bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear morphometry as a biomarker for bronchial intraepithelial neoplasia: Correlation with genetic damage and cancer development
Authors: Guillaud Martial , le Riche Jean C. , Dawe Chris , Korbelik Jagoda , Coldman Andy , Wistuba Ignacio I. , Park In‐Won , Gazdar Adi , Lam Stephen , MacAulay Calum E. 
Published: December 2004

AbstractBackgroundBronchial carcinomas are preceded by epithelial morphologic changes. The variation in interpretation of these grades of intraepithelial neoplasia makes it difficult to determine its natural history and utility of histopathology as a surrogate endpoint biomarker. The objective of this study was to quantitate morphologic changes of intraepitherlial neoplasia and validate its utility through correlation with histopathology, allelic loss, and cancer development.MethodsQuantitative nuclear morphometry was performed on 47 normal bronchial biopsies and 28 invasive cancer to generate a morphometry index (MI) that was applied to 1,096 bronchial biopsies from 230 volunteers who were current smokers (≥25 pack‐years) and 30 patients who had cancer. In a subset of 631 biopsies, MI was correlated with frequency of loss of heterozygosity at nine chromosomal regions (14 polymorphic markers).ResultsA significant correlation was found between MI and allelic loss in six of nine chromosomal regions. As part of patient long‐term follow‐up, 12 sites that progressed to cancer were identified and had significantly increased MIs relative to nonprogressing sites. Significant overlap in the MIs was found between most grades of intraepithelial neoplasia.ConclusionsIn chemoprevention trials, nuclear morphometry can supplement histopathology as a Surrogate Endpont Biomarker (SEB) because it is quantitative, collelates well with genetic damage, and may predict cancer development. © 2004 Wiley‐Liss, Inc.
Antimicrobial peptides: Resistant‐proof antibiotics of the new millennium
Authors: Ding Jeak Ling , Ho Bow 
Published: December 2004

AbstractThis review encompasses an update on the worldwide research activities made towards developing antimicrobials against the persistent threats from multidrug‐resistant gram‐negative infection. The lethality of endotoxin or lipopolysaccharide and its conserved bioactive moiety, lipid A, is discussed. We include documentation of our own research efforts towards the development of novel endotoxin antagonists and antimicrobials such as Sushi peptides, derived from the horseshoe crab Factor C, which show great promise for future prophylactic/therapeutic applications. The mechanism of microbicidal action of the Sushi peptides is postulated. In addition to Sushi peptides, we also present other approaches we have undertaken, such as screening for anti‐endotoxic peptides from a phage‐display library; a computational approach towards rational design of anti‐endotoxic and antimicrobial peptides; and finally, a novel alternative that is best analogized by the ancient Chinese medical practice of using “poison to kill poison,” which, in modern parlance, entails the innovative application of nonendotoxic Helicobacter pylori lipopolysaccharide/lipid A as a competitor to antagonize the endotoxicity of LPS, and hence, the display of antimicrobial properties. Drug Dev. Res. 62:317–335, 2004. © 2004 Wiley‐Liss, Inc.
Identification of neural genes using Xenopus DNA microarrays
Authors: Shin Yongchol , Kitayama Atsushi , Koide Tetsuya , Peiffer Daniel A. , Mochii Makoto , Liao Arnold , Ueno Naoto , Cho Ken W.Y. 
Published: December 2004

AbstractTo isolate novel genes regulating neural induction, we used a DNA microarray approach. As neural induction is thought to occur by means of the inhibition of bone morphogenetic protein (BMP) signaling, BMP signaling was inhibited in ectodermal cells by overexpression of a dominant‐negative receptor. RNAs were isolated from control animal cap explants and from dominant‐negative BMP receptor expressing animal caps and subjected to a microarray experiment using newly generated high‐density Xenopus DNA microarray chips representing over 17,000 unigenes. We have identified 77 genes that are induced in animal caps after inhibition of BMP signaling, and all of these genes were subjected to whole‐mount in situ hybridization analysis. Thirty‐two genes showed specific expression in neural tissues. Of the 32, 14 genes have never been linked to neural induction. Two genes that are highly induced by BMP inhibition are inhibitors of Wnt signaling, suggesting that a key step in neural induction is to produce Wnt antagonists to promote anterior neural plate development. Our current analysis also proves that a microarray approach is useful in identifying novel candidate factors involved in neural induction and patterning. Developmental Dynamics 232:432–444, 2005. © 2004 Wiley‐Liss, Inc.
Control of basement membrane remodeling and epithelial branching morphogenesis in embryonic lung by Rho and cytoskeletal tension
Authors: Moore Kimberly A. , Polte Tom , Huang Sui , Shi Bin , Alsberg Eben , Sunday Mary E. , Ingber Donald E. 
Published: December 2004

AbstractLocal alterations in the mechanical compliance of the basement membrane that alter the level of isometric tension in the cell have been postulated to influence tissue morphogenesis. To explore whether cell tension contributes to tissue pattern formation in vivo, we modulated cytoskeletal force generation in embryonic mouse lung (embryonic days 12–14) rudiments using inhibitors of Rho‐associated kinase (ROCK), myosin light chain kinase, myosin ATPase, and microfilament integrity, or a Rho stimulator (cytotoxic necrotizing factor‐1). Tension inhibition resulted in loss of normal differentials in basement membrane thickness, inhibition of new terminal bud formation, and disorganization of epithelial growth patterns as well as disruption of capillary blood vessels. In contrast, increasing cell tension through Rho activation, as confirmed by quantitation of myosin light chain phosphorylation and immunohistocytochemical analysis of actin organization, accelerated lung branching and increase capillary elongation. These data suggest that changes in cytoskeletal tension mediated by Rho signaling through ROCK may play an important role in the establishment of the spatial differentials in cell growth and extracellular matrix remodeling that drive embryonic lung development. Developmental Dynamics 232:268–281, 2005. © 2004 Wiley‐Liss, Inc.
Role of a spatial distribution of IP3 receptors in the Ca2+ dynamics of the Xenopus embryo at the mid‐blastula transition stage
Authors: Díaz José , Pastor Nina , Martínez‐Mekler Gustavo 
Published: December 2004

AbstractPeriodic calcium activity correlates temporally with the onset of gene expression in the embryo, suggesting a causal relation between these two events. Calcium transients are elicited by the action of fibroblast growth factor (FGF) through the activation of phospholipase C. In this work, we present a reaction–diffusion model that extends our previous results on the generation of calcium oscillations for a single and two coupled blastomere cells to a meridian of the Xenopus embryo at the mid‐blastula transition. In the model, all cells are subject to the same amount of FGF and contain the same concentration of intracellular components, except for the amount of IP3 receptors (IP3R). A bell‐shaped distribution of IP3R produces the correct shape of the calcium transients experimentally observed in the Xenopus blastula at stage 8 (mid‐blastula transition stage). The model is also capable of predicting period and amplitude values close to the experimental values. In our model, calcium transients induce spatially localized ERK periodic transients that could activate specific nuclear genes, allowing for the regional differentiation of the cells in the zone under the influence of the calcium signal. Developmental Dynamics 232:301–312, 2005. © 2004 Wiley‐Liss, Inc.
N‐cadherin is not essential for limb mesenchymal chondrogenesis
Authors: Luo Yang , Kostetskii Igor , Radice Glenn L. 
Published: December 2004

AbstractThe cell adhesion molecule N‐cadherin is implicated in many morphogenetic processes, including mesenchyme condensation during limb development. To further understand N‐cadherin function, we characterized a new N‐cadherin allele containing the lacZ reporter gene under the regulation of the mouse N‐cadherin promoter. The reporter gene recapitulates the expression pattern of the N‐cadherin gene, including expression in heart, neural tube, and somites. In addition, strong expression was observed in areas of active cellular condensation, a prerequisite for chondrogenic differentiation, including the developing mandible, vertebrae, and limbs. Previous studies from our laboratory have shown that limb buds can form in N‐cadherin–null embryos expressing a cardiac‐specific cadherin transgene, however, these partially rescued embryos do not survive long enough to observe limb development. To overcome the embryonic lethality, we used an organ culture system to examine limb development ex vivo. We demonstrate that N‐cadherin–deficient limb buds were capable of mesenchymal condensation and chondrogenesis, resulting in skeletal structures. In contrast to previous studies in chicken using N‐cadherin–perturbing antibodies, our organ culture studies with mouse tissue demonstrate that N‐cadherin is not essential for limb mesenchymal chondrogenesis. We postulate that another cell adhesion molecule, possibly cadherin‐11, is responsible for chondrogenesis in the N‐cadherin–deficient limb. Developmental Dynamics 232:336–344, 2005. © 2004 Wiley‐Liss, Inc.
Expression of a novel zebrafish zinc finger gene, gli2b, is affected in Hedgehog and Notch signaling related mutants during embryonic development
Authors: Ke Zhiyuan , Emelyanov Alexander , Lim Simon Eng Seng , Korzh Vladimir , Gong Zhiyuan 
Published: December 2004

AbstractGli zinc‐finger proteins are known as downstream mediators of the evolutionary conserved Hedgehog pathway. In zebrafish, gli2 functions differently from Gli2 in mammals. This difference could be due to the gli2 duplication in teleosts evolution and partial redundancy between two duplicated genes. Here, we report a novel zebrafish gli2‐like cDNA. Its structure, genetic location, and distinct expression pattern in the central nervous system suggested that this gene might represent a second gli2 of teleosts, and we named it gli2b. gli2b was expressed in the neural keel, excluding the forebrain–midbrain boundary, while gli2 expression complemented this pattern. After 24 hours postfertilization, several specific domains of gli2b expression were observed in the lateral and medial hindbrain and hypothalamus. In mutants affecting the Hedgehog and Notch signaling pathways, gli2b expression was either disrupted or extended in different regions. Developmental Dynamics 232:479–486, 2005. © 2005 Wiley‐Liss, Inc.
Distinct tissue‐specificity of three zebrafish ext1 genes encoding proteoglycan modifying enzymes and their relationship to somitic Sonic hedgehog signaling
Authors: Siekmann Arndt F. , Brand Michael 
Published: December 2004

AbstractProteins of the EXT (Exostosin) 1 family are known for their role in human disease. Mutations in EXT1 cause hereditary multiple exostoses (HME), benign outgrowths of the bones, and therefore were classed as tumor suppressors. More recently, their role during embryonic development of Drosophila and mouse was addressed, revealing important functions of EXT1 genes in major signaling pathways. Here, we report the isolation of three zebrafish members of the EXT1 family, which we named ext1a, ext1b, and ext1c, respectively. They are expressed in restricted temporal and spatial domains during development. Both ext1a and ext1b are provided maternally and expressed during gastrulation: ext1a in the neurectoderm and ext1b in the embryonic midline and in the involuting mesendoderm of the germ ring. During somitogenesis stages, transcripts of all three ext genes can be found in the somitic mesoderm. Furthermore, ext1a is expressed in the dorsal neural tube. These expression domains become more pronounced at 24 hr postfertilization (hpf). At 48 hpf, ext1 genes are present in the brain, while somitic expression ceases. Zebrafish have three members of the EXT1 family, in contrast to only one EXT1 gene in mammals or Xenopus, consistent with the occurrence of partial genome duplications in the teleost lineage. Our expression analysis reveals that the three ext genes have distinct expression patterns, reflecting functional divergence after duplication. In addition, expression of ext1a and ext1c responds to elevated and reduced levels of Sonic hedgehog (shh) signaling in the somites, whereas expression of ext1b does not. This suggests a differential relationship between the shh pathway and individual ext gene function in zebrafish. Developmental Dynamics 232:498–505, 2005. © 2004 Wiley‐Liss, Inc.
Visualizing morphogenesis in transgenic zebrafish embryos using BODIPY TR methyl ester dye as a vital counterstain for GFP
Authors: Cooper Mark S. , Szeto Daniel P. , Sommers‐Herivel Greg , Topczewski Jacek , Solnica‐Krezel Lila , Kang Hee‐Chol , Johnson Iain , Kimelman David 
Published: December 2004

AbstractGreen fluorescent protein (GFP) technology is rapidly advancing the study of morphogenesis, by allowing researchers to specifically focus on a subset of labeled cells within the living embryo. However, when imaging GFP‐labeled cells using confocal microscopy, it is often essential to simultaneously visualize all of the cells in the embryo using dual‐channel fluorescence to provide an embryological context for the cells expressing GFP. Although various counterstains are available, part of their fluorescence overlaps with the GFP emission spectra, making it difficult to clearly identify the cells expressing GFP. In this study, we report that a new fluorophore, BODIPY TR methyl ester dye, serves as a versatile vital counterstain for visualizing the cellular dynamics of morphogenesis within living GFP transgenic zebrafish embryos. The fluorescence of this photostable synthetic dye is spectrally separate from GFP fluorescence, allowing dual‐channel, three‐dimensional (3D) and four‐dimensional (4D) confocal image data sets of living specimens to be easily acquired. These image data sets can be rendered subsequently into uniquely informative 3D and 4D visualizations using computer‐assisted visualization software. We discuss a variety of immediate and potential applications of BODIPY TR methyl ester dye as a vital visualization counterstain for GFP in transgenic zebrafish embryos. Developmental Dynamics 232:359–368, 2005. © 2004 Wiley‐Liss, Inc.
Preimplantation genetic diagnosis for β‐thalassaemia: the Sardinian experience
Authors: Monni Giovanni , Cau Giuseppina , Usai Valeria , Perra Graziella , Lai Rosalba , Ibba Giuseppe , Faà Valeria , Incani Federica , Rosatelli Maria Cristina 
Published: December 2004

AbstractObjectivesTo report the experiences on preimplantation genetic diagnosis (PGD) in couples at risk for ß‐thalassaemia in Sardinia.Methods23 couples at risk for ß‐thalassaemia were included in the PGD programme with a total of 42 cycles performed. Among these, 11 couples were fertile, while the remaining 12 had associated fertility problems. In vitro Fertilization (IVF), PGD and prenatal genetic molecular confirmation protocols and results are reported.ResultsAll the patients followed the protocol of ovarian stimulation, oocyte retrieval, intracytoplasmic sperm injection (ICSI), embryo biopsy and genetic analysis. A total of 272 oocytes were fertilized in the regular way, and embryo biopsy was performed on 202 embryos. Out of these 202 embryos, 192 (95%) were successful. The genetic diagnosis was performed on 150 embryos (78.1%). Ninety‐eight were identified as unaffected and 75 were transferred in 31 cycles. In the infertile patient group, two biochemical pregnancies (11.1% per transfer), in the fertile patient group, four clinical pregnancies, two twin and two singleton pregnancies (30.8% per transfer), were obtained. The genetic molecular results were confirmed in all pregnancies by first‐trimester chorionic villus sampling (CVS).ConclusionOur study shows that PGD for ß‐thalassaemia is an available procedure for couples who wish to avoid termination of pregnancy, except in cases where the IVF cycle efficiency is very poor. Copyright © 2004 John Wiley & Sons, Ltd.
Prenatal diagnosis of propionic acidemia
Authors: Pérez‐Cerdá C. , Pérez B. , Merinero B. , Desviat L. R. , Pombo P. Rodríguez , Ugarte M. 
Published: December 2004

AbstractIn this report we summarize our experience in prenatal diagnosis of propionic acidemia (PA) since 1987. Overall, we have investigated 25 pregnancies at risk from 19 unrelated families. Until genetic structure of the genes involved in PA was elucidated, prenatal diagnosis has been successfully performed by means of metabolite quantitation and/or enzymatic assays in foetal issue. Today, direct propionyl‐CoA carboxylase activity assay in combination with molecular analysis in chorion villi can be regarded as a fast and reliable method of choice for prenatal diagnosis of this organic acidemia. Copyright © 2004 John Wiley & Sons, Ltd.
Fetal heart scanning in the first trimester
Authors: Carvalho Julene S. 
Published: December 2004

AbstractThe detailed study of the fetal cardiac anatomy in the first trimester of pregnancy by means of ultrasound, transvaginally or transabdominally, is feasible and remains a safe procedure provided thermal and mechanical indices are taken into account. Optimal time for successful imaging of the four chambers and great arteries in early gestation appears to be between 13 to 14 weeks. In experienced hands, first‐trimester fetal echocardiography is accurate in detecting major structural cardiac abnormalities and yields a high negative predictive value. Thus, in a clinical setting, it can be offered to families considered to be ‘at risk’ of cardiac defects (e.g. those with previous family history or when fetal nuchal translucency is increased) and can be a powerful tool to reassure families regarding normality of major cardiac structures and connections. However, the early detection of an important structural abnormality (chromosomally normal or not) may be associated with a high termination rate if this is an acceptable option. The high prevalence of associated chromosomal and extracardiac abnormalities for many of the high‐risk families, who may benefit from this approach, cannot be ignored. Therefore, fetal heart scanning in the first trimester should be performed in conjunction with detailed first‐trimester obstetric scanning. Copyright © 2004 John Wiley & Sons, Ltd.
Congenital heart disease and aneuploidy
Authors: Wimalasundera R. C. , Gardiner H. M. 
Published: December 2004

AbstractCongenital heart disease (CHD) is one of the commonest prenatal diagnoses made on routine ultrasound screening. Overall, up to 33% of CHD are associated with fetal aneuploidy. However, some specific cardiac lesions have a significantly greater association with particular chromosomal abnormalities. The majority of fetuses with CHD and aneuploidy also have extra‐cardiac anomalies and are best managed by a multidisciplinary team where the management and prognosis of the cardiac defect can be discussed in the context of the baby as a whole. It is therefore important for clinicians involved in the management of fetuses with CHD to be aware of the association of aneuploidy as well as the prognosis and management of these cases, so that they can appropriately counsel the parents. In this chapter, we review the frequency and types of aneuploidy associated with the commonly diagnosed CHD and discuss their management. Copyright © 2004 John Wiley & Sons, Ltd.
Natural history and outcome of prenatally diagnosed cystic hygroma
Authors: Ganapathy R. , Guven M. , Sethna F. , Vivekananda U. , Thilaganathan B. 
Published: December 2004

AbstractObjectiveTo define the outcome in cases of cystic hygroma diagnosed from a routine obstetric population.MethodThis was a retrospective study of 42 cases of fetal cystic hygroma detected at 11 to 23 weeks' gestation in a routine obstetric population of 25 352 pregnancies. Fetal cystic hygroma was categorized according to position, severity, presence of cardiac defects and Hydrops fetalis.ResultsThere were 20 (47.6%) cases with aneuploidy (9 trisomies and 11 Turner's syndrome). Major congenital cardiac defects were identified in 12 (28.6%) cases. Regression of the hygroma was noted in 2/20 (10%) of the aneuploid pregnancies and 3/17 (17.6%) of the euploid pregnancies. The majority (90.0%) of the aneuploid fetuses were female. In contrast, 70.58% of the fetuses in the euploid group were male and all the surviving normal babies were also male (n = 3).ConclusionThe findings of this study would support invasive prenatal diagnosis for an ultrasound finding of fetal cystic hygroma. Even in euploid pregnancies with cystic hygroma, there is a high mortality with associated abnormalities. The data also suggest a guarded pregnancy prognosis for the finding of fetal cystic hygroma, and that it is improved with spontaneous resolution, especially in male fetuses of normal karyotype. Copyright © 2004 John Wiley & Sons, Ltd.
Indentation induced mechanical and electrical response in ferroelectric crystal investigated by acoustic mode AFM
Authors: Yu H. F. , Zeng H. R. , Ma X. D. , Chu R. Q. , Li G. R. , Luo H. S. , Yin Q. R. 
Published: December 2004

AbstractThe mechanical and electrical response of Pb (Mg1/3Nb2/3)‐
O3–PbTiO3 single crystals to micro‐indentation are investigated using the newly developed low frequency scanning probe acoustic microscopy which is based on the atomic force microscope. There are three ways to release the stress produced by indentation. Plastic deformation emerged directly underneath the indentor and along the indentation diagonals. In addition, indentation‐induced micro‐cracks and new non‐180° domain structures which are perpendicular to each other are also observed in the indented surface. Based on the experimental results, the relationship between the cracks and the domain patterns was discussed. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Scalability evaluation of theYimastreaming media architecture
Authors: Zimmermann Roger , Shahabi Cyrus , Fu Kun , Yao Shu‐Yuen Didi 
Published: December 2004

AbstractOver the last decade research has been pursued on all aspects of streaming media. While many theoretical results have been reported in the literature, few performance results of large‐scale systems have been published. In this report we specifically explore the scalability aspects of our Yima streaming media architecture in an end‐to‐end test environment. With Yima, it was our goal to design and implement an architecture that would scale in performance from small to large systems. Some of the design features include (1) a multi‐node cluster architecture based on commodity hardware and custom software, (2) media type independence (support ranges from 500 Kb s$^{-1}$MPEG‐4 to 45 Mb s$^{-1}$HDTV, at both variable and constant bitrates), (3) fine‐grained online scale up/down capabilities, and (4) a client‐controlled rate smoothing protocol. We briefly discuss the design and implementation of these capabilities of Yima and then thoroughly evaluate its scalability through several sets of experiments. Our results show that Yima scales linearly (within the range of our test parameters) as a function of the cluster size and also as a function of available resources such as network bandwidth and CPU performance. Copyright © 2004 John Wiley & Sons, Ltd.