bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arachidonic acid activation of intratumoral steroid synthesis during prostate cancer progression to castration resistance
Authors: Locke Jennifer A. , Guns Emma S. Tomlinson , Lehman Melanie L. , Ettinger Susan , Zoubeidi Amina , Lubik Amy , Margiotti Katia , Fazli Ladan , Adomat Hans , Wasan Kishor M. , Gleave Martin E. , Nelson Colleen C. 
Published: September 2009

AbstractBACKGROUNDDe novo androgen synthesis and subsequent androgen receptor (AR) activation has recently been shown to contribute to castration‐resistant prostate cancer (CRPC) progression. Herein we provide evidence that fatty acids (FA) can trigger androgen synthesis within steroid starved prostate cancer (CaP) tumor cells.METHODSTumoral FA and steroid levels were assessed by GC–MS and LC–MS, respectively. Profiles of genes and proteins involved in FA activation of steroidogenesis were assessed by fluorescence microscopy, immunohistochemistry, microarray expression profiling and Western blot analysis.RESULTSIn human CaP tissues the levels of proteins responsible for FA activation of steroid synthesis were observed to be altered during progression to CRPC. Further investigating this mechanism in LNCaP cells, we demonstrate that specific FA, arachidonic acid, is synthesized in an androgen‐dependent and AR‐mediated manner. Arachidonic acid is known to induce steroidogenic acute regulatory protein (StAR) in steroidogenic cells. When bound to hormone sensitive lipase (HSL), StAR shuttles free cholesterol into the mitochondria for downstream conversion into androgens. We show that arachidonic acid induces androgen production in steroid starved LNCaP cells coincidently in the same conditions that HSL and StAR are predominantly localized in the mitochondria. Furthermore, their activities are verified by a functional increase in mitochondrial uptake of cholesterol in this steroid starved environment.CONCLUSIONSWe propose that this characterized arachidonic acid induced steroidogenesis mechanism significantly contributes to the activation of AR in CRPC progression and therefore recommend that fatty acid pathways be targeted therapeutically in progressing CaP. Prostate 70: 239–251, 2010. © 2009 Wiley‐Liss, Inc.
Antiandrogen withdrawal syndrome and alternative antiandrogen therapy associated with the W741C mutant androgen receptor in a novel prostate cancer xenograft
Authors: Terada Naoki , Shimizu Yosuke , Yoshida Toru , Maeno Atsushi , Kamba Tomomi , Inoue Takahiro , Nakamura Eijiro , Kamoto Toshiyuki , Ogawa Osamu 
Published: September 2009

AbstractBACKGROUNDThe mechanisms underlying antiandrogen withdrawal syndrome (AWS) and alternative antiandrogen therapy (AAT) effectiveness were assumed to be mutations in the androgen receptor (AR), which resulted in an altered response to antiandrogens. The aim of the present study was to test this assumption using the novel prostate cancer xenograft model KUCaP‐1 harboring the W741C mutant AR (Yoshida et al., Cancer Res 2005; 65(21): 9611–9616).METHODSMice bearing xenograft tumors were castrated, and the long‐term sequential changes in tumor volume were observed. To determine whether AWS was observed in this model, bicalutamide (BCL) was orally administered to the castrated mice and then withdrawn. The effect of flutamide (FLT) on the W741C mutant AR was examined with transactivation assays in vitro and with the oral administration of FLT to non‐castrated mice harboring KUCaP‐1 in vivo. The AAT efficacy against KUCaP‐1 was evaluated by changing BCL with FLT.RESULTSKUCaP‐1 regressed significantly after castration and did not re‐grow. KUCaP‐1 treated with BCL continued to grow even after castration and started regressing 2 months after BCL withdrawal, replicating clinically recognized AWS. The antagonistic effect of FLT against the W741C mutant AR was revealed in vitro and in vivo. AAT with FLT suppressed tumor growth after BCL withdrawal.CONCLUSIONSKUCaP‐1 was an entirely androgen‐dependent xenograft and mimicked the clinical phenomena of AWS and AAT caused by the agonistic and antagonistic activity of BCL and FLT, respectively. KUCaP‐1 could be an in vivo model for screening novel antiandrogens for the treatment of BCL resistant prostate cancer harboring the W741C mutation in the AR. Prostate 70: 252–261, 2010. © 2009 Wiley‐Liss, Inc.
The pH sensitivity of histidine‐contain‐ ing lytic peptides
Authors: Tu Zhigang , Young Albert , Murphy Christopher , Liang Jun F. 
Published: September 2009

AbstractMany bioactive peptides are featured by their unique amino acid compositions such as argine/lysine‐rich peptides. However, histidine‐rich bioactive peptides are hardly found. In this study, histidine‐containing peptides were constructed by selectively replacing the corresponded lysine residues in a lytic peptide LL‐1 with histidines. Interestingly, all resulting peptides demonstrated pH‐dependent activities. The cell lysis activities of these peptides could be increased up to four times as the solution pHs dropped from pH = 7.4 to pH = 5.5. The pH sensitivity of a histidine‐containing peptide was determined by histidine substitution numbers. Peptide derivatives with more histidines were associated with increased pH sensitivity. Results showed that not the secondary structures but pH‐affected cell affinity changes were responsible for the pH‐dependent activities of histidine‐containing peptides. The histidine substitution approach demonstrated here may present a general strategy to construct bioactive peptides with desired pH sensitivity for various applications. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.
Supreme shear modulus predicted in the monocarbide system: the Rex W1–xC alloy
Authors: Zhang Xinyu , Chen Zhouwen , Fan Changzeng , Ma Mingzhen , Jing Qin , Liu Riping 
Published: September 2009

AbstractThe energetic, mechanical and electronic properties as a function of composition for Rex W1–x C alloys in the WC structure have been investigated. It has been demonstrated that the shear modulus of WC can be enhanced by alloying with a small amount of Re, to a maximum shear modulus of 311 GPa at x = 0.23. The designed alloy is energetically stable and could be expected to be a potential extremely hard transition‐metal monocarbide, which is attributed to the strong metal–metalloid interaction with modulated valence electron concentration with respect to WC. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Validation of commercial computerised systems using a single life cycle document (integrated validation document)
Authors: McDowall R. D. 
Published: September 2009

AbstractA risk‐based approach to the validation of low risk commercially available computerised systems is described. To determine if validation is required, the business process automated by the system is assessed to see if it is regulated. If validation is required, then the Good Automated Manufacturing Practice (GAMP) software category is mapped against the impact of the records generated by the system to determine if full or reduced validation is required. If reduced validation is indicated, the use of a single integrated validation document is proposed and illustrated with two case study examples. The use of a Validation Master Plan (VMP) to facilitate this validation process is also presented and described. Copyright © 2009 John Wiley & Sons, Ltd.
Dissociation constants of 2‐azidoethanamines in aqueous solution
Authors: Stevenson William H. , McQuaid Michael J. 
Published: September 2009

AbstractAqueous‐phase dissociation constants (Ka) for the conjugate acids of a series of 2‐azidoethanamine bases: R1N(R2)CH2CH2N3 (1, R1 = CH3, R2 = H; 2, R1 = CH3, R2 = CH3; 3, R1 = CH2CH3, R2 = CH2CH3; 4, R1/R2 = CH2CH2CH2CH2; 5, R1/R2 = CH2CH2OCH2CH2; 6, R1 = CH2CH3, R2 = CH2CH2N3) were measured and found to fall between those for analogous unfunctionalized and cyano‐functionalized ethanamines. To explore the possibility of a relationship existing between the constants and molecular geometry, a theoretically based study was conducted. In it, the Gibbs free energies of aqueous‐phase (equilibrium) conformers of the bases and their conjugate acids were determined via a density functional theory/polarizable continuum model method. The results indicate that an attractive interaction between the amine and azide groups that underlies the lowest‐energy gas‐phase conformer of 2 is negated in an aqueous environment by solvent–solute interactions. The magnitudes of the free energy changes of solvation and −TS (entropic) energies of the conformers of the 2‐azidoethanamines and their conjugate acids are observed to correlate with the magnitude of the separation between the conformers' amine and azide groups. However, those correlations are not by themselves sufficient to predict the relative free energies of a molecule's conformers in an aqueous environment. That insufficiency is due to the influence of the correlations being mitigated by three other parameters that arise within the thermodynamic framework employed to compute the observable. The nature of those parameters is discussed. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Density functional theory study of the oxidative dehydrogenation of propane on the (001) surface of V2O5
Authors: Nguyen Ngoc Ha , Tran Thanh Hue , Nguyen Minh Tho , Le Minh Cam 
Published: September 2009

AbstractThe density functional theory using a plane‐waves basis set and pseudopotential has been used to study the reaction pathways for ODH of propane on the V2O5(001) surface. The calculations indicated that propane adsoprtion step was initiated by the insertion of vanadyl oxygen O (1) into methylene CH bond forming an iso‐propanol structure. This step is the rate‐determining step with an activation energy of 23.3 kcal/mol. The subsequent step involved the abstraction of the second hydrogen by O (1) site leading the formation of propene. This process had an activation energy of 22.5 kcal/mol. The elimination of surface bound water molecule at the O (1) was a barrierless process. The energy required for this process was compensated from O2 dissociative adsorption. Finally, the electronic density of state has been applied to prove the reality of the calculated results. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Acute effects of microcystins on the transcription of 14 glutathione S‐transferase isoforms in Wistar rat
Authors: Li Guangyu , Xie Ping , Li Huiying , Hao Le , Xiong Qian , Qiu Tong , Liu Ying 
Published: September 2009

AbstractThe glutathione S‐transferases (GST) play important roles in the detoxification of microcystins (MCs). For better understanding of the responses of GST isforms to MCs exposure, informations about the effects of MCs on GSTs are necessary. In this experiment, we cloned the full length cDNA of 14 GST isoforms (GST alpha, kappa, mu, omega, pi, theta, zeta, and microsomal GST) from Wistar rat. The mRNA abundance of each rat GST isoform in the liver, kidney, and testis was analyzed by real time quantitative PCR. Multiple GST isoforms were constitutively expressed in all examined organs, but some isoforms were expressed at higher level in one organ than in others. The relative changes of the mRNA abundance in the liver, kidney, and testis of Wiatar rat i.v. injected with crude MCs extract at dose of 1LD50 were also analyzed. Generally, the expression of most GSTs in the liver and testis was suppressed while that in kidney was induced after being injected with MCs. It is suggested that the transcription of GST isoforms varied in different ways within an organ and between organs of Wistar rat exposed to MCs. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 187–194, 2011.
Adnexal torsion in a postmenopausal woman on tamoxifen
Authors: Matiluko Adebimpe F. , Crystal Alan M. 
Published: September 2009

AbstractThe authors describe the case of a postmenopausal woman who presented with sudden‐onset abdominal pain and vomiting, found to be caused by a torted haemorrhagic ovarian cyst. The case highlights the occurrence of ovarian cyst formation and endometrial stimulation in patients treated with tamoxifen. Copyright © 2009 Wiley Interface Ltd
Antenatal detection of cleft lip with or without cleft palate: incidence of associated chromosomal and structural anomalies
Authors: Gillham J. C. , Anand S. , Bullen P. J. 
Published: September 2009

AbstractObjectiveTo ascertain how many fetuses with prenatally diagnosed cleft lip with or without cleft palate have associated congenital structural and/or chromosomal abnormalities and whether there is an association with the anatomical type of cleft lip or palate.MethodsThis was a retrospective review of infants referred to the North‐West England Regional Cleft Lip and Palate (CLAP) team between January 2000 and January 2006. Referrals made to the Regional Fetal Management Unit (FMU) in the same time period were investigated to identify the corresponding antenatal ultrasound findings and data on termination of pregnancy and intrauterine fetal death.ResultsOver the 6‐year period investigated, 570 infants were referred to the FMU and/or CLAP team. Among these, there were 24 terminations of pregnancy, two intrauterine fetal deaths and one early neonatal death identified. Data on 69 of the 543 patients that survived were incomplete. Of 188 cases with unilateral and 34 cases with bilateral cleft lip ± palate there were no karyotypical abnormalities without other structural abnormalities. The incidence of associated structural abnormalities varied with the anatomical type of cleft: that of unilateral cleft lip ± palate was 9.8% (19/194), that of bilateral cleft lip and palate was 25% (11/44) and that of midline cleft lip and palate was 100% (11/11). None of 252 cases with isolated cleft palate was identified antenatally; of these, 5.6% (n = 14) had either karyotypical or associated structural abnormalities and 21.0% (n = 53) had a genetic syndrome as an underlying diagnosis.ConclusionsIt is essential to tailor the antenatal counseling of patients to the specific scan diagnosis, considering both the anatomical type of cleft and the presence or absence of associated abnormalities. It is inappropriate to offer invasive testing to all patients. The use of three‐dimensional ultrasound as an adjunct should be considered in these patients to improve the accuracy of prenatal diagnosis. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Contribution of the myocardial performance index and aortic isthmus blood flow index to predicting mortality in preterm growth‐restricted fetuses
Authors: Hernandez‐Andrade E. , Crispi F. , Benavides‐Serralde J. A. , Plasencia W. , Diesel H. F. , Eixarch E. , Acosta‐Rojas R. , Figueras F. , Nicolaides K. , Gratacós E. 
Published: September 2009

AbstractObjectivesTo evaluate the predictive value for perinatal death of the myocardial performance index (MPI) and aortic isthmus flow index (IFI), as isolated parameters and in a combined model including currently used Doppler indices, in preterm growth restricted (IUGR) fetuses.MethodsUmbilical artery, fetal middle cerebral artery (MCA) and ductus venosus (DV) pulsatility indices (PIs) were recorded, along with IFI and MPI, in a cohort of 97 preterm (delivered at between 24 and 34 weeks) IUGR fetuses. Logistic regression analysis was performed to identify those variables that were independently associated with perinatal mortality, and an algorithm to estimate probability of death was constructed including the best combination of parameters.ResultsWith the exception of MCA, all Doppler indices were significantly associated with perinatal death as isolated parameters, but only DV‐PI and MPI were found to be independent predictors on multivariate analysis. An algorithm combining DV atrial flow (positive or absent/reversed) and MPI (normal or above 95th percentile) had a better predictive accuracy than did any single parameter. The risk for death in IUGR fetuses below 28 weeks' gestation with present atrial flow in the DV and normal MPI was 18%, with either characteristic abnormal it was 70–73%, and with both abnormal it was 97%. The risk for death in IUGR fetuses above 28 weeks with present atrial flow in the DV and normal MPI was 0.1%, with either abnormal it was 6–7%, and with both abnormal it was 45%.ConclusionsMPI is an independent predictor of perinatal death in preterm IUGR fetuses with accuracy similar to that of DV flow. A combination of DV flow with MPI may better stratify the estimated probability of death. IFI does not add to the prediction of perinatal death when used in combination with DV flow. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
The network as the target
Authors: Baggs Julie E. , Hughes Michael E. , Hogenesch John B. 
Published: September 2009

AbstractThe conventional target centric model of drug discovery is pinned under the weight of prior success and the traditional problems of safety and efficacy for new molecules. An alternative to target centric drug development is to shift focus to the pathways that mediate both biology and pathophysiology. This method has the advantage of not requiring a priori knowledge of the small molecule target, but also comes with it several challenges including target determination. We suggest extending this notion more broadly across the drug discovery process using quantitative network structure‐activity relationships (QNSAR), and discuss the steps necessary to test the hypothesis that systems biology approaches can be used to improve the drug discovery process. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under:

Translational, Genomic, and Systems Medicine > Therapeutic Methods
Increasing Detection and Increasing Incidence in Thyroid Cancer
Authors: Hall Stephen F. , Walker Hugh , Siemens Robert , Schneeberg Amy 
Published: September 2009

AbstractBackgroundIt has been proposed that the increasing incidence of thyroid cancer is due to increasing detection.MethodsUsing administrative data, we compare by year from 1993 to 2006, the rates of diagnostic imaging tests of the neck (computed axial tomography—CT, magnetic resonance imaging—MRI, and non‐obstetrical ultrasound—US) to the incidence of thyroid cancer for the population of the Province of Ontario Canada.ResultsWomen and men have different rates of tests, and those rates reflect the rates of new diagnoses of thyroid cancer.ConclusionsThe rising incidence of thyroid disease in women is associated with increasing numbers of diagnostic imaging tests.
Is distribution of hydraulic constraints within tree crowns reflected in photosynthetic water‐use efficiency? An example of Betula pendula
Authors: Sellin Arne , Eensalu Eve , Niglas Aigar 
Published: September 2009

AbstractSpatial and daily variation in photosynthetic water‐use efficiency was examined in leaves of Betula pendula Roth with respect to distribution of hydraulic conductance within the crown, morphological properties of stomata, and water availability. Intrinsic water‐use efficiency (An/gs) was determined from gas‐exchange measurements performed both in situ in a natural forest stand and on detached shoots under laboratory conditions. In intact foliage, sun leaves demonstrated significantly higher (P < 0.001) An/gs than shade leaves, as photosynthesis in the lower canopy was chronically limited by low light availability. However, this difference reversed in the mid‐day period under sufficient irradiance (I > 800 µmol m−2 s−1): An/gs averaged 28.8 and 24.0 µmol mol−1 (P < 0.01) for shade and sun leaves, respectively. This last finding coincided with the data obtained in laboratory conditions: under equivalent leaf water supply and light, An/gs in shade foliage was greater (P < 0.001) than in sun foliage across a wide range of irradiance. Thus, shade foliage of B. pendula is characterized by inherently higher An/gs than sun foliage, associated with more conservative stomatal behavior, and lower soil‐to‐leaf (KT) and leaf hydraulic conductances. Under unlimited light conditions, a within‐crown trade‐off between An/gs and KT becomes apparent. Differences in stomatal conductance between the detached shoots from sunlit and shaded canopy layers were largely attributable to the variation in stomatal morphology; significant relationships were established with characteristics combining stomatal size and density (relative stomatal surface, stomatal pore area index). Stomatal morphology is very likely involved in long‐term adjustment of photosynthetic WUE.
Secondary succession of plant communities in a subtropical mountainous region of SW China
Authors: Tang Cindy Q. , Zhao Mei‐Hua , Li Xiao‐Shuang , Ohsawa Masahiko , Ou Xiao‐Kun 
Published: September 2009

AbstractSince 1985, originally forested mountainous areas of China have been allowed to return to their natural state after years of exploitation including agriculture, development, and logging. The reforms began earlier in less accessible locations, so that today the successional process is more advanced there. The vegetation in Luquan, Qiongzhusi, and Xishan near Kunming, central Yunnan, exhibits, in a limited area, a range of stages of plant succession that are widely encountered throughout the broader region, and thus affords a special opportunity for a comprehensive study. We analyzed the successional sequence of these various plant communities. They ranged from pioneer coniferous and/or pioneer deciduous broad‐leaved stands to pre‐mature semi‐humid evergreen broad‐leaved stands, through mixed coniferous and broad‐leaved or mixed deciduous and evergreen broad‐leaved stands. The succession proceeded from pioneer coniferous Pinus and Keteleeria, and deciduous Platycarya and Alnus, to late‐successional evergreen broad‐leaved Cyclobalanopsis and Castanopsis. Two regeneration types of woody species in either the early successional (15–50 years), the mid‐successional (40–80 years), or the late‐successional (80–180 years) stage were classified. Relatively high species diversity was found in the seral phase at the three study sites. The late‐successional stage was commonest where human disturbance was least evident. Poor soil chemical properties under pioneer Pinus were seen as a limitation to plant growth, while the abundance of Alnus at the early stage led to an improved level of organic matter and nitrogen.
Effects of Weight Loss on Lipid Transfer Proteins in Morbidly Obese Women
Authors: Laimer Markus W. , Engl Julia , Tschoner Alexander , Kaser Susanne , Ritsch Andreas , Tatarczyk Tobias , Rauchenzauner Markus , Weiss Helmut , Aigner Franz , Patsch Josef R. , Ebenbichler Christoph F. 
Published: September 2009

AbstractObesity is associated with lipid abnormalities leading to an increased morbidity and mortality from atherosclerotic disease. Lipid transfer proteins such as Cholesteryl Ester Transfer Protein (CETP) and Phospholipid Transfer Protein (PLTP), and lipases such as lipoprotein lipase (LPL) and hepatic lipase (HL) are involved in the pathogenesis of the obesity associated proatherogenic dyslipidemia. Nineteen severely obese female subjects undergoing laparosopic gastric banding participated in this prospective study. Subjects were examined with respect to body composition, lipid profile, CETP, PLTP, LPL and HL before and 1 year after surgical treatment. Mean weight loss was 22.2 kg, mainly due to losses in the fat depots. Triglycerides decreased and HDL2‐C increased significantly. In respect to transfer proteins mean CETP mass decreased from 1.82 to 1.71 μg mL−1 (P = 0.043) and mean PLTP activity was reduced from 7.15 to 6.12 μmol mL−1 h−1 (P = 0.002), in parallel. In addition, both mean LPL activity and mean HL activity tended to decrease from 297 to 248 nmol mL−1 h−1 for LPL (P = 0.139) and from 371 to 319 nmol mL−1 h−1 for HL (P = 0.170), respectively. We conclude that weight loss induced by bariatric surgery is associated with the amelioration of the obesity‐associated dyslipidemic state. This improvement may be attributable to decreased mass and action of the adipocyte tissue derived lipid transfer proteins CETP and PLTP.