bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Localization of VEGF‐A Isoforms in the Mouse Postnatal Growth Plate
Authors: Evans Kristin D. , Oberbauer Anita M.
Published: December 2007

Vascular endothelial growth factor (VEGF) is implicated as a key angiogenic factor in the development of endochondral long bone. Several studies have evaluated the role of VEGF in prenatal endochondral bone development, but few have evaluated VEGF postnatally. Growth plates from mice at postnatal ages 14 (P14), 35 (P35), 49 (P49), and 77 (P77) days were examined for differential expression of the primary VEGF‐A mRNA isoforms: VEGF 120, VEGF 164, and VEGF 188. VEGF 120 isoform expression was stable across all ages, whereas VEGF 164 had significantly less expression at P35 and P49 and VEGF l88 expression increased with increasing age. The proportion of transcript isoforms expressed at a given age also changed with VEGF 120 being expressed more highly at P35 and P49 than the other two isoforms. Changes in VEGF mRNA isoforms across cell types within the growth plate were assessed by Percoll fractionation of growth plate cells at age P28. Cells of the proliferative and early hypertrophic regions had significantly higher total VEGF mRNA expression relative to the resting and late hypertrophic regions. VEGF protein expression assessed by immunohistochemistry showed variable expression patterns with increasing postnatal age. In contrast, FLK‐1 (VEGF Receptor‐2) expression was restricted to the hypertrophic region. These results indicate that VEGF continues to play a significant role in endochondral bone development throughout the entire growth phase of postnatal bone development. Anat Rec, 291:6–13, 2007. © 2007 Wiley‐Liss, Inc.
Cyclone‐induced mixing does not cool SST in the post‐monsoon north Bay of Bengal
Authors: Sengupta Debasis , Goddalehundi Bharath Raj , Anitha D. S.
Published: December 2007

High‐resolution data from the TRMM satellite shows that sea surface temperature (SST) cools by 3 °C under the tracks of pre‐monsoon tropical cyclones in the north Indian Ocean. However, even the strongest post‐monsoon cyclones do not cool the open north Bay of Bengal. In this region, a shallow layer of freshwater from river runoff and monsoon rain caps a deep warm layer. Therefore, storm‐induced mixing is not deep, and it entrains warm subsurface water. It is possible that the hydrography of the post‐monsoon north Bay favours intense cyclones. Copyright © 2007 Royal Meteorological Society
Lektionen von Rabenvögeln und Gänsen. Instinkt oder Verstand?
Authors: Christian  , Kotrschal Kurt , Thomas
Published: December 2007

Lange war die geistige Leistungsfähigkeit der Tiere kaum ein Thema (verhaltens)biologischer Forschung. In den vergangenen 20 Jahren setzte sich schließlich die Erkenntnis durch, dass auch kognitive Leistungen als evolutionäre Anpassungen an die ökologische, vor allem aber soziale Umwelt gelten können. Trotzdem entwickelte sich ganz offensichtlich kein “artspezifischer Wildwuchs” in der Differenzierung der kognitiven Bewältigungsstrategien. Man findet erstaunliche zwischenartliche Übereinstimmungen der sozialen Organisation und geistigen Leistungsfähigkeit über weite Bereiche des Wirbeltierstammbaums, etwa zwischen Säugetieren und Vögeln. Dies ist einerseits durch die gemeinsamen ökologisch‐evolutionären Rahmenbedingungen für soziale Systeme, andererseits durch das evolutionär höchst konservative Gehirn der Wirbeltiere zu erklären. So ähneln manche Papageien und Rabenvögel in ihren kognitiven Leistungen den Menschenaffen. Und selbst die Graugänse zeigen eine erstaunlich primatenähnliche soziale Organisation, was noch erhebliche Überraschungen bezüglich der sozialen Kognition dieser bislang kaum als “Hirntiere” bekannten Tiere erwarten lässt.
A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone‐refractory prostate cancer who are refractory to docetaxel
Authors: Ross Robert W. , Beer Tomasz M. , Jacobus Susanna , Bubley Glenn J. , Taplin Mary‐Ellen , Ryan Christopher W. , Huang Jiaoti , Oh William K.
Published: December 2007

BACKGROUND.

Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second‐line therapy for docetaxel‐refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone‐refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting.

METHODS.

Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel‐based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m2 plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity.

RESULTS.

Thirty‐four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56% of patients), but there was only 1 episode of febrile neutropenia reported. Prostate‐specific antigen (PSA) declines ≥50% were noted in 18% of patients, and measurable responses were observed in 14%. The median duration of PSA response was 5.7 months. The median progression‐free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel.

CONCLUSIONS.

In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane‐refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option. Cancer 2008. © 2007 American Cancer Society.
Disparities in participation in cancer clinical trials in the United States
Authors: Colon‐Otero Gerardo , Smallridge Robert C. , Solberg Lawrence A. , Keith Thomas D. , Woodward Timothy A. , Willis Floyd B. , Dunn Ajani N.
Published: December 2007

Disparities in minorities' representation in cancer clinical trials have been shown only in adult populations, which suggest that the main causes of these disparities relate to health system‐based barriers, including issues of poverty (lack of insurance), poor access to trials, and an inadequate number of clinical trials. Initiatives that increase the participation of community physicians in cancer clinical research trials and increase low socioeconomic status patients' access to cancer trials will likely ameliorate this problem. Cancer 2008. © 2007 American Cancer Society.
Identification of serum biomarkers for nasopharyngeal carcinoma by proteomic analysis
Authors: Wei Ye‐Sheng , Zheng Yan‐Hua , Liang Wei‐Bo , Zhang Jian‐Zhong , Yang Zhi‐Hui , Lv Mei‐Li , Jia Jing , Zhang Lin
Published: December 2007

BACKGROUND.

Early diagnosis of nasopharyngeal carcinoma (NPC) remains a challenge. Serum protein profiling is a promising approach for the classification of cancer versus noncancer samples. The objective of the current study was to assess the feasibility of mass spectrometry‐based protein profiling and a classification tree algorithm for discriminating between patients with NPC and noncancer controls.

METHODS.

Serum samples from patients with NPC and noncancer controls were analyzed by using surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF‐MS). The study was divided into a preliminary training set and a blind test set: A preliminary training set and a classification tree of spectra derived from 55 patients with NPC and a group of 60 noncancer controls were used to develop a proteomic model that discriminated cancer from noncancer effectively. Then, the validity of the classification tree was challenged with a blind test set, which included another 25 patients with NPC and 28 noncancer controls.

RESULTS.

Four protein peaks at 4097 daltons (Da), 4180 Da, 5912 Da, and 8295 Da were chosen automatically as a biomarker pattern in the training set that discriminated cancer from noncancer with sensitivity of 94.5% and specificity of 96.7%. When the SELDI marker pattern was tested with the blinded test set, it yielded a sensitivity of 92%, a specificity of 92.9%, and an accuracy rate of 92.5%. The accuracy of 2 protein peaks (4581 Da and 7802 Da) was 80% for predicting stage I and II NPC and 86% for predicting stage III and IV NPC.

CONCLUSIONS.

The high sensitivity and specificity obtained by the serum protein profiling approach demonstrated that SELDI‐TOF‐MS combined with a tree analysis model both can facilitate discriminating between NPC and noncancer controls and can provide an innovative clinical diagnostic platform to improve the detection of NPC. Cancer 2008. © 2007 American Cancer Society.
Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia
Authors: Kantarjian Hagop , O'Brien Susan , Shan Jianqin , Huang Xuelin , Garcia‐Manero Guillermo , Faderl Stefan , Ravandi‐Kashani Farhad , Verstovsek Srdan , Beth Rios Mary , Cortes Jorge
Published: December 2007

BACKGROUND.

Response rates in chronic myeloid leukemia (CML) are now reported based on the cumulative incidence of a single‐time best response. The study aim was to examine the significance of different response criteria for CML on imatinib therapy.

METHODS.

In all, 276 patients with chronic phase CML on imatinib therapy were analyzed. Cytogenetic and molecular responses were coded as to single best response and response at specific intervals of treatment.

RESULTS.

The cumulative incidence of complete cytogenetic response (CGCR) with imatinib was 91%; however, the incidence of CGCR at 48 months into therapy was only 78%. Similarly, the incidence of major molecular responses (best cumulative vs landmark at 48 months) were 74% versus 62%, and of undetectable BCR‐ABL transcripts 38% versus 24%. There was a strong association between achievement of major cytogenetic response (Philadelphia chromosome [Ph]‐positivity ≤35%) at 6 months to 12 months and survival as well as progression‐free survival (PFS). Achievement of major molecular response (vs lesser molecular response) in patients in complete cytogenetic response was not associated with significant differences in survival, but showed some association with PFS. Durable CGCR and major molecular responses (documented continuously for ≥12 months) were associated with longer PFS duration but not with survival duration differences. Of interest, major molecular responses documented at least twice were noted in 71% of patients on imatinib therapy; undetectable BCR‐ABL transcripts documented at least twice were noted in 34%.

CONCLUSIONS.

Achievement and durability of CGCR and of major and complete molecular responses at landmark times predict outcome in CML, and may help in comparing the efficacy of different treatments. Cancer 2008. © 2007 American Cancer Society.
Differential localization of GABAAreceptor subunits within the substantia nigra of the human brain: An immunohistochemical study
Authors: Waldvogel H.J. , Baer K. , Gai W.‐P. , Gilbert R.T. , Rees M.I. , Mohler H. , Faull R.L.M.
Published: December 2007

γ‐Aminobutyric acidA(GABAA) receptors (GABAAR) are inhibitory heteropentameric chloride ion channels comprising a variety of subunits and are localized at postsynaptic sites within the central nervous system. In this study we present the first detailed immunohistochemical investigation on the regional, cellular, and subcellular localisation of α1, α2, α3, β2,3, and γ2subunits of the GABAAR in the human substantia nigra (SN). The SN comprises two major regions, the SN pars compacta (SNc) consisting of dopaminergic projection neurons, and the SN pars reticulata (SNr) consisting of GABAergic parvalbumin‐positive projection neurons. The results of our single‐ and double‐labeling studies demonstrate that in the SNr GABAAreceptors contain α1, α3, β2,3, and γ2subunits and are localized in a weblike network over the cell soma, dendrites, and spines of SNr parvalbumin‐positive nonpigmented neurons. By contrast, GABAARs on the SNc dopaminergic pigmented neurons contain predominantly α3and γ2subunits; however there is GABAAR heterogeneity in the SNc, with a small subpopulation (6.5%) of pigmented SNc neurons additionally containing α1and β2,3GABAAR subunits. Also, in the SNr, parvalbumin‐positive terminals are adjacent to GABAAR on the soma and proximal dendrites of SNr neurons, whereas linear arrangements of substance P‐positive terminals are adjacent to GABAAreceptors on all regions of the dendritic tree. These results show marked GABAAR subunit hetereogeneity in the SN, suggesting that GABA exerts quite different effects on pars compacta and pars reticulata neurons in the human SN via GABAAreceptors of different subunit configurations. J. Comp. Neurol. 506:912–929, 2008. © 2007 Wiley‐Liss, Inc.
PI3K signaling effects in hypothalamic neurons mediated by estrogen
Authors: Malyala Anna , Zhang Chunguang , Bryant Damani N. , Kelly Martin J. , Rønnekleiv Oline K.
Published: December 2007

Multiple mechanisms mediate the effects of estrogen in the central nervous system, including signal transduction pathways such as protein kinase A, protein kinase C, and phosphatidylinositol 3‐kinase (PI3K) pathways. Previously we demonstrated that estrogen regulates a number of PI3K‐related genes in the hypothalamus, including the PI3K p55γ regulatory subunit. We hypothesized that PI3K activation is critical for the effects of estrogen and that the p55γ subunit may be more prevalent than the p85α regulatory subunit in the hypothalamus. Therefore, in the present study, we compared the mRNA distribution of the p55γ and p85α regulatory subunits by using in situ hybridization in guinea pig. Expression level of p55γ mRNA was greater than p85α in most hypothalamic nuclei. Twenty‐four hours of estrogen treatment increased p55γ mRNA expression in the paraventricular, suprachiasmatic, arcuate, and ventromedial nuclei, and little or no change was observed for p85α mRNA. Quantitative real‐time PCR confirmed the in situ hybridization results. Next, we investigated the general role of PI3K signaling in the estrogen‐mediated changes of arcuate proopiomelanocortin (POMC) neuronal excitability by using whole‐cell recording. One cellular mechanism by which estrogen increases neuronal excitability is to desensitize (uncouple) γ‐aminobutyric acid type B (GABAB) receptors from their G‐protein‐gated inwardly rectifying K+ channels in hypothalamic neurons. We found that the PI3K inhibitors wortmannin and LY294002 significantly reduced the estrogen‐mediated GABAB receptor desensitization in POMC arcuate neurons, suggesting that PI3K signaling is a critical downstream mediator of the estrogen‐mediated rapid effects. Collectively, these data suggest that the interplay between estrogen and PI3K occurs at multiple levels, including transcriptional and membrane‐initiated signaling events that ultimately lead to changes in homeostatic function. J. Comp. Neurol. 506:895–911, 2008. © 2007 Wiley‐Liss, Inc.
Enkephalin co‐expression with classic neurotransmitters in the amygdaloid complex of the rat
Authors: Poulin Jean‐François , Castonguay‐Lebel Zoé , Laforest Sylvie , Drolet Guy
Published: December 2007

This study aimed at characterizing the neurotransmitter phenotype of enkephalin neurons in the rat amygdaloid complex. We first established the detailed distribution of vesicular glutamate transporters 1 and 2 (VGLUT1 and ‐2) and glutamate decarboxylase 65 (GAD65) in the amygdala by using in situ hybridization. In the amygdaloid complex, GAD65 is strongly expressed in striatal‐like divisions, namely, the anterior amygdaloid area, the central nucleus (CEA), the intercalated nuclei, and the dorsal part of the medial nucleus (MEA). VGLUT1 and ‐2 expression is mostly segregated to specific divisions of the amygdale, with VGLUT2 being expressed only in the MEA, the anterior cortical nucleus (COAa), and the anterior basomedial nucleus (BMAa), whereas VGLUT1 is expressed in all other divisions of the amygdala. Second, we assessed the co‐expression of preproenkephalin (ppENK) with GAD65, VGLUT1, or VGLUT2 by using double fluorescent in situ hybridization. We found that ppENK mRNA co‐localized exclusively with GAD65 in all striatal‐like structures of the amygdaloid complex with the exception of the MEA, where ENK also co‐localized with VGLUT2 mRNA. This co‐localization is most apparent in the posteroventral part of the MEA, where 70% of ENKergic cells expressed VGLUT2. In addition, ppENK also co‐localized with VGLUT1 because more than 95% of ENK cells in the basolateral amygdala expressed VGLUT1. In contrast, less than 25% of ENKergic cells expressed VGLUT1 in the lateral nucleus of the amygdale, with the majority of ENK cells expressing GAD65 mRNA in this nucleus. These results have broad implications for understanding the functional roles of enkephalinergic neurotransmission in the amygdaloid complex. J. Comp. Neurol. 506:943–959, 2008. © 2007 Wiley‐Liss, Inc.
Upwind isoparametric interpolation finite point method for 2D scalar conservation equation
Authors: Yin Li , Shen Longjun
Published: December 2007

A new upwind isoparametric interpolation finite point (UIIFP) scheme for meshless solver is proposed. This method is developed based on the least‐squares procedure and an upwind isoparametric interpolation approximation of the fictitious interface directional flux. The accuracy of UIIFP scheme and 2D test computation is presented. Copyright © 2007 John Wiley & Sons, Ltd.
Gene environment interplay: Nonhuman primate models in the study of resilience and vulnerability
Authors: Bennett Allyson J.
Published: December 2007

Identifying how individual differences in risk for disease emerge is a major target for biomedical research. In many cases, however, the most lightly traversed avenues of this type of basic and clinical research are those that begin with a focus on early development. It appears likely that early influences may be pivotal in lifetime risk of disease and other adverse outcomes. Nonetheless, understanding the constellation of interacting biological, experiential, social factors that influence this risk has proved a relatively elusive target. Better specification of routes of interplay between these factors, as well as definitions of the mechanisms by which they affect change, are essential goals for numerous research areas. Furthermore, progress towards these goals is unlikely without meaningful integration of diverse disciplines, among them biology and developmental science. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 50: 48–59, 2008.
Phagocytosis‐induced apoptosis of macrophages is linked to uptake, killing and degradation of bacteria
Authors: Frankenberg Tobias , Kirschnek Susanne , Häcker Hans , Häcker Georg
Published: December 2007

Phagocytosis and intracellular destruction of pathogens by phagocytes is a crucial defense mechanism of the innate immune response during infection. It has been reported a number of times that the interaction with pyogenic, extracellular bacteria leads to the apoptotic death of phagocytes. The signaling events that cause this form of cell death are largely unknown. In this study, we demonstrate a link between uptake, killing and degradation of Escherichia coli bacteria and induction of apoptosis in macrophages. Treatment of murine RAW 264.7 macrophages with bafilomycin A1, a phagosome acidification inhibitor, reduced killing and degradation of phagocytosed bacteria and significantly decreased macrophage apoptosis. The stable overexpression of constitutively active or dominant‐negative mutants of the small GTPase Rab5a increased bacterial phagocytosis and consecutively apoptosis. In these cells, relative killing and degradation were not affected, linking the increased apoptosis to enhanced uptake and suggesting that the apoptosis‐inducing signal derives from the higher incidence of degradation events or an accumulation of phagosomes of a late maturation stage. These results thus provide a link between bacterial phagocytosis and degradation and the induction of apoptosis in macrophages. We propose that this form of apoptosis is the physiological conclusion of an innate immune response against pyogenic bacteria.
Nanocrystalline diamond: In vitro biocompatibility assessment by MG63 and human bone marrow cells cultures
Authors: Amaral M. , Dias A. G. , Gomes P. S. , Lopes M. A. , Silva R. F. , Santos J. D. , Fernandes M. H.
Published: December 2007

Nanocrystalline diamond (NCD) has a great potential for prosthetic implants coating. Nevertheless, its biocompatibility still has to be better understood. To do so, we employed several materials characterization techniques (SEM, AFM, micro‐Raman spectroscopy) and cell culture assays using MG63 osteoblast‐like and human bone marrow cells. Biochemical routines (MTT assays, Lowry's method, ALP activity) supported by SEM and confocal microscopy characterization were carried out. We used silicon nitride (Si3N4) substrates for NCD coatings based on a previous demonstration of the superior adhesion and tribological performance of these NCD coated ceramics. Results demonstrate an improved human osteoblast proliferation and the stimulation of differentiated markers, like ALP activity and matrix mineralization, compared with standard polystyrene tissue culture plates. The nanometric featuring of NCD, associated to its chemical affinity are key points for bone regeneration purposes. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
The artificial surface‐induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent
Authors: Lappegård K. T. , Bergseth G. , Riesenfeld J. , Pharo A. , Magotti P. , Lambris J. D. , Mollnes T. E.
Published: December 2007

Exposing blood to an artificial surface results in a systemic inflammatory response, including cytokine release and complement activation. We studied the artificial surface‐induced inflammation in human whole blood using an extensive panel of inflammatory mediators including proinflammatory cytokines, chemokines and growth‐factors and investigated the role of the complement system in the induction of this response. Using multiplex technology, 27 different inflammatory mediators were measured after circulating blood for 4 hours in polyvinyl chloride tubing. The C3 inhibitor compstatin was used to block complement activation. A significant (p < 0.05) increase in 14 of the 27 mediators was induced by the surface, of which 7 were chemokines (IL‐8, MCP‐1, MIP‐1α, MIP‐1β, RANTES, eotaxin and IP‐10) and 5 were growth‐factors (G‐CSF, GM‐CSF, VEGF, PDGF and FGF). The traditional proinflammatory cytokines like IL‐1β, TNFα and IL‐6 were not induced, although IL‐6, as well as IL‐15 and IL‐17 increased if the surface was coated with highly bioincompatible laminaran. Inhibition of complement activation with compstatin significantly (p < 0.05) reduced the formation of 12 of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or more, for the remaining two the inhibition was more moderate. A highly biocompatible heparin‐coated PVC surface was used as negative control and completely abolished the whole inflammatory response. The artificial surface PVC markedly induced a broad spectrum of chemokines and growth‐factors, which was largely dependent on activation of complement. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Gene expression analysis of osteoblasts seeded in coral scaffold
Authors: Foo Lean Heong , Suzina A. H. , Azlina A. , Kannan T. P.
Published: December 2007

Coral matrix of Porites sp. has the suitable properties for bone cell growth. This study was aimed to study the gene expression levels of osteoblast specific genetic markers; RUNX2, osteopontin, alkaline phosphatase and osteocalcin from osteoblasts seeded in coral scaffold, which are important in determining the feasibility of osteoblasts. Human osteoblasts were inoculated onto the processed coral in Dulbecco's Minimum Essential Medium. The cells were trypsinized on day 1, 7, 14, 18, and 21 and added with RNALater for preservation of RNA in cells. The RNA was extracted using commercial RNA extraction kit and the respective genes were amplified using RT‐PCR kit and analyzed qualitatively on 1.5% agarose gel. The expressions were evaluated with the Integrated Density Value based on the intensity of band for different periods of cell harvest. Increased expressions of the RUNX2, osteopontin, alkaline phosphatase and osteocalcin genes in the present study proved that coral is a favorable carrier for osteogenetically competent cells to attach and remain viable. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Evaluation of bone healing with eggshell‐derived bone graft substitutes in rat calvaria: A pilot study
Authors: Park Jin‐Woo , Bae Sang‐Ryul , Suh Jo‐Young , Lee Dong‐Hee , Kim Sang‐Hyun , Kim Hyungjun , Lee Chong‐Soo
Published: December 2007

The purpose of this study was to investigate the potential effectiveness of a surface‐modified natural calcium carbonate, hen eggshell (ES) as a bone graft substitute. The surface characteristics, cell viability on, and osteoconductivity of, particulated ES with and without hydrothermal treatment in phosphate solutions were evaluated. Hydrothermal treatment partially converted ES to calcium‐deficient hydroxyapatite (HA) with surface microstructure. MTT assay indicated higher osteoblast viability on surface‐modified ES compared with a commercially available bone substitute, anorganic bovine bone (Bio‐Oss, BO) (p < 0.001). Histological and histomorphometric analysis showed significantly greater new bone formation and mineralized bone‐to‐graft contact of surface‐modified ES, especially with hydrothermally treated ES, compared with BO in 5‐mm diameter calvarial defects in rats at 4 and 8 weeks of healing (p < 0.01). Complete bony bridging was more frequently found with hydrothermally treated ES. The results of this pilot study indicate the potential efficacy of surface‐modified particulated hen eggshell as an osteoconductive bone substitute in a rat calvarial defect model. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
The evolution of female mole ovotestes evidences high plasticity of mammalian gonad development
Authors: Carmona F. David , Motokawa Masaharu , Tokita Masayoshi , Tsuchiya Kimiyuki , Jiménez Rafael , Sánchez‐Villagra Marcelo R.
Published: December 2007

Previous studies of the reproductive biology and genetics of European moles (Talpa spp.) showed that all females of these species have ovotestes (gonads with testicular and ovarian tissue) instead of normal ovaries, a unique specialization among mammals. Females are fertile as their ovarian tissue is fully functional. Testicular tissue is abnormal and sterile, but produces high levels of testosterone. This phenomenon also characterizes other talpid species from Europe and North America. To study the origin of this singular reproductive specialization, we examined the gonads of several female specimens belonging to two critical taxa. Although large Japanese moles (Mogera wogura) posses ovotestes, greater Japanese shrew moles (Urotrichus talpoides) are characterized by normal ovaries. The results fit parsimoniously with a recent phylogenetic study that places Urotrichus relatively basal in the talpid tree and separate from the American shrew mole. Parsimony reconstruction on alternative phylogenetic hypotheses clearly indicates that reversal(s) must have occurred and suggests that a relatively simple genetic mechanism must be associated with the evolution of female hermaphroditism in moles. J. Exp. Zool. (Mol. Dev. Evol.) 310B:259–266, 2008. © 2007 Wiley‐Liss, Inc.
Developing strategies for detection of gene doping
Authors: Baoutina Anna , Alexander Ian E. , Rasko John E. J. , Emslie Kerry R.
Published: December 2007

It is feared that the use of gene transfer technology to enhance athletic performance, the practice that has received the term ‘gene doping’, may soon become a real threat to the world of sport. As recognised by the anti‐doping community, gene doping, like doping in any form, undermines principles of fair play in sport and most importantly, involves major health risks to athletes who partake in gene doping. One attraction of gene doping for such athletes and their entourage lies in the apparent difficulty of detecting its use. Since the realisation of the threat of gene doping to sport in 2001, the anti‐doping community and scientists from different disciplines concerned with potential misuse of gene therapy technologies for performance enhancement have focused extensive efforts on developing robust methods for gene doping detection which could be used by the World Anti‐Doping Agency to monitor athletes and would meet the requirements of a legally defensible test. Here we review the approaches and technologies which are being evaluated for the detection of gene doping, as well as for monitoring the efficacy of legitimate gene therapy, in relation to the detection target, the type of sample required for analysis and detection methods. We examine the accumulated knowledge on responses of the body, at both cellular and systemic levels, to gene transfer and evaluate strategies for gene doping detection based on current knowledge of gene technology, immunology, transcriptomics, proteomics, biochemistry and physiology. Copyright © 2008 John Wiley & Sons, Ltd.
Mass spectrometric study of selected precursors and degradation products of chemical warfare agents
Authors: Papoušková Barbora , Bednář Petr , Fryšová Iveta , Stýskala Jakub , Hlaváč Jan , Barták Petr , Ulrichová Jitka , Jirkovský Jaromír , Lemr Karel
Published: December 2007

Selected precursors and degradation products of chemical warfare agents namely N,N‐dialkylaminoethane‐2‐ols, N,N‐dialkylaminoethyl‐2‐chlorides and some of related N‐quaternary salts were studied by means of electrospray ionization‐multiple tandem mass spectrometry (ESI‐MSn). Proposed structures were confirmed with accurate mass measurement. General fragmentation patterns of these compounds are discussed in detail and suggested processes are confirmed using deuterated standards. The typical processes are elimination of alkene, hydrogen chloride, or water, respectively. Besides, elimination of ethene from propyl chain under specific conditions was observed and unambiguously confirmed using exact mass measurement and labelled standard. The potential of mass spectrometry to distinguish the positional isomers occurring among the studied compounds is reviewed in detail using two different MS instruments (i.e. ion trap and hybrid quadrupole‐time of flight (Q‐TOF) analyzer). A new microcolumn liquid chromatography (µLC)/MSn method was designed for the cases where the resolution based solely on differences in fragmentation is not sufficient. Low retention of the derivatives on reversed phase (RP) was overcome by using addition of less typical ion pairing agent (1 mM/l, 3,5‐dinitrobenzoic acid) to the mobile phase (mixture water : acetonitrile). Copyright © 2007 John Wiley & Sons, Ltd.
De novo sequencing of a 21‐kDa cytochrome c4 from Thiocapsa roseopersicina by nanoelectrospray ionization ion‐trap and Fourier‐transform ion‐cyclotron resonance mass spectrometry
Authors: Branca Rui Miguel Mamede , Bodó Gabriella , Bagyinka Csaba , Prokai Laszlo
Published: December 2007

We have determined the primary structure of cytochrome c4 from Thiocapsa roseopersicina by de novo protein sequencing using the ‘bottom up’ approach. Three different enzymes (trypsin, endoproteinase Lys‐C, and endoproteinase Glu‐C) were employed to prepare four different sets of proteolytic digests. The digestion strategy was designed to permit a gradual buildup of smaller peptides into larger ones that were overlapped to yield the complete protein sequence. In this way we countered the main problem: peptides larger than about 1500 Da were difficult to sequence fully by tandem mass spectrometry. Direct infusion and online liquid chromatography were used on a linear ion trap Fourier‐transform ion‐cyclotron resonance hybrid instrument. The high resolving power, high mass accuracy and the availability of electron capture dissociation and collision‐induced dissociation were essential to achieve full sequence coverage. The software DeNovoX complemented by manual interpretation was used to generate sequence information from tandem mass spectra. The predominantly automated nature of data acquisition and handling allowed for a relatively straightforward and fast procedure, which could compete with the mainstream alternative of nucleotide sequence determination. Copyright © 2007 John Wiley & Sons, Ltd.
An investigation on the nature of the peptide at m/z 904, overexpressed in plasma of patients with colorectal cancer and familial adenomatous polyposis
Authors: Seraglia Roberta , Molin Laura , Tonidandel Loris , Pucciarelli Salvatore , Agostini Marco , Urso Emanuele Damiano , Bedin Chiara , Quaia Michele , Nitti Donato , Traldi Pietro
Published: December 2007

In an investigation devoted to the search for plasma markers for colorectal cancer (CRC), carried out by matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry, a series of overexpressed peptides were identified in the plasma of patients. Among them the peptide with molecular weight 903 Da was the most abundant one, with a mean ± (SD) relative abundance of 37 ± 17% and a frequency over 60%. Interestingly, also in plasma samples of ten subjects affected by familial adenomatous polyposis (FAP), the peptide with molecular weight 903 was overexpressed. In this investigation, MALDI/MS/MS experiments were carried out on the ion at m/z 904 detected in the MALDI mass spectra of CRC and FAP patients. The data analysis by SwissProt.2007.01.09 indicates that this peptide is due to the sequence RPPGFSPF, found in the kininogen‐1 precursor, which is an α‐2‐thiol proteinase inhibitor. In the case of subjects affected by a particular FAP syndrome, the MALDI/MS/MS spectra were quite different from those obtained from CRC and FAP patients. In fact, two sequences have been evidenced: RPPGFSPF belonging to kininogen‐1 precursor, and PRKSSSSR belonging to Forkhead box protein 01A. Copyright © 2007 John Wiley & Sons, Ltd.
Development of an HPLC multi‐residue method for the determination of ten quinolones in bovine liver and porcine kidney according to the European Union Decision 2002/657/EC
Authors: Christodoulou Eleni A. , Samanidou Victoria F. , Papadoyannis Ioannis N.
Published: December 2007

A sensitive multi‐residue analytical method was developed for the determination of ten quinolones: enoxacin, ofloxacin, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, sarafloxacin, oxolinic acid, nalidixic acid, and flumequine in bovine liver and porcine kidney. A simple liquid extraction step followed by a solid phase extraction clean up procedure was applied for the extraction of quinolones from liver and kidney tissues. Recoveries of the extraction varied between 82 and 88% for bovine liver and 92 and 95% for porcine kidney. Separation was performed on an ODS‐3 PerfectSil Target (250×4 mm) 5 μm analytical column at 25°C. The mobile phase consisted of a mixture of TFA 0.1%–CH3CN–CH3OH, delivered at a flow rate of 1.2 mL/min according to a gradient program. Elution of quinolones and the internal standard (caffeine, 7.5 ng/μL) was complete within 27 min. Photodiode array detection was used for monitoring the eluants at 275 and 255 nm. The method was fully validated according to the European Union Decision 2002/657/EC, determining linearity, selectivity, decision limit, detection capability, accuracy, and precision. The LODs of the specific method of quinolone determination in bovine liver varied between 3 and 7 μg/kg and in porcine kidney between 3 and 4 μg/kg.
Attenuation of DNA damage‐induced p53 expression by arsenic: A possible mechanism for arsenic co‐carcinogenesis
Authors: Shen Shengwen , Lee Jane , Weinfeld Michael , Le X. Chris
Published: December 2007

Inhibition of DNA repair processes has been suggested as one predominant mechanism in arsenic co‐genotoxicity. However, the underlying mode of action responsible for DNA repair inhibition by arsenic remains elusive. To further elucidate the mechanism of repair inhibition by arsenic, we examined the effect of trivalent inorganic and methylated arsenic metabolites on the repair of benzo(a)pyrene diol epoxide (BPDE)–DNA adducts in normal human primary fibroblasts and their effect on repair‐related protein expression. We observed that monomethylarsonous acid (MMAIII) was the most potent inhibitor of the DNA repair. MMAIII did not change the expression levels of some key repair proteins involved upstream of the dual incision in the global nucleotide excision repair (NER) pathway, including p48, XPC, xeroderma pigmentosum complementation group A (XPA), and p62‐TFIIH. However, it led to a marked impairment of p53 induction in response to BPDE treatment. The abrogated p53 expression translated into reduced p53 DNA‐binding activity, suggesting a possibility of downregulating downstream repair genes by p53. A p53‐null cell line failed to exhibit the inhibitory effect of MMAIII on NER, implicating a role for p53 in the NER inhibition by MMAIII. Further investigation revealed that MMAIII dramatically inhibited p53 phosphorylation at serine 15, implying that MMAIII destabilized p53 by inhibiting its phosphorylation. Because p53 is required for proficient global NER, our data suggest that arsenic inhibits NER through suppressing p53 induction in response to DNA damage in cells with normal p53 gene expression. © 2007 Wiley‐Liss, Inc.
Adaptive through‐thickness integration for accurate springback prediction
Authors: Burchitz I. A. , Meinders T.
Published: December 2007

Accurate numerical prediction of springback in sheet metal forming is essential for the automotive industry. Numerous factors influence the accuracy of prediction of this complex phenomenon by using the finite element method. One of them is the numerical integration through the thickness of shell elements. It is known that the traditional numerical schemes are very inefficient in elastic–plastic analysis and even for simple problems they require up to 50 integration points for an accurate springback prediction. An adaptive through‐thickness integration strategy can be a good alternative. The main characteristic feature of the strategy is that it defines abscissas and weights depending on the integrand's properties and, thus, can adapt itself to improve the accuracy of integration. A concept of an adaptive through‐thickness integration strategy for shell elements is presented in this paper. Its potential is demonstrated using two examples. Calculations of a simple test—bending a beam under tension—show that for a similar set of material and process parameters the adaptive rule with seven integration points performs significantly better than the traditional trapezoidal rule with 50 points. Simulations of an unconstrained cylindrical bending problem demonstrate that the adaptive through‐thickness integration strategy for shell elements can guarantee an accurate springback prediction at minimal costs. Copyright © 2007 John Wiley & Sons, Ltd.
Transcription factor SOX‐5 enhances nasopharyngeal carcinoma progression by down‐regulating SPARC gene expression
Authors: Huang D‐Y , Lin Y‐T , Jan P‐S , Hwang Y‐C , Liang S‐T , Peng Y , Huang C‐YF , Wu H‐C , Lin C‐T
Published: December 2007

Nasopharyngeal carcinoma (NPC) is prevalent in south‐eastern Asia, and its tumourigenesis is rather complex. The purpose of this research was to identify the pivotal genes that may be altered during the early stage of NPC progression. Eleven genes were selected by comparative microarray analysis of NPC versus normal nasomucosal cells. The expression of SPARC (secreted protein, acidic, cysteine‐rich) was statistically significantly down‐regulated in NPC cells. In exploring the mechanism underlying the decreased transcription of SPARC in NPC cells, we found that the transcription factor SRY (sex‐determining region Y)‐box 5 (SOX‐5) is up‐regulated in NPC cells. RNA interference of SOX‐5 by short hairpin RNA (shRNA) in NPC cells caused a dramatic increase in SPARC and chromosome immunoprecipitation assay showed that SOX‐5 can bind directly to the SPARC promoter, suggesting that SOX‐5 acts as a key transcriptional repressor of SPARC. We further demonstrated that shRNA knockdown of SOX‐5 suppressed the proliferation of NPC cells, as well as their migratory ability, which was also observed when SPARC was over‐expressed in NPC cells. Alternatively, blocking SPARC with an antagonistic antibody reversed the effects of SOX‐5 knockdown. In 66 NPC patients, over‐expression of SOX‐5 in tumour cells correlated clinically with poor survival. Our study suggests that SOX‐5 transcriptionally down‐regulates SPARC expression and plays an important role in the regulation of NPC progression. SOX‐5 is a potential tumour marker for poor NPC prognosis. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mössbauer studies of Fe‐Zn sulphur spinels
Authors: Bae Sung Hwan , Kim Sam Jin , Kim Chul Sung
Published: December 2007

The polycrystalline sample of Zn doped Fe1–xZnxCr2S4(x = 0.1, 0.3) were prepared by solid state reaction. The crystal structure was determined to be the normal cubic spinel of space group Fd 3m and the lattice constants(x = 0.1, 0.3) were a0 = 9.9967(3) Å and a0 = 9.9926(3) Å, respectively. The magnetic moment values of Fe1–xZnxCr2S4 for the x = 0.3 were observed higher than that of the x = 0.1. The Néel temperatures were decreased to 153 K (x = 0.1), 135 K (x = 0.3) with Zn substitution concentration. This result is due to the decrease of A‐B superexchange interaction by the replacement of Zn ions for A site. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Superexchange interactions in inverse spinel lithium ferrites
Authors: Hyun Sung Wook , Kim Chul Sung
Published: December 2007

Spinel ferrites, MFe2O4 (M = Ni, Mg, Co, Li) samples were prepared by sol‐gel method. It has been studied by X‐ray diffraction, Mössbauer spectroscopy. X‐ray diffraction patterns were analyzed by the Rietveld refinement. The samples have been cubic spinel structure with the lattice constant (a0) is 8.326 ∼ 8.390 Å. The temperature dependence of the magnetic hyperfine field is analyzed by the Néel theory of ferrimagnetism. The intersublattice A‐O‐B and intrasublattice A‐O‐A superexchange interactions are found to be antiferromagnetic while the intrasublattice B‐O‐B superexchange interaction is ferromagnetic for the MFe2O4 (M = Ni, Mg, Co) samples as shown in Table 1. On the other hand, the intersublattice superexchange interaction is found to be antiferromagnetic while the intrasublattice superexchange interactions are ferromagnetic for the lithium ferrite sample. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Relation between Mössbauer spectroscopy and geometrical frustration factors in MCr1.9857Fe0.02O4 (M = Co, Zn)
Authors: Choi Kang Ryong , Kouh Taejoon , Kim Sam Jin , Kim Chul Sung
Published: December 2007

In order to elucidate the role of Cr ions in MCr2O4(M = Co, Zn) exhibiting geometrically frustration and multiferroic property, we have substituted a small amount of Fe ions for Cr sites and investigated the magnetic behavior of Fe ions with Mössbauer spectroscopy. The crystal structure was found to be single‐phase cubic spinel with space group of Fd3m. The lattice constants a0 and the internal structural parameter (x) of the oxygen were determined to be 8.340, 8.331 Å and 0.261 and 0.260, respectively. The Mössbauer absorption spectra at 4.2 K show that the well‐developed two sextets are superposed with small difference of hyperfine fields(Hhf). The hyperfine fields of CoCr1.9857Fe0.02O4 and ZnCr1.9857Fe0.02O4 were determined to be 490 ∼ 480 kOe and 460 ∼ 450 kOe, respectively. Isomer shift values (δ) of the two sextets are found to be 0.33 ∼ 0.35 mm/s relative to those of Fe metal, which are consistent with the high spin Fe3+ charge state. From the results of Mössbauer measurement, it is suggested that Cr3+ ions have two different magnetic sites, and there is a correlation between hyperfine fields and degree of magnetic geometrical frustration. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Magnetism of linear Fe, Co, and Ni nanowires encapsulated in zigzag (n,0) carbon nanotubes (CNT) with n = 5 to 9: A first‐principles study
Authors: Jang Y.‐R. , Lee J. I.
Published: December 2007

We investigated the magnetic properties of linear Fe, Co, and Ni nanowires (NW) encapsulated in zigzag (n,0) (n = 5, 6, 7, 8, and 9) carbon nanotubes (CNT) using the first‐principles plane wave calculation with the generalized gradient approximation. The magnetic moments per atom for transition metal atoms in the zigzag (n,0) with n = 8 and 9 were slightly smaller than those of freestanding transition metal nanowires with the same bond length, but the values were decreased abruptly for the NW in (6,0) and (5,0). These results suggest that the magnetic properties of linear NW in zigzag CNT are mainly determined by the size of CNT and also by the electronic property of surrounding CNT. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of spin‐flip tunneling on temperature and voltage dependence of TMR
Authors: Takada I. , Ozeki J. , Itoh H. , Inoue J.
Published: December 2007

We study the temperature and voltage dependence of the tunnel magnetoresistance (TMR) using a phenomenological theory which takes into account the spin‐flip tunneling. We show that the temperature dependence becomes strong when the spin‐flip tunneling exists. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Inhomogeneous spin accumulation in Py/Au/Py spin valve
Authors: Ku Jang Hae , Chang Joonyeon , Eom Jonghwa , Koo Hyuncheol , Han Suk‐Hee , Kim Gyutae
Published: December 2007

We present that inhomogeneous spin accumulation in a Py/Au/Py spin valve is due to the formation of an edge point contact at the interface. Nonlocal measurements with different voltage probe configurations were carried out to understand the effect of probe location on the spin signal. The spin signal is strongly affected by the probe configuration because of inhomogeneous spin current distribution in the channel as well as different channel length depending on the probe position. Inhomogeneous spin accumulation initiating from the point contact induces the different distribution of spin accumulation flowing into a detector. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The contribution of the exchange biased field direction in multilayer thin films to planar Hall resistance
Authors: Hung Tran Quang , Quang Pham Hong , Thanh Nguyen Trung , Sunjong Oh , Bajaj Bharat , CheolGi Kim
Published: December 2007

Recently, planar Hall effect (PHE) has been widely pursued due to its application potential for biosensors. Planar Hall sensor is based on the anisotropy magnetoresistance and exhibits many advantages, such as large signal‐to‐noise ratio at low frequencies and high sensitivity at low applied field. The planar Hall resistance (PHR) curve in multilayer thin films with spinvalve structure has pre‐eminent sensitivity when compared to single layer and bilayer thin films. In this work, we report a model for PHR calculation that includes the behaviour of single domain basic structure in the external magnetic field. Our results show a qualitative dependence between PHR curves and the angle (β) between the exchange biased field direction and the easy axis of the free layer. As the β increases the sensitivity of the PHR curves also increases. Further, it is shown that our calculation helps to determine the exchange biased field direction. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)