bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invariant Ser211 is involved in the catalysis of PD‐L4, type I RIP from Phytolacca dioica leaves
Authors: Chambery Angela , Pisante Marianna , Di Maro Antimo , Di Zazzo Erika , Ruvo Menotti , Costantini Susan , Colonna Giovanni , Parente Augusto 
Published: January 2007

AbstractMultiple sequence alignment analysis of ribosome inactivating proteins (RIPs) has revealed the occurrence of an invariant seryl residue in proximity of the catalytic tryptophan. The involvement of this seryl residue in the catalytic mechanism of RIPs was investigated by site‐directed mutagenesis in PD‐L4, type 1 RIP isolated from Phytolacca dioica leaves. We show that the replacement of Ser211 with Ala apparently does not influence the N‐β‐glycosidase activity on ribosomes (determined as IC50 in a cell‐free system), but it reduces the adenine polynucleotide glycosylase activity (APG), assayed spectrophotometrically on other substrates such as DNA, rRNA, and poly(A). The ability of PD‐L4 to deadenylate polynucleotides appears more sensitive to the Ser211Ala replacement when poly(A) is used as substrate, as only 33% activity is retained by the mutant, while with more complex and heterogeneous substrates such as DNA and rRNA, its APG activity is 73% and 66%, respectively. While the mutated protein shows a conserved secondary structure by CD, it also exhibits a remarkably enhanced tryptophan fluorescence. This indicates that, although the overall protein tridimensional structure is maintained, removal of the hydroxyl group locally affects the environment of a Trp residue. Modelling and docking analyses confirm the interaction between Ser211 and Trp207, which is located within the active site, thus affecting RIP adenine polynucleotide glycosylase activity. Data accumulated so far confirm the potential involvement of Ser211 in the catalytic mechanism of type 1 RIP PD‐L4 and a possible role in stabilizing the conformation of Trp207 side chain, which participates actively in the protein enzymatic activity. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Atomic resolution crystal structures of HIV‐1 protease and mutants V82A and I84V with saquinavir
Authors: Tie Yunfeng , Kovalevsky Andrey Y. , Boross Peter , Wang Yuan‐Fang , Ghosh Arun K. , Tozser Jozsef , Harrison Robert W. , Weber Irene T. 
Published: January 2007

AbstractSaquinavir (SQV), the first antiviral HIV‐1 protease (PR) inhibitor approved for AIDS therapy, has been studied in complexes with PR and the variants PRI84V and PRV82A containing the single mutations I84V and V82A that provide resistance to all the clinical inhibitors. Atomic resolution crystal structures (0.97–1.25 Å) of the SQV complexes were analyzed in comparison to the protease complexes with darunavir, a new drug that targets resistant HIV, in order to understand the molecular basis of drug resistance. PRI84V and PRV82A complexes were obtained in both the space groups P21212 and P212121, which provided experimental limits for the conformational flexibility. The SQV interactions with PR were very similar in the mutant complexes, consistent with the similar inhibition constants. The mutation from bigger to smaller amino acids allows more space to accommodate the large group at P1′ of SQV, unlike the reduced interactions observed in darunavir complexes. The residues 79–82 have adjusted to accommodate the large hydrophobic groups of SQV, suggesting that these residues are intrinsically flexible and their conformation depends more on the nature of the inhibitor than on the mutations in this region. This analysis will assist with development of more effective antiviral inhibitors. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Convergence of molecular dynamics simulations of membrane proteins
Authors: Grossfield Alan , Feller Scott E. , Pitman Michael C. 
Published: January 2007

AbstractThe central question in evaluating almost any result from a molecular dynamics simulation is whether the calculation has converged. Unfortunately, assessing the ergodicity of a single trajectory is very difficult to do. In this work, we assess the sampling of molecular dynamics simulations of the membrane protein rhodopsin by comparing the results from 26 independent trajectories, each run for 100 ns. By examining principal components and cluster populations, we show that rhodopsin's fluctuations are not well described by 100 ns of dynamics, and that the sampling is not fully converged even for individual loops. The results serve as a reminder of the caution required when interpreting molecular dynamics simulations of macromolecules. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Analysis of progression‐free survival in oncology trials: some common statistical issues
Authors: Carroll Kevin J. 
Published: January 2007

AbstractWith the advent of ever more effective second and third line cancer treatments and the growing use of ‘crossover’ trial designs in oncology, in which patients switch to the alternate randomized treatment upon disease progression, progression‐free survival (PFS) is an increasingly important endpoint in oncologic drug development. However, several concerns exist regarding the use of PFS as a basis to compare treatments. Unlike survival, the exact time of progression is unknown, so progression times might be over‐estimated and, consequently, bias may be introduced when comparing treatments. Further, it is not uncommon for randomized therapy to be stopped prior to progression being documented due to toxicity or the initiation of additional anti‐cancer therapy; in such cases patients are frequently not followed further for progression and, consequently, are right‐censored in the analysis. This article reviews these issues and concludes that concerns relating to the exact timing of progression are generally overstated, with analysis techniques and simple alternative endpoints available to either remove bias entirely or at least provide reassurance via supportive analyses that bias is not present. Further, it is concluded that the regularly recommended manoeuvre to censor PFS time at dropout due to toxicity or upon the initiation of additional anti‐cancer therapy is likely to favour the more toxic, less efficacious treatment and so should be avoided whenever possible. Copyright © 2007 John Wiley & Sons, Ltd.
Ultra‐performance liquid chromatography/time‐of‐flight mass spectrometry based metabolomics of raw and steamed Panax notoginseng
Authors: Chan Eric C. Y. , Yap Swee‐Lee , Lau Aik‐Jiang , Leow Pay‐Chin , Toh Ding‐Fung , Koh Hwee‐Ling 
Published: January 2007

AbstractAt present, metabolite profiling is of growing importance in herbal medicine fields such as breeding, formulation, quality control and clinical trials. This preliminary study indicated that ultra‐performance liquid chromatography/time‐of‐flight mass spectrometry (UPLC/TOFMS)‐based metabolomics allows direct detection of down‐stream derivatives of metabolites, arising from the herbal formulation process. This analytical approach allows the discrimination and tentative authentication of unique biomarkers related to different herbal extracts using unsupervised multivariate principal component analysis (PCA). The tentative identification of biomarkers is complemented significantly by the accurate mass measurement of TOFMS and the high resolution and high retention time reproducibility rendered by UPLC. The application of this approach in herbal extract discrimination and ginsenoside biomarker discovery of raw and steamed Panax notoginseng (Burk.) F.H. Chen is demonstrated and discussed. Copyright © 2007 John Wiley & Sons, Ltd.
Implementing inquiry kit curriculum: Obstacles, adaptations, and practical knowledge development in two middle school science teachers
Authors: Jones Mark T. , Eick Charles J. 
Published: January 2007

AbstractTwo elementary certified middle school science teachers are studied for changes in practical knowledge supporting the implementation of kit‐based inquiry as part of a schoolwide reform effort. Emphasis is placed on studying how these two pilot teachers enact guided inquiry within their unique pedagogical and curricular interests, and what adaptations they make in their use of Science and Technology for Children™ and Science and Technology Concepts for Middle School™ curriculum. Case study results support the notion that reform is complex and personal, and teachers as professionals need collective and individual support in the classroom as they make incremental changes in practice toward becoming inquiry‐oriented teachers. © 2007 Wiley Periodicals, Inc. Sci Ed 91:492–513, 2007
A comparison of the statistical power of different methods for the analysis of cluster randomization trials with binary outcomes
Authors: Austin Peter C. 
Published: January 2007

AbstractCluster randomization trials are randomized controlled trials (RCTs) in which intact clusters of subjects are randomized to either the intervention or to the control. Cluster randomization trials require different statistical methods of analysis than do conventional randomized controlled trials due to the potential presence of within‐cluster homogeneity in responses. A variety of statistical methods have been proposed in the literature for the analysis of cluster randomization trials with binary outcomes. However, little is known about the relative statistical power of these methods to detect a statistically significant intervention effect. We conducted a series of Monte Carlo simulations to examine the statistical power of three methods that compare cluster‐specific response rates between arms of the trial: the t‐test, the Wilcoxon rank sum test, and the permutation test; and three methods that compare subject‐level response rates: an adjusted chi‐square test, a logistic‐normal random effects model, and a generalized estimating equations (GEE) method. In our simulations we allowed the number of clusters, the number of subjects per cluster, the intraclass correlation coefficient and the magnitude of the intervention effect to vary. We demonstrated that the GEE approach tended to have the highest power for detecting a statistically significant intervention effect. However, in most of the 240 scenarios examined, the differences between the competing statistical methods were negligible. The largest mean difference in power between any two different statistical methods across the 240 scenarios was 0.02. The largest observed difference in power between two different statistical methods across the 240 scenarios and 15 pair‐wise comparisons of methods was 0.14. Copyright © 2007 John Wiley & Sons, Ltd.
Tetrahydrobiopterin availability, nitric oxide metabolism and glutathione status in the hph‐1 mouse; implications for the pathogenesis and treatment of tetrahydrobiopterin deficiency states
Authors: Lam A. A. J. , Hyland K. , Heales S. J. R. 
Published: January 2007

AbstractTetrahydrobiopterin (BH4) is an essential cofactor for all isoforms of nitric oxide synthase. While it is well established that BH4 deficiency states are associated with impairment of dopamine, serotonin and phenylalanine metabolism, less is known with regard to the effects of deficiency of the cofactor upon nitric oxide (NO) metabolism. In this study, we have evaluated the effects of partial BH4 deficiency upon (a) tissue availability of the antioxidant glutathione, (b) basal NO production and (c) NO generation following exposure to lipopolysaccharide (LPS), which is known to increase expression of the inducible form of nitric oxide synthase. Using the hph‐1 mouse, which displays a partial BH4 deficiency owing to impaired activity of GTP cyclohydrolase, we report decreased levels of glutathione in brain and kidney and evidence for decreased basal generation of nitric oxide in the periphery (as judged by the plasma nitrate plus nitrite concentration). Following LPS administration, peripheral NO generation increases. However, the concentration of plasma nitrate plus nitrite achieved was significantly decreased in the hph‐1 mouse. Furthermore, LPS administration caused loss of glutathione in both wild‐type and hph‐1 liver and kidney. It is concluded that cofactor replacement, sufficient to fully correct a cellular BH4 deficiency, may be of benefit to patients with inborn errors of BH4 metabolism.
Seasonal adaptations of the fall webworm Hyphantria cunea (Drury) (Lepidoptera: Arctiidae) following its invasion of Japan
Authors: Gomi Tadashi 
Published: January 2007

AbstractThe fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), invaded Japan from North America about 60 years ago. Immediately after its invasion – and for the first three decades – its life cycle was bivoltine, two generations per year throughout its entire distribution in Japan. Thereafter, its life cycle shifted to trivoltine in the southwestern areas of Japan. In the present study we examined the life‐history traits proposed to be implicated in this event with the aim of clarifying the mechanism of this life‐cycle shift. The critical photoperiod for diapause induction, as defined by the photoperiod at which 50% of individuals enter diapause, was shorter in the trivoltine populations than in their bivoltine counterparts. The temperature sensitivity of the photoperiodic response, as defined by the difference in the critical photoperiod between 20 and 25°C, was greater in the trivoltine populations than in the bivoltine ones. The geographic variation in larval and pupal periods was positively correlated to the latitude of the original localities of the populations. The change in the number of larval instars would be one of the main factors accounting for the regional differences in the developmental period. These results suggest that some life‐history traits of H. cunea have changed following its invasion of Japan as an adaptive response to local climates.
Rediscovery of Cerebrosterol
Authors: Björkhem Ingemar 
Published: January 2007

Abstract24S‐hydroxycholesterol was identified more than half a century ago and was initially given the name “cerebrosterol” due to the fact that it was abundant in the brain. A decade ago, we showed that the most important mechanism by which cholesterol is eliminated from the mammalian brain involves a hydroxylation into cerebrosterol followed by diffusion of this steroid over the blood–brain barrier. Using an 18O2 inhalation technique, we showed that about two‐thirds of the cholesterol synthesis in rat brain is balanced by conversion into cerebrosterol. The hydroxylase responsible for the reaction was found to be dependent upon NADPH and oxygen, consistent with involvement of a species of cytochrome, P‐450. The gene coding for the cytochrome P‐450 responsible for the reaction was later cloned by the group of David Russell in Dallas and the enzyme was found to be located to neuronal cells in the brain. Recent studies by us and others on this new pathway for elimination of cholesterol from the brain have given new insights into the mechanisms by which cholesterol homeostasis is maintained in this organ. In addition, these studies have resulted in new diagnostic and prognostic tools in connection with neurological and neurodegenerative diseases. An overview of the studies is presented here and the possibility is discussed that the cholesterol 24S‐hydroxylase in the brain may be a new drug target in connection with neurodegenerative diseases.
Lymphatic Absorption and Deposition of Various Plant Sterols in Stroke‐Prone Spontaneously Hypertensive Rats, a Strain Having a Mutation in ATP binding cassette transporter G5
Authors: Hamada Tadateru , Egashira Nami , Nishizono Shoko , Tomoyori Hiroko , Nakagiri Hideaki , Imaizumi Katsumi , Ikeda Ikuo 
Published: January 2007

AbstractATP binding cassette transporter G5 (ABCG5) and ATP binding cassette transporter G8 (ABCG8) have been suggested to transport absorbed plant sterols and cholesterol from enterocytes to the intestinal lumen and from hepatocytes to bile. It has been thought that mutations of ABCG5 or ABCG8 cause the deposition of plant sterols in the body. In the present study, lymphatic absorption of various plant sterols and their deposition in various tissues was investigated in stroke‐prone spontaneously hypertensive rats (SHRSP), having a mutation in Abcg5 and depositing plant sterols in the body. The order of lymphatic 24‐h recovery of plant sterols was as follows: campesterol > sitosterol > brassicasterol > stigmasterol = sitostanol. When SHRSP were fed a diet containing one of the plant sterols, the depositions of campesterol and sitosterol were comparatively higher than those of brassicasterol, stigmasterol and sitostanol. Highly positive correlations were obtained between lymphatic recovery of plant sterols and their levels in plasma, liver, adipose tissue and heart. The tendency of differential absorption of plant sterols to the lymph in SHRSP was similar to that in normal Wistar rats previously reported by us (Hamada et al. Lipids 41:551–556, 2006). These observations suggest that differential absorption of various plant sterols is kept in SHRSP in spite of a mutation in Abcg5.
Binary Phase Behavior of 1,3‐Dipalmitoyl‐2‐oleoyl‐sn‐glycerol and 1,2‐Dioleoyl‐3‐palmitoyl‐rac‐glycerol
Authors: Zhang L. , Ueno S. , Miura S. , Sato K. 
Published: January 2007

Abstract1,3‐Dipalmitoyl‐2‐oleoyl‐sn‐glycerol (POP) and 1,2‐dioleoyl‐3‐palmitoyl‐rac‐glycerol (OOP) are two major molecular species that account for roughly half of the total triacylglycerols in palm oil. The binary phase behavior of a POP/OOP mixture plays an important role in the crystallization of palm oil. We conducted thermodynamic and kinetic studies of OOP and its mixtures with POP using differential scanning calorimetry and X‐ray diffraction with a conventional generator and synchrotron radiation. We found that OOP has two polymorphs, α as a metastable form and β′ as the most stable form, and that the two forms are stacked in a triple‐chain‐length structure. The POP/OOP mixtures exhibited immiscible eutectic natures in both their metastable and their most stable states, in contrast to POP/1,2‐dipalmitoyl‐3‐oleoyl‐rac‐glycerol and POP/1,3‐dioleoyl‐2‐palmitoyl‐sn‐glycerol mixtures, in which molecular compounds of a double‐chain‐length structure were formed. A time‐resolved synchrotron radiation X‐ray diffraction study undertaken during the cooling and heating processes indicated that the α and β′ forms of the POP and OOP fractions crystallized and melted in separate manners, and that crystallization of the β′ form and the polymorphic transformation from α to β′ of POP and OOP are promoted in the presence of another component. The absence of molecular compound crystals in the binary mixtures of POP/OOP is explained by taking into account the molecular interactions of acyl chain packing, glycerol conformation, and methyl end stacking, among which glycerol conformation appeared to be most influential.
A polysaccharide of the marine alga Capsosiphon fulvescens induces apoptosis in AGS gastric cancer cells via an IGF‐IR‐mediated PI3K/Akt pathway
Authors: Kwon Mi‐Jin , Nam Taek‐Jeong 
Published: January 2007

AbstractBecause seaweed extracts have recently been found to have antioxidant and anti‐tumor activities, we analyzed a hot‐water‐soluble polysaccharide (PS) of the marine alga Capsosiphon fulvescens for its potential as a functional foodstuff by determining its effects on cell growth and DNA synthesis. MTS assays showed that the C. fulvescens PS (Cf‐PS) significantly inhibited the proliferation of cultured human cancer cells in a dose‐dependent manner. Cf‐PS‐treated AGS cells exhibited a marked increase in caspase‐3 activation and a decrease in Bcl‐2 expression. In addition, phosphorylation of insulin‐like growth factor‐I receptor (IGF‐IR) was decreased in Cf‐PS‐treated AGS cells as compared to non‐treated control cells, which is consistent with PI3‐kinase (PI3K)/Akt activation. Cf‐PS also decreased IGF‐I‐stimulated recruitment of p85 to IGF‐IR and IRS‐1. These results indicate that Cf‐PS inhibits cell proliferation and induces apoptosis by inhibiting IGF‐IR signaling and the PI3K/Akt pathway.
Ectopic osteogenesis and chondrogenesis of bone marrow stromal stem cells in alginate system
Authors: Cai Xiaoxiao , Lin Yunfeng , Ou Guomin , Luo En , Man Yi , Yuan Quan , Gong Ping 
Published: January 2007

AbstractIn orthopedics, the regeneration and repair of cartilage or bone defects after trauma, cancer, or metabolic disorders is still a major clinical challenge. Through developmental plasticity, bone marrow mesenchymal stem cells (BMSSCs) are important seed cells for the musculoskeletal tissue engineering approach. The present study sought to determine the ectopic osteogenic and chondrogenic ability of BMSSCs in combination with a scaffolding material made from alginate gel. After isolation from the bone marrow of BALB/C mice, BMSSCs were expanded in vitro and induced to chondrogenesis or osteogenesis for 14 days, respectively. Subsequently, these induced cells were seeded into alginate gel, and the constructs implanted into BALB/C nude mice subcutaneously for up to 8 weeks. In the histological analysis, the transmission electron microscopy of the retrieved specimens at various intervals showed obvious trends of ectopic cartilage or bone formation along with the alteration of the cellular phenotype. Simultaneously, the results of the immunohistochemical staining and RT‐PCR both confirmed the expression of specific extracellular matrix (ECM) markers for cartilaginous tissue, such as collagen type II (Col‐II), SOX9, and aggrecan, or alternatively, markers for osteoid tissue, such as osteopontin (OPN), osteocalcin (OCN), and collagen type I (Col‐I). During subcutaneous implantation, the elevating production of ECM and the initiation of the characteristic structure were closely correlated with the increase of time. In contrast, there was an apparent degradation and resorption of the scaffolding material in blank controls, but with no newly formed tissues. Finally, the constructs that were made of non‐induced BMSSCs nearly disappeared during the 8 weeks after implantation. Therefore, it is suggested that alginate gel, which is combined with BMSSCs undergoing differentiation into skeletal lineages, may represent a useful strategy for the clinical reconstruction of bone and cartilage defects.
Proteomic analysis of Tiam1‐mediated metastasis in colorectal cancer
Authors: Liu Li , Zhao Liang , Zhang Yanfei , Zhang Qinling , Ding Yanqing 
Published: January 2007

AbstractTiam1 (T lymphoma invasion and metastasis 1), a guanine nucleotide exchange factor that activates Rac, was recently identified as a novel colorectal cancer metastasis‐related gene. To better understand the mechanism underlying Tiam1‐mediated metastasis, we applied two‐dimensional polyacrylamide gel electrophoresis (2‐DE) and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) analysis to identify differentially expressed proteins between Tiam1 transfected and mock transfected colorectal cancer HT29 cells. Eleven differentially expressed proteins were identified and further validated by Western blot and/or real‐time PCR. The results revealed that Tiam1 transfection in colorectal cancer cells could upregulate the expression of Fascin‐1, heat shock protein 27 (HSP27), high‐mobility group box 1 (HMGB1), glutathione S‐transferase omega 1 (GSTO1) and downregulate the expression of annexin IV. These differentially expressed proteins may be directly or indirectly regulated by Tiam1 and be helpful in studying mechanisms that lead to the function of Tiam1. These results give some clues to elucidate the mechanism of Tiam1‐mediated metastasis for colorectal cancer.