bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering zinc finger protein transcription factors to downregulate the epithelial glycoprotein‐2 promoter as a novel anti‐cancer treatment
Authors: Gommans Willemijn M. , McLaughlin Pamela M.J. , Lindhout Beatrice I. , Segal David J. , Wiegman D.J. , Haisma Hidde J. , van der Zaal Bert J. , Rots Marianne G. 
Published: December 2006

AbstractZinc finger protein transcription factors (ZFP‐TFs) are emerging as powerful novel tools for the treatment of many different diseases. ZFPs are DNA‐binding motifs and consist of modular zinc finger domains. Each domain can be engineered to recognize a specific DNA triplet, and stitching six domains together results in the recognition of a gene‐specific sequence. Inhibition of gene expression can be achieved by fusing a repressor domain to these DNA‐binding motifs. In this study, we engineered ZFP‐TFs to downregulate the activity of the epithelial glycoprotein‐2 (EGP‐2) promoter. The protein EGP‐2 is overexpressed in a wide variety of cancer types and EGP‐2 downregulation has been shown to result in a decreased oncogenic potential of tumor cells. Therefore, downregulation of EGP‐2 expression by ZFP‐TFs provides a novel anti‐cancer therapeutic. Using a straightforward strategy, we engineered a 3‐ZFP that could bind a 9 bp sequence within the EGP‐2 promoter. After the addition of a repressor domain, this 3‐ZFP‐TF could efficiently downregulate EGP‐2 promoter activity by 60%. To demonstrate the flexibility of this technology, we coupled an activation domain to the engineered ZFP, resulting in a nearly 200% increase in EGP‐2 promoter activity. To inhibit the endogenous EGP‐2 promoter, we engineered 6‐ZFP‐TFs. Although none of the constructed ZFP‐TFs could convincingly modulate the endogenous promoter, efficient and specific inhibition of the exogenous promoter was observed. Overall, ZFP‐TFs are versatile bi‐directional modulators of gene expression and downregulation of EGP‐2 promoter activity using ZFP‐TFs can ultimately result in a novel anti‐cancer treatment. © 2006 Wiley‐Liss, Inc.
Four novel single nucleotide polymorphisms within the promoter region of p53 gene and their associations with uterine leiomyoma
Authors: Hsieh Yao‐Yuan , Wang Jui‐Ping , Lin Chich‐Sheng 
Published: December 2006

AbstractDysregulated p53 expression has been implicated as a major contributor to numerous tumorigenesis. Single nucleotide polymorphisms (SNPs) within the functional consequence of the novel p53 promoter region remains obscure. Herein, we aimed to establish the extent of genetic variability within the promoter region of p53 gene as well as their association with leiomyoma susceptibility. Women were divided into two groups, leiomyoma (n = 160) and nonleiomyoma controls (n = 200). Total DNA was isolated from the peripheral blood of subjects. The DNA fragment containing p53 promoter regions (+64 ∼ −404 bp) were obtained by amplification of polymerase chain reaction. The variations of DNA fragments were detected by DNA sequencing or restriction fragment length polymorphism (RFLP). Sequence alignment was used to identify sequence variations in p53 promoter regions. Genotypes were analyzed by method of RFLP. Genotypes/allelic frequencies in the leiomyoma and control groups were compared. A total of 15 sequence variations within p53 promoter region were identified, including −408 T/C, −382 A/G, −359 A/G, −325 T/C, −250 A/G, −216 T/C, −205 G/A, −198 G/A, −177 T/C, −103 A/G, −81 G/A, −71 G/A, −51 T/A, −33 A/G, and −17 T/C. Among these variations, four SNPs (−250 A/G, −216 T/C, −103 A/G, and −33 A/G) were established. Allele frequencies of −250*G/−216*C/−103*G/−33*G in the leiomyoma group and control group 6.9/5.0/5.9/3.8% and 3.8/1.8/2.3/4.0%, respectively. Two of them (−216*C and −103*G) are associated with higher leiomyoma susceptibility. We concluded that some sequence variations were observed within the promoter region of p53 gene. The SNPs of −216*C and −103*G among the identical sequence variations are associated with leiomyoma development. Mol. Reprod. Dev. 74: 815–820, 2007. © 2006 Wiley‐Liss, Inc.
A vasa‐like gene in the giant freshwater prawn, Macrobrachium rosenbergii
Authors: Nakkrasae La‐Iad , Damrongphol Praneet 
Published: December 2006

AbstractA molecular marker for germ cells of the giant freshwater prawn, Macrobrachium rosenbergii, was studied. A vasa‐like gene, Mrvlg, from the ovary was isolated and characterized by a reverse transcriptase‐polymerase chain reaction (RT‐PCR) method. A full‐length sequence was obtained by the rapid amplification of cDNA end (RACE) method. Analysis of the nucleotide sequence revealed that Mrvlg comprises 2,686 bps with an open reading frame of 2,130 bps encoding 710 amino acids. The deduced amino acid sequence contains four arginine–glycine–glycine motifs and eight conserved motifs belonging to the DEAD‐box protein family. The MrVLG sequence shows high similarity to Vasa homologue of zebrafish (73%). In the adult tissues, the Mrvlg transcripts were specifically detected in the germ cells. In situ hybridization analysis showed that Mrvlg RNA was detected in the cytoplasm of oogonia, previtellogenic, and vitellogenic oocytes and was also detected in the nucleoplasm of mature oocytes. In the testis, the Mrvlg transcript was detected in the cytoplasm of spermatogonia and primary spermatocytes but was detected in the nuclei of secondary spermatocytes and sperm. Sequence similarity and specific localization in the germ cells suggest that Mrvlg is the prawn vasa homologue of the Drosophila gene and can be used as a molecular marker for prawn germ cells. Mol. Reprod. Dev. 74: 835–842, 2007. © 2006 Wiley‐Liss, Inc.
Reference values for sleep‐related respiratory variables in asymptomatic European children and adolescents
Authors: Verhulst S.L. , Schrauwen N. , Haentjens D. , Van Gaal L. , De Backer W.A. , Desager K.N. 
Published: December 2006

AbstractAim:Only a limited number of studies, designed to establish normal values for sleep‐related respiratory variables in children, have been reported, and all are non‐European. The aim of this study was to expand the knowledge on normative data in children.Methods:Subjects ranging from 6 to 16 years were recruited and underwent full polysomnography. Only subjects without sleep disordered breathing or other sleep problems as assessed by clinical history were included.Results:Sixty subjects were studied (〈age〉 = 11.7 ± 2.6 years; 28 boys; 〈relBMI〉 = 118.8 ± 30.6%). 〈Central apnea index〉 was 0.85 ± 1.06 (range: 0.0–5.5). 〈Obstructive apnea index〉 was 0.06 ± 0.16 (range: 0.0–0.9); 11 patients had a total of 31 obstructive apneas. Only five obstructive hypopneas were detected with 〈obstructive apnea hypopnea index〉 = 0.08 ± 0.17 (range: 0.0–0.9). 〈Respiratory disturbance index〉 was 1.98 ± 1.39 (range: 0.1–7.2). 〈SaO2〉 was 97.0 ± 0.6% (range: 96.0–98.0); 〈SaO2nadir〉 was 91.8 ± 2.7% (range: 82.0–96.0); 〈% of total sleep time with SaO2 ≥ 95%〉 was 98.7 ± 2.1% (range: 90.8–100.0); 〈oxygen desaturation index〉 was 0.8 ± 0.9 (range: 0.0–4.9) and 〈arousal index〉 was 6.1 ± 1.8 (range: 2.7–10.9). Snoring was detected in 15 patients (4 overweight subjects), with no difference in patient characteristics and sleep‐related respiratory variables between snorers and non‐snorers. Subjects in the overweight group (n = 22) had a lower SaO2nadir (90.8 ± 2.7 vs. 92.4 ± 2.6; P = 0.01) and a higher ODI (1.3 ± 1.3 vs. 0.4 ± 0.4; P = 0.0002) than their normal weight peers.Conclusion:Our data are in agreement with other non‐European studies, designed to establish normal values in children. Pediatr Pulmonol. 2007; 42:159–167. © 2006 Wiley‐Liss, Inc.
The mutations Lys 114 → Gln and Asp 126 → Asn disrupt an intersubunit salt bridge and convert Listeria innocua Dps into its natural mutant Listeria monocytogenes Dps. Effects on protein stability at Low pH
Authors: Bellapadrona Giuliano , Chiaraluce Roberta , Consalvi Valerio , Ilari Andrea , Stefanini Simonetta , Chiancone Emilia 
Published: December 2006

AbstractThe stability of the dodecameric Listeria monocytogenes Dps has been compared with that of the Listeria innocua protein. The two proteins differ only in two amino acid residues that form an intersubunit salt‐bridge in L. innocua Dps. This salt‐bridge is replaced by a hydrogen bonding network in L. monocytogenes Dps as revealed by the X‐ray crystal structure. The resistance to low pH and high temperature was assayed for both Dps proteins under equilibrium conditions and kinetically. Despite the identical equilibrium behavior, significant differences in the kinetic stability and activation energy of the unfolding process are apparent at pH 1.5. The higher stability of L. monocytogenes Dps has been accounted for in terms of the persistence of the hydrogen bonding network at this low pH value. In contrast, the salt‐bridge between Lys 114 and Asp 126 characteristic of L. innocua Dps is most likely abolished due to protonation of Asp 126. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Locating missing water molecules in protein cavities by the three‐dimensional reference interaction site model theory of molecular solvation
Authors: Imai Takashi , Hiraoka Ryusuke , Kovalenko Andriy , Hirata Fumio 
Published: December 2006

AbstractWater molecules confined in protein cavities are of great importance in understanding the protein structure and functions. However, it is a nontrivial task to locate such water molecules in protein by the ordinary molecular simulation and modeling techniques as well as experimental methods. The present study proves that the three‐dimensional reference interaction site model (3D‐RISM) theory, a recently developed statistical–mechanical theory of molecular solvation, has an outstanding advantage in locating such water molecules. In this paper, we demonstrate that the 3D‐RISM theory is able to reproduce the structure and the number of water molecules in cavities of hen egg‐white lysozyme observed commonly in the X‐ray structures of different resolutions and conditions. Furthermore, we show that the theory successfully identified a water molecule in a cavity, the existence of which has been ambiguous even from the X‐ray results. In contrast, we confirmed that molecular dynamics simulation is helpless at present to find such water molecules because the results substantially depend on the initial coordinates of water molecules. Possible applications of the theory to problems in the fields of biochemistry and biophysics are also discussed. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Modifications in the bradykinin main chain are not necessary for antagonistic activity in rat blood pressure assay
Authors: Prahl Adam 
Published: December 2006

AbstractPrevious studies demonstrated that the presence of a bulky acyl substituent at the N‐terminus of B2 antagonists significantly influenced the interaction of the peptide with B2 receptors, thus increasing potency in the blood pressure test. Reported results also suggested that even minor changes in the structure of analogues might be of importance in designing more potent B2 antagonists. On the other hand, it was learned that the effects of acylation might vary substantially with the chemical character of the acyl group. It seemed that either the positive or the negative charge on the N‐terminal acyl group influenced the activity of the analogues because a suppressed antagonistic potency due to these modifications was observed.Bearing all these findings in mind, it was decided to check how N‐terminal acylation would affect the pharmacological activity of bradykinin. Of the many acylating agents tested previously on B2 antagonists, it was decided to use acridin‐9‐ylacetic acid (Ana) and anthracen‐9‐ylacetic acid (Ata). The potencies of the analogues were assessed by their ability to inhibit vasodepressor response of exogenous BK in conscious rats and by their ability to inhibit the contractions of isolated rat uterus evoked by BK. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.
Antibacterial activity of flavonoids and phenylpropanoids from Marrubium globosum ssp. libanoticum
Authors: Rigano Daniela , Formisano Carmen , Basile Adriana , Lavitola Alfredo , Senatore Felice , Rosselli Sergio , Bruno Maurizio 
Published: December 2006

AbstractMarrubium globosum Montbr. et Auch. ex Benth. ssp. libanoticum Boiss. (Lamiaceae) is a medicinal plant used for the treatment of inflammatory diseases, asthma, coughs and other pulmonary and urinary problems. The goal of our study was to assess the biological activity of M. globosum testing the methanol extract of aerial parts for its antibacterial activity against bacteria known to cause respiratory, gastrointestinal, skin and urinary disorders; the extract showed antibacterial effects against all the strains of bacteria used. A purification of this active extract showed the presence, as main constituents, of verbascoside, isorhamnetin 3‐O‐β‐d‐rutinoside, quercetin 3‐O‐β‐d‐rutinoside, naringenin 7‐O‐β‐d‐glucoside, kaempferol 3‐O‐β‐d‐rutinoside, isorhamnetin 3‐O‐β‐d‐glucoside, quercetin 3‐O‐β‐d‐glucoside, apigenin 7‐O‐(3″‐p‐coumaryl)‐glucoside, p‐methoxy‐cinnamic acid, kaempferol 3‐O‐β‐d‐glucoside and apigenin 7‐O‐β‐d‐glucoside. The pure compounds were tested for their antibacterial activity; quercetin 3‐O‐β‐d‐rutinoside, verbascoside and naringenin 7‐O‐β‐d‐glucoside showed the greatest activity. Copyright © 2006 John Wiley & Sons, Ltd.
Novel antitumor activities of Kushen flavonoids In Vitro and In Vivo
Authors: Sun Mingyu , Han Jun , Duan Jifeng , Cui Yumin , Wang Tao , Zhang Weihan , Liu Wei , Hong Jianrong , Yao Minghui , Xiong Sidong , Yan Xiaoqiang 
Published: December 2006

AbstractKushen (KS), the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS‐As) and Kushen flavonoids (KS‐Fs) are the well characterized components in KS. KS‐As have been considered biologically active and developed in China as anticancer drugs. In an effort to screen novel antitumor agents from botanicals, more potent antitumor activities were identified in KS‐Fs than in KS‐As. KS‐Fs were able to inhibit the growth of a panel of tumor cell lines and enhanced the antitumor activities of Taxol in vitro. The antitumor activities of KS‐Fs and Kur, a single KS‐Fs compound, were demonstrated in murine and xenograft human tumor models. Further, it was shown that KS‐Fs and Kur were able to enhance the effect of Taxol to inhibit the growth of H460 and Eca‐109 xenograft tumors. In addition, peripheral blood cell counts were not significantly affected in normal mice treated with KS‐Fs at 200 mg/kg/day for 2 weeks. These results suggest that KS‐Fs may be developed as novel antitumor agents and that the currently marketed KS‐As drugs in China may have missed the major antitumor activities in Kushen. Copyright © 2006 John Wiley & Sons, Ltd.
Modelling of short‐term frequency scaling for rain attenuation using ITALSAT data
Authors: Bertorelli S. , Paraboni A. 
Published: December 2006

AbstractIn this article we describe a statistical model for the assessment of the short‐term frequency scaling ratio between rain attenuations at cm and mm wavelengths, taking into consideration the fluctuations arising from the type of rain (mainly the raindrop size distribution). The model has been derived from measured data, using the large attenuation database collected in Spino d'Adda, Italy, during the ITALSAT 8‐years experiment at 18.7, 39.6 and 49.5 GHz, but can be applied to any pair of frequencies. By applying the model it is possible to generate, by means of a generator of random Gaussian numbers, samples of the up‐link attenuation, for a given down link attenuation, to be employed in the simulation of up‐link power control (ULPC) slant path channels. Copyright © 2006 John Wiley & Sons, Ltd.
Implementing the electron backscattering factor in quantitative sputter depth profiling using AES
Authors: Hofmann Siegfried , Wang Jiang Yong 
Published: December 2006

AbstractSputter depth profiling using Auger electron spectroscopy (AES) is influenced by the electron backscattering contribution to the AES intensity. When approaching an interface between two components having a different backscattering factor, the shape of the profile is characteristically distorted. This distortion is taken into account in a modified version of the mixing‐roughness‐information depth (MRI) model. The modification is based on the simplified assumption that the influence of the backscattering effect of the component below the interface increases exponentially with decreasing distance of the actual surface to the interface. Application of the modified MRI model is shown to yield excellent results of profile calculation for AES depth profiling of Si/W, C/Ta, C/Ti, and Au/TiO2 interfaces, with backscattering factor ratios close to those predicted by the Ichimura–Shimizu relation. A simple correction of the backscattering influence is proposed and discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Monte Carlo simulation of spatial distribution of X rays in multifilm targets. III: optimum design as applied to W/Al‐film targets
Authors: Yamaguchi Yoshikazu , Shimizu Ryuichi 
Published: December 2006

AbstractThe brightness of the X‐ray source in a W/Al‐film target used for X‐ray projection microscopy was studied by an approach using the Monte Carlo simulation. Since continuous X rays generated in a thin film have a specific angular distribution of emission, the brightness of the continuous X‐ray source cannot simply be estimated on the assumption that the angular distribution is homogeneous.The newly developed approach using the Monte Carlo simulation enables the evaluation of the effective source size, angular distribution, and brightness of a continuous X‐ray source with sufficient accuracy that it leads to the optimum design of a high‐brightness X‐ray source for uses such as X‐ray projection microscopy.The Monte Carlo calculations were performed for W(Δz)/Al (200 µm)‐film targets with different thicknesses of W film, Δz, under bombardment of 60 kV electrons. The results have suggested an optimum design consisting of a W (2 µm)/Al (200 µm)‐film target as most promising for providing an X‐ray source of higher brightness than the W (5 µm)/Al (200 µm)‐film target, which has already been in practice for X‐ray projection microscopy. Copyright © 2006 John Wiley & Sons, Ltd.
A comparison of regression trees, logistic regression, generalized additive models, and multivariate adaptive regression splines for predicting AMI mortality
Authors: Austin Peter C. 
Published: December 2006

AbstractClinicians and health service researchers are frequently interested in predicting patient‐specific probabilities of adverse events (e.g. death, disease recurrence, post‐operative complications, hospital readmission). There is an increasing interest in the use of classification and regression trees (CART) for predicting outcomes in clinical studies. We compared the predictive accuracy of logistic regression with that of regression trees for predicting mortality after hospitalization with an acute myocardial infarction (AMI). We also examined the predictive ability of two other types of data‐driven models: generalized additive models (GAMs) and multivariate adaptive regression splines (MARS). We used data on 9484 patients admitted to hospital with an AMI in Ontario. We used repeated split‐sample validation: the data were randomly divided into derivation and validation samples. Predictive models were estimated using the derivation sample and the predictive accuracy of the resultant model was assessed using the area under the receiver operating characteristic (ROC) curve in the validation sample. This process was repeated 1000 times—the initial data set was randomly divided into derivation and validation samples 1000 times, and the predictive accuracy of each method was assessed each time. The mean ROC curve area for the regression tree models in the 1000 derivation samples was 0.762, while the mean ROC curve area of a simple logistic regression model was 0.845. The mean ROC curve areas for the other methods ranged from a low of 0.831 to a high of 0.851. Our study shows that regression trees do not perform as well as logistic regression for predicting mortality following AMI. However, the logistic regression model had performance comparable to that of more flexible, data‐driven models such as GAMs and MARS. Copyright © 2006 John Wiley & Sons, Ltd.
Student affect and conceptual understanding in learning chemistry
Authors: Nieswandt Martina 
Published: December 2006

AbstractThis study explores the relationship between affective and cognitive variables in grade 9 chemistry students (n = 73). In particular, it explores how students' situational interest, their attitudes toward chemistry, and their chemistry‐specific self‐concept influence their understanding of chemistry concepts over the course of a school year. All affective variables were assessed at two time points: at the middle of the first semester of grade 9, and at the end of the second semester of grade 9, and then related to students' postinstructional understanding of chemical concepts. Results reveal that none of the affective variables measured at the earliest time point have a significant direct effect on postinstructional conceptual understanding. Looking at the different affective variables as intermediary constructs, however, reveals a pattern in which self‐concept and situational interest measured at the middle of grade 9 contribute to self‐concept measured at the end of grade 9, which in turn, has a positive, significant effect on students' postinstructional conceptual understanding. These results reveal the importance of a strong and positive self‐concept, the feeling of doing well in the chemistry class, for developing a meaningful understanding of scientific concepts. © 2006 Wiley Periodicals, Inc. J Res Sci Teach 44: 908–937, 2007
Social compatibility in a newly formed all‐male group of white crowned mangabeys (Cercocebus atys lunulatus)
Authors: Fàbregas María , Guillén‐Salazar Federico 
Published: December 2006

AbstractSurplus males in primate captive populations are a common problem for zoos. Some captive breeding programs promote all‐male groups as an adequate option to house surplus males, but there have been few attempts to assess the feasibility of this management technique across primate species. The present study provides preliminary data regarding social compatibility within a newly formed all‐male group of four white crowned mangabeys (Cercocebus atys lunulatus). The study was conducted at the Valencia Zoo (Spain), where data on social behavior were collected over 6 months using continuous focal animal sampling for a total of 87 hr of observation. Results show that low intensity aggressive behaviors (facial threats) were expressed at high rates, whereas physical aggression (fights) rarely occurred. Aggression was more frequent among individuals belonging to the same age–gender class. Regarding affiliative behaviors, every individual actively sought proximity to all other group members through positive approaches, and although not all males carried out social grooming, every male was groomed by at least one group member. Our results suggest that the group was compatible socially because social relationships among the individuals were not neutral, and physical aggression occurred at low rates. The present study provides preliminary data supporting the feasibility of all‐male groups as a management option for surplus males in captive populations of white crowned mangabeys. Nevertheless, further studies are needed to be able to generalize both within and across species. Zoo Biol 0:1–7, 2007. © 2006 Wiley‐Liss, Inc.