bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise
Authors: Jankord Ryan , McAllister Richard M. , Ganjam Venkataseshu K. , Laughlin M. Harold
Published: January 2009

Exercise can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and regular exercise training can impact how the HPA axis responds to stress. The mechanism by which acute exercise induces HPA activity is unclear. Therefore, the purpose of this study was to test the hypothesis that nitric oxide modulates the neuroendocrine component of the HPA axis during exercise. Female Yucatan miniature swine were treated with N-nitro-l-arginine methyl ester (l-NAME) to test the effect of chronic nitric oxide synthase (NOS) inhibition on the ACTH response to exercise. In addition, we tested the effect of NOS inhibition on blood flow to tissues of the HPA axis and report the effects of handling and treadmill exercise on the plasma concentrations of ACTH and cortisol. Chronic NOS inhibition decreased plasma NOx levels by 44%, increased mean arterial blood pressure by 46%, and increased expression of neuronal NOS in carotid arteries. Vascular conductance was decreased in the frontal cortex, the hypothalamus, and the adrenal gland. Chronic NOS inhibition exaggerated the ACTH response to exercise. In contrast, chronic NOS inhibition decreased the ACTH response to restraint, suggesting that the role of NO in modulating HPA activity is stressor dependent. These results demonstrate that NOS activity modulates the response of the neuroendocrine component of the HPA axis during exercise stress.
Role of multiple phosphorylation sites in the COOH-terminal tail of aquaporin-2 for water transport: evidence against channel gating
Authors: Moeller Hanne B. , MacAulay Nanna , Knepper Mark A. , Fenton Robert A.
Published: January 2009

Arginine vasopressin (AVP)-regulated phosphorylation of the water channel aquaporin-2 (AQP2) at serine 256 (S256) is essential for its accumulation in the apical plasma membrane of collecting duct principal cells. In this study, we examined the role of additional AVP-regulated phosphorylation sites in the COOH-terminal tail of AQP2 on protein function. When expressed in Xenopus laevis oocytes, prevention of AQP2 phosphorylation at S256A (S256A-AQP2) reduced osmotic water permeability threefold compared with wild-type (WT) AQP2-injected oocytes. In contrast, prevention of AQP2 single phosphorylation at S261 (S261A), S264 (S264A), and S269 (S269A), or all three sites in combination had no significant effect on water permeability. Similarly, oocytes expressing S264D-AQP2 and S269D-AQP2, mimicking AQP2 phosphorylated at these residues, had similar water permeabilities to WT-AQP2-expressing oocytes. The use of high-resolution confocal laser-scanning microscopy, as well as biochemical analysis demonstrated that all AQP2 mutants, with the exception of S256A-AQP2, had equal abundance in the oocyte plasma membrane. Correlation of osmotic water permeability relative to plasma membrane abundance demonstrated that lack of phosphorylation at S256, S261, S264, or S269 had no effect on AQP2 unit water transport. Similarly, no effect on AQP2 unit water transport was observed for the 264D and 269D forms, indicating that phosphorylation of the COOH-terminal tail of AQP2 is not involved in gating of the channel. The use of phosphospecific antibodies demonstrated that AQP2 S256 phosphorylation is not dependent on any of the other phosphorylation sites, whereas S264 and S269 phosphorylation depend on prior phosphorylation of S256. In contrast, AQP2 S261 phosphorylation is independent of the phosphorylation status of S256.
Protein Kinase D1–Mediated Phosphorylation and Subcellular Localization of β-Catenin
Authors: Du Cheng , Jaggi Meena , Zhang Chuanyou , Balaji K.C.
Published: January 2009

β-Catenin is essential for E-cadherin–mediated cell adhesion in epithelial cells and also acts as a key cofactor for transcription activity. We previously showed that protein kinase D1 (PKD1), founding member of the PKD family of signal transduction proteins, is down-regulated in advanced prostate cancer and interacts with E-cadherin. This study provides evidence that PKD1 interacts with and phosphorylates β-catenin at Thr112 and Thr120 residues in vitro and in vivo; mutation of Thr112 and Thr120 results in increased nuclear localization of β-catenin and is associated with altered β-catenin–mediated transcription activity. It is known that mutation of Thr120 residue abolishes binding of β-catenin to α-catenin, which links to cytoskeleton, suggesting that PKD1 phosphorylation of Thr120 could be critical for cell-cell adhesion. Overexpression of PKD1 represses β-catenin–mediated transcriptional activity and cell proliferation. Epistatic studies suggest that PKD1 and E-cadherin are within the same signaling pathway. Understanding the molecular basis of PKD1–β-catenin interaction provides a novel strategy to target β-catenin function in cells including prostate cancer. [Cancer Res 2009;69(3):1117–24]
Steroid Sulfatase and Estrogen Sulfotransferase in Colon Carcinoma: Regulators of Intratumoral Estrogen Concentrations and Potent Prognostic Factors
Authors: Sato Ryuichiro , Suzuki Takashi , Katayose Yu , Miura Koh , Shiiba Kenichi , Tateno Hiroo , Miki Yasuhiro , Akahira Junichi , Kamogawa Yukiko , Nagasaki Shuji , Yamamoto Kuniharu , Ii Takayuki , Egawa Shinichi , Evans Dean B. , Unno Michiaki , Sasano Hironobu
Published: January 2009

Previous epidemiologic and in vitro studies have indicated a potential involvement of estrogens in the pathogenesis of human colon carcinoma, but the precise roles of estrogens have remained largely unknown. Therefore, in this study, we first measured intratumoral concentrations of estrogens in 53 colon carcinomas using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS). Tissue concentrations of total estrogen [estrone (E1) + estradiol] and E1 were significantly (2.0- and 2.4-fold, respectively) higher in colon carcinoma tissues than in nonneoplastic colonic mucosa (n = 31), and higher intratumoral concentrations of total estrogen and E1 were significantly associated with adverse clinical outcome. Intratumoral concentration of total estrogen was significantly associated with the combined status of steroid sulfatase (STS) and estrogen sulfotransferase (EST), but not with that of aromatase. Thus, we subsequently examined the STS/EST status in 328 colon carcinomas using immunohistochemistry. Immunoreactivities for STS and EST were detected in 61% and 44% of the cases, respectively. The −/+ group of the STS/EST status was inversely associated with Dukes' stage, depth of invasion, lymph node metastasis, and distant metastasis and positively correlated with Ki-67 labeling index of the carcinomas. In addition, this −/+ group had significantly longer survival, and a multivariate analysis revealed the STS/EST status as an independent prognostic factor. Results from our present study showed that the STS/EST status of carcinoma tissue determined intratumoral estrogen levels and could be a significant prognostic factor in colon carcinoma, suggesting that estrogens are locally produced mainly through the sulfatase pathway and play important roles in the progression of the disease. [Cancer Res 2009;69(3):914–22]
Rapid DNA Double-Strand Breaks Resulting from Processing of Cr-DNA Cross-Links by Both MutS Dimers
Authors: Reynolds Mindy F. , Peterson-Roth Elizabeth C. , Bespalov Ivan A. , Johnston Tatiana , Gurel Volkan M. , Menard Haley L. , Zhitkovich Anatoly
Published: January 2009

Mismatch repair (MMR) strongly enhances cyto- and genotoxicity of several chemotherapeutic agents and environmental carcinogens. DNA double-strand breaks (DSB) formed after two replication cycles play a major role in MMR-dependent cell death by DNA alkylating drugs. Here, we examined DNA damage detection and the mechanisms of the unusually rapid induction of DSB by MMR proteins in response to carcinogenic chromium(VI). We found that MSH2-MSH6 (MutSα) dimer effectively bound DNA probes containing ascorbate-Cr-DNA and cysteine-Cr-DNA cross-links. Binary Cr-DNA adducts, the most abundant form of Cr-DNA damage, were poor substrates for MSH2-MSH6, and their toxicity in cells was weak and MMR independent. Although not involved in the initial recognition of Cr-DNA damage, MSH2-MSH3 (MutSβ) complex was essential for the induction of DSB, micronuclei, and apoptosis in human cells by chromate. In situ fractionation of Cr-treated cells revealed MSH6 and MSH3 chromatin foci that originated in late S phase and did not require replication of damaged DNA. Formation of MSH3 foci was MSH6 and MLH1 dependent, whereas MSH6 foci were unaffected by MSH3 status. DSB production was associated with progression of cells from S into G2 phase and was completely blocked by the DNA synthesis inhibitor aphidicolin. Interestingly, chromosome 3 transfer into MSH3-null HCT116 cells activated an alternative, MSH3-like activity that restored dinucleotide repeat stability and sensitivity to chromate. Thus, sequential recruitment and unprecedented cooperation of MutSα and MutSβ branches of MMR in processing of Cr-DNA cross-links is the main cause of DSB and chromosomal breakage at low and moderate Cr(VI) doses. [Cancer Res 2009;69(3):1071–9]
Both TEAD-Binding and WW Domains Are Required for the Growth Stimulation and Oncogenic Transformation Activity of Yes-Associated Protein
Authors: Zhao Bin , Kim Joungmok , Ye Xin , Lai Zhi-Chun , Guan Kun-Liang
Published: January 2009

The Yes-associated protein (YAP) transcription coactivator is a candidate human oncogene and a key regulator of organ size. It is phosphorylated and inhibited by the Hippo tumor suppressor pathway. TEAD family transcription factors were recently shown to play a key role in mediating the biological functions of YAP. Here, we show that the WW domain of YAP has a critical role in inducing a subset of YAP target genes independent of or in cooperation with TEAD. Mutation of the WW domains diminishes the ability of YAP to stimulate cell proliferation and oncogenic transformation. Inhibition of YAP oncogenic-transforming activity depends on intact serine residues 127 and 381, two sites that could be phosphorylated by the Hippo pathway. Furthermore, genetic experiments in Drosophila support that WW domains of YAP and Yki, the fly YAP homologue, have an important role in stimulating tissue growth. Our data suggest a model in which YAP induces gene expression and exerts its biological functions by interacting with transcription factors through both the TEAD-binding and WW domains. [Cancer Res 2009;69(3):1089–98]
Sorafenib induces growth suppression in mouse models of gastrointestinal stromal tumor
Authors: Huynh Hung , Lee Jonathan W.J. , Chow Pierce K.H. , Ngo Van Chanh , Lew Guo Bin , Lam Irene W.L. , Ong Hock Soo , Chung Alexander , Soo Khee Chee
Published: January 2009

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Current therapeutic options include surgery and targeted molecular approaches such as imatinib and sunitinib. Our aim was to establish patient-derived GIST xenografts for the use of screening new drugs and improving current treatment regimens used in GIST. In this present study, we investigate the antitumor activity of sorafenib against patient-derived GIST xenografts. Murine xenograft models were given two oral doses of sorafenib daily for 30 days and growth of established tumor xenografts was monitored at least twice weekly by vernier caliper measurements. Western blotting was then used to determine changes in proteins in these xenografts before and after sorafenib therapy. Apoptotic and cell proliferation were analyzed by immunohistochemisty. Our data found that oral administration of sorafenib to mice, bearing patient-derived GIST xenografts, resulted in dose-dependent inhibition of tumor growth. Sorafenib-induced growth inhibition was associated with decreased cell proliferation, increased apoptosis, and reduction in tumor angiogenesis. Western blot analysis revealed that sorafenib inhibited C-Raf, phospho-extracellular signal-regulated kinase 1/2, and phospho-MEK1 (Thr286) slightly as well as phospho-c-Kit (Tyr568/Tyr570), phospho- platelet-derived growth factor receptor β (Tyr1021), and phospho-Flk1 (Tyr951), suggesting that sorafenib inhibited GIST growth by blocking the Raf/MEK/extracellular signal-regulated kinase pathway and angiogenesis. Sorafenib also induced cell cycle arrest, evident through increased levels of p15 and p27 and decreased levels of p21, cyclin A, cyclin B1, and cdc-2. Our study provides a strong rationale for the clinical investigation of sorafenib in patients with GIST as well as an established platform for further drug evaluation studies using GIST xenograft models. [Mol Cancer Ther 2009;8(1):152–9]
Telomerase-specific virotherapy in an animal model of human head and neck cancer
Authors: Nakajima Oumi , Matsunaga Atsuko , Ichimaru Daiju , Urata Yasuo , Fujiwara Toshiyoshi , Kawakami Koji
Published: January 2009

Telomerase-specific replication-competent adenovirus, Telomelysin (OBP-301), has a human telomerase reverse transcriptase promoter that regulates viral replication and efficiently kills human cancer cells. The objectives of this study are to examine the effects of OBP-301 in squamous cell carcinoma of the head and neck cells in vitro and in xenografted animals in vivo. OBP-301 was found to be cytotoxic to the YCUT892, KCCT873, KCCT891, KCCL871, YCUM862, HN12, and KCCOR891 cell lines in vitro. However, the level of cytotoxicity is not correlated with the expression levels of adenoviral receptors, which may be required for adenoviral infection in squamous cell carcinoma of the head and neck cells. OBP-301 shows remarkable antitumor activity against established s.c. KCCT873 tumors in immunodeficient animals in a dose-dependent manner. In addition, no significant toxicity was observed in animals receiving treatment. These results suggest that OBP-301 is a novel therapeutic agent with promise for the treatment of human head and neck cancers. [Mol Cancer Ther 2009;8(1):171–7]
NS-398, ibuprofen, and cyclooxygenase-2 RNA interference produce significantly different gene expression profiles in prostate cancer cells
Authors: John-Aryankalayil Molykutty , Palayoor Sanjeewani T. , Cerna David , Falduto Michael T. , Magnuson Scott R. , Coleman C. Norman
Published: January 2009

Cyclooxygenase-2 (COX-2) plays a significant role in tumor development and progression. Nonsteroidal anti-inflammatory drugs (NSAID) exhibit potent anticancer effects in vitro and in vivo by COX-2-dependent and COX-2-independent mechanisms. In this study, we used microarray analysis to identify the change of expression profile regulated by a COX-2-specific NSAID NS-398 (0.01 and 0.1 mmol/L), a nonspecific NSAID ibuprofen (0.1 and 1.5 mmol/L) and RNA interference (RNAi)-mediated COX-2 inhibition in PC3 prostate cancer cells. A total of 3,362 differentially expressed genes with 2-fold change and P < 0.05 were identified. Low concentrations of NSAIDs and COX-2 RNAi altered very few genes (1-3%) compared with the higher concentration of NS-398 (17%) and ibuprofen (80%). Ingenuity Pathway Analysis was used for distributing the differentially expressed genes into biological networks and for evaluation of functional significance. The top 3 networks for both NSAIDs included functional categories of DNA replication, recombination and repair, and gastrointestinal disease. Immunoresponse function was specific to NS-398, and cell cycle and cellular movement were among the top functions for ibuprofen. Ingenuity Pathway Analysis also identified renal and urologic disease as a function specific for ibuprofen. This comprehensive study identified several COX-2-independent targets of NSAIDs, which may help explain the antitumor and radiosensitizing effects of NSAIDs. However, none of these categories were reflected in the identified networks in PC3 cells treated with clinically relevant low concentrations of NS-398 and ibuprofen or with COX-2 RNAi, suggesting the benefit to fingerprinting preclinical drug concentrations to improve their relevance to the clinical setting. [Mol Cancer Ther 2009;8(1):261–73]
Endocrine-Immune-Paracrine Interactions in Prostate Cells as Targeted by Phytomedicines
Authors: Gray Nora E. , Liu Xunxian , Choi Renee , Blackman Marc R. , Arnold Julia T.
Published: January 2009

Dehydroepiandrosterone (DHEA) is used as a dietary supplement and can be metabolized to androgens and/or estrogens in the prostate. We investigated the hypothesis that DHEA metabolism may be increased in a reactive prostate stroma environment in the presence of proinflammatory cytokines such as transforming growth factor β1 (TGFβ1), and further, whether red clover extract, which contains a variety of compounds including isoflavones, can reverse this effect. LAPC-4 prostate cancer cells were grown in coculture with prostate stromal cells (6S) and treated with DHEA +/− TGFβ1 or interleukin-6. Prostate-specific antigen (PSA) expression and testosterone secretion in LAPC-4/6S cocultures were compared with those in monocultured epithelial and stromal cells by real-time PCR and/or ELISA. Combined administration of TGFβ1 + DHEA to cocultures increased PSA protein secretion two to four times, and PSA gene expression up to 50-fold. DHEA + TGFβ1 also increased coculture production of testosterone over DHEA treatment alone. Red clover isoflavone treatment led to a dose-dependent decrease in PSA protein and gene expression and testosterone metabolism induced by TGFβ1 + DHEA in prostate LAPC-4/6S cocultures. In this coculture model of endocrine-immune-paracrine interactions in the prostate, TGFβ1 greatly increased stromal-mediated DHEA effects on testosterone production and epithelial cell PSA production, whereas red clover isoflavones reversed these effects.
Bilateral Cochlear Implants in Children: Binaural Unmasking
Authors: van Deun Lieselot , van Wieringen Astrid , Francart Tom , Scherf Fanny , Dhooge Ingeborg J. , Deggouj Naïma , Desloovere Christian , Van de Heyning Paul H. , Offeciers F. Erwin , De Raeve Leo , Wouters Jan
Published: January 2009

Bilateral cochlear implants (CIs) may offer deaf children a range of advantages compared to unilateral CIs. However, speech perception in noise is mainly facilitated by better-ear effects and much less by interaural comparisons or true ‘binaural’ hearing. Little is known about the development of the binaural auditory system with CIs provided at a young age. It is possible that, as with adults, binaural sensitivity exists but is not accessed due to technical limitations in electrical stimulation methods. In this paper, we present results on binaural hearing in children with bilateral CIs. Binaural masking level differences (BMLDs) were measured for a 180-degree phase shift in a 125-Hz sinusoid, presented in a 50-Hz-wide noise band and modulating a 1000-pps carrier pulse train. Stimuli were presented to a single electrode in the middle of the electrode array at both ears. Eight children between 6 and 15 years of age participated in this study. Six children had a significantly better detection threshold when the signal was out of phase (dichotic) between two ears than when it was in phase (diotic), with a mean difference (BMLD) of 6.4 dB. The present results show that children with bilateral CIs are sensitive to binaural cues in electrical stimuli, similar to adults, even when implants are provided at a later age and with a longer delay between implantations.
Paricalcitol Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients on Sevelamer Hydrochloride: Which Dialysate Calcium Concentration to Use?
Authors: Sonikian Macroui , Metaxaki Polyxeni , Karatzas Ioannis , Vlassopoulos Dimosthenis
Published: January 2009

Background: Optimal dialysate calcium concentration (DCa) has not been determined under less hypercalcemic vitamin D analogues and Ca-free phosphate (P) binders. Methods: Twelve hyperparathyroidic hemodialysis patients under sevelamer hydrochloride were treated with paricalcitol in three periods (A, B and C) under DCa of 3.5, 3 and 2.5 mEq/l, respectively, in a 3-way open-label randomized crossover study. Results: Serum parathyroid hormone decreased in all periods. Under DCa = 2.5 mEq/l, there was a need for longer treatment duration, higher paricalcitol doses and increased sevelamer doses for higher serum P levels. No differences in serum Ca were observed. Ca × P values followed P changes. Episodes of Ca × P >55 mg2/dl2 were more frequent in the C period. Conclusions: Under paricalcitol and sevelamer, serum parathyroid hormone decreased without Ca increase under any DCa. DCa of 2.5 mEq/l resulted in higher paricalcitol doses, increased serum P levels and more frequent high Ca × P episodes and may not be optimal with the new medications.
Religiosity/Spirituality and Mortality
Authors: Chida Yoichi , Steptoe Andrew , Powell Lynda H.
Published: January 2009

Background: The relationship between religiosity/spirituality and physical health has been the subject of growing interest in epidemiological research. We systematically reviewed prospective observational cohort studies of the association between this potentially protective psychological factor and mortality using meta-analytic methods. Methods: We searched general bibliographic databases: Medline, PsycINFO, Web of Science and PubMed (up to 20 March, 2008). Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. Random effects meta-analyses, subgrouping, and sensitivity analysis were performed. Results: There were 69 studies (28 articles) and 22 studies (11 articles) investigating the association between religiosity/spirituality and mortality in initially healthy populations and diseased populations, respectively. The results of the meta-analyses showed that religiosity/spirituality was associated with reduced mortality in healthy population studies (combined hazard ratio = 0.82, 95% CI = 0.76–0.87, p <0.001), but not in diseased population studies (combined hazard ratio = 0.98, 95% CI = 0.94–1.01, p = 0.19). Notably, the protective effect of religiosity/spirituality in the initially healthy population studies was independent of behavioral factors (smoking, drinking, exercising, and socioeconomic status), negative affect, and social support. We divided studies according to the aspects of religiosity/spirituality measure examined, and found that organizational activity (e.g. church attendance) was associated with greater survival in healthy population studies. Multi-dimensional aspects were related to survival in both the healthy and diseased populations. Religiosity/spirituality was negatively associated with cardiovascular mortality in healthy population studies. Conclusions: The current review suggests that religiosity/spirituality has a favorable effect on survival, although the presence of publication biases indicates that results should be interpreted with caution.
Incidence and Management of Colonoscopic Perforations in Korea
Authors: Kang Hae Yeon , Kang Hyoun Woo , Kim Sang Gyun , Kim Joo Sung , Park Kyu-Joo , Jung Hyun Chae , Song In Sung
Published: January 2009

Background and Aim: Despite the low incidence of perforation after endoscopic procedures in the colon, the increasing use of these procedures is likely to cause a commensurate increase in such problems. This study was undertaken to determine the incidence of iatrogenic perforation of the colon, to define clinical characteristics, and to assess the management of these complications. Methods: A retrospective review of the medical records was performed for all patients with iatrogenic colon perforations after endoscopy between January 2000 and June 2007. Results: Over this 7-year study period, a total of 20,660 sigmoidoscopies, 17,102 colonoscopies, and 6,772 therapeutic procedures were performed, and 53 (0.12%) perforations were determined to be related to endoscopy. A diagnostic procedure was undertaken in 26 of these 53 perforation cases (perforation rate, 0.07%; 1 per 1,452 procedures), and a therapeutic procedure in the remaining 27 (perforation rate, 0.40%; 1 per 251 procedures). Nineteen patients (36%) were treated conservatively, and the remaining 34 (64%) required surgical management. Endoscopic clipping was performed in 9 patients, and conservative treatment was possible in 7 patients with successful closure. No procedure-related mortality occurred. Conclusions: Endoscopic repair of iatrogenic colon perforations with clips could reduce immediate operative intervention rates.
ACTN4 Gene Mutations and Single Nucleotide Polymorphisms in Idiopathic Focal Segmental Glomerulosclerosis
Authors: Dai Shengchuan , Wang Zhaohui , Pan Xiaoxia , Chen Xiaonong , Wang Weiming , Ren Hong , Feng Qi , He John Cijiang , Han Bin , Chen Nan
Published: January 2009

Aim: To investigate the association between mutations or single nucleotide polymorphisms (SNPs) of the gene ACTN4 in Chinese patients with idiopathic focal segmental glomerulosclerosis (FSGS). Materials and Methods: Genomic DNA of 82 Chinese idiopathic FSGS patients and 70 healthy people were used to analyze ACTN4 gene mutations by polymerase chain reaction, direct sequencing and GenBank matching. Hair follicle DNA of novel mutated patients’ parents were sequenced and α-actinin-4 expression in patients’ kidney was examined by immunofluorescence. For SNPs, after the Hardy-Weinberg equilibrium test, allele association and the frequencies of genotypes were analyzed, followed by association analysis between genotypes and clinical diagnosis. Results: We found a heterozygous candidate mutation 184T>A (S62T) in 1 patient and a 5′ UTR candidate mutation 1-34C>T in another patient. Both patients had non-nephrotic syndrome FSGS with reduced kidney α-actinin-4 expression. Promoter activity analysis suggests that the 1-34C>T candidate mutation may affect the transcriptional regulation of ACTN4 gene. Additionally, 6 novel silent variants and 2 novel SNPs were also found in this study. Novel SNP 484 + 87C>G had a significant association with the level of urine protein excretion in these idiopathic FSGS patients. Conclusions: Our data suggest that mutations and SNP of ACTN4 gene may contribute to be associated with Chinese idiopathic FSGS.
Patterns and Predictors of Kidney Function Decline in the Last Year prior to Dialysis
Authors: Ambrogi Vanina , Thilly Nathalie , Boini Stéphanie , Virion Jean-Marc , Kessler Michèle , Briançon Serge , Frimat Luc
Published: January 2009

Background: Establishing a comprehensive characterization of kidney function decline before dialysis is necessary to predict dialysis onset and prepare patients for replacement therapy. Aims: To investigate kidney function as measured by pattern and rate of decline in glomerular filtration rate (GFR) over the year preceding dialysis and to identify factors associated with a nonlinear GFR decline. Methods: We enrolled patients beginning dialysis in Lorraine (France) in 2005 and 2006, who were referred to a nephrologist more than 4 months before dialysis and had received more than 3 predialysis serum creatinine tests. From medical records, we retrospectively collected demographic and clinical data, as well as biological data during nephrologist follow-up, limited to 1 year before dialysis. A curve of GFR evolution by time was drawn for each patient and his linearity was evaluated graphically and confirmed by R2 > 0.7. Factors associated with a nonlinear decline in GFR were identified by logistic regression. Results: A total of 342 patients were included; the mean length of predialysis nephrologist care was 10.0 ± 9.7 months and the median number of serum creatinine tests per patient was 9 . Among these patients, 185 (54.1%) showed a linear decline in GFR and 157 (45.9%) a nonlinear decline. Patients with cardiovascular disease were 2.6 times more likely to show a nonlinear than linear decline in GFR (p < 0.0001). Conclusion: For patients with a linear decline in GFR, but not those with a nonlinear decline, date of dialysis onset can be estimated.
Anthocyanin-Rich Aronox Extract from Aroniamelanocarpa E Protects against 7β-Hydroxycholesterol-Induced Apoptosis of Endothelial Cells
Authors: Zapolska-Downar Danuta , Nowicka Grażyna , Sygitowicz Grażyna , Jarosz Mirosław
Published: January 2009

Aims: It has been previously reported that dietary polyphenolic compounds have a positive effect in cardiovascular diseases, although the underlying mechanisms remain unknown. In this study, the effects of Aronox, an anthocyanin-rich extract from Aronia melanocarpa E, on human umbilical vein endothelial cell (HUVEC) apoptosis was investigated. Methods: Apoptosis was measured in HUVEC pretreated with Aronox and than treated with 7β-hydroxycholesterol (20 μg/ml). For the evaluation of apoptosis we used the cell binding of annexin V, the propidium iodide uptake method and the TUNEL assay. We also measured the generation of reactive oxygen species (ROS) in the cells, using fluorescent probe 2′,7′-dichlorofluorescein acetate. Moreover, alteration of the mitochondrial membrane potential with subsequent cytochrome c release, activation of caspase-3, and the level of anti-apoptotic Bcl-2 were investigated. Results: Aronox significantly decreased 7β-hydroxycholesterol-induced apoptosis and ROS generation, and ameliorated the collapse of the mitochondrial transmembrane potential with subsequent inhibition of cytochrome c release. Furthermore, down-regulation of Bcl-2 and up-regulation of caspase-3 activation were reversed by Aronox. Conclusion: The protective action of the extract against apoptosis in endothelial cells may contribute to the potential benefits drawn from consumption of plant polyphenols.
Heterochrony and Artificial Embryogeny: A Method for Analyzing Artificial Embryogenies Based on Developmental Dynamics
Authors: Matos Artur , Suzuki Reiji , Arita Takaya
Published: January 2009

Artificial embryogenies are an extension to evolutionary algorithms, in which genotypes specify a process to grow phenotypes. This approach has become rather popular recently, with new kinds of embryogenies being increasingly reported in the literature. Nevertheless, it is still difficult to analyze and compare the available embryogenies, especially if they are based on very different paradigms. We propose a method to analyze embryogenies based on growth dynamics, and how evolution is able to change them (heterochrony). We define several quantitative measures that allow us to establish the variation in growth dynamics that an embryogeny can create, the degree of change in growth dynamics caused by mutations, and the degree to which an embryogeny allows mutations to change the growth of a genotype, but without changing the final phenotype reached. These measures are based on an heterochrony framework, due to Alberch, Gould, Oster, & Wake (1979 Size and shape in ontogeny and phylogeny, Paleobiology, 5(3), 296–317) that is used in real biological organisms. The measures are general enough to be applied to any embryogeny, and can be easily computed from simple experiments. We further illustrate how to compute these measures by applying them to two simple embryogenies. These embryogenies exhibit rather different growth dynamics, and both allow for mutations that changed growth without affecting the final phenotype.
A Hypercube-Based Encoding for Evolving Large-Scale Neural Networks
Authors: Stanley Kenneth O. , D'Ambrosio David B. , Gauci Jason
Published: January 2009

Research in neuroevolution—that is, evolving artificial neural networks (ANNs) through evolutionary algorithms—is inspired by the evolution of biological brains, which can contain trillions of connections. Yet while neuroevolution has produced successful results, the scale of natural brains remains far beyond reach. This article presents a method called hypercube-based NeuroEvolution of Augmenting Topologies (HyperNEAT) that aims to narrow this gap. HyperNEAT employs an indirect encoding called connective compositional pattern-producing networks (CPPNs) that can produce connectivity patterns with symmetries and repeating motifs by interpreting spatial patterns generated within a hypercube as connectivity patterns in a lower-dimensional space. This approach can exploit the geometry of the task by mapping its regularities onto the topology of the network, thereby shifting problem difficulty away from dimensionality to the underlying problem structure. Furthermore, connective CPPNs can represent the same connectivity pattern at any resolution, allowing ANNs to scale to new numbers of inputs and outputs without further evolution. HyperNEAT is demonstrated through visual discrimination and food-gathering tasks, including successful visual discrimination networks containing over eight million connections. The main conclusion is that the ability to explore the space of regular connectivity patterns opens up a new class of complex high-dimensional tasks to neuroevolution.
Stochastic Simulation of the Chemoton
Authors: Van Segbroeck Sven , Nowé Ann , Lenaerts Tom
Published: January 2009

Gánti's chemoton model is an illustrious example of a minimal cell model. It is composed of three stoichiometrically coupled autocatalytic subsystems: a metabolism, a template replication process, and a membrane enclosing the other two. Earlier studies on chemoton dynamics yield inconsistent results. Furthermore, they all appealed to deterministic simulations, which do not take into account the stochastic effects induced by small population sizes. We present, for the first time, results of a chemoton simulation in which these stochastic effects have been taken into account. We investigate the dynamics of the system and analyze in depth the mechanisms responsible for the observed behavior. Our results suggest that, in contrast to the most recent study by Munteanu and Solé, the stochastic chemoton reaches a unique stable division time after a short transient phase. We confirm the existence of an optimal template length and show that this is a consequence of the monomer concentration, which depends on the template length and the initiation threshold. Since longer templates imply shorter division times, these results motivate the selective pressure toward longer templates observed in nature.
Nonlinear Representation of the Quasi-Biennial Oscillation
Authors: Lu Bei-Wei , Pandolfo Lionel , Hamilton Kevin
Published: January 2009

A nonlinear principal component analysis (NLPCA) is applied to monthly mean zonal wind observations from January 1956 through December 2007 taken at seven pressure levels between 10 and 70 hPa in the stratosphere near the equator to represent the well-known quasi-biennial oscillation (QBO) and investigate its variability and structure. The NLPCA is conducted using a simplified two–hidden layer feed-forward neural network that alleviates the problems of nonuniqueness of solutions and data overfitting that plague nonlinear techniques of principal component analysis. The QBO is used as a test bed for the new compact model of NLPCA.

The two nonlinear principal components of the dataset of the equatorial stratospheric zonal winds, determined by the compact NLPCA, offer a clear picture of the QBO. In particular, their structure shows that the QBO phase consists of a predominant 28.3-month cycle that is modulated by an 11-yr cycle as well as by longer cycles. The differences in wind variability between westerly and easterly regimes and between Northern Hemisphere winter and summer seasons and the tendency for a seasonal synchronization of the QBO phases are well captured.
Do Models and Observations Disagree on the Rainfall Response to Global Warming?
Authors: Liepert Beate G. , Previdi Michael
Published: January 2009

Recently analyzed satellite-derived global precipitation datasets from 1987 to 2006 indicate an increase in global-mean precipitation of 1.1%–1.4% decade−1. This trend corresponds to a hydrological sensitivity (HS) of 7% K−1 of global warming, which is close to the Clausius–Clapeyron (CC) rate expected from the increase in saturation water vapor pressure with temperature. Analysis of two available global ocean evaporation datasets confirms this observed intensification of the atmospheric water cycle. The observed hydrological sensitivity over the past 20-yr period is higher by a factor of 5 than the average HS of 1.4% K−1 simulated in state-of-the-art coupled atmosphere–ocean climate models for the twentieth and twenty-first centuries. However, the analysis shows that the interdecadal variability in HS in the models is high—in particular in the twentieth-century runs, which are forced by both increasing greenhouse gas (GHG) and tropospheric aerosol concentrations. About 12% of the 20-yr time intervals of eight twentieth-century climate simulations from the third phase of the Coupled Model Intercomparison Project (CMIP3) have an HS magnitude greater than the CC rate of 6.5% K−1. The analysis further indicates different HS characteristics for GHG and tropospheric aerosol forcing agents. Aerosol-forced HS is a factor of 2 greater, on average, and the interdecadal variability is significantly larger, with about 23% of the 20-yr sensitivities being above the CC rate. By thermodynamically constraining global precipitation changes, it is shown that such changes are linearly related to the difference in the radiative imbalance at the top of the atmosphere (TOA) and the surface (i.e., the atmospheric radiative energy imbalance). The strength of this relationship is controlled by the modified Bowen ratio (here, global sensible heat flux change divided by latent heat flux change). Hydrological sensitivity to aerosols is greater than the sensitivity to GHG because the former have a stronger effect on the shortwave transmissivity of the atmosphere, and thus produce a larger change in the atmospheric radiative energy imbalance. It is found that the observed global precipitation increase of 13 mm yr−1 decade−1 from 1987 to 2006 would require a trend of the atmospheric radiative imbalance (difference between the TOA and the surface) of 0.7 W m−2 decade−1. The recovery from the El Chichón and Mount Pinatubo volcanic aerosol injections in 1982 and 1991, the satellite-observed reductions in cloudiness during the phase of increasing ENSO events in the 1990s, and presumably the observed reduction of anthropogenic aerosol concentrations could have caused such a radiative imbalance trend over the past 20 years. Observational evidence, however, is currently inconclusive, and it will require more detailed investigations and longer satellite time series to answer this question.
Distribution and Modification of North Pacific Intermediate Water around the Subarctic Frontal Zone East of 150°E
Authors: Masujima Masachika , Yasuda Ichiro
Published: January 2009

Modification and distribution of North Pacific Intermediate Water (NPIW) in the area north of 30°N and east of 150°E are discussed based on an isopycnal particle tracking experiment with the velocity field estimated from a β-spiral inverse method based on climatological data, annual climatological data analysis, and isopycnal-tracking profiling float data. NPIW emanating from 149.5°E between 35.5° and 37.5°N retains its salinity minimum structure along the eastward flow of the northern subtropical gyre, and these pathways occupy the northern part of the NPIW distribution. On the other hand, NPIW from 149.5°E between 37.5° and 40.5°N loses its salinity minimum as it flows eastward to the “transition domain.” The extinction of the salinity minimum structure is caused by a salinity decrease in the upper layer (26.5–26.6 σθ) in the region at 40°–45°N, 155°–165°E where a winter mixed layer is developed to a depth of 300 m and a density of 26.7 σθ. This extinction was observed by a profiling float tracking a 26.7-σθ isopycnal density surface. Low-salinity subarctic water advected southward across the Subarctic Front by wind-induced Ekman drift from strong westerlies in winter is suggested as the source of the low-salinity mixed layer. After the extinction of the salinity minimum structure, a state without salinity minimum is maintained during transport eastward in the transition domain because the winter mixed layer in the area east of the deep mixed layer region reaches a density surface shallower than 26.5 σθ.
Coastal Wind-Driven Circulation in the Vicinity of a Bank. Part II: Modeling Flow over the Heceta Bank Complex on the Oregon Coast
Authors: Whitney Michael M. , Allen J. S.
Published: January 2009

This study investigates wind-driven circulation in the vicinity of the Heceta Bank complex along the Oregon shelf. Numerical experiments forced with steady winds (0.1 Pa) are conducted; upwelling and downwelling cases are compared. The asymmetric bank bathymetry is the only configurational difference from the symmetric bank runs analyzed in Part I (Whitney and Allen). Upwelling-favorable winds generate an upwelling front and southward baroclinic jet. Model results indicate the upwelling jet is centered on the 100-m isobath along the straight shelf. The jet follows this isobath offshore around the northern part of the bank but separates from sharply turning isobaths in the southern half and flows over deeper waters. The jet turns back toward the coast farther downstream. Inshore of the main jet, currents reverse and flow back onto the bank. These reversed currents turn southward again (at the bank center) and join a secondary southward coastal upwelling jet. This secondary coastal jet converges with the stronger main jet farther downstream. Upwelling is intense at the northern bank edge near the coast, where a dense water tongue is advected over the bank. Upwelling also is strong on the southern bank half where the flow turns and reverses. Other areas of the bank have reduced upwelling or even downwelling during upwelling-favorable winds. Downwelling-favorable winds drive a near-bottom density front and a northward jet. The slower downwelling jet flows along the 130-m isobath over the straight shelf. The jet departs from isobaths over the southern bank half and follows a straighter path over shallower waters. There are no reversed currents over the bank. The bank is an area of reduced downwelling. Some of the differences in the evolution of the current and density fields are linked to fundamental differences between the upwelling and downwelling regimes; these are anticipated by the symmetric bank results of Part I. Other differences arise because of the bank asymmetry and opposite flow directions over the bank.

The lowest-order depth-averaged across-stream momentum balance remains geostrophic over the bank. Advection, ageostrophic pressure gradients, wind stress, and bottom stress all are important in the depth-averaged alongstream momentum balance over the Heceta Bank complex. Both across-shelf and alongshelf density advection are important. Barotropic potential vorticity is not conserved over the bank, but the tendency for relative vorticity changes and depth changes to partially counter each other influences the different paths of the upwelling and downwelling jets. There are several regions of active upwelling and downwelling over the bank. In these areas, vertical velocities at the top of the bottom boundary layer are linked to topographic upwelling and downwelling and Ekman pumping. There is considerable spatial variability in the currents, densities, and dynamics over the Heceta Bank complex.
Model Estimates of M2 Internal Tide Generation over Mid-Atlantic Ridge Topography
Authors: Zilberman N. V. , Becker J. M. , Merrifield M. A. , Carter G. S.
Published: January 2009

The conversion of barotropic to baroclinic M2 tidal energy is examined for a section of the Mid-Atlantic Ridge in the Brazil Basin using a primitive equation model. Model runs are made with different horizontal smoothing (1.5, 6, and 15 km) applied to a 192 km × 183 km section of multibeam bathymetry to characterize the influence of topographic resolution on the model conversion rates. In all model simulations, barotropic to baroclinic conversion is highest over near- and supercritical slopes on the flanks of abyssal hills and discordant zones. From these generation sites, internal tides propagate upward and downward as tidal beams. The most energetic internal tide mode generated is mode 2, consistent with the dominant length scales of the topographic slope spectrum (50 km). The topographic smoothing significantly affects the model conversion amplitudes, with the domain-averaged conversion rate from the 1.5-km run (15.1 mW m−2) 4% and 19% higher than for the 6-km (14.5 mW m−2) and 15-km runs (12.2 mW m−2), respectively. Analytical models for internal tide generation by subcritical topography predict conversion rates with modal dependence and spatial patterns qualitatively similar to the Princeton Ocean Model (POM) and also show a decrease in conversion with smoother topography. The POM conversion rates are approximately 20% higher than the analytical estimates for all model grids, which is attributed to spatial variations in the barotropic flow and near-bottom stratification over generation sites, which are incorporated in the model but not in the analytical estimates.
Religious dimensions and work obligation: A country institutional profile model
Authors: Praveen Parboteeah K. , Hoegl Martin , Cullen John
Published: January 2009

The influence of religion as an important element of national contexts has been largely neglected in international management research, even though all major religions promote particular values that believers express at work. In this article, we apply the country institutional profile (Kostova, 1999) to specify cognitive, normative, and regulative elements of national religious contexts and relate them to individuals' work obligation norms. Using Hierarchical Linear Modeling (HLM) on data from 62,128 individuals in 45 countries, we find support for our hypotheses regarding positive relationships with one cognitive component (importance of God) and one normative component (behavioral aspect of religion). Our hypothesis for the negative relationship between the regulative component (state religion) and work obligation is also supported. We also propose that religious pluralism will weaken the relationships between the cognitive and normative aspects of religion and work obligations. Results provide varying support for the interactive effects of religious pluralism. We discuss theoretical and practical implications of our results and argue for the analytical importance of religion in understanding workplace behaviors.
`We're not banks': Exploring self-discipline, subjectivity and co-operative work
Authors: Mangan Anita
Published: January 2009

In studies of the workplace, the enterprising employee is theorized as autonomous, self-actualizing and calculating; self-discipline is linked to self-interest. This article explores the question of self-discipline by drawing on empirical material from a longitudinal study of the Irish credit union movement. As financial co-operatives, credit unions have a tradition of helping local communities under the aegis of mutuality and co-operative credit. The article theorizes two interrelated, yet antagonistic discourses within the credit union movement; an older community service discourse and an emerging enterprise discourse. In tracing the question of what it means to be a credit union volunteer, the article explores some of the tensions and contradictions between the two discourses, as experienced by volunteers who struggle with the question of how to balance the movement's traditional self-help ethos with the growing pressures to become more entrepreneurial.