may be a mediator of such cognitive deficits in ecstasy users. The present study sought to investigate this proposed relationship.MethodsAspects of cognitive functioning in 104 ecstasy users and 103 nonusers obtained from our previous studies were reanalysed to explore the extent to which ecstasy‐related group differences were attributable to differences in sleep quality. Cognitive function was assessed via the computation span test, consonant updating, paired associate learning, syllogistic reasoning and word fluency. Sleep quality was measured via the Epworth Sleepiness Scale (ESS), and the Karolinska Sleepiness Scale (KSS).ResultsEcstasy users performed worse than nonusers on all cognitive measures. While no differences were observed on the ESS, ecstasy users reported greater tiredness at the beginning of testing than nonusers. When the sleep variables were included as covariates, the effects of ecstasy on all cognitive measures remained significant.ConclusionsThe results of the present study suggest little evidence for the mediating effects of sleep on cognitive function in ecstasy users. Copyright © 2007 John Wiley & Sons, Ltd.
Assessing the impact of climate variability and human activities on streamflow from the Wuding River basin in China
Authors: Li Li‐Juan , Zhang Lu , Wang Hao , Wang Juan , Yang Jun‐Wei , Jiang De‐Juan , Li Jiu‐Yi , Qin Da‐Yong 
Published: October 2007

AbstractLocated in the Loess Plateau of China, the Wuding River basin (30 261 km2) contributes significantly to the total sediment yield in the Yellow River. To reduce sediment yield from the catchment, large‐scale soil conservation measures have been implemented in the last four decades. These included building terraces and sediment‐trapping dams and changing land cover by planting trees and improving pastures. It is important to assess the impact of these measures on the hydrology of the catchment and to provide a scientific basis for future soil conservation planning. The non‐parametric Mann–Kendall–Sneyers rank test was employed to detect trends and changes in annual streamflow for the period of 1961 to 1997. Two methods were used to assess the impact of climate variability on mean annual streamflow. The first is based on a framework describing the sensitivity of annual streamflow to precipitation and potential evaporation, and the second relies on relationships between annual streamflow and precipitation. The two methods produced consistent results. A significant downward trend was found for annual streamflow, and an abrupt change occurred in 1972. The reduction in annual streamflow between 1972 and 1997 was 42% compared with the baseline period (1961–1971). Flood‐season streamflow showed an even greater reduction of 49%. The streamflow regime of the catchment showed a relative reduction of 31% for most percentile flows, except for low flows, which showed a 57% reduction. The soil conservation measures reduced streamflow variability, leading to more uniform streamflow. It was estimated that the soil conservation measures account for 87% of the total reduction in mean annual streamflow in the period of 1972 to 1997, and the reduction due to changes in precipitation and potential evaporation was 13%. Copyright © 2007 John Wiley & Sons, Ltd.
Effect of climate changes and water‐related human activities on annual stream flows of the Shiyang river basin in arid north‐west China
Authors: Huo Zailin , Feng Shaoyuan , Kang Shaozhong , Li Wangcheng , Chen Shaojun 
Published: October 2007

AbstractThe change of annual stream flow in the Shiyang river basin, a typical arid‐inland basin in north‐west China, was investigated using hydrological, meteorological and water‐related human activities' data of the past 50 years. The long‐term trends of the hydrological time series were examined by non‐parametric techniques, including the Pettitt and Mann–Kendall tests. Double cumulative curves and multi‐regression methods were used to separate and quantify the effects of climate changes and human activities on the stream flows. The results show that the study area has been experiencing a significant upward warming trend since 1986 and precipitation shows a decreasing trend in the mountainous region but an increasing trend in the plains region. All stream flows in the upper reach and lower reaches of the Shiyang river exhibit decreasing tendencies. Since 1970, human activities, such as irrigation, have had a significant effect on the upstream flow, and account for 60% of total flow decreases in the 1970s. However, climate changes are the main reason for the observed flow decreases in the 1980s and 1990s, with contributions to total flow decrease of 68% and 63%, respectively. Before 1975, flow decreases in the upper reaches were the main factor causing reduced flows in the lower reaches of the Shiyang river. After 1975, the effect of human activities became more pronounced, with contributions of 63%, 68% and 56% to total flow decreases in the lower reaches of the Shiyang river in the periods 1975 to 1980, 1980s and 1990s, respectively. As a result, climate change is responsible for a large proportion of the flow decreases in the upstream section of the catchment during the 1980s and 1990s, while human activities have caused flow decreases downstream during the same period. Copyright © 2007 John Wiley & Sons, Ltd.
Monitoring response to treatment in melanoma patients: Potential of a serum glycomic marker
Authors: Selvan Senthamil R. , Dillman Robert O. , Fowler Abner W. , Carbonell Denysha J. , Ravindranath Mepur H. 
Published: October 2007

AbstractA mechanistic marker correlating with tumor progression and clinical response is useful for assessing therapeutic response and determining the course of therapy. Since serum‐total‐ganglioside (sTG) and antiganglioside‐IgM antibody levels reflected tumor progression, the feasibility of utilizing sTG for assessing the response to immunotherapy of metastatic‐melanoma was tested. Patients (n = 34) were immunized with dendritic cells cocultured with irradiated, IFNγ‐treated autologous tumor cells admixed with GM‐CSF. Levels of sTG and antiganglioside‐IgM antibody titers were measured in sera of vaccine recipients at 0, 4 and 24 weeks of treatment. Based on sTG‐level, whether lower (L) or higher (H) than the mean + 1 SD of normal and healthy volunteers on weeks 0, 4 and 24, patients were categorized into cohorts‐I (LLL, n = 16), II (HHL/HLL, n = 4), III (LLH/LHH/LHL, n = 7) and IV (HHH/HLH, n = 7). The cohorts were regrouped as sTG‐ downregulators (sTG‐DR; n = 20) and upregulators (sTG‐UR; n = 14). These two cohorts differed significantly in their overall (p < 0.012) and progression‐free (p = 0.0001) survival post‐treatment. 43% sTG‐UR died within 39 months, with a median survival of 39 months, whereas 61% of the sTG‐DR survived for 48 months. Both endogenous and vaccine‐induced antiganglioside‐IgM antibodies appeared to regulate sTG levels. Nonresponders had increased sTG with no or low IgM antibody response. The sTG level is regulated within 24 weeks post‐treatment and therefore, may serve as an ideal biomarker for assessing therapeutic responses in patients. Clinical correlations of sTG indicate that sTG‐downregulating therapy may be an effective treatment strategy for melanoma. © 2007 Wiley‐Liss, Inc.
Ovarian cancers overexpress the antimicrobial protein hCAP‐18 and its derivative LL‐37 increases ovarian cancer cell proliferation and invasion
Authors: Coffelt Seth B. , Waterman Ruth S. , Florez Luisa , Bentrup Kerstin Höner zu , Zwezdaryk Kevin J. , Tomchuck Suzanne L. , LaMarca Heather L. , Danka Elizabeth S. , Morris Cindy A. , Scandurro Aline B. 
Published: October 2007

AbstractThe role of the pro‐inflammatory peptide, LL‐37, and its pro‐form, human cationic antimicrobial protein 18 (hCAP‐18), in cancer development and progression is poorly understood. In damaged and inflamed tissue, LL‐37 functions as a chemoattractant, mitogen and pro‐angiogenic factor suggesting that the peptide may potentiate tumor progression. The aim of this study was to characterize the distribution of hCAP‐18/LL‐37 in normal and cancerous ovarian tissue and to examine the effects of LL‐37 on ovarian cancer cells. Expression of hCAP‐18/LL‐37 was localized to immune and granulosa cells of normal ovarian tissue. By contrast, ovarian tumors displayed significantly higher levels of hCAP‐18/LL‐37 where expression was observed in tumor and stromal cells. Protein expression was statistically compared to the degree of immune cell infiltration and microvessel density in epithelial‐derived ovarian tumors and a significant correlation was observed for both. It was demonstrated that ovarian tumor tissue lysates and ovarian cancer cell lines express hCAP‐18/LL‐37. Treatment of ovarian cancer cell lines with recombinant LL‐37 stimulated proliferation, chemotaxis, invasion and matrix metalloproteinase expression. These data demonstrate for the first time that hCAP‐18/LL‐37 is significantly overexpressed in ovarian tumors and suggest LL‐37 may contribute to ovarian tumorigenesis through direct stimulation of tumor cells, initiation of angiogenesis and recruitment of immune cells. These data provide further evidence of the existing relationship between pro‐inflammatory molecules and ovarian cancer progression. © 2007 Wiley‐Liss, Inc.
Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas
Authors: Marie Suely K.N. , Okamoto Oswaldo K. , Uno Miyuki , Hasegawa Ana Paula G. , Oba‐Shinjo Sueli M. , Cohen Tzeela , Camargo Anamaria A. , Kosoy Ana , Carlotti Carlos G. , Toledo Silvia , Moreira‐Filho Carlos A. , Zago Marco A. , Simpson Andrew J. , Caballero Otavia L. 
Published: October 2007

AbstractWe have performed cDNA microarray analyses to identify gene expression differences between highly invasive glioblastoma multiforme (GBM) and typically benign pilocytic astrocytomas (PA). Despite the significant clinical and pathological differences between the 2 tumor types, only 63 genes were found to exhibit 2‐fold or greater overexpression in GBM as compared to PA. Forty percent of these genes are related to the regulation of the cell cycle and mitosis. QT‐PCR validation of 6 overexpressed genes: MELK, AUKB, ASPM, PRC1, IL13RA2 and KIAA0101 confirmed at least a 5‐fold increase in the average expression levels in GBM. Maternal embryonic leucine zipper kinase (MELK) exhibited the most statistically significant difference. A more detailed investigation of MELK expression was undertaken to study its oncogenic relevance. In the examination of more than 100 tumors of the central nervous system, we found progressively higher expression of MELK with astrocytoma grade and a noteworthy uniformity of high level expression in GBM. Similar level of overexpression was also observed in medulloblastoma. We found neither gene promoter hypomethylation nor amplification to be a factor in MELK expression, but were able to demonstrate that MELK knockdown in malignant astrocytoma cell lines caused a reduction in proliferation and anchorage‐independent growth in in vitro assays. Our results indicate that GBM and PA differ by the expression of surprisingly few genes. Among them, MELK correlated with malignancy grade in astrocytomas and represents a therapeutic target for the management of the most frequent brain tumors in adult and children. © 2007 Wiley‐Liss, Inc.
Deregulation of β‐catenin signal by Helicobacter pylori CagA requires the CagA‐multimerization sequence
Authors: Kurashima Yo , Murata‐Kamiya Naoko , Kikuchi Kenji , Higashi Hideaki , Azuma Takeshi , Kondo Satoshi , Hatakeyama Masanori 
Published: October 2007

AbstractInfection with Helicobacter pylori cagA‐positive strains causes gastritis and peptic ulceration and is associated with gastric adenocarcinoma. The cagA gene product CagA is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases at the C‐terminal EPIYA‐repeat region. Tyrosine‐phosphorylated CagA specifically binds and activates SHP‐2 tyrosine phosphatase, causing cell morphological transformation known as the hummingbird phenotype. CagA also destabilizes the E‐cadherin/β‐catenin complex to elicit aberrant activation of the β‐catenin signal that underlies intestinal metaplasia. Here we show that translocalization of membranous β‐catenin and subsequent activation of the β‐catenin signal by CagA requires the EPIYA‐repeat region, which is characterized by structural variation between CagA of H. pylori isolated in Western countries (Western CagA) and that of East Asian H. pylori isolates (East Asian CagA), but is independent of CagA tyrosine phosphorylation. Detailed analysis using a series of Western and East Asian CagA mutants revealed that deregulation of β‐catenin requires residues 1009–1086 and residues 908–1012 of ABCCC Western CagA and ABD East Asian CagA, respectively, and is mediated by the 16‐amino‐acid CagA multimerization sequence that is conserved between the 2 geographically distinct H. pylori CagA species. Our results indicate that aberrant activation of the β‐catenin signal, which promotes precancerous intestinal metaplasia, is an inherent and fundamental CagA activity that is independent of the structural polymorphism of CagA. © 2007 Wiley‐Liss, Inc.
Osteopontin‐c is a selective marker of breast cancer
Authors: Mirza Mana , Shaughnessy Elizabeth , Hurley John K. , Vanpatten Kristie A. , Pestano Gary A. , He Bin , Weber Georg F. 
Published: October 2007

AbstractWhile the acquisition of invasiveness is a critical step in early stage breast carcinomas (DCIS), no established molecular markers reliably identify tumor progression. The metastasis gene osteopontin is subject to alternative splicing, which yields 3 messages, osteopontin‐a, osteopontin‐b and osteopontin‐c. Osteopontin‐c is selectively expressed in invasive, but not in noninvasive, breast tumor cell lines, and it effectively supports anchorage independence. We evaluated osteopontin‐c as a biomarker. The RNA message for osteopontin‐c was present in 16 of 20 breast cancers (80%), but was undetectable in 22 normal specimens obtained from reduction mammoplasty. In contrast, osteopontin‐a RNA was expressed at various levels in all 20 breast cancers, 11 tumor‐surrounding tissues and 21 normal samples. The splice variant osteopontin‐b was present at barely detectable levels in 18 of 20 cancers and in 6 of 22 normal breasts. By immunohistochemistry, 66 of 69 normal breasts were negative, while 3 showed low level staining. Among the breast cancers, 43 of 56 cores (77%) stained positive for osteopontin‐c. When correlated with tumor grade, the staining for osteopontin‐c increased from grade 1 to grade 3. In a total of 178 breast specimens analyzed, osteopontin‐c was present in 78% of cancers, 36% of surrounding tissues and 0% of normal tissues. Furthermore, osteopontin‐c detects a higher fraction of breast cancers than estrogen receptor (ER), progesterone receptor or HER2. In conjunction, osteopontin‐c, ER and HER2 reliably predict grade 2–3 breast cancer. Hence, osteopontin‐c is a diagnostic and prognostic marker that may have value in a diagnostic panel together with conventional breast cancer markers. © 2007 Wiley‐Liss, Inc.
BCL‐2 functions as an activator of the AKT signaling pathway in pancreatic cancer
Authors: Mortenson Melinda M. , Galante Joseph G. , Gilad Oren , Schlieman Michael G. , Virudachalam Subbulakshmi , Kung Hsing‐Jien , Bold Richard J. 
Published: October 2007

AbstractBCL‐2 is the prototypic anti‐apoptotic protein involved in the regulation of apoptosis. Overexpression of BCL‐2 is common in pancreatic cancer and confers resistance to the apoptotic effect of chemo‐ and radiotherapy. Although these cellular effects of BCL‐2 are traditionally related to pathways involving the mitochondrial membrane, we sought to investigate whether BCL‐2 is involved in other signaling pathways regulating cell survival and focused on AKT. We examined the effect of overexpression of BCL‐2 in the MIA‐PaCa‐2 human pancreatic cancer cell line on the function and subcellular location of AKT. We observed that the stable subclones of MIA‐PaCa‐2 overexpressing BCL‐2 demonstrated increased activity of AKT as well as IKK (a downstream target of AKT), increasing the transcriptional activity of NF‐κB. Using immunoprecipitation techniques, we observed co‐immunoprecipitation of AKT and BCL‐2. Immunocytochemistry demonstrated co‐localization of BCL‐2 and AKT, which was abrogated by treatment with HA14‐1, a small molecule inhibitor of BH‐3‐mediated protein interaction by BCL‐2. Furthermore, treatment with HA14‐1 decreased phosphorylation of AKT and increased sensitivity to the apoptotic effect of the chemotherapeutic agent, paclitaxel. These results demonstrate an additional mechanism of regulation of cell survival mediated by BCL‐2, namely through AKT activation, in the MIA‐PaCa‐2 pancreatic cancer cell line. Therefore, directed inhibition of BCL‐2 may alter diverse pathways controlling cell survival and overcome the apoptotic resistance that is the hallmark of pancreatic cancer. J. Cell. Biochem. 102: 1171–1179, 2007. © 2007 Wiley‐Liss, Inc.
Differential expression of estrogen receptor alpha (ERα) protein in MCF‐7 breast cancer cells chronically exposed to TCDD
Authors: Marquez‐Bravo Lydia G. , Gierthy John F. 
Published: October 2007

AbstractEstrogens play a key role in the development and evolution of breast cancer tumors. Estrogen receptor alpha (ERα) mediates many of the biological activities of estrogens, and its expression is associated with low invasiveness and good prognosis. Recent epidemiological reports suggest that long‐term exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is implicated in the increased incidence of breast cancer in exposed women. TCDD interferes with the expression of some ERα‐dependent genes and inhibits estradiol (E2)‐ dependent growth of breast cancer cells in vitro. However, E2‐dependent xenographs of MCF‐7 human breast cancer cells resumed growth after a 2‐week exposure to TCDD. The mechanisms involved in the resumption of cell growth are not completely understood. In this study, we show that short term‐exposure (16 days) to 1 nM TCDD results in the suppression of ERα protein expression, while chronic exposure for more than 1 year (LTDX cells) results in the partial re‐expression of the receptor. Immunocytochemistry studies showed that re‐expression of ERα in LTDX cells occurred in some of the cells. Analysis by Western immunoblots indicated that four out of five LTDX clones expressed ERα at levels comparable to those in unexposed MCF‐7 cells. Removal of TCDD treatment for 16 days restored the expression of ERα in the ERα‐negative clonal cells. These results suggest that MCF‐7 cells chronically exposed to TCDD contain at least two cell subpopulations that may respond differently to the ERα‐mediated effects of TCDD. J. Cell. Biochem. 103: 636–647, 2008. © 2007 Wiley‐Liss, Inc.
Atrial natriuretic peptide attenuates high glucose‐activated transforming growth factor‐β, Smad and collagen synthesis in renal proximal tubular cells
Authors: Lo Chao‐Sheng , Chen Zhao‐Hong , Hsieh Tusty‐Jiuan , Shin Shyi‐Jang 
Published: October 2007

AbstractAtrial natriuretic peptide, besides its role in the regulation of volume homeostasis, has been noted to exert cytoprotective effects in several cell types from hypoxia. The present study was performed to explore the effect of ANP on high glucose‐activated transforming growth factor‐beta1 (TGF‐β1), Smad and collagen synthesis in renal proximal epithelial cells. Cultured NRK‐52E cells were divided into five groups: (1) normal glucose (5.5 mM), (2) high glucose (35 mM), (3) D‐mannitol (29.5 mM), (4) high glucose plus ANP (10−6–10−9 M), and (5) high glucose plus ANP (10−6 M) and guanylate cyclase inhibitor LY83583 (10−7 M) groups. Messenger RNA levels of TGF‐β1, Smad2, and collagens were measured by RT‐PCR. ELISA, immunocytochemistry and Western blotting were used to detect protein levels of TGF‐β1, Smad2, phospho‐Smad 2/3 and collagen type 1. We found high glucose to significantly increase mRNA levels of TGF‐β1, Smad 2, collagen types I and III and protein levels of TGF‐β1, phospho‐Smad 2/3 and collagen type 1, but mannitol did not affect their expression. The addition of ANP significantly attenuated high glucose‐enhanced mRNA and protein levels of TGF‐β1, Smad and collagens. LY83583 blocked the influence of ANP on high glucose‐activated TGF‐β1, Smad and collagen synthesis. This is the first study to demonstrate that activation of TGF‐β1, Smad and collagen synthesis stimulated by high glucose can also be inhibited by exogenous ANP in renal tubular epithelial cells. J. Cell. Biochem. 103: 1999–2009, 2008. © 2007 Wiley‐Liss, Inc.