bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices
Authors: Tremblay Marie‐Ève , Zettel Martha L. , Ison James R. , Allen Paul D. , Majewska Ania K. 
Published: January 2012

AbstractNormal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age‐related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age‐related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age‐related sensory loss. Together, our results suggest that the age‐related alteration of glial cells in sensory cortical areas can be accelerated by activity‐driven central mechanisms that result from an age‐related loss of peripheral sensitivity. In light of our observations, these age‐related changes in sensory function should be considered when investigating cellular, cortical, and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models. © 2012 Wiley Periodicals, Inc.
B‐cells and IL‐4 promote methylcholanthrene‐induced carcinogenesis but there is no evidence for a role of T/NKT‐cells and their effector molecules (Fas‐ligand, TNF‐α, perforin)
Authors: Kammertoens Thomas , Qin Zhihai , Briesemeister Dana , Bendelac Albert , Blankenstein Thomas 
Published: December 2011

AbstractMice deficient either in subtypes of immune cells, cytokines or lytic pathways have been subjected to chemical carcinogenesis by methylcholanthrene to evaluate whether these components of the immune system affect tumor development. Inbred mice of the same genotype but from different sources differed in tumor development in magnitude comparable to that previously attributed to differences in immunocompetence. This suggested that genetic drift between separate inbred colonies of mice and/or environmental factors (e.g., transport of the animals) influenced carcinogenesis. Therefore, littermates were used as control in subsequent experiments. Although deficiency of T‐cells, NKT‐cells, perforin, Fas‐ligand, TNF‐α‐receptor failed to reveal significant differences in tumor development, the presence of B‐cells and IL‐4 enhanced tumor development under similar experimental conditions.
PEA15 impairs cell migration and correlates with clinical features predicting good prognosis in neuroblastoma
Authors: Gawecka Joanna E. , Geerts Dirk , Koster Jan , Caliva Maisel J. , Sulzmaier Florian J. , Opoku‐Ansah John , Wada Randal K. , Bachmann André S. , Ramos Joe W. 
Published: December 2011

AbstractERK and RSK2 drive proliferation and invasion of many cancers. Phosphoprotein enriched in astrocytes 15 (PEA15) binds ERK and RSK2 and high PEA15 levels can impair ERK‐ and RSK2‐dependent transcription. PEA15 expression also inversely correlates with cell motility and invasiveness. We therefore tested PEA15 effects on neuroblastoma cells in vitro. We further analyzed PEA15 expression in the context of clinical and genetic features of neuroblastoma in tumor samples to determine its correlation with disease progression. Affymetrix microarray analysis was performed using 24 different neuroblastoma cell lines. Cell lines expressing low to intermediate levels of PEA15 were chosen for in vitro functional studies. The cell line results were verified by Affymetrix analysis of three different neuroblastic tumor types (total of 110 samples) PEA15 overexpression inhibited neuroblastoma migration in vitro. We verified that inhibition of motility required PEA15 interaction with its binding partners ERK and RSK2. Additionally, synthetic inhibitors of RSK2 suppressed integrin‐dependent migration. PEA15 expression correlates with clinical parameters and a 25% increase in patient survival rate. The highest PEA15 levels were found in low stage, more differentiated and less metastatic neuroblastic tumors, and correlated with lack of MYCN amplification. PEA15 blocks neuroblastoma migration through inhibition of ERK/RSK2 signaling. PEA15 expression levels correlate with favorable clinical features suggesting that PEA15 limits metastatic progression of neuroblastoma. Thus, PEA15 and its partners ERK and RSK2 are potential targets for the development of new therapeutics to impede progression of minimal residual disease in patients with high‐risk neuroblastoma.
Fine‐mapping of a region of chromosome 5p15.33 (TERT‐CLPTM1L) suggests a novel locus in TERT and a CLPTM1L haplotype are associated with glioma susceptibility in a Chinese population
Authors: Zhao Yingjie , Chen Gong , Zhao Yao , Song Xiao , Chen Hongyan , Mao Ying , Lu Daru 
Published: December 2011

AbstractTwo genome‐wide association studies (GWAS) have identified 5p15.33 (TERT‐CLPTM1L) as one of the susceptible regions for glioma in European background. A replication research of our group highlighted the association signals in the TERT gene of this region in a Chinese Han population. To comprehensively explore the region of glioma association at 5p15.33 and to refine the potential causal variants to a smaller critical region, we conducted a fine‐mapping association study among 983 cases and 1,024 controls in a Chinese Han population. Using Hapmap3 datasets as a reference, we genotyped 16 tag SNPs across this 87.9‐kb region encompassing TERT. Significant association with glioma risk was observed for rs2853677 [GG vs. GA: adjusted OR = 1.46, p = 5.51 × 10−6, GG vs. AA: adjusted OR = 1.72, p = 7.64 × 10−6, GG vs. GA and AA: adjusted OR = 1.96, p = 6.8 × 10−6] in TERT and an uncommon CLPTM1L haplotype G–T–A of rs4635969, rs6554759 and rs414965 (haplotype frequency = 0.07) was associated with higher glioma risk compared with the most common G–C–G haplotype (adjusted OR = 1.44, simulated p = 6.00 × 10−3 under additive model). Our results indicate that sequence variants in the region flanking rs2853677 may account for the GWAS and replication signals identified in 5p15.33 for glioma susceptibility in Chinese population; besides, haplotype G–T–A in CLPTM1L also confers a risk to glioma suggesting CLPTM1L is also involved in the etiology of glioma. Additional studies especially those taking advantage of sequencing platforms are warranted to further confirm the conclusions and go deeper with our findings.
CD31, EDNRB and TSPAN7 are promising prognostic markers in clear‐cell renal cell carcinoma revealed by genome‐wide expression analyses of primary tumors and metastases
Authors: Wuttig Daniela , Zastrow Stefan , Füssel Susanne , Toma Marieta I. , Meinhardt Matthias , Kalman Kristin , Junker Kerstin , Sanjmyatav Jimsgene , Boll Kerstin , Hackermüller Jörg , Rolle Axel , Grimm Marc‐Oliver , Wirth Manfred P. 
Published: December 2011

AbstractCurrently used clinicopathological parameters are insufficient for a reliable prediction of metastatic risk and disease‐free survival (DFS) of patients with clear‐cell renal cell carcinoma (ccRCC). To identify prognostic genes, the expression profiles of primary ccRCC obtained from patients with different DFS — eight synchronously, nine metachronously and seven not metastasized tumors — were determined by genome‐wide expression analyses. Synchronously and metachronously metastasized primary ccRCC differed in the expression of 167 genes. Thirty‐six of these genes were also differentially expressed in synchronously vs. metachronously developed pulmonary metastases analyzed in a previous study. Because of their DFS‐associated deregulation that is concordant in metastases and primary ccRCC, these genes are potentially functionally involved in metastatic tumor growth and are also prognostically useful. A prognostic impact was confirmed for the genes CD31,
EDNRB and TSPAN7 at the mRNA level (n = 86), and for TSPAN7 at the protein level (n = 106). Patients with a higher gene expression of EDNRB or TSPAN7, or with TSPAN7‐positive vessels in both cores investigated on tissue microarrays had a significantly longer DFS and tumor‐specific survival (TSS). Patients with a higher CD31 gene expression showed a significantly longer TSS. EDNRB was an independent prognostic marker for the DFS. CD31, EDNRB and TSPAN7 had an independent impact on the TSS. In summary, comparative analysis of primary tumors and metastases is appropriate to identify independent prognostic markers in ccRCC. Gene expression of CD31 and EDNRB, and endothelial TSPAN7 protein level are potentially useful to improve outcome prediction because of their independent prognostic impact.
The influence of prediagnostic demographic and lifestyle factors on esophageal squamous cell carcinoma survival
Authors: Thrift Aaron P. , Nagle Christina M. , Fahey Paul P. , Russell Anne , Smithers Bernard M. , Watson David I. , Whiteman David C. ,   for the Australian Cancer Study Clinical Follow‐Up Study
Published: December 2011

AbstractDemographic and lifestyle factors, in particular tobacco smoking and alcohol, are well established causes of esophageal squamous cell carcinoma (ESCC); however, little is known about the effect of these factors on survival. We included all 301 patients with incident ESCC, recruited into a population‐based case–control study of esophageal cancer in Australia. Detailed information about demographic and lifestyle factors was obtained at diagnosis, and deaths were identified using the National Death Index. Median follow‐up for all‐cause mortality was 6.4 years. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated from Cox proportional hazards models, adjusted for age, sex, pretreatment AJCC tumor stage, treatment and presence of comorbidities. Two hundred and thirteen patients (71%) died during follow‐up. High lifetime alcohol consumption was independently associated with poor survival. Relative to life‐long nondrinkers and those consuming <1 drink/week, the HRs for those with average consumption of 7–20 drinks/week or ≥21 drinks/week were 2.21 (95% CI = 1.27–3.84) and 2.08 (95% CI = 1.18–3.69), respectively. There was a suggestion of worse survival among current smokers (HR = 1.42, 95% CI = 0.89–2.28); however, the risk of early death was greatest among current smokers who reported regularly (≥7 drinks/week) consuming alcohol (HR = 3.84, 95% CI = 2.02–7.32). Other lifestyle factors putatively associated with risk of developing ESCC were not associated with survival. In addition to increasing disease risk, heavy alcohol consumption may be independently associated with worse survival among patients with ESCC. Future clinical follow‐up studies should consider alcohol as a potential prognosticator, in addition to known clinicopathologic factors.
DNA methylation of the CYP1A1 enhancer is associated with smoking‐induced genetic alterations in human lung
Authors: Tekpli Xavier , Zienolddiny Shanbeh , Skaug Vidar , Stangeland Lodve , Haugen Aage , Mollerup Steen 
Published: December 2011

AbstractCYP1A1 (cytochrome P4501A1) catalyze the conversion of polycyclic aromatic hydrocarbons into reactive metabolites, which may induce DNA damage. We hypothesized that DNA methylation of the CYP1A1 enhancer could be involved in inter‐individual differences in mRNA levels of CYP1A1 or affect the smoking‐induced DNA damage in human lung. Using DNA bisulfite conversion and pyrosequencing, we show that DNA methylation of the CYP1A1 enhancer is affected by smoking. In adjacent histologically normal lung from lung cancer patients (n = 120), low levels of DNA methylation of the CYP1A1 enhancer were related to high levels of smoking‐induced hydrophobic DNA adduct (p < 0.03), and to the presence of TP53 or K‐ras mutations in the corresponding lung tumors (p < 0.03). We found an inverse correlation between DNA methylation of the CYP1A1 enhancer and mRNA levels in vivo (Spearman r = −0.54; p < 0.0001). Thus, in lung tumor tissues, the CYP1A1 enhancer hypermethylation was associated with lower mRNA levels compared to adjacent histologically normal tissue (p < 0.0001). In vitro, using a panel of cultured human lung cells, we found hypermethylation of the CYP1A1 enhancer in cancer cell lines and an inverse correlation between DNA methylation and mRNA levels (Spearman r = −0.53; p = 0.003). Altogether, our results indicated that low levels of DNA methylation of the CYP1A1 enhancer in histologically normal human lung were associated with high CYP1A1 mRNA levels and with smoking‐induced genetic alterations; thus, it may play a role in the initiation of lung carcinogenesis.
Effects of cold ischemia and inflammatory tumor microenvironment on detection of PI3K/AKT and MAPK pathway activation patterns in clinical cancer samples
Authors: Bonnas Christel , Specht Katja , Spleiss Olivia , Froehner Stefanie , Dietmann Gabriele , Krüger Juliane M. , Arbogast Susanne , Feuerhake Friedrich 
Published: December 2011

AbstractThe accuracy of common markers for PI3K/AKT and MAPK pathway activation in preclinical and clinical cancer biomarker studies depends on phosphoepitope stability and changes of phosphorylation under ischemia. Herein, we define conditions under which phosphoepitope‐specific duplex immunohistochemistry (IHC) on formalin‐fixed, paraffin‐embedded tumor tissues reflects pathway activation in situ as accurately as possible, and identify activation patterns linked to mutational status, pathway dependency and tumor microenvironment in clinical tumor samples, cell culture and xenograft tissues. Systematically assessing robustness of pAKT, pERK1/2, pMEK1/2 and pmTOR detection and related markers in xenograft tissues exposed to ischemia, we show that control of preprocessing and ischemia times allows accurate interpretation of staining results. Phosphorylation patterns were then analyzed in 33 xenograft models and in 58 cases with breast cancer, including 21 paired samples of core‐needle biopsies with corresponding mastectomy specimens, and 37 mastectomy samples obtained under rigorously controlled conditions minimizing ischemia time. Patterns of pAKT and pERK1/2 staining (predominant PI3K/AKT, predominant MAPK and concomitant activation) were associated with sensitivity to pathway inhibition and partially with the mutational status in cell lines and corresponding xenograft tumors. In contrast, no clear correlation between mutational status and staining patterns was observed in clinical breast cancer samples, suggesting that interaction with the human tumor microenvironment may interfere with the use of phosphoepitope‐specific IHC as potential markers for pathway dependency. In contrast to core needle biopsies, surgically resected breast cancer samples showed evidence of severe signal changes comparable to those effects observed in xenograft tumors exposed to controlled ischemia.
Oxidative stress and apoptosis induced by hydroxyapatite nanoparticles in C6 cells
Authors: Xu Jing , Xu Pengjuan , Li Zhigui , Huang Jie , Yang Zhuo 
Published: December 2011

AbstractHydroxyapatite (HA) nanoparticles have been reported to exhibit anti‐tumor effects on various human cancers, but the effects of HA on glioma cells remain unclear. The aim of this study was to explore whether HA can inhibit the proliferation and induce the apoptosis of C6 cells. Use of the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay indicated that HA induced C6 cell death in a concentration‐dependent and time‐dependent manner. Results from hoechst 33342 staining and flow cytometry assay showed that HA induced C6 cell apoptosis significantly. Meanwhile, the flow cytometric assay gave clear indication that HA induced intracellular accumulation of reactive oxygen species (ROS). The measurement of superoxide dismutase (SOD) generation showed that HA decreased the total SOD of cellular levels. Interestingly, pretreatment of N‐(mercaptopropionyl)‐glycine (N‐MPG), known as a type of ROS scavenger formulations, could somehow inhibit C6 cell apoptosis induced by HA. These results may provide potential anti‐glioma treatment in the future. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Simultaneous treatment of methane and swine slurry by biofiltration
Authors: Girard Matthieu , Viens Pascal , Ramirez Antonio Avalos , Brzezinski Ryszard , Buelna Gerardo , Heitz Michèle 
Published: January 2012

AbstractBACKGROUND: The piggery industry is important both worldwide and in Canada, but localized production of large quantities of swine slurry causes severe environmental problems such as aquatic pollution and greenhouse gas emissions. The main objective of this study was to determine whether it is possible to simultaneously treat methane (CH4) and swine slurry using an inorganic biofilter.RESULTS: A novel biofilter was designed to overcome the inhibition of CH4 biodegradation by swine slurry. The CH4 elimination capacity increased with the inlet load and a maximum value of 18.8 ± 1.0 g m−3 h−1 was obtained at an inlet load of 46.7 ± 0.9 g m−3 h−1 and a CH4 concentration of 3.3 g m−3. Four pure strains of fungi were used in an attempt to improve the removal of CH4, but no significant effect was observed. Between 0.35 and 3.4 g m−3, the CH4 concentration had no effect on swine slurry treatment with removal efficiencies of 67 ± 10% for organic carbon and 70 ± 7% for ammonium. The influence of the slurry supply was analyzed and the best results were obtained with a supply method of six doses of 50 mL per day.CONCLUSION: Even though the results were lower than those obtained for the biofiltration of CH4 alone, this study demonstrated the feasibility of treating CH4 and swine slurry with the same biofilter using a novel design. Copyright © 2012 Society of Chemical Industry
Morphology, ultrastructure, and probable functions of the sense organs on the ovipositor stylets of the hymenoptran parasitoid, Venturia canescens (Gravenhorst)
Authors: Shah Zahid Ali 
Published: January 2012

AbstractTo help understand the mechanism of host discrimination during oviposition of a parasitoid wasp, Venturia canescens (Gravenhorst) (Hymenoptera: Ichneumonidae), the ultrastructure and morphology of the sense organs on the dorsal and ventral stylets of the ovipositor were examined using scanning and transmission electron microscopy. Ovipositor stylets were scanned for sense organs, because only unsheathed ovipositors are used for probing, stabbing, and host discrimination. Five types of sensilla and secretary pores were identified. Based on their pattern of innervation, the surface‐dome and pitted‐dome sensilla were thought to have a gustatory function and, thus, are the best candidates for host‐discrimination. The arrangements of dendrites of type I and type II campaniform sensilla suggested that these acted as pressure‐ and mechano‐receptors, respectively. Coeloconic sensilla might act as thermo‐hygroreceptors, whilst secretary pores might provide lubrication during the process of stabbing for oviposition. Surface‐dome sensilla were the most numerous type found followed by secretary pores, pitted‐dome sensilla, and coeloconic sensilla. Almost all the sensilla and secretary pores were more numerous on the dorsal than on the ventral stylets, and the maximum number of these sensilla and secretary pores occurred on the distal end of the ovipositor stylets and decreased toward the proximal end. The surface‐dome sensilla and secretary pores occurred in alternate rows while the pitted‐dome sensilla were scattered all over the surface of the ovipositor stylets, especially on the sides of the stylets. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Mineralization pattern of vertebral bone material following fragility fracture of the spine
Authors: Hofstaetter Jochen G. , Hofstaetter Stefan G. , Nawrot‐Wawrzyniak Kamilla , Hiertz Helmut , Grohs Josef G. , Trieb Klemens , Windhager Reinhard , Klaushofer Klaus , Roschger Paul 
Published: January 2012

AbstractLittle is known whether trabecular bone matrix mineralization is altered at the site of osteoporotic vertebral fractures. Bone mineralization density distribution (BMDD) was assessed in trabecular bone of acute, single‐level compression fractures of the spine at various stages of fracture repair using quantitative backscattered electron imaging (qBEI). The grading of the repair stage was performed by histological methods. From 20 patients, who underwent either kyphoplasty (n = 18) or vertebroplasty (n = 2), a vertebral bone biopsy was taken prior to cement augmentation. Six patients took bisphosphonates (BP) prior to fracture. Three study groups were formed: N1 = early‐, N2 = late‐healing and B = BP treatment at late healing stage. In general, all groups had an altered BMDD when compared to historical normative reference data. Mean matrix mineralization (CaMean) was significantly (p < 0.001) lower in all groups (N1: −5%, N2: −16%, and B2: −16%). In N2, CaMean was −13.1% (p < 0.001) lower than N1. At this stage, deposition of new bone matrix and/or formation of woven bone are seen, which also explains the more heterogeneous matrix mineralization (CaWidth). Moreover, BP treatment (B2) led to a significant reduction in CaWidth (−28.5%, p < 0.001), when compared to N2. Bone tissue from vertebrae with acute compression fractures reveals a large variation in matrix mineralization depending on the stage of repair. Bisphosphonate treatment does affect the mineralization pattern of tissue repair. The low mineralization values found in early stage of repair suggest that altered bone material properties may play a role in the occurrence of fragility fractures of the spine. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1089–1094, 2012
Footprint‐based estimates of arch structure are confounded by body composition in adults
Authors: Wearing Scott C. , Grigg Nicole L. , Lau Hin C. , Smeathers James E. 
Published: January 2012

AbstractPrevious research employing indirect measures of arch structure, such as those derived from footprints, have indicated that obesity results in a “flatter” foot type. In the absence of radiographic measures, however, definitive conclusions regarding the osseous alignment of the foot cannot be made. We determined the effect of body mass index (BMI) on radiographic and footprint‐based measures of arch structure. The research was a cross‐sectional study in which radiographic and footprint‐based measures of foot structure were made in 30 subjects (10 males, 20 female) in addition to standard anthropometric measures of height, weight, and BMI. Multiple (univariate) regression analysis demonstrated that both BMI (β = 0.39, t26 = 2.12, p = 0.04) and radiographic arch alignment (β = 0.51, t26 = 3.32, p < 0.01) were significant predictors of footprint‐based measures of arch height after controlling for all variables in the model (R2 = 0.59, F3,26 = 12.3, p < 0.01). In contrast, radiographic arch alignment was not significantly associated with BMI (β = −0.03, t26 = −0.13, p = 0.89) when Arch Index and age were held constant (R2 = 0.52, F3,26 = 9.3, p < 0.01). Adult obesity does not influence osseous alignment of the medial longitudinal arch, but selectively distorts footprint‐based measures of arch structure. Footprint‐based measures of arch structure should be interpreted with caution when comparing groups of varying body composition. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1351–1354, 2012