bluuebunny/crossref_metadata_2025 huggingface dataset:
A genetic framework for fruit patterning inArabidopsis thaliana
Authors: Dinneny José R. , Weigel Detlef , Yanofsky Martin F.
Published: September 2005

In the model plant Arabidopsis thaliana, the establishment of organ polarity leads to the expression of FILAMENTOUS FLOWER(FIL) and YABBY3 (YAB3) on one side of an organ. One important question that has remained unanswered is how does this positional information lead to the correct spatial activation of genes controlling tissue identity? We provide the first functional link between polarity establishment and the regulation of tissue identity by showing that FIL and YAB3 control the non-overlapping expression patterns of FRUITFULL (FUL) and SHATTERPROOF (SHP),genes necessary to form stripes of valve margin tissue that allow the fruit to shatter along two defined borders and disperse the seeds. FIL and YAB3 activate FUL and SHP redundantly with JAGGED (JAG), a gene that also promotes growth in organs,indicating that several pathways converge to regulate these genes. These activities are negatively regulated by REPLUMLESS (RPL),which divides FIL/JAG activity, creating two distinct stripes of valve margin.
β-Catenin is essential for pancreatic acinar but not islet development
Authors: Murtaugh L. Charles , Law Anica C. , Dor Yuval , Melton Douglas A.
Published: September 2005

Despite our increasingly sophisticated understanding of transcriptional regulation in pancreas development, we know relatively little about the extrinsic signaling pathways involved in this process. We show here that the early pancreatic epithelium exhibits a specific enrichment in unphosphorylatedβ-catenin protein, a hallmark of activation of the canonical Wnt signaling pathway. To determine if this pathway is functionally required for normal pancreas development, we have specifically deleted the β-catenin gene in these cells. Pancreata developing without β-catenin are hypoplastic, although their early progenitors appear normal and exhibit no premature differentiation or death. Surprisingly, and in marked contrast to its role in the intestine, loss of β-catenin does not significantly perturb islet endocrine cell mass or function. The major defect of theβ-catenin-deficient pancreas is an almost complete lack of acinar cells,which normally comprise the majority of the organ. β-Catenin appears to be cell-autonomously required for the specification of acinar cells, rather than for their survival or maintenance, as deletion of β-catenin specifically in differentiated acinar cells has no effect. Thus, our data are consistent with a crucial role for canonical Wnt signals in acinar lineage specification and differentiation.
Building regional governance in England: the view from Whitehall
Authors: Ayres Sarah , Pearce Graham
Published: September 2005

English

Constitutional arrangements in parts of the UK have been transformed by political devolution. In England, however, reliance has been placed on strengthening the regional tier through administrative decentralisation. Drawing on the views of Whitehall civil servants, this article explores how central–regional relations are being recalibrated and how government is building a regional perspective into its activities. We conclude that, in the absence of regional government, Whitehall is pursuing a cautious approach to regional working and greater attention needs to be given to incorporating regional priorities in national spending programmes and developing a more coherent approach to regional strategy making.
UK higher education policy and the ‘global Third Way’
Authors: Jary David
Published: September 2005

English

This article reviews developments in UK higher education in the light of the central tenets of Third Way theory. It contends that, although they build on Tory policies grounded in neo-liberal and mainstream management theory, New Labour policies differ significantly, not least in combining an emphasis on sound public finance and strong public services. The article sees specific higher education policies as strong embodiments of Third Way principles and suggests that they provide the best way forward for a higher education that matches the needs of the ‘global knowledge economy’ and enhances social inclusion and social justice.
Stealing the skills agenda? Devolution, business and post-16 education and training in Wales
Authors: Phelps N.A. , Valler D.C. , Wood A.
Published: September 2005

English

This article considers the role of business interests within the devolved political and governmental arrangements introduced by New Labour. We focus on the involvement of business in shaping post-16 education and training policy in Wales. Continuities apparent in the process of devolution across its administrative and political forms have produced a distinctive Welsh political economy involving public sector-dominated policy agendas periodically punctured by specific business interests. Devolution appears to have underlined such continuities. An increased imperviousness of public sector-dominated post-16 education and training strategy-making to business interests coexists with the ability of specific business interests to distort such strategies at an operational level.
Vanadium(III) binding strengths of small biomolecules
Authors: Buglyó Péter , Nagy Eszter Márta , Sóvágó Imre
Published: October 2005

The hydrolysis of vanadium(III) and the complex formation reactions between V(III) and weakly coordinating [glycine (GLY), DL-aspartic acid (ASP), D-penicillamine (PEN), DL-histidine (HIS)] or strongly coordinating [N,O] donor [picolinic (PIC) or 6-methylpicolinic acid (MePIC)] and [O,O] donor [maltol (MALT), 1,2-dimethyl-3-hydroxy-4-(1H)-pyridinone (DHP), tiron (TIR)] ligands were studied at 25.0 °C and an ionic strength of 0.20 M (KCl) in aqueous solution using combined pH-potentiometric and UV-vis spectroscopic techniques. Although some interaction between the amino acids and V(III) was found, we could not obtain reliable models for these systems owing to the intensive hydrolysis of the metal ion and the formation of polynuclear hydroxo complexes. With pyridine carboxylates or [O,O] donor ligands 1:1, 1:2 (in the latter case, also 1:3 species) were found to be present as major complexes in solution. The similarities and differences in binding V(III) by these ligands are discussed.
Synthetic and computational modeling of the vanadium-dependent haloperoxidases
Authors: Yudenfreund Kravitz Joslyn , Pecoraro Vincent L.
Published: October 2005

Vanadium-dependent haloperoxidases that catalyze the halogenation of organic substrates using hydrogen peroxide to oxidize halides are a rare class of enzymes which have an absolute requirement for vanadium. In this article, we describe studies using synthetic, small-molecule analogs of the vanadium(V) active site to functionally mimic the oxidation of bromide and thioethers. In addition, we describe computational studies using density functional theory that help describe the mechanism of catalysis.
Modeling the active site structures of vanadate-dependent peroxidases and vanadate-inhibited phosphatases
Authors: Rehder Dieter , Ebel Martin , Wikete Cornelia , Santoni Gabriella , Gätjens Jessica
Published: October 2005

The active center of vanadate-dependent peroxidases (VPOs) is represented by vanadate covalently attached to a histidine, with vanadium in a trigonal-bipyramidal environment. Protein phosphatases and kinases are inhibited by the phosphate analog vanadate [VVO2(OH)2
- and VIVO(OH)3
-], which can be related to the coordination of vanadium to histidine or a hydroxide function as provided by tyrosinate or serinate. The vanadium centers in these proteins have been modeled by employing chiral ONO ligands. The penta-coordinated chiral complexes [VO(OMe)(L1)] (H2L1 = substituted diethanolamine) are distorted trigonal-bipyramidal with the methoxy group and the amine-N in the axial positions. These structural models of VPO also mimic the sulfide-oxidation activity of the peroxidases. The complexes [VO(H2O)L3] (H2L3 = Schiff-base ligands based on salicylaldehyde derivatives (o-vanillin; 2-hydroxy-naphthylaldehyde) and L- or D,L-tyrosine, or D,L-serine are tetragonal-pyramidal; the OH functions of the amino acid moieties are not directly coordinated to vanadium; they are involved, however, in complex hydrogen-bonding networks. The oxo/peroxo anion [VO(O2)(L2)2]3- (H2L2 = 2,5-dipicolinic acid) contains a slightly asymmetrically bonded O2
2-, featuring structural characteristics of the peroxo/hydroperoxo intermediates of the peroxidases. XD structure results are reported for the following complexes: R,S- and R,R-[VO(OMe)(L1)], K3[VO(O2)(L2)2].4.5H2O, the Tyr derivatives L-[VO(H2O)L3].MeOH and D,L-[VO(H2O)L3].H2O, and the Ser derivative D,L-[VO(H2O)L3].2H2O.
Postgenomic chemistry (IUPAC Technical Report)
Authors: Varfolomeyev Sergey , Efremenko Elena , Beletskaya Irina P. , Bertini Ivano , Blackburn G. Michael , Bogdanov Alexey , Cunin Raimond , Eichler Jutta , Galaev Igor , Gladyshev Vadim , O'Hagan David , Haertle Thomas , Jarv Jaak , Karyakin Arkadiy , Kurochkin Ilia , Mikołajczyk Marian , Poroikov Vladimir , Sakharov Ivan , Spener Friedrich , Voyer Normand , Wild James
Published: October 2005

Numerous areas of chemistry can benefit from the ongoing genomic revolution. Here, we discuss and highlight trends in chemistry in the postgenomic era. The areas of interest include combinatorial approaches in organic chemistry; design and analysis of proteins containing unnatural amino acids; trace element-containing proteins; design and characterization of new enzyme types; applications of postgenomic chemistry in drug design; identification of lipid networks and global characterization of lipid molecular species; development of recombinant and self-proliferating polymers; and applications in food chemistry and bioanalytical chemistry based on new nanoanalytical systems and novel recognition elements.
“Designer” scaffolds for tissue engineering and regeneration
Authors: Dvir Tal , Tsur‐Gang Orna , Cohen Smadar
Published: September 2005

Tissue engineering entails the in vitro or in vivo generation of replacement tissues from cells with the aid of supporting scaffolds and stimulating biomolecules, in order to provide biological substitutes for restoration and maintenance of human tissue functions. In this review, we summarize the main classes of degradable polymeric scaffolds, natural and synthetic ones, and the evolution made in this field from adaptation of materials in clinical use to the fabrication of “designer” scaffolds.
Process analysis of a reactor‐separator system: Enzymic degradation of polymeric substrates
Authors: Filo Orna , Guzy Serge , Sivan Sarit , Sideman Samuel , Lotan Noah
Published: September 2005

The analysis deals with an integrated system in which enzymic de‐polymerization of a macromolecular substrate and concomitant separation of the reaction products take place. The enzyme is immobilized within a packed‐bed reactor and products are separated by ultrafiltration. A compartmental model was set up and used to simulate the performance of the system in terms of yield, purity, and productivity of the monomer obtained, and as a function of the system operating mode (batch or continuous), recirculation ratio, enzyme mode of action (preferred attack or exo‐type), and initial polymer concentration. Results, calculated using the analytical model, are in good agreement with our experimental findings concerning the depolymerization of inulin by exo‐inulinase. Future applications include engineering design of the system and optimization of its operational parameters.
Poly(ß‐amino ester)s for DNA delivery
Authors: Zugates Gregory T. , Little Steven R. , Anderson Daniel G. , Langer Robert
Published: September 2005

Nucleotide‐based therapeutics have the potential to treat many inherited and acquired diseases. However, for this form of therapy to become clinically successful, safe and efficient delivery vehicles need to be developed. In this article, we review the synthesis, properties, and use of poly(ß‐amino ester)s as vectors for gene delivery. High‐throughput synthesis and screening studies have identified poly(ß‐amino ester)s that can complex DNA and mediate transfection with efficiencies that are superior to the best commercially available polymer‐ and lipid‐based transfection reagents. Structure‐function studies show that high‐molecular‐weight (>10 kDa) amine‐terminated polymers with primary alcohol side chains are the most efficient vectors to date. In vivo, the most effective polymer, C32, delivers plasmid DNA at high levels following intra‐tumor injection, with excellent biocompatibility. Interestingly, C32 inhibits transfection to surrounding muscle tissue, making it a good candidate for local gene therapy. In addition to simple polymer/DNA complexes insoluble microparticles can be formed using poly(ß‐amino ester)s to physically encapsulate DNA and with sizes appropriate for phagocytosis by antigen‐presenting cells. Uptake of these particles by macrophages results in protein expression levels up to 5 orders of magnitude higher than traditional poly(lactic‐co‐glycolic acid) microparticles containing DNA and can be potent stimulators of antigen presenting cells. Furthermore, in vivo delivery of poly(ß‐amino ester) microparticle genetic vaccines leads to an antigen‐specific, immune‐mediated rejection of a lethal tumor dosage. Taken together, these results show that poly(ß‐amino ester)s have broad potential as delivery systems for drug and gene therapies.
In vitro and in vivo analysis of antide delivery from multi‐phase microspheres fabricated via solvent removal
Authors: Branton Jennifer F.(Godbee) , Cheifetz Peter M. , Scott Evan A. , Bubbers Emily J. , Mathiowitz Edith
Published: September 2005

Antide, a gonadotropin releasing hormone (GnRH) antagonist, has been studied as a new drug for treatment of various gonadotropin‐dependent disorders, including hormone‐dependent prostate and breast cancer. Antide was encapsulated into multi‐phase microspheres composed of poly(l‐lactic)acid (PLLA) and poly(fumaric‐co‐sebacic)anhydride (P(FA:SA)) fabricated via solvent removal and loaded at 5% and 20% (w/w). In vitro release kinetics and the in vivo therapeutic effect (changes in the testosterone levels) were evaluated. In vivo studies were conducted in male rats at a dose of 12.5 mg antide/kg for both the 5% and 20% loaded particles as well as 31.5 mg antide/kg for the 20% loaded particles. The 5% loaded particles achieved a decrease in testosterone levels below the castration level (0.5 ng/mL) over the course of 11 weeks. The 20% loaded particles resulted in testosterone levels below the castration level for 7 weeks. The results of these studies demonstrate that it is possible to encapsulate antide into a controlled delivery system for more than 2 months. Furthermore, we were able to achieve a therapeutic response in vivo indicated by serum testosterone levels below the castration level of 0.5 ng/mL for at least 11 weeks.
Nano patterned covalent surface modification of poly(e‐caprolactone)
Authors: Edlund Ulrica , Källrot Martina , Albertsson Ann‐Christine
Published: September 2005

Using our new vapor‐phase grafting technique, we have simultaneously chemically and physically modified the surface of poly(e‐caprolactone) (PCL) films. The substrates were covered with nano patterned silicone rubber stamps and subjected to UV irradiation in the presence of the solvent‐free vapor phase of either N‐vinyl pyrrolidone or maleic anhydride, and a photoinitiator, under reduced pressure. The treated films display a surface pattern of grafted channels of 450‐nm width, as confirmed by AFM and SEM. The grafting was further verified with ATR‐FTIR, and contact angle measurements show an increased wettability of the surfaces.
Are Corals Colorful?
Authors: Matz Mikhail V. , Marshall N. Justin , Vorobyev Misha
Published: September 2005

Using in situ spectrometry data and visual system modeling, we investigate whether the colors conferred to the reef‐building corals by GFP‐like proteins would look colorful not only to humans, but also to fish occupying different ecological niches on the reef. Some GFP‐like proteins, most notably fluorescent greens and nonfluorescent chromoproteins, indeed generate intense color signals. An unexpected finding was that fluorescent proteins might also make corals appear less colorful to fish, counterbalancing the effect of absorption by the photo‐synthetic pigments of the endosymbiotic algae, which might be a form of protection against herbivores. We conclude that GFP‐determined coloration of corals may be an important factor in visual ecology of the reef fishes.
Efficiency and Selectivity of Gill Nets for Assessing Fish Community Composition of Large Rivers
Authors: Argent David G. , Kimmel William G.
Published: September 2005

To evaluate the efficiency and selectivity of gill netting for assessing fish biodiversity in the upper Ohio River system, we compared the efficiency of five gill-net types for sampling large-bodied fishes (adult total length greater than 250 mm) during fall 2001 and spring and fall 2002. Mesh sizes ranged from 3.8 cm to 14 cm (bar measure). We set the gill nets in selected pools of the Allegheny, Monongahela, and Ohio rivers 186 times over three seasons for a total of 1,644 net-hours. Nets were attached to a variety of structures, including trees and rootwads, bridge pylons, lock and dam chambers, and channel marker buoys. Nets were fished from late evening to first light, and all fish captured were identified, enumerated, and released. A total of 823 individuals representing 30 species or hybrids were captured. All net types captured common carp Cyprinus carpio and flathead catfish Pylodictis olivaris, but we captured a significantly greater diversity of fishes in graded-mesh gill nets with small mesh (38 m in length with variable-bar mesh and 15.2 m in length with 3.8-cm-bar mesh). When adjusted for length, smaller-bar mesh nets (3.8-cm-bar mesh) were more efficient for capturing target species than graded-mesh nets. To maximize species richness, 200–225 h of effort were necessary to characterize target fish communities of large-bodied riverine species.
Habitat Selection by Apache Trout in Six East‐Central Arizona Streams
Authors: Cantrell Christopher J. , Robinson Anthony T. , Avenetti Lorraine D.
Published: September 2005

Information on habitat selection by Apache trout Oncorhynchus gilae apache is needed to help recovery efforts for this federally threatened species. We investigated Apache trout habitat selection in six White Mountain streams in east‐central Arizona. We measured environmental characteristics at used sites and randomly selected available sites and modeled habitat selection using forward step‐wise logistic regression, for two size‐classes of Apache trout (≤100 mm and >100 mm total length [TL]). We also compared overall habitat type selection using contingency table analysis and G‐tests. Our logistic regression models correctly predicted habitat selection by 100‐mm TL or smaller Apache trout for 62.8% of sites over all streams surveyed and that by Apache trout larger than 100 mm TL for 75% of sites. Logistic regression models determined that larger width, lower width: Depth ratio, more eddy flows, and more cover in the form of overhanging vegetation, debris, and boulders were significant predictors for locations of Apache trout larger than 100 mm TL. Slower current velocity was the only significant predictor for locations of Apache trout 100 mm TL or less. Contingency table analysis indicated that in five of six streams, Apache trout had a greater frequency of occurrence in pool habitat. Habitat management techniques that shift stream conditions toward slower current velocities, larger widths, lower width: Depth ratios, more eddy flows, and increased cover (overhanging vegetation, debris, and boulders) should be implemented. This may mitigate for Apache trout habitat loss and may lead to an increase in the species' production.
Guided Self-Change Model of Treatment for Substance Use Disorders
Authors: Sobell Mark B. , Sobell Linda Carter
Published: September 2005

Guided self-change (GSC) treatment, a brief, cognitive-behavioral, motivational intervention first developed for use with problem drinkers, has now been evaluated with drug abusers, adolescents and Spanish-speaking alcohol abusers. This article reviews the foundations for the development of GSC; describes the results from several studies using this model of treatment, including an extension of the principles to a community-level study; speculates on the effective cognitive elements of the approach; and presents suggestions for future research.
Mindfulness-Based Relapse Prevention for Alcohol and Substance Use Disorders
Authors: Witkiewitz Katie , Marlatt G. Alan , Walker Denise
Published: September 2005

Cognitive-behavioral approaches to alcohol and drug use disorders have received considerable empirical support over the past 20 years. One cognitive-behavioral treatment, relapse prevention, was initially designed as an adjunct to existing treatments. It has also been extensively used as a stand-alone treatment and serves as the basis for several other cognitive and behavioral treatments. After a brief review of relapse prevention, as well as the hypothesized mechanisms of change in cognitive and behavioral treatments, we will describe a “new” approach to alcohol and drug problems called mindfulness-based relapse prevention. Preliminary data in support of mindfulness-meditation as a treatment for addictive behavior are provided and directions for future research are discussed.
The Community Reinforcement Approach: History and New Directions
Authors: Meyers Robert J. , Villanueva Michael , Smith Jane Ellen
Published: September 2005

This article provides an overview of 2 closely linked treatment approaches for the substance abusing client: The Community Reinforcement Approach (CRA) and Community Reinforcement and Family Training (CRAFT). In 1973, Hunt and Azrin created CRA in an attempt to restructure an individual’s “community” so that a sober lifestyle was more rewarding than one dominated by alcohol. One salient CRA premise was that an individual’s substance abuse recovery was heavily influenced by his or her social and occupational environment. Sisson and Azrin (1986) later built upon this premise in their work with a new type of client; the loved one of an alcoholic individual who refused to enter treatment. This program was an early version of CRAFT, which is an intervention that works through a nonusing individual to affect the behavior of a substance abuser. This article provides an empirical review of the evolution of these 2 interventions, including their application to illicit drug using clients. It also outlines the clinical procedures that comprise CRA and CRAFT, and considers future research directions.
Do we forgive physical aggression in the same way that we forgive psychological aggression?
Authors: Gauché Mélanie , Mullet Etienne
Published: October 2005

The present study examined variations in the impact of social proximity, apologies, intent to harm, cancellation of consequences, and attitude of others on the willingness to forgive an aggressor as a function of the type of aggression—physical aggression or psychological aggression. The participants were instructed to express their willingness to forgive in two contexts—physical aggression and psychological aggression—which constituted a within‐subject factor. Five sets of scenarios corresponding to the five between‐subject factors (from social proximity to intent to harm) were used. Participants were 215 adults aged 17–60 years. As hypothesized, the cancellation of the consequences had less impact, and the apologies and the intent to harm had more impact, on the willingness to forgive in the case of physical aggression than in the case of psychological aggression. This result was a robust one; it did not depend on the participant's gender and age. Aggr. Behav. 00:1–12, 2005. © 2005 Wiley‐Liss, Inc.
Fluorescence enhancement effect of the morin–Al3+–sodium dodecyl benzene sulphonate–protein system and the determination of proteins
Authors: Wang Fei , Yang Jinghe , Wu Xia , Sun Changxia , Liu Shufang , Wang Feng , Jia Zhen
Published: October 2005

The fluorescence intensity of the morin–Al3+ complex was greatly enhanced by proteins in the presence of sodium dodecyl benzene sulphonate (SDBS). Based on this, a new fluorimetric method for the determination of protein was developed. Under optimum conditions, the enhanced intensity of fluorescence was in proportion to the concentration of proteins in the range 1.0 × 10−8–1.3 × 10−5 g/mL for bovine serum albumin (BSA), 4.0 × 10−8–1.2 × 10−5 g/mL for egg albumin (EA) and 5.0 × 10−8–1.2 × 10−5 g/mL for human serum albumin (HSA). Their detection limits (S:N = 3) were 5.0 × 10−9, 1.8 × 10−8 and 1.6 × 10−8 g/mL, respectively. The interaction mechanism was also studied. Copyright © 2005 John Wiley & Sons, Ltd.
Resonance light scattering technique for the determination of proteins with Congo red and Triton X‐100
Authors: Wu Xia , Sun Shuna , Guo Changying , Yang Jinghe , Sun Changxia , Zhou Chengrong , Wu Tao
Published: October 2005

Resonance light scattering (RLS) of Congo red (CR) was greatly enhanced by BSA (HSA) in the presence of Triton X‐100 (TX‐100). In sodium citrate–HCl buffer (pH 2.7–3.0), the enhanced intensity of resonance light scattering at 360 nm was in proportion to the concentration. The linear relationship was obtained between the resonance light scattering intensity and proteins in the range 5.0 × 10−8–8.0 × 10−6 g/mL and 1.0 × 10−9–6.0 × 10−6 g/mL for BSA and HSA, respectively. Their detection limits were 1.4 × 10−8 g/mL and 2.8 × 10−10 g/mL (S:N = 3), respectively. Synthetic and actual samples were analysed satisfactorily. Copyright © 2005 John Wiley & Sons, Ltd.
Enthalpy distribution functions for the unwinding of a short DNA duplex
Authors: Poland Douglas
Published: October 2005

In this article we use the published heat capacity data of Dragan et al. (J Mol Biol 2003, 327, 293–411) for a short DNA duplex to calculate the enthalpy probability distribution for this species as a function of temperature. Our approach is based on a procedure that we developed (Poland, D. J Chem Phys 2000, 112, 6554) whereby one obtains moments of the enthalpy distribution from the temperature dependence of the heat capacity. One then uses the maximum‐entropy method to construct the enthalpy probability distribution from the set of enthalpy moments. For the DNA duplex treated here the heat capacity goes through a maximum as a function of temperature reflecting the unwinding of the duplex structure. In the neighborhood of the heat capacity maximum, the enthalpy distribution functions show a clear bimodal structure, indicating the coexistence of two distinct states, the duplex and the single‐strand state. The probabilities of theses two states can be estimated from the enthalpy distribution functions and can be used to calculate the temperature dependence of the equilibrium constant for the unwinding of the DNA duplex. This example illustrates that the temperature dependence of the heat capacity can be used to give a detailed picture of conformational transitions in biological macromolecules. In particular, the structure of the enthalpy distribution in this case allows one to see the temperature evolution of the two‐state distribution in detail. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 127–135, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Retention of chromosome arm 5q in stage II colon cancers identifies 83% of liver metastasis occurrences
Authors: Zeitoun Guy , Buecher Bruno , Bayer Jan , Tanguy Marie‐Laure , Thomas Gilles , Olschwang Sylviane
Published: October 2005

The decision to use chemotherapy in the treatment of colon cancer patients depends on the risk of developing metastases, as estimated by clinicopathological staging combining body imaging and pathological findings. The aim of this study was to identify all chromosome arms that, when allelotyped, correlate with the metastatic process, add prognostic information to pathology, and are of relevance for predicting metachronous metastases. A 5‐year follow‐up survey enrolled 401 MSS (microsatellite stable) colon cancer patients who were divided into three groups. Staging was performed with and without imaging data (called tumor and patient staging, respectively). The first 192 patients were used to construct a model prognosticating metastases. The subsequent 146 patients were used to validate this model. The third group evaluated its consistency by comparing the status of the relevant chromosome arms in 63 liver metastases and primary tumors that did or did not metastasize. The first group identified three factors: tumor staging (P < 0.0001), 5q status (P = 0.003), and gender (P = 0.02). The second group confirmed 5q as a marker of metastasis occurrence (P = 0.004). Merged data predicted that, when both 5q arms are retained, metastatic risk increases 4.3‐fold in stage II patients. The third group corroborated these findings, with a 5q retention rate in metastases comparable to that of primary tumors that metastasize, but significantly higher than that observed in nonmetastatic tumors (one‐tail, P = 0.0005). Long arm of chromosome 5 allelotyping detects high‐risk stage II tumors. This simple, easily implemented, and inexpensive test increases the power of randomized studies that evaluate chemotherapy. © 2005 Wiley‐Liss, Inc.
Localization of breast cancer susceptibility loci by genome‐wide SNP linkage disequilibrium mapping
Authors: Ellis Nathan A. , Kirchhoff Tomas , Mitra Nandita , Ye Tian‐Zhang , Chuai Shaokun , Huang Helen , Nafa Khedoudja , Norton Larry , Neuhausen Susan , Gordon Derek , Struewing Jeffery P. , Narod Steven , Offit Kenneth
Published: October 2005

We studied the feasibility of a novel approach to localize breast cancer susceptibility genes, using a low‐density genome‐wide panel of single‐nucleotide polymorphisms and taking advantage of large regions of linkage disequilibrium (LD) flanking Jewish disease genes in high‐risk cases. With Affymetrix GeneChip arrays, we genotyped 8,576 polymorphisms in three sets of Ashkenazi Jewish breast cancer cases: a “validation” set of 27 breast cancer cases, all of whom carried the BRCA2*6174delT founder mutation; a “field” set of 19 breast cancer cases from male breast cancer kindreds, which simulated conditions for finding new genes; and a “test” set of 57 probands from breast cancer kindreds (4 or more cases/kindred), in which mutations in BRCA1 and BRCA2 had been excluded. To identify associations, we compared the frequency of genotypes and haplotypes in cases vs. controls by the Fisher's exact test and a maximum likelihood ratio test. In the “validation” set, we demonstrated the presence of a region of linkage disequilibrium on BRCA2*6174delT chromosomes that spanned over 5 million bases. In the “field” set, we showed that this large region of linkage disequilibrium flanking BRCA2 was detectable despite the presence of heterogeneity in the sample set. Finally, in the “test” set, at least three regions of interest emerged that could contain novel breast cancer genes, one of which had been identified previously by linkage analysis. While these results demonstrate the feasibility of genome‐wide association strategies, further application of this approach will critically depend on optimizing the density and distribution of SNPs and the size and type of study design. Genet. Epidemiol. 2005. © 2005 Wiley‐Liss, Inc.
Pathological dynamics of activated microglia following medial forebrain bundle transection
Authors: Cho Byung P. , Song Dae Y. , Sugama Shuei , Shin Dong H. , Shimizu Yoshinori , Kim Sung S. , Kim Yoon S. , Joh Tong H.
Published: October 2005

To elucidate the role and pathological dynamics of activated microglia, this study assessed the phagocytic, immunophenotypic, morphological, and migratory properties of activated microglia in the medial forebrain bundle (MFB) axotomized rat brain. Activated microglia were identified using two different monoclonal antibodies: ED1 for phagocytic activity and OX6 for major histocompatibility complex (MHC) class II. Phagocytic microglia, characterized by ED1‐immunoreactivity or ED1‐ and OX6‐immunoreactivity, appeared in the MFB and substantia nigra (SN) as early as 1–3 days post‐lesion (dpl), when there was no apparent loss of SN dopamine (DA) neurons. Thereafter, a great number of activated microglia selectively adhered to degenerating axons, dendrites and DA neuronal somas of the SN. This was followed by significant loss of these fibers and nigral DA neurons. Activation of microglia into phagocytic stage was most pronounced between 14∼28 dpl and gradually subsided, but phagocytic microglia persisted until 70 dpl, the last time point examined. ED1 expression preceded MHC II expression in phagocytic microglia. All phagocytic microglia sticking to DA neurons showed activated but ramified form with enlarged somas and thickened processes. They were recruited to the SNc from cranial, dorsal and ventral aspects along various structures and finally stuck to DA neurons of the SNc. Characteristic rod‐shaped microglia in the white matter were thought to migrate a long distance. The present study strongly suggests that neurons undergoing delayed neurodegeneration may be phagocytosed by numerous phagocytic, ramified microglia at various sites where specific surface signals are exposed or diffusible molecules are released. © 2005 Wiley‐Liss, Inc.
Graft copolymers of methyl methacrylate and poly([R]‐3‐hydroxybutyrate) macromonomers as candidates for inclusion in acrylic bone cement formulations: Compression testing
Authors: Nguyen Sophie , Marchessault Robert H.
Published: October 2005

Graft copolymers of methyl methacrylate and biodegradable, biocompatible bacterial poly([R]‐3‐hydroxybutyrate) (PHB) blocks were synthesized and evaluated as possible constituents in acrylic bone cements for use in orthopaedic applications. The copolymers were produced by conventional free radical copolymerization and incorporated in one commercially available acrylic bone cement brand, Antibiotic Simplex® (AKZ). Cements with formulations containing 6.7 and 13.5 wt % of PMMA‐graft‐PHB were prepared. The morphology of the graft copolymer particles was suggested to influence the ability of the modified cement to be processed. Formulations containing more than about 20 wt % of the graft copolymer resulted in cement doughs that, both after first preparation and several hours later, were either sandy or soft spongy in texture and, thus, would be unacceptable for use in orthopaedic applications. The morphologies of the powders and the volumetric porosity (p) and ultimate compressive strength (UCS) of the cured cements were determined. Micro computed tomography showed that the cements presented average porosities of 13.5–16.9%. It was found that, while the powder particle shape and size for the experimental cements were markedly different from those of AKZ, there was no significant difference in either p or UCS for these cements. The latter was determined to be about 85 MPa for the modified cements and 84 MPa for Antibiotic Simplex. Furthermore, the UCS of all the cements exceeded the minimum level for acrylic bone cements, as stipulated by ASTM F‐451. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Effect of adding an anaerobic fungal culture isolated from a wild blue bull (Boselophus tragocamelus) to rumen fluid from buffaloes on in vitro fibrolytic enzyme activity, fermentation and degradation of tannins and tannin‐containing Kachnar tree (Bauhinia variegata) leaves and wheat straw
Authors: Paul Shyam S , Kamra Devki N , Sastry Vadali RB , Sahu Narottam P
Published: October 2005

The study investigated the effects of adding an anaerobic fungus (Piromyces sp FNG5; isolated from the faeces of a wild blue bull) to the rumen fluid of buffaloes consuming a basal diet of wheat straw and concentrates on in vitro enzyme activities, fermentation and degradation of tannins and tannin‐rich tree leaves and wheat straw. In experiment 1, strained rumen fluid was incubated for 24 and 48 h, in quadruplicate, with or without fungal culture using condensed tannin‐rich Bauhinia variegata leaves as substrates. In experiment 2, in vitro incubation medium containing wheat straw and different concentrations of added tannic acid (0–1.2 mg mL−1) were incubated for 48 h, in quadruplicate, with strained buffalo rumen fluid with or without fungal culture. In experiment 3, tolerance of the fungal isolate to tannic acid was tested by estimating fungal growth in pure culture medium containing different concentrations (0–50 g L−1) of tannic acid. In in vitro studies with Bauhinia variegata tree leaves, addition of the fungal isolate to buffalo strained rumen liquor resulted in significant (P < 0.01) increase in neutral detergent fibre (NDF) digestibility and activities of carboxymethyl cellulase (P < 0.05) and xylanase (P < 0.05) at 24 h fermentation. There was 12.35% increase (P < 0.01) in condensed tannin (CT) degradation on addition of the fungal isolate at 48 h fermentation. In in vitro studies with wheat straw, addition of the fungus caused an increase in apparent digestibility (P < 0.01), true digestibility (P < 0.05), NDF digestibility (P < 0.05), activities of carboxymethyl cellulase (P < 0.001), β‐glucosidase (P < 0.001), xylanase (P < 0.001), acetyl esterase (P < 0.001) and degradation of tannic acid (P < 0.05). Rumen liquor from buffaloes which had never been exposed to tannin‐containing diet had been found to have substantial inherent tannic acid‐degrading ability (degraded 55.3% of added tannic acid within 24 h of fermentation). The fungus could tolerate tannic acid concentration up to 20 g L−1 in growth medium. The results of this study suggest that introduction of an anaerobic fungal isolate with superior lignocellulolytic activity isolated from the faeces of a wild herbivore may improve fibre digestion from tannin‐containing feeds and degradation of tannins in the rumen of buffaloes. Copyright © 2005 Society of Chemical Industry
Responses of growing Japanese quails (heavy body weight line) to graded levels of essential amino acid concentrations in diets with or without fishmeal
Authors: Kaur Sarabmeet , Mandal Asit B , Singh Kunwer B , Narayan Raj
Published: October 2005

The influence of dietary amino acid profile on growth and immune response was investigated in growing quails (n = 928) divided into 24 subgroups. Eight dietary treatments with four levels of essential amino acids (EAA), viz. 90, 100, 110 and 120% of NRC, each with or without fishmeal (FM), were formulated following a four (EAA levels) times two (protein type) factorial design. Each treatment was allotted to three replicates up to 5 weeks of age. After 5 weeks of age 10 quails were randomly sacrificed from each treatment to study the relative weight of immune organs. Live weight gain was significantly higher (P < 0.05) in diets containing 120% EAA with or without FM and 110% EAA with FM during 0 to 21 days of age. However, live weight gain from 21 to 35 days of age was higher (P < 0.01) in quails received diets containing 90% EAA with or without FM and 100% EAA without FM than in other dietary treatments. Live weight gain increased linearly (P < 0.01) with the increase in EAA levels overall (0–35 days). Feed intake was higher (P < 0.01) in diets with higher EAA levels (110 and 120%) from 0 to 21 days. The interaction of EAA and protein type influenced (P < 0.05) feed intake from 21 to 35 days of age. There was linear decrease (P < 0.01) in feed intake with the lowering of EAA level up to 100% during 0 to 35 days. Feed conversion ratio (FCR) was better (P < 0.01) up to day 21 at higher EAA levels (110 or 120%) while during days 21 to 35 better FCR was calculated (P < 0.01) in diet with low EAA levels (90 or 100%). FCR was improved in all vegetable protein diet in comparison with FM diet. Energy efficiency up to 21 days of age was better (P < 0.01) at high EAA levels (110 and 120%), while thereafter better at low (P < 0.01) EAA levels (90 and 100%). Protein efficiency improved linearly (P < 0.01) with decreasing EAA level. Humoral (SRBC) and cellular (PHA‐P) immune response did not differ in response to EAA levels or protein type. Higher (P < 0.01) relative weight of spleen was recorded at 100% EAA level, while the relative weight of thymus was higher in diet containing 110% EAA level without fishmeal. Copyright © 2005 Society of Chemical Industry
Magnetic resonance imaging of mouse spinal cord
Authors: Bilgen Mehmet , Al‐Hafez Baraa , Berman Nancy E.J. , Festoff Barry W.
Published: October 2005

The feasibility of performing high‐resolution in vivo MRI on mouse spinal cord (SC) at 9.4 T magnetic field strength is demonstrated. The MR properties of the cord tissue were measured and the characteristics of water diffusion in the SC were quantified. The data indicate that the differences in the proton density (PD) and transverse relaxation time between gray matter (GM) and white matter (WM) dominate the contrast seen on the mouse SC images at 9.4 T. However, on heavily T2‐weighted images these differences result in a reversal of contrast. The diffusion of water in the cord is anisotropic, but the WM exhibits greater anisotropy and principal diffusivity than the GM. The quantitative data presented here should establish a standard for comparing similar measurements obtained from the SCs of genetically engineered mouse or mouse models of SC injury (SCI). Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.
High‐resolution 1H chemical shift imaging in the monkey visual cortex
Authors: Juchem Christoph , Logothetis Nikos K. , Pfeuffer Josef
Published: October 2005

Functionally distinct anatomic subdivisions of the brain can often be only a few millimeters in one or more dimensions. The study of metabolic differences in such structures by means of localized in vivo MR spectroscopy is therefore challenging, if not impossible. In fact, the spatial resolution of chemical shift imaging (CSI) in humans is typically in the range of centimeters. The aim of the present study was to optimize 1H CSI in monkeys and demonstrate the feasibility of high spatial resolutions up to 1.4 × 2 × 1.4 mm3. The obtained spatial resolution permitted the segregation of gray and white matter in the visual cortex based on the concentration of different metabolites and neurotransmitters like N‐acetylaspartate, glutamate, and creatine. Concentration ratios of white matter versus gray matter tissue as well as between metabolites matched those reported in the literature from healthy human brain, demonstrating the consistency and reliability of the procedure. Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.
Non‐linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome
Authors: Frühwald Michael C. , Hasselblatt Martin , Wirth Sebastian , Köhler Gabriele , Schneppenheim Reinhard , Subero Jose Igancio Martin , Siebert Reiner , Kordes Uwe , Jürgens Heribert , Vormoor Josef
Published: October 2005

Background

Rhabdoid tumors represent an independent entity among embryonal neoplasms. These tumors affect the kidney (RTK, rhabdoid tumor of kidney) and central nervous system (AT/RT, atypical teratoid, rhabdoid tumor), but may also be found in peripheral soft tissue. Unifying features include immunohistochemical characteristics and inactivation of the putative tumor suppressor gene SMARCB1 (hSNF5/INI1) in chromosome 22q11.2. Several familial cases have been published and summarized under the term rhabdoid tumor predisposition syndrome. In all of the published familial cases, inactivation of SMARCB1 was detected in tumor tissues.

Procedure and Results

We report on a family with three children, two of which were affected by rhabdoid tumors, one RTK, the other an AT/RT. While both children demonstrated typical morphological and clinical features neither the RTK nor the AT/RT showed evidence for inactivation of SMARCB1 in molecular studies including CGH and array CGH, FISH, gene dosage analysis by dHPLC, and DNA‐sequencing. Immunohistochemistry for SMARCB1 showed normal expression within the nuclei of tumor cells. Furthermore, both children inherited different paternal and maternal SMARCB1 alleles evidenced by haplotype analysis. Conventional cytogenetic, FISH, and mutation analyses lacked evidence for SMARCB1 aberrations or gross chromosomal changes in the parents.

Conclusions

We thus demonstrate a family with rhabdoid tumor predisposition syndrome without linkage to SMARCB1. This finding indicates that other loci than SMARCB1 below the resolution of array CGH are involved in the origin of these tumors. Our data impact on the clinical counseling of affected families and warrant further studies in the molecular biology of these enigmatic tumors. Pediatr Blood Cancer 2006;47:273–278. © 2005 Wiley‐Liss, Inc.
T‐cell acute lymphoblastic leukemia relapsing as acute myelogenous leukemia
Authors: Mantadakis Elpis , Danilatou Vassiliki , Stiakaki Eftichia , Paterakis George , Papadhimitriou Stefanos , Kalmanti Maria
Published: October 2005

We present the unusual case of a 16‐year‐old girl with T‐cell acute lymphoblastic leukemia (ALL) with an early thymocyte immunophenotype without myeloid markers, who after 13 months of complete hematological remission relapsed as acute myelogenous leukemia (AML) with minimal differentiation and died of her disease. Whether the AML represented a relapse with lineage switch of the original immature T‐cell clone or a new secondary malignancy, could not be proven due to the absence of molecular or clonal markers. This report suggests that a subset of CD7+ T‐cell leukemias without mature T‐cell antigens (CD4‐, CD8‐) are minimally differentiated and can relapse as AML. Pediatr Blood Cancer 2007;48:354–357. © 2005 Wiley‐Liss, Inc.
Isolated pulmonary Langerhans cell histiocytosis presenting with recurrent pneumothorax
Authors: Braier Jorge , Latella Antonio , Balancini Blanca , Castaños Claudio , Goldberg Julio
Published: October 2005

We describe the outcome of a 20‐month‐old female and a 6‐year‐old male, both of whom had acutely developed severe respiratory distress with tachypnea, cyanosis and, in Patient 2, thoracic pain. Chest X‐ray and CT scan showed interstitial pulmonary involvement and a bullous process with bilateral pneumothoraces for both children. Pulmonary biopsy confirmed the diagnosis of Langerhans cell histiocytosis (LCH). Laboratory testing and skeletal radiography did not reveal any other involvement of LCH. The patients received chemotherapy (prednisone, vinblastine, 6‐mercaptopurine). They had recurrent episodes of pneumothorax during follow‐up and placement of chest tubes was the treatment chosen. They were asymptomatic, with regression of bullae and disappearance of pneumothorax at 58 and 63 months of follow‐up, respectively. Pulmonary function tests done during follow‐up were normal in both patients. Despite severe pulmonary involvement, conservative surgical treatment and moderate chemotherapy produced good results in these two rare cases. Pediatr Blood Cancer 2007;48:241–244. © 2006 Wiley‐Liss, Inc.
CGH evaluation of two de novo synchronous tumors in a child with a germline p53 mutation
Authors: Roque Lúcia , Lacerda Ana , Rodrigues Raquel , Almeida Odete , Salgueiro João , Pinto Carla
Published: October 2005

We report the case of a child who developed two de novo synchronous tumors: an osteosarcoma and an embryonal rhabdomyosarcoma. The patient was determined to be a de novo carrier of a P53 germline mutation. Comparative genomic hybridization (CGH) analysis revealed that each of the neoplasms was characterized by a specific set of chromosomal imbalances and high‐level amplification (HLA) regions. Our CGH findings provide evidence that cancer development is a cellular/organ specific event. Pediatr Blood Cancer © 2005 Wiley‐Liss, Inc.