bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of FoxC, FoxF, FoxL1, and FoxQ1 genes in the dogfish Scyliorhinus canicula defines ancient and derived roles for fox genes in vertebrate development
Authors: Wotton Karl R. , Mazet Françoise , Shimeld Sebastian M.
Published: May 2008

In the human genome, members of the FoxC, FoxF, FoxL1, and FoxQ1 gene families are found in two paralagous clusters. Here we characterize all four gene families in the dogfish Scyliorhinus canicula, a member of the cartilaginous fish lineage that diverged before the radiation of osteichthyan vertebrates. We identify two FoxC genes, two FoxF genes, and single FoxQ1 and FoxL1 genes, demonstrating cluster duplication preceded the radiation of gnathostomes. The expression of all six genes was analyzed by in situ hybridization. The results show conserved expression of FoxL1, FoxF, and FoxC genes in different compartments of the mesoderm and of FoxQ1 in pharyngeal endoderm and its derivatives, confirming these as ancient sites of Fox gene expression, and also illustrate multiple cases of lineage‐specific expression domains. Comparison to invertebrate chordates shows that the majority of conserved vertebrate expression domains mark tissues that are part of the primitive chordate body plan. Developmental Dynamics 237:1590‐1603, 2008. © 2008 Wiley‐Liss, Inc.
Expression of TGF‐βs in the embryonic nervous system: Analysis of interbalance between isoforms
Authors: Mecha M. , Rabadán M.A. , Peña‐Melián A. , Valencia M. , Mondéjar T. , Blanco M.J.
Published: May 2008

Transforming growth factor‐beta (TGF‐β) is a family of growth factors with essential and multiple roles during embryonic development. In mammals, three isoforms (TGF‐β1, TGF‐β2, TGF‐β3) have been described. In the nervous system, the presence of TGF‐β1 has remained undetectable in other structures than meninges and choroids plexus, while TGF‐β2 and TGF‐β3 were considered as the neural members of the family. In the present study, we have analysed the expression pattern of the three isoforms in the neural tube, brain, and spinal cord during development in both mouse and chicken. The data reveal specific patterns for each isoform. This work also shows that both TGF‐β1 and TGF‐β3 are expressed in neural crest cells. In addition, we demonstrate the existence of interbalance between TGF‐β1 and TGF‐β3 with possible functional implications, which, together with the expression of TGF‐β1 in the CNS, represents one of the most important contributions of this work. Developmental Dynamics 237:1709–1717, 2008. © 2008 Wiley‐Liss, Inc.
Expression of zebrafish nos2b surrounds oral cavity
Authors: Poon Kar‐Lai , Richardson Michael , Korzh Vladimir
Published: May 2008

Inducible nitric oxide synthase (NOS2) catalyzes the production of nitric oxide (NO), and is one of the factors establishing innate immunity. In zebrafish, Nos2 is represented by nos2a and nos2b. Here, we report the cloning and expression pattern of the zebrafish nos2b gene, which does not seem to participate in induced immune response. nos2b was mapped to zebrafish linkage group 15. The spatial and temporal expression pattern of nos2b in embryonic zebrafish was analyzed by whole‐mount in situ hybridization. nos2b is expressed constitutively in two primordia located along the ventral midline. The first group of cells contributes to the neurohypophysis. Initially at the level of the ventral hindbrain, the second group of cells migrates closely with the thyroid primordium to its final position at the basihyal by 3 dpf. Thus, the analysis of expression pattern of nos2b reveals complex morphogenetic movements resulting in its expression surrounding the oral cavity. Developmental Dynamics 237:1662–1667, 2008. © 2008 Wiley‐Liss, Inc.
The role of transforming growth factor‐β signalling in the patterning of the proximal processes of the murine dentary
Authors: Anthwal Neal , Chai Yang , Tucker Abigail S.
Published: May 2008

The evolution of the novel mammalian jaw articulation has resulted in an increased complexity of the dentary bone, reflecting the multiple roles it now fulfils as the primary bone of the mandible. Signalling through the Tgf‐β type II receptor is important in the development and patterning of the proximal dentary processes, especially the angular process, and secondary cartilages. We show that expression of Tgf‐β2 is associated with the developing angular process, and that the connective tissue marker Scleraxis is co‐expressed with Tgf‐β2. Scleraxis expression is lost around the angular process of Tgfbr2 conditional knockouts and Tgf‐β signalling can induce Scleraxis expression in explant culture. Induction of secondary cartilages in explant culture can be prevented by inhibition of Tgf‐β signalling. This study suggests that the proper development of the processes and their secondary cartilages relies on both Tgf‐β signalling and mechanical forces working in concert. Developmental Dynamics 237:1604–1613, 2008. © 2008 Wiley‐Liss, Inc.
All‐trans retinoic acid‐induced ectopic limb and caudal structures: Murine strain sensitivities and pathogenesis
Authors: Liao Xiaoyan , Collins Michael D.
Published: May 2008

Treatment of pregnant mice at the egg cylinder stage with retinoic acid (RA) has caused ectopic hindlimbs in the offspring. Proposed causes of ectopic hindlimbs include homeotic transformation or multiple axis formation. Two mouse strains were determined to be divergent in susceptibility to this malformation (C57BL/6N, highly sensitive; SWV/Fnn, less sensitive). Ectopic limbs were hindlimbs (expressing Pitx1 and Tbx4 but not Tbx5), yet they also expressed the predominantly forelimb Hoxb8. Ectopic body axis formation was indicated by gene expression for ectopic primitive streaks, notochords, and nodes, as well as inhibition of anterior visceral endoderm and mesodermal migration. The earlier in development that embryos were examined, the higher the rate of ectopic hindlimb development and axis formation. Ectopic axis formation and cell migration inhibition had the same strain susceptibility as the dysmorphogenesis. We propose that all extra hindlimbs were derived from ectopic axis formation, perturbation of which is genetic background dependent. Developmental Dynamics 237:1553–1564, 2008. © 2008 Wiley‐Liss, Inc.
Comparative analysis of proneural gene expression in the embryonic cerebellum
Authors: Zordan Paola , Croci Laura , Hawkes Richard , Consalez G. Giacomo
Published: May 2008

The embryonic cerebellum contains two germinative epithelia: the rhombic lip and the ventricular zone. While the lineage of glutamatergic neurons arising from the rhombic lip has been characterized, plenty remains to be learned about the factors giving rise to the array of ventricular zone‐derived γ‐aminobutyric acid (GABA)ergic neurons. In the present study, we describe the expression of proneural genes Mash1/Ascl1, Ngn1/Neurog1, and Ngn2/Neurog2 in the cerebellar primordium at key stages of Purkinje cell and interneuron development, and compare them with the expression of other genes active in the same context. Our results indicate that Ngn1, Ngn2 and Mash1 are expressed at relevant stages of cerebellar neurogenesis in the prospective cerebellar nuclei and in the ventricular zone, excluding the Math1/Atoh1‐positive rhombic lip. Their expression domains are only partially overlapping, suggesting that they may contribute selectively to ventricular zone regionalization, giving rise to the diversity of cerebellar GABA neurons and, possibly, Purkinje cell subtypes. Developmental Dynamics 237:1726–1735, 2008. © 2008 Wiley‐Liss, Inc.
Peptide hormones as developmental growth and differentiation factors
Authors: Sanders Esmond J. , Harvey Steve
Published: May 2008

Peptide hormones, usually considered to be endocrine factors responsible for communication between tissues remotely located from each other, are increasingly being found to be synthesized in developing tissues, where they act locally. Several hormones are now known to be produced in developing tissues that are unrelated to the endocrine gland of origin in the adult. These hormones are synthesized locally, and are active as differentiation and survival factors, before the developing adult endocrine tissue becomes functional. There is increasing evidence for paracrine and/or autocrine actions for these factors during development, thus, placing them among the conventional growth and differentiation factors. We review the evidence for the view that thyroid hormones, growth hormone, prolactin, insulin, and parathyroid hormone‐related protein are developmental growth and differentiation factors. Developmental Dynamics 237:1537–1552, 2008. © 2008 Wiley‐Liss, Inc.
Id2, Id3, and Id4 proteins show dynamic changes in expression during vibrissae follicle development
Authors: Hammond Nigel L. , Jahoda Colin A.B.
Published: May 2008

Id proteins are involved in the transcriptional control of many fundamental biological processes, including differentiation and lineage commitment. We studied Id2, Id3, and Id4 protein expression during different stages of rat vibrissa follicle development using immunohistochemistry. Id2 was highly expressed in the cytoplasm of specialized cells in the basal epidermis and outer root sheath during early stages of follicle development. These cells were identified as Merkel cells (MCs) by means of double‐immunolabeling with synaptophysin and cytokeratin‐20, and persisted in neonatal follicles. Id3 immunofluorescence was characterized by membrane‐associated expression in basal epithelial cells of follicles early in development. Subsequently follicle epithelial cells switched to have strong nuclear labeling, also a feature of newly forming dermal papilla cells. Id4 expression was primarily associated with innervation of the developing follicle musculature. These observations illustrate dynamic expression patterns of Id2 and Id3 proteins in developing follicles and specifically link Id2 expression to Merkel cell specification. Developmental Dynamics 237:1653–1661, 2008. © 2008 Wiley‐Liss, Inc.
Brd4 associates with mitotic chromosomes throughout early zebrafish embryogenesis
Authors: Toyama Reiko , Rebbert Martha L , Dey Anup , Ozato Keiko , Dawid Igor B.
Published: May 2008

Brd4 is a member of the BET (bromodomains and extraterminal) subfamily of bromodomain proteins that includes chromatin‐modifying proteins and transcriptional regulators. Brd4 has a role in cell cycle progression, making it indispensable in mouse embryos and cultured cells. The N‐terminal domain of Brd4 participates in a fusion oncogene. Brd4 associates with acetylated histones in chromatin, and this association persists during mitosis implicating Brd4 in epigenetic memory. Brd4 sequence, particularly the bromodomains and ET domain, is conserved in the zebrafish and Xenopus laevis proteins reported here. Brd4 is expressed and localized on mitotic chromosomes in early zebrafish embryos before and after the midblastula transition (MBT), indicating that the Brd4‐chromosome association is a conserved property that is maintained even before zygotic transcription. The association of Brd4 with acetylated histones may also be conserved in early embryos as we found that histones H3 and H4 are already acetylated during pre‐MBT stages. Developmental Dynamics 237:1636–1644, 2008. Published 2008 Wiley‐Liss, Inc.
The eye organizes neural crest cell migration
Authors: Langenberg Tobias , Kahana Alon , Wszalek Joseph A. , Halloran Mary C.
Published: May 2008

In the anterior vertebrate head, a population of neural crest cells (NCCs) migrates to the periocular mesenchyme and makes critical contributions to the developing eye and orbit. Improper migration and differentiation of these NCCs have been implicated in human diseases such as congenital glaucoma and anterior segment dysgenesis syndromes. The mechanisms by which these cells migrate to their target tissues within and around the eye are not well understood. We present a fate map of zebrafish diencephalic and mesencephalic NCC contributions to the eye and orbit. The fate map closely resembles that in chick and mice, demonstrating evolutionary conservation. To gain insight into the mechanisms of anterior NCC guidance, we used the eyeless mutant chokh/rx3. We show that, in chokh mutants, dorsal anterior NCC migration is severely disorganized. Time‐lapse analysis shows that NCCs have significantly reduced migration rates and directionality in chokh mutants. Developmental Dynamics 237:1645–1652, 2008. © 2008 Wiley‐Liss, Inc.
Differential expression pattern of the four mitochondrial adenine nucleotide transporter ant genes and their roles during the development of Caenorhabditis elegans
Authors: Farina Francesca , Alberti Adriana , Breuil Norman , Bolotin‐Fukuhara Monique , Pinto Moïse , Culetto Emmanuel
Published: May 2008

The adenine nucleotide transporter (ANT) mediates exchange of cytosolic ADP and mitochondrial ATP. Although most species contain more than one ANT family member, it is not known whether their roles in developmental processes are redundant or specific. Here, we show that the Caenorhabditis elegans genome encodes four candidate ant genes (ant‐1.1, ant‐1.2, ant‐1.3, and ant‐1.4). We have investigated their spatiotemporal expression patterns and discovered that, whereas ANT‐1.1 is a ubiquitously expressed mitochondrial protein, the other three ANT proteins show a restricted range of cell type expression. Moreover, only the disruption of ant‐1.1 function, through RNA interference (RNAi), gives a mutant phenotype. Most of the ant‐1.1(RNAi) mutant embryos arrest before the morphogenesis stage. Furthermore, ant‐1.1 is also required postembryonically because RNAi mutants exhibit small size and life‐span extension. Our results suggest that ant‐1.1 is the only ant gene strictly required for embryonic and postembryonic development in C. elegans. Developmental Dynamics 237:1668–1681, 2008. © 2008 Wiley‐Liss, Inc.
WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growth
Authors: Potok Mary Anne , Cha Kelly B. , Hunt Andrea , Brinkmeier Michelle L. , Leitges Michael , Kispert Andreas , Camper Sally A.
Published: May 2008

WNT5A deficiency causes pituitary dysmorphology and ectopic melanotrope differentiation. Immunohistochemistry for prohormone convertase 2 (PC2) marks melanotrope cells, which are normally confined to the intermediate lobe of the pituitary gland. Wnt5a mutant mice contain ectopic melanotropes in a region of dysmorphology adjacent to the intermediate lobe. We show a coronal section from an e18.5 Wnt5a mutant pituitary gland stained with a PC2 specific antibody, developed with the chromagen diaminobenzidine, and counterstained with hematoxylin. The image is artistically arranged as a mirror image duplication with the dorsal aspect of the pituitary facing the outer edges and the ventral aspect towards the center plane. See Potok et al., Developmental Dynamics 237:1006–1020, 2008. © 2008 Wiley‐Liss, Inc.
Improvement and validation of a snow saltation model using wind tunnel measurements
Authors: Clifton Andrew , Lehning Michael
Published: May 2008

A Lagrangian snow saltation model has been extended for application to a wide variety of snow surfaces. Important factors of the saltation process, namely number of entrained particles, ejection angle and speed, have been parameterized from data in the literature. The model can now be run using simple descriptors of weather and snow conditions, such as wind, ambient pressure and temperature, snow particle sizes and surface density. Sensitivity of the total mass flux to the new parameterizations is small. However, the model refinements also allow concentration and mass flux profiles to be calculated, for comparison with measurements. Sensitivity of the profiles to the new parameterizations is considerable. Model results have then been compared with a complete set of drifting snow data from our cold wind tunnel. Simulation mass flux results agree with wind tunnel data to within the bounds of measurement uncertainty. Simulated particle sizes at 50 mm above the surface are generally larger than seen in the tunnel, probably as the model only describes particles in saltation, while additional smaller particles may be present in the wind tunnel at this height because of suspension. However, the smaller particles carry little mass, and so the impact on the mass flux is low. The use of simple input data, and parameterization of the saltation process, allows the model to be used predictively. This could include applications from avalanche warning to glacier mass balance. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of altered flow regime on bankfull area of the Lower Yellow River, China
Authors: Wu Baosheng , Xia Junqiang , Fu Xudong , Zhang Yuanfeng , Wang Guangqian
Published: May 2008

The adjustment of the bankfull channel area in the Lower Yellow River has been dramatically affected by altered flow regimes caused by human activities. This paper presents a study on the effects of altered discharge and suspended sediment load on the bankfull area at Gaocun, a representative hydrometric station in the Lower Yellow River. The analysis demonstrates the cumulative effect of previous years' flow and sediment conditions on channel adjustment, a phenomenon commonly occurring in geomorphic systems due to the delayed channel response to flow and sediment conditions. A methodology for the prediction of bankfull area was developed based on the general concept that the rate of adjustment is proportional to the difference between the bankfull area and its equilibrium value. The proposed methodology is not only applicable for the prediction of the bankfull area in response to the changes in flow and sediment conditions in the Lower Yellow River, but can also be extended to other studies where the response times have a key role to play in the assessment of channel adjustment to external changes. Copyright © 2008 John Wiley & Sons, Ltd.
Terrestrial photogrammetric techniques applied to the control of a parabolic dune in the Liencres dune system, Cantabria (Spain)
Authors: Arteaga Carlos , Juan de Sanjosé José , Serrano Enrique
Published: May 2008

The spatial–temporal variations of a dune system can be determined by using diverse ‘geomatic’ methodologies: geodesy, global positioning system (GPS) and photogrammetry. In the case of the Liencres dune system, a study will be carried out using the ‘close‐range’ photogrammetry technique and the topography technique (total station and GPS). In order to determine the dynamic of the dune system it is necessary to repeat the process of study after a specific interval of time. For this reason, three dimensional data should be available in two different time periods, between which the displacement of the object of analysis (the front portion of the dune) will be significant enough to evaluate its magnitude. This work analyses the viability of photogrammetry for the determination of the spatial–temporal changes of a coastal parabolic dune. Two factors have been analysed: first, the comparison of the photogrammetric results with the results obtained from topographic methods (total station and GPS), and second, the quantification of the displacement of the dune system. The analysis of the correspondence between the movement of different parts of the dune and the influence of the intensity and direction of the prevailing wind in the area is also desired. The dune advanced 12·15 ± 0·06 m (an average of 8·5 m/yr), and the partial implications for the dynamic of human modified processes on the natural park have been established. Copyright © 2008 John Wiley & Sons, Ltd.
Implications of the saltation–abrasion bedrock incision model for steady‐state river longitudinal profile relief and concavity
Authors: Sklar Leonard S. , Dietrich William E.
Published: May 2008

The saltation–abrasion model predicts rates of river incision into bedrock as an explicit function of sediment supply, grain size, boundary shear stress and rock strength. Here we use this experimentally calibrated model to explore the controls on river longitudinal profile concavity and relief for the simple but illustrative case of steady‐state topography. Over a wide range of rock uplift rates we find a characteristic downstream trend, in which upstream reaches are close to the threshold of sediment motion with large extents of bedrock exposure in the channel bed, while downstream reaches have higher excess shear stresses and lesser extents of bedrock exposure. Profile concavity is most sensitive to spatial gradients in runoff and the rate of downstream sediment fining. Concavity is also sensitive to the supply rate of coarse sediment, which varies with rock uplift rate and with the fraction of the total sediment load in the bedload size class. Variations in rock strength have little influence on profile concavity. Profile relief is most sensitive to grain size and amount of runoff. Rock uplift rate and rock strength influence relief most strongly for high rates of rock uplift. Analysis of potential covariation of grain size with rock uplift rate and rock strength suggests that the influence of these variables on profile form could occur in large part through their influence on grain size. Similarly, covariation between grain size and the fraction of sediment load in the bedload size class provides another indirect avenue for rock uplift and strength to influence profile form. Copyright © 2008 John Wiley & Sons, Ltd.
A geomatics‐based approach for the derivation of the spatial distribution of sediment transport processes in periglacial mountain environments
Authors: Bartsch A. , Gude M. , Gurney S. D.
Published: May 2008

Within this paper modern techniques such as satellite image analysis and tools provided by geographic information systems (GIS) are exploited in order to extend and improve existing techniques for mapping the spatial distribution of sediment transport processes. The processes of interest comprise mass movements such as solifluction, slope wash, dirty avalanches and rock‐ and boulder falls. They differ considerably in nature and therefore different approaches for the derivation of their spatial extent are required. A major challenge is addressing the differences between the comparably coarse resolution of the available satellite data (Landsat TM/ETM+, 30 m × 30 m) and the actual scale of sediment transport in this environment. A three‐stepped approach has been developed which is based on the concept of Geomorphic Process Units (GPUs): parameterization, process area delineation and combination. Parameters include land cover from satellite data and digital elevation model derivatives. Process areas are identified using a hierarchical classification scheme utilizing thresholds and definition of topology. The approach has been developed for the Kärkevagge in Sweden and could be successfully transferred to the Rabotsbekken catchment at Okstindan, Norway using similar input data. Copyright © 2008 John Wiley & Sons, Ltd.
Expressions for outage probability
Authors: Nadarajah Saralees
Published: May 2008

The outage probability for most wireless communications networks can be approximated by$R = {\rm Pr}(X_2 < X_1)$whereX1andX2are independent random variables. Here, a comprehensive collection of formulae is derived forRby assuming the most commonly known models forX1andX2. A discussion is provided of four possible applications to problems in wireless communications. Copyright © 2008 John Wiley & Sons, Ltd.
Evaluation of effect of cognitive intervention programs for the community‐dwelling elderly with subjective memory complaints
Authors: Tsai Athena Yi‐jung , Yang Ming‐Jen , Lan Chun‐Fu , Chen Cheng‐Sheng
Published: May 2008

Purpose

To compare the efficacy of cognitive training (CT) and cognitive stimulation (CS) programs for the community elderly with subjective memory complaints (SMC).

Method

The single‐blind non‐randomized controlled study was applied. The numbers of CT and CS participants were 14 and 11. The mean ages of CT and CS participants were 68.71 and 70.36. Memory training and problem solving strategies were applied in the CT group. There were ten 2‐hourly sessions of CT, held twice weekly. CS group met once weekly in a 1.5‐h class for eight classes. Cognitive performance tests of general cognitive performance, verbal memory and executive function were measured before/after the training and at 6 months follow‐up.

Results

In both training conditions, the general cognitive performance were enhanced. The CT group showed improvement in the verbal memory test. The CS group did not trigger any training effect in the verbal memory test but the executive function. All cognitive progresses remained at follow‐up.

Conclusion

Both cognitive training and cognitive stimulation programs showed training effects and remained until 6 months. Copyright © 2008 John Wiley & Sons, Ltd.
Disparity between prostate tumor interior versus peripheral vasculature in response to verteporfin‐mediated vascular‐targeting therapy
Authors: Chen Bin , Crane Curtis , He Chong , Gondek David , Agharkar Priyanka , Savellano Mark D. , Hoopes P. Jack , Pogue Brian W.
Published: May 2008

Photodynamic therapy (PDT) is a light‐based cancer treatment modality. Here we employed both in vivo and ex vivo fluorescence imaging to visualize vascular response and tumor cell survival after verteporfin‐mediated PDT designed to target tumor vasculature. EGFP‐MatLyLu prostate tumor cells, transduced with EGFP using lentivirus vectors, were implanted in athymic nude mice. Immediately after PDT with different doses of verteporfin, tumor‐bearing animals were injected with a fluorochrome‐labeled albumin. The extravasation of fluorescent albumin along with tumor EGFP fluorescence was monitored noninvasively with a whole‐body fluorescence imaging system. Ex vivo fluorescence microscopy was performed on frozen sections of tumor tissues taken at different times after treatment. Both in vivo and ex vivo imaging demonstrated that vascular‐targeting PDT with verteporfin significantly increased the extravasation of fluorochrome‐labeled albumin in the tumor tissue, especially in the tumor periphery. Although PDT induced substantial vascular shutdown in interior blood vessels, some peripheral tumor vessels were able to maintain perfusion function up to 24 hr after treatment. As a result, viable tumor cells were typically detected in the tumor periphery in spite of extensive tumor cell death. Our results demonstrate that vascular‐targeting PDT with verteporfin causes a dose‐ and time‐dependent increase in vascular permeability and decrease in blood perfusion. However, compared to the interior blood vessels, peripheral tumor blood vessels were found less sensitive to PDT‐induced vascular shutdown, which was associated with subsequent tumor recurrence in the tumor periphery. © 2008 Wiley‐Liss, Inc.
Pathway based analysis of SNPs with relevance to 5‐FU therapy: Relation to intratumoral mRNA expression and survival
Authors: Nordgard Silje H. , Alnæs Grethe I.G. , Hihn Björn , Lingjærde Ole Christian , Liestøl Knut , Tsalenko Anya , Sørlie Therese , Lønning Per Eystein , Børresen‐Dale Anne‐Lise , Kristensen Vessela N.
Published: May 2008

Genetic factors are thought to play a role in resistance towards chemotherapeutic agents such as 5‐fluorouracil (5‐FU). Approximately 30 genes are directly or indirectly involved in 5‐FU metabolism, and genetic variation in any of these may contribute to anti‐tumor response. Polymorphisms in these genes were analyzed in relation to tumoral mRNA levels of 5‐FU metabolizing genes, response to chemotherapy and survival. A total of 21 genetic variants were studied in 35 breast cancer patients treated with 5‐FluoroUracil, mitomycin (FUMI) and in a similar cohort of 90 doxorubicin treated breast cancer patients. Genotype distributions were compared using 109 healthy controls. No significant association was found between any polymorphisms and response to chemotherapy as measured by shrinkage of tumor. However, carriers of 3 copies of the TYMS 5′UTR repeat had shorter survival than noncarriers (p = .048) in the FUMI treatment group, but not in the doxorubicin treated group. Carriers of 3 copies of the repeat were also more frequently observed in both patients groups than in healthy controls (p = .034). Several highly significant associations were observed between genotypes and expression levels of 5‐FU metabolizing genes. A SNP in codon 72 of TP53 was revealed to be a key regulator of 5‐FU metabolizing genes such as DHFR and MTHFR, constituting 50% of all significant associations observed after FUMI therapy. These data suggest that 3 copies of the TYMS 5′UTR repeat may give a treatment specific reduced survival in breast cancer patients, and that TP53 may have a direct, allele specific, role in 5‐FU mediated response. © 2008 Wiley‐Liss, Inc.
Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T‐lymphocytes and preserved MHC class I antigen expression
Authors: van Houdt Inge S. , Sluijter Berbel J.R. , Moesbergen Laura M. , Vos Wim M. , de Gruijl Tanja D. , Molenkamp Barbara G. , van den Eertwegh Alfons J.M. , Hooijberg Erik , van Leeuwen Paul A.M. , Meijer Chris J.L.M. , Oudejans Joost J.
Published: May 2008

In this study we investigated whether the presence of specific populations of tumor infiltrating lymphocytes (TILs) in diagnostic primary melanoma biopsies are related to outcome in clinically stage II melanoma patients. Moreover, we investigated whether the presence of TILs correlates with expression of MHC class I antigen and MHC class II antigen on tumor cells and/or tumor infiltrating antigen presenting cells. Diagnostic primary melanoma samples of 15 patients with an unfavorable outcome were compared with 20 patients with favorable outcome. Patients were matched for age, gender and Breslow thickness. Biopsies were examined for the presence of granzyme B+, CD8+, CD4+ and CD56+ TILs and for expression of MHC class I antigen and MHC class II antigen on tumor and/or tumor infiltrating cells. A favorable clinical outcome was strongly associated with the presence of GrB+ and CD4+ TILs, with expression of MHC class I antigen on tumor cells and with expression of MHC class II antigen on intratumoral antigen presenting cells. These data strongly support the notion that in melanoma patients the cellular immune response is a major factor in preventing melanoma cell dissemination. © 2008 Wiley‐Liss, Inc.
Reduced local immunity in HPV‐related VIN: Expression of chemokines and involvement of immunocompetent cells
Authors: Santegoets Lindy A.M. , van Seters Manon , Heijmans‐Antonissen Claudia , KleinJan Alex , van Beurden Marc , Ewing Patricia C. , Kühne Liesbeth C.M. , Beckmann Ilse , Burger Curt W. , Helmerhorst Theo J.M. , Blok Leen J.
Published: May 2008

Usual type VIN is a premalignant disorder caused by persistent HPV infection. High prevalence of VIN in immuno‐suppressed women suggests that a good innate and adaptive immune response is important for defense against HPV. Here, we explored expression levels of chemokines and related these to the presence or absence of immuno‐competent cells (dendritic and T‐cells) in affected (HPV‐positive VIN) and non‐affected (HPV‐negative) vulvar tissues from the same patients. Combining microarray data with quantitative real‐time RT‐PCR, it was observed that several important chemokines were differentially expressed between VIN and control samples (up‐regulation of IL8, CXCL10, CCL20 and CCL22 and down‐regulation of CXCL12, CCL21 and CCL14). Furthermore, an increased number of mature dendritic cells (CD208+) seemed to be bottled up in the dermis, and although a T‐cell response (increased CD4+ and CD8+ cells) was observed in VIN, a much larger response is required to clear the infection. In summary, it seems that most mature dendritic cells do not receive the proper chemokine signal for migration and will stay in the dermis, not able to present viral antigen to naive T‐cells in the lymph node. Consequently the adaptive immune response diminishes, resulting in a persistent HPV infection with increased risk for neoplasia. © 2008 Wiley‐Liss, Inc.
Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death
Authors: Lan Yongsheng , Zhang Yongyou , Wang Jianghua , Lin Chunhong , Ittmann Michael M. , Wang Fen
Published: May 2008

The mammalian Cks family consists of 2 well‐conserved small proteins, Cks1 and Cks2. Cks1 has been shown to promote cell‐cycle progression by triggering degradation of p27kip1. The function of Cks2 in somatic mammalian cells is not well understood although it is required for the first metaphase/anaphase transition during the meiosis. Emerging evidence shows that elevated expression of Cks1 and Cks2 is often found in a variety of tumors, and is correlated with poor survival rate of the patients. Here we demonstrated that expression of Cks1 and Cks2 were elevated in prostate tumors of human and animal models, as well as prostatic cancer cell lines. Forced expression of Cks1 and Cks2 in benign prostate tumor epithelial cells promoted cell population growth. Knockdown of Cks1 expression in malignant prostate tumor cells inhibited proliferation, anchorage‐independent growth, and migration activities, whereas knockdown of Cks2 expression induced programmed cell death and inhibited the tumorigenicity. Collectively, the data suggest that elevated expression of Cks1 contributes to the tumorigenicity of prostate tumor cells by promoting cell growth and elevated expression of Cks2 protects the cells from apoptosis. Thus, the finding suggests a novel therapeutic strategy for prostatic cancer based on inhibiting Cks1 and Cks2 activity. © 2008 Wiley‐Liss, Inc.
αvβ3 Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide
Authors: Yoshimoto Mitsuyoshi , Ogawa Kazuma , Washiyama Kohshin , Shikano Naoto , Mori Hirofumi , Amano Ryohei , Kawai Keiichi
Published: May 2008

The αvβ3 integrin plays a pivotal role in angiogenesis and tumor metastasis. Angiogenic blood vessels overexpress αvβ3 integrin, as in tumor neovascularization, and αvβ3 integrin expression in other microvascular beds and organs is limited. Therefore, αvβ3 integrin is a suitable receptor for tumor‐targeting imaging and therapy. Recently, tetrameric and dimeric RGD peptides have been developed to enhance specificity to αvβ3 integrin. In comparison to the corresponding monomeric peptide, however, these peptides show high levels of accumulation in kidney and liver. The purpose of this study is to evaluate tumor‐targeting properties and the therapeutic potential of 111In‐ and 90Y‐labeled monomeric RGD peptides in BALB/c nude mice with SKOV‐3 human ovarian carcinoma tumors. DOTA‐c(RGDfK) was labeled with 111In or 90Y and purified by HPLC. A biodistribution study and scintigraphic images revealed the specific uptake to αvβ3 integrin and the rapid clearance from normal tissues. These peptides were renally excreted. At 10 min after injection of tracers, 111In‐DOTA‐c(RGDfK) and 90Y‐DOTA‐c(RGDfK) showed high uptake in tumors (7.3 ± 0.6% ID/g and 4.6 ± 0.8% ID/g, respectively) and gradually decreased over time (2.3 ± 0.4% ID/g and 1.5 ± 0.5% ID/g at 24 hr, respectively). High tumor‐to‐blood and ‐muscle ratios were obtained from these peptides. In radionuclide therapeutic study, multiple‐dose administration of 90Y‐DOTA‐c(RGDfK) (3 × 11.1 MBq) suppressed tumor growth in comparison to the control group and a single‐dose administration (11.1 MBq). Monomeric RGD peptides, 111In‐DOTA‐c(RGDfK) and 90Y‐DOTA‐c(RGDfK), could be promising tracers for αvβ3 integrin‐targeting imaging and radiotherapy. © 2008 Wiley‐Liss, Inc.
Multiple B‐vitamin inadequacy amplifies alterations induced by folate depletion in p53 expression and its downstream effector MDM2
Authors: Liu Zhenhua , Choi Sang‐Woon , Crott Jimmy W. , Smith Donald E. , Mason Joel B.
Published: May 2008

Folate is required for biological methylation and nucleotide synthesis, aberrations of which are thought to be the mechanisms that enhance colorectal carcinogenesis produced by folate inadequacy. These functions of folate also depend on the availability of other B‐vitamins that participate in “one‐carbon metabolism,” including B2, B6 and B12. Our study therefore investigated whether combined dietary restriction of these vitamins amplifies aberrations in the epigenetic and genetic integrity of the p53 gene that is induced by folate depletion alone. Ninety‐six mice were group pair‐fed diets with different combinations of B‐vitamin depletion over 10 weeks. DNA and RNA were extracted from epithelial cells isolated from the colon. Within the hypermutable region of p53 (exons 5–8), DNA strand breaks were induced within exons 6 and 8 by folate combined with B2, B6 and B12 restriction (p < 0.05); such effects were not significantly induced by mild folate depletion alone. Similarly, a minor degree of hypomethylation of exon 6 produced by isolated folate depletion was significantly amplified (p ≤ 0.05) by simultaneous depletion of all 4 B‐vitamins. Furthermore, the expression of p53 and MDM2 were significantly decreased (p ≤ 0.05) by the combined depletion state but not by folate depletion alone. These data indicate that inadequacies of other 1‐carbon vitamins may amplify aberrations of the p53 gene induced by folate depletion alone, implying that concurrent inadequacies in several of these vitamins may have added tumorigenic potential beyond that observed with isolated folate depletion. © 2008 Wiley‐Liss, Inc.
FRAT1 overexpression leads to aberrant activation of β‐catenin/TCF pathway in esophageal squamous cell carcinoma
Authors: Wang Yihua , Liu Shuang , Zhu Hongxia , Zhang Wei , Zhang Guo , Zhou Xiaobo , Zhou Cuiqi , Quan Lanping , Bai Jinfeng , Xue Liyan , Lu Ning , Xu Ningzhi
Published: May 2008

Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a poor prognosis. Although aberrant activation of β‐catenin/T‐cell factor (TCF) pathway has been observed in ESCC, mechanisms underlying this phenomenon remain unknown. Frequently rearranged in advanced T‐cell lymphomas‐1 (FRAT1), overexpressed in some ESCC lines, is a positive regulator of β‐catenin/TCF pathway. However, little is known about the molecular relationship between FRAT1 and β‐catenin/TCF in ESCC. In this study, we analyzed freshly resected ESCC specimens and demonstrated that FRAT1 was overexpressed in approximately 74% of tumor samples compared with matched normal tissue. Overexpression of FRAT1 significantly promoted esophageal cancer cells growth, whereas suppression of FRAT1 level by RNAi markedly inhibited their growth. In addition, FRAT1 overexpression induced the nuclear accumulation of β‐catenin and promoted the transcriptional activity of β‐catenin/TCF. These effects were reversed by coexpression of GSK 3β or ΔN TCF4. Furthermore, accumulation of β‐catenin was correlated with FRAT1 overexpression in ESCC and the basal layer of normal esophageal epithelium. Finally, continued expression of c‐Myc is necessary and sufficient for maintenance of the growth state in cells expressing FRAT1. Taken together, these results support the novel hypothesis that aberrant activation of β‐catenin/TCF pathway in esophageal cancer appears to be due to upstream events such as FRAT1 overexpression, and c‐Myc may be an important element in oncogenesis of human ESCC induced by FRAT1. © 2008 Wiley‐Liss, Inc.
The many histories of community psychology: analyses of current trends and future prospects
Authors: Fowler Patrick J. , Toro Paul A.
Published: May 2008

Forty years since the seminal Swampscott Conference, the principles of community psychology transcend multiple areas of action and research, as well as international boundaries. The extensive development of community psychology offers an opportunity to examine from where the field has come and where it is going. Yet, a systematic approach to creating a history of community psychology is required to avoid distorting or excluding the voices of its diverse members. This special issue provides eight articles that highlight the importance of a pluralistic approach to historical analysis of the field. Of particular importance is the recognition of often‐underemphasized members of community psychology, including the important role of women, ethnic minorities, applied community psychologists, and international influences on the field. © 2008 Wiley Periodicals, Inc.
Some questions about “The history of community psychology”
Authors: Fryer David
Published: May 2008

Most histories of the discipline of community psychology attribute its beginning to the Swampscott Conference that occurred in the mid‐20th century. The author argues that recognition of the community perspective on human behavior and on its positive as well as pathological characteristics arose far earlier and is reflected in the work of European social scientists. Work in central Europe in the 1930s by Marie Jahoda and her colleagues, for example, should be appreciated as an earlier manifestation of community psychology. The author also argues that the very project of trying to locate the historical origin for community psychology is by its very nature problematic! He views this effort as evidence of the intellectual colonizing of diverse indigenous community psychologies around the world by a culturally specific, largely acritical, United States–based community psychology. The author proposes that, rather than focusing on the origin of the discipline, scholars share his commitment to uncovering diverse historical community psychologies with their specific pasts and the construction of diverse community psychology futures, including most importantly of all, critical community psychologies. © 2008 Wiley Periodicals, Inc.
An insider's look at the development and current state of community psychology in Latin America
Authors: Montero Maritza
Published: May 2008

This article presents the rich history of community psychology in Latin America, describing how the field was systematically built during the second half of the 20th century. Discussed are social and political influences such as the critique of individualistic emphasis dominant at that moment, Paulo Freire's popular education, critical sociology (Fals Borda), and the need to intervene to transform unequal societies. Also described are early characteristics of Latin American community psychology, its rapid development during the 1980 s, marked by the emphasis on social transformation, participation, power and empowerment in communities, and a critical orientation. The construction of a paradigm during the 1990 s, as well as two models used in community psychology projects coexisting in Latin America societies, are presented. Current trends in community psychology in Latin America are summarized. © 2008 Wiley Periodicals, Inc.
Personal lineages and the development of community psychology: 1965 to 2005
Authors: Fowler Patrick J. , Toro Paul A.
Published: May 2008

The purpose of this study was twofold: (a) to examine and document the role of personal influence in the history of community psychology, and (b) to measure the field's inclusion of traditionally marginalized populations. In addition to presenting visually the genealogy of community psychology, results suggest that people have mattered in the development of the field independently from intellectual influence. Furthermore, community psychology has become more inclusive of ethnic minorities and women in positions of authority. Yet, representation of real‐world community psychologists appears to have stalled. Implications of findings on interventions to increase representation are discussed. © 2008 Wiley Periodicals, Inc.
Reflections on “Real‐World” community psychology
Authors: Wolff Tom , Swift Carolyn
Published: May 2008

Reflections on the history of real‐world (applied) community psychologists trace their participation in the field's official guild, the Society for Community Research and Action (SCRA), beginning with the Swampscott Conference in 1965 through the current date. Four benchmarks are examined. The issues these real‐world psychologists bring to the field include academic and community legitimacy, community psychology as an interdisciplinary field, and politics and advocacy. Challenges these issues create among community psychologists—real‐world and academic—are briefly addressed. These reflections end with a vision of the future of community psychology that includes a strong recommitment to social change and social justice. © 2008 Wiley Periodicals, Inc.
Women in community psychology: the trailblazer story
Authors: Ayala‐Alcantar Christina , Dello Stritto Mary Ellen , Guzmán Bianca L.
Published: May 2008

This article is an archival document which chronicles a herstory project organized and directed by the Society for Community Research and Action (Division 27 of the American Psychological Association) Women's Committee. The experiences of 55 trailblazing women in the field of community psychology are examined, and the authors' journey in collecting, documenting, and presenting the information is also included. © 2008 Wiley Periodicals, Inc. © 2008 Wiley Periodicals, Inc.
Influence of vanadate on migrating fibroblast orientation within a fibrin matrix
Authors: Lee Michael Y. , Ehrlich H. Paul
Published: May 2008

Treating rats with vanadate, a nonspecific inhibitor of protein tyrosine phosphatases, optimizes the uniform packing of collagen fiber bundles in wound granulation tissue and doubles wound breaking strength in rat incisional wounds. The speculation is vanadate optimizes the packing of collagen fiber bundles through the orientation of newly arrived wound fibroblasts in the fibrin clot filling the defect. Segments of 14 day chick embryo tendons were placed on fibrin clots and maintained in organ culture with and without 30 µM vanadate. On day 7 explants were examined histologically and biochemically. Tendon fibroblast outgrowth from untreated explants migrated in a random fashion, while fibroblasts from vanadate‐treated explants migrated out in linear arrays. Fibroblasts were elongated by 20% form vanadate treated explant compared to controls. Myosin ATPase, required for optimal cell motility, is optimized by the phosphorylation of its myosin light chain (MLC). Western blot analysis of lysates from the fibroblasts that migrated into the fibrin showed vanadate increased MLC‐P levles. These findings support the notion that vanadate promotes the deposition of regular, parallel collagen fiber bundles by advancing the orientation of fibroblasts in parallel linear arrays early in the wound repair process. J. Cell. Physiol. 217: 72–76, 2008. © 2008 Wiley‐Liss, Inc.