bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiplex SNaPshot for detection of BRCA1/2 common mutations in Spanish and Spanish related breast/ovarian cancer families
Authors: Filippini Sandra , Blanco Ana , Fernández-Marmiesse Ana , Álvarez-Iglesias Vanesa , Ruíz-Ponte Clara , Carracedo Ángel , Vega Ana
Published: June 2007

Background

It is estimated that 5–10% of all breast cancer are hereditary and attributable to mutations in the highly penetrance susceptibility genes BRCA1 and BRCA2. The genetic analysis of these genes is complex and expensive essentially because their length. Nevertheless, the presence of recurrent and founder mutations allows a pre-screening for the identification of the most frequent mutations found in each geographical region. In Spain, five mutations in BRCA1 and other five in BRCA2 account for approximately 50% of the mutations detected in Spanish families.

Methods

We have developed a novel PCR multiplex SNaPshot reaction that targets all ten recurrent and founder mutations identified in BRCA1 and BRCA2 in Spain to date.

Results

The SNaPshot reaction was performed on samples previously analyzed by direct sequencing and all mutations were concordant. This strategy permits the analysis of approximately 50% of all mutations observed to be responsible for breast/ovarian cancer in Spanish families using a single reaction per patient sample.

Conclusion

The SNaPshot assay developed is sensitive, rapid, with minimum cost per sample and additionally can be automated for high-throughput genotyping. The SNaPshot assay outlined here is not only useful for analysis of Spanish breast/ovarian cancer families, but also e.g. for populations with Spanish ancestry, such as those in Latin America.
Outcomes of adoption from public care: research and practice issues
Authors: Rushton Alan
Published: June 2007

The article covers the state of play of adoption from local authority care in the UK and research into the factors influencing placement outcomes. The major contentious issues about placement are discussed in relation to competing opinions and available evidence. Ways of intervening in adoptive families in difficulty are considered, together with current efforts to establish what makes for effective support services. This article recommends comprehensive assessments of the children to be placed and carefully targeted adoption-aware psychosocial interventions.
Monitoring electroconvulsive therapy by electroencephalogram: an update for ECT practitioners
Authors: Scott Allan I. F.
Published: June 2007

The purpose of this article is to update practitioners on the latest published research into the prevalence of prolonged cerebral seizure activity following electroconvulsive therapy (ECT). This research is drawing attention to the real practical challenges of recording and reading an electroencephalogram (EEG) tracing in the ECT clinic. In particular, determination of the seizure end-point is not always practicable and this poses a major problem in the detection and management of prolonged cerebral seizure activity. Some practical tips are suggested, and an update is given on the status of EEG monitoring in the assessment of seizure adequacy.
Depressive symptoms during pregnancy and low birth weight at term
Authors: Evans Jonathan , Heron Jon , Patel Roshni R. , Wiles Nicola
Published: June 2007

There is conflicting evidence regarding the effect of depression during pregnancy on birth weight. We used data from the Avon Longitudinal Study of Parents and Children to investigate whether depressive symptoms during pregnancy in 10 967 women led to low birth weight at term in their offspring. Those with a high depressive symptom score during pregnancy were more likely to have babies of low birth weight (95% CI 1.16–2.40, P < 0.01), but this attenuated after adjustment for confounders (OR = 1.29, 95% CI 0.87–1.91, P = 0.210). Hence there is little evidence of an independent association between depressive symptoms during pregnancy and birth weight.
Influence of drug company authorship and sponsorship on drug trial outcomes
Authors: Tungaraza Tongeji , Poole Rob
Published: June 2007

Studies of drug treatments are more likely to report favourable outcomes when they are funded by the pharmaceutical industry. We compared drug trials reported in three major psychiatric journals to investigate these influences. Independent studies were more likely to report negative findings than industry-funded studies. However, the involvement of a drug company employee had a much greater effect on study outcome than financial sponsorship alone.
Asylum claims and memory of trauma: sharing our knowledge
Authors: Herlihy Jane , Turner Stuart W.
Published: June 2007

Decisions about asylum are extremely difficult because of the absence of a body of objective evidence. Psychiatrists and psychologists have a breadth of knowledge relating to the memory of trauma which could help to inform the asylum process, but we need to investigate how to apply this knowledge and how to make it accessible to decision makers.
Acute in-patient psychiatry: residential alternatives to hospital admission
Authors: Johnson Sonia , Gilburt Helen , Lloyd-Evans Brynmor , Slade Mike
Published: June 2007

There is a consensus that mental health in-patient services need improvement, and one potential approach is the development of residential alternatives in the community. We review published accounts of such alternatives and outline a new study that will describe and evaluate currently available services of this type.
Dialectical behaviour treatment: implementation and outcomes
Authors: Zinkler Martin , Gaglia Amy , Arokiadass S. M. Rajagopal , Farhy Eldad
Published: June 2007

Aims and Method

Dialectical behaviour therapy is an evidence-based treatment for people with borderline personality disorder. We describe implementation and outcomes of a new service.

Results

Hospital use and frequency of self-harm were reduced dramatically with dialectical behaviour therapy. Moreover, the therapy can be implemented successfully in a relatively short time at modest costs.

Clinical Implications

Dialectical behaviour therapy provides a useful model of treatment for people with borderline personality disorder and/or self-harm in community mental health settings.
Neuregulin Expression Modulates Clinical Response to Trastuzumab in Patients With Metastatic Breast Cancer
Authors: de Alava Enrique , Ocaña Alberto , Abad Mar , Montero Juan Carlos , Esparís-Ogando Azucena , Rodríguez César A. , Otero Ana P. , Hernández Teresa , Cruz Juan J. , Pandiella Atanasio
Published: June 2007

Purpose

Human epidermal growth factor receptor 2 (HER-2) overexpression has been associated with the genesis and progression of a subset of breast cancers. The function of HER-2 may be upregulated by overexpression or by the availability of neuregulins (NRGs), a group of transmembrane growth factors. Transmembrane NRGs strongly activated HER-2 and cell proliferation in breast cancer cells that did not overexpress HER-2, and treatment with trastuzumab prevented the proliferative action of transmembrane NRG. This raised the relevant clinical question of whether patients considered as HER-2 negative, but expressing transmembrane NRG, may benefit from treatment with trastuzumab.

Patients and Methods

MCF7 cells expressing transmembrane NRG (MCF7-NRGα2c) were injected into mice, and their sensitivity to trastuzumab was assessed. A retrospective study of 124 patients with early-stage or metastatic breast cancer was conducted. Expression of transmembrane NRG was evaluated by immunohistochemistry. In 11 patients, Western blot for NRGs was also carried out. Statistics were performed to analyze possible correlations between NRG expression and response to trastuzumab-based therapies, event-free survival, and overall survival (OS).

Results

Trastuzumab inhibited tumor growth in mice injected with MCF7-NRGα2c cells. Transmembrane NRG was frequently expressed in breast cancer patients. Overexpression of transmembrane NRG significantly correlated with a longer event-free survival and OS in patients with low or normal HER-2 expression who were treated with trastuzumab-based therapies but not in patients with HER-2 overexpression.

Conclusion

We suggest that the spectrum of patients who may benefit from trastuzumab-based therapies may be widened to include patients with metastatic breast cancer without HER-2 amplification but who express transmembrane NRGs.
Rhesus glycoprotein gene expression in the mangrove killifishKryptolebias marmoratusexposed to elevated environmental ammonia levels and air
Authors: Hung C. Y. C. , Tsui K. N. T. , Wilson J. M. , Nawata C. M. , Wood C. M. , Wright P. A.
Published: June 2007

The mechanism(s) of ammonia excretion in the presence of elevated external ammonia are not well understood in fish. Recent studies in other organisms have revealed a new class of ammonia transporters, Rhesus glycoprotein genes(Rh genes), which may also play a role in ammonia excretion in fish. The first objective of this study was to clone and characterize Rhgenes in a fish species with a relatively high tolerance to environmental ammonia, the mangrove killifish Kryptolebias marmoratus (formerly Rivulus marmoratus). We obtained full-length cDNAs of three Rh genes in K. marmoratus: RhBG (1736 bp), RhCG1 (1920 bp) and RhCG2 (2021 bp), which are highly homologous with other known Rh gene sequences. Hydropathy analysis revealed that all three Rh genes encode membrane proteins with 10–12 predicted transmembrane domains. RhBG, RhCG1 and RhCG2 are highly expressed in gill tissue, with RhBG also present in skin of K. marmoratus. Exposure to elevated environmental ammonia (2 mmol l–1 NH4HCO3) for 5 days resulted in a modest (+37%) increase in whole-body ammonia levels, whereas gill RhCG2 and skin RhCG1 mRNA levels were upregulated by 5.8- and 7.7-fold, respectively. RhBG mRNA levels were also increased in various tissues, with 3- to 7-fold increases in the liver and skeletal muscle. In a separate group of killifish exposed to air for 24 h, RhCG1 and RhCG2 mRNA levels were elevated by 4- to 6-fold in the skin. Thus, the multifold induction of Rh mRNA levels in excretory tissues (gills and skin) and internal tissues in response to conditions that perturb normal ammonia excretion suggests that RhBG, RhCG1 and RhCG2 may be involved in facilitating ammonia transport in this species. Furthermore, the findings support earlier studies demonstrating that the skin is an important site of ammonia excretion in K. marmoratus.
Morphological predictors of swimming speed: a case study of pre-settlement juvenile coral reef fishes
Authors: Fisher Rebecca , Hogan J. Derek
Published: June 2007

The swimming abilities of fishes are of vital importance to their ecology,and studies on fish swimming have been the focus of research for over a century. Here we explore the relationship between swimming ability and external body morphology, using data on Ucrit swimming speeds of 100 species of pre-settlement juvenile coral reef fishes (at the transition between the larval and adult habitats), comprising 26 different families from 5 orders. The taxonomic diversity of this methodologically consistent dataset provides a unique opportunity to examine the relationship between form and function in fish swimming across a broad taxonomic range. Overall, we found that a predictive model incorporating total length(TL), the square of caudal peduncle depth factor(CPDF2) and aspect ratio (AR) can be used to accurately predict swimming performance of a wide range of fish families, and was able to explain 69% of the variability in swimming performance of these pre-settlement juvenile fishes. The model was also able to successfully predict the swimming speed of an out-group salmonid species (Oncorhynchus mykiss). There was no evidence that the model fit differed among taxonomic groups, despite the inclusion of five different orders of fishes,suggesting that body morphology sufficiently explains the bulk of differences in swimming performance. Furthermore, the model appears to work equally well for fishes from the Great Barrier Reef and the Caribbean, and for families with different adult habitat associations and swimming modes. It remains to be determined how well the model predicts the swimming abilities of temperate species as well as adults of these same species. This model provides an invaluable means of predicting swimming abilities of pre-settlement juvenile fishes that are unable to be reared in the laboratory, do not perform well in swimming flumes or are unable to be captured live in the field.
Stimulus frequency differentially affects chirping in two species of weakly electric fish: implications for the evolution of signal structure and function
Authors: Kolodziejski Johanna A. , Sanford Sara E. , Smith G. Troy
Published: June 2007

During social interactions, apteronotid electric fish modulate their electric organ discharges (EODs) to produce transient communication signals known as chirps. Chirps vary widely across species and sex in both number and structure. In Apteronotus leptorhynchus, males chirp far more than females and their chirps have greater frequency modulation than those of females. High-frequency chirps are produced by males most often in response to female-like electric signals. As such, they have been hypothesized to function in courtship. The more common low-frequency chirps, produced by both males and females in response to same-sex signals, are hypothesized to function as aggressive signals. To determine whether the two chirp types in the closely related Apteronotus albifrons have similar functions, we stimulated chirping in male and female A. leptorhynchus and A. albifrons with playbacks simulating the EODs of same-sex versusopposite-sex conspecifics. As in A. leptorhynchus, male and female A. albifrons produced low-frequency chirps most often to same-sex signals. Unlike A. leptorhynchus, however, A. albifrons also produced more high-frequency chirps to same-sex stimuli than to opposite-sex stimuli. This suggests that high-frequency chirps in A. albifrons,unlike those in A. leptorhynchus, may not function as courtship signals and that the function of similar chirp types has diversified in Apteronotus. Examples such as this, in which the function of a communication signal has changed in closely related species, are rare. The electrocommunication signals of apteronotids may thus provide a remarkable opportunity to investigate the evolutionary interactions of signal structure and function.
Facile Synthesis of Self-aggregative Zinc Bacteriochlorins by Modifying Naturally Occurring Chlorophyll-a
Authors: Kunieda Michio , Yamamoto Kohei , Sasaki Shin-ichi , Tamiaki Hitoshi
Published: June 2007

We prepared zinc 7,8-cis-dihydroxy-3-hydroxymethyl-131-oxo-bacteriochlorin 1 by modifying naturally occurring chlorophyll-a and examined its self-aggregation mimicking self-aggregates of natural bacteriochlorophylls-c/d/e in the main light-harvesting antenna system of green photosynthetic bacteria. Bacteriochlorin 1 has interactive hydroxy groups not only at the 31-position but also at the 7,8-positions, and the latter two hydroxy groups did not disturb its self-aggregation process.
Experimental induction of cervical lymphadenitis in guinea-pigs with group C streptococci
Authors: Olson L. D. , Schueler R. L. , Riley G. M. , Morehouse L. G.
Published: June 2007

Streptococcal lymphadenitis with macroscopic abscesses was induced in guinea-pigs when an isolate of Lancefield's group C streptococci of guinea-pig origin was sprayed orally. The disease was also produced in guinea-pigs when another isolate was injected sublingually but not when it was sprayed orally. Treatment with prednisolone did not increase the susceptibility to the latter isolant when sprayed orally.

Abscesses could not be induced in the cervical lymph nodes of guineapigs exposed by injecting group E streptococci sublingually, although the organism was isolated from the cervical lymph nodes 2 days after inoculation. Neither could abscesses be induced by injecting these streptococci sublingually in guinea-pigs treated with prednisolone.
Is 'inconsistency' in research ethics committee decision-making really a problem? An empirical investigation and reflection
Authors: Angell E L , Jackson C J , Ashcroft R E , Bryman A , Windridge K , Dixon-Woods M
Published: June 2007

Research Ethics Committees (RECs) are frequently a focus of complaints from researchers, but evidence about the operation and decisions of RECs tends to be anecdotal. We conducted a systematic study to identify and compare the ethical issues raised in 54 letters to researchers about the same 18 applications submitted to three RECs over one year. The most common type of ethical trouble identified in REC letters related to informed consent, followed by scientific design and conduct, care and protection of research participants, confidentiality, recruitment and documentation. Community considerations were least frequently raised. There was evidence of variability in the ethical troubles identified and the remedies recommended. This analysis suggests that some principles may be more institutionalized than others, and offers some evidence of inconsistency between RECs. Inconsistency is often treated as evidence of incompetence and caprice, but a more sophisticated understanding of the role of RECs and their functioning is required.
Performance Regimes and Marketing Policy Shifts
Authors: Pauwels Koen , Hanssens Dominique M.
Published: June 2007

Even in mature markets, managers are expected to improve their brands’ performance year after year. When successful, they can expect to continue executing on an established marketing strategy. However, when the results are disappointing, a change or turnaround strategy may be called for to help performance get back on track. In such cases, performance diagnostics are needed to identify turnarounds and to quantify the role of marketing policy shifts in this process. This paper proposes a framework for such a diagnosis and applies several methods to provide converging evidence for two main findings. First, contrary to prevailing beliefs, the performance of brands in mature markets is not always stable. Instead, brands systematically improve or deteriorate their performance outlook in clearly identifiable time windows that are relatively short compared to windows of stability. Second, these shifts in performance regimes are associated with the brand’s marketing actions and policy shifts, as opposed to competitive marketing. Promotion-oriented marketing policy shifts are particularly potent in improving a brand’s performance outlook.
Designing Price Contracts for Boundedly Rational Customers: Does the Number of Blocks Matter?
Authors: Lim Noah , Ho Teck-Hua
Published: June 2007

When designing price contracts, one of the major questions confronting managers is how many blocks there should be in the contract. We investigate this question in the setting of a manufacturer-retailer dyad facing a linear deterministic consumer demand. Theoretical marketing models predict that the manufacturer’s profits rise dramatically when the number of blocks in the contract is increased from one to two because both channel efficiency and its share of channel profits increase. However, increasing the number of blocks to three yields no incremental profits.

We test these predictions experimentally and find that increasing the number of blocks from one to two raises channel efficiency but not the manufacturer’s share of profits. Surprisingly, having three blocks in the contract increases channel efficiency even further and also gives the manufacturer a slightly higher share of profits. We show that these results can be explained by a quantal response equilibrium model in which the manufacturer accounts for noisy best response due to nonpecuniary payoff components in the retailer’s utility. We also show that the retailer is sensitive to the counterfactual profits it could have earned if it were charged a lower marginal price for earlier blocks in the multiple-block contract.
The Value of Moderate Obsession: Insights from a New Model of Organizational Search
Authors: Winter Sidney G. , Cattani Gino , Dorsch Alex
Published: June 2007

This study presents a new model of search on a rugged landscape, which employs modeling techniques from fractal geometry rather than the now-familiar NK-modeling technique. In our simulations, firms search locally in a two-dimensional fitness landscape, choosing moves in a way that responds both to local payoff considerations and to a more global sense of opportunity represented by a firm-specific preferred direction. The latter concept provides a simple device for introducing cognitive or motivational considerations into the formal account of search behavior, alongside payoff considerations. After describing the objectives and the structure of the model, we report a first experiment that explores how the ruggedness of the landscape affects the interplay of local payoff and cognitive considerations (preferred direction) in search. We show that an intermediate search strategy, combining the guidance of local search with a moderate level of nonlocal obsession, is distinctly advantageous in searching a rugged landscape. We also explore the effects of other considerations, including the objective validity of the preferred direction and the degree of dispersion of firm strategies. We conclude by noting available features of the model that are not exercised in this experiment. Given the inherent flexibility of the model, the range of questions that might potentially be explored is extremely large.
A Disposable Multianalyte Electrochemical Immunosensor Array for Automated Simultaneous Determination of Tumor Markers
Authors: Wu Jie , Yan Feng , Tang Jinhai , Zhai Chun , Ju Huangxian
Published: June 2007

Background: Automated and convenient multianalyte detection with high throughput is increasingly needed in clinical diagnosis. We developed a disposable 4-by-2 array for programmed simultaneous amperometric immunoassay of 4 tumor markers.

Methods: We used a screen-printed technique, 1-step immobilization method, and flow injection technique. We immobilized carcinoembryonic antigen, α-fetoprotein, β-human choriogonadotropin, and carcinoma antigen 125 as model analytes in a redox mediator–grafted, biopolymer-modified, screen-printed carbon electrode array to capture corresponding horseradish peroxidase-labeled antibodies in competitive immunoreactions. The simultaneous multianalyte immunoassay was automatically carried out to amperometrically monitor the mediator-catalyzed enzymatic response to hydrogen peroxide, which decreased in proportion to the concentrations of analytes in samples.

Results: The multianalyte immunosensor array had a throughput of 60 samples/h and allowed simultaneous detection of carcinoembryonic antigen, α-fetoprotein, β-human choriogonadotropin, and carcinoma antigen 125 in clinical serum samples with concentrations up to 188 μg/L, 250 μg/L, 266 IU/L, and 334 kIU/L, respectively. The detection limits (limits of the blank, mean of blank plus 3 SD) were 1.1 μg/L, 1.7 μg/L, 1.2 IU/L, and 1.7 kIU/L. The inter- and intraassay imprecision (CVs) of the immunosensor arrays were <7.8% and <9.0%, respectively. The immunosensor arrays were stable for 28 days.

Conclusions: This newly constructed immunosensor array provides a simple, automated, simultaneous multianalyte immunoassay with high throughput, short analytical time, and sufficiently low detection limits for clinical application. This method offers the capability of miniaturizing the multianalyte detection device.
Concise Review: Roles of Polycomb Group Proteins in Development and Disease: A Stem Cell Perspective
Authors: Rajasekhar Vinagolu K. , Begemann Martin
Published: June 2007

The acquisition and maintenance of cell fate are essential for metazoan growth and development. A strict coordination between genetic and epigenetic programs regulates cell fate determination and maintenance. Polycomb group (PcG) genes are identified as essential in these epigenetic developmental processes. These genes encode components of multimeric transcriptional repressor complexes that are crucial in maintaining cell fate. PcG proteins have also been shown to play a central role in stem cell maintenance and lineage specification. PcG proteins, together with a battery of components including sequence-specific DNA binding/accessory factors, chromatin remodeling factors, signaling pathway intermediates, noncoding small RNAs, and RNA interference machinery, generally define a dynamic cellular identity through tight regulation of specific gene expression patterns. Epigenetic modification of chromatin structure that results in expression silencing of specific genes is now emerging as an important molecular mechanism in this process. In embryonic stem (ES) cells and adult stem cells, such specific genes represent those associated with differentiation and development, and silencing of these genes in a PcG protein-dependent manner confers stemness. ES cells also contain novel chromatin motifs enriched in epigenetic modifications associated with both activation and repression of genes, suggesting that certain genes are poised for activation or repression. Interestingly, these chromatin domains are highly coincident with the promoters of developmental regulators, which are also found to be occupied by PcG proteins. The epigenetic integrity is compromised, however, by mutations or other alterations that affect the function of PcG proteins in stem cells leading to aberrant cell proliferation and tissue transformation, a hallmark of cancer.

Disclosure of potential conflicts of interest is found at the end of this article.
E2F-6 Suppresses Growth-Associated Apoptosis of Human Hematopoietic Progenitor Cells by Counteracting Proapoptotic Activity of E2F-1
Authors: Kikuchi Jiro , Shimizu Rumi , Wada Taeko , Ando Hidenobu , Nakamura Mitsuru , Ozawa Keiya , Furukawa Yusuke
Published: June 2007

E2F-6 is a dominant-negative transcriptional repressor against other members of the E2F family. In this study, we investigated the expression and function of E2F-6 in human hematopoietic progenitor cells to clarify its role in hematopoiesis. We found that among E2F subunits, E2F-1, E2F-2, E2F-4, and E2F-6 were expressed in CD34+ human hematopoietic progenitor cells. The expression of E2F-6 increased along with proliferation and decreased during differentiation of hematopoietic progenitors, whereas the other three species were upregulated in CD34− bone marrow mononuclear cells. Overexpression of E2F-6 did not affect the growth of immature hematopoietic cell line K562 but suppressed E2F-1-induced apoptosis, whereas it failed to inhibit apoptosis induced by differentiation inducers and anticancer drugs. Among E2F-1-dependent apoptosis-related molecules, E2F-6 specifically inhibited upregulation of Apaf-1 by competing with E2F-1 for promoter binding. E2F-6 similarly suppressed apoptosis and Apaf-1 upregulation in primary hematopoietic progenitor cells during cytokine-induced proliferation but had no effect when they were differentiated. As a result, E2F-6 enhanced the clonogenic growth of colony-forming unit-granulocyte, erythroid, macrophage, and megakaryocyte. These results suggest that E2F-6 provides a failsafe mechanism against loss of hematopoietic progenitor cells during proliferation.

Disclosure of potential conflicts of interest is found at the end of this article.
Extended Resection for Pancreatic Adenocarcinoma
Authors: Reddy Srinevas K. , Tyler Douglas S. , Pappas Theodore N. , Clary Bryan M.
Published: June 2007

Learning Objectives

After completing this course, the reader will be able to: Discuss the evidence in favor of and against the role of surgical resection in the management of pancreatic adenocarcinoma.Explain how the components of an extended pancreatectomy, including total pancreatectomy, extended lymph node dissection, and major intestinal arterial resection, do not improve survival above what is provided after pancreaticoduodenectomy and are associated with substantial morbidity.Discuss how portal/mesenteric vein resection to achieve negative resection margins does not add to the morbidity of pancreaticoduodenectomy, does not worsen survival after resection, and is most often performed because of tumor location.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
New Drugs for Myeloma
Authors: Richardson Paul G. , Mitsiades Constantine , Schlossman Robert , Munshi Nikhil , Anderson Kenneth
Published: June 2007

Learning Objectives

After completing this course, the reader will be able to: Discuss the impact of novel agents on the treatment paradigm for multiple myeloma.Explain the importance of combination regimens and in particular the ability to rechallenge patients with a combination of drugs that may each have been administered separately before.Describe the toxicity profiles of the agents being used with a focus on key side effects and discuss the potential value of these agents in special populations, such as those with renal failure.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Evaluation of the reproductive effects of tamoxifen citrate in partial and full life-cycle studies using fathead minnows (Pimephales Promelas)
Authors: Williams Tim D. , Caunter John E. , Lillicrap Adam D. , Hutchinson Thomas H. , Gillings Edward G. , Duffell Stephen
Published: June 2007

Laboratory studies were conducted to investigate potential adverse effects on development, growth, reproduction and biomarker responses (vitellogenin [VTG] and gonad histology) in fathead minnows (Pimephales promelas) exposed to tamoxifen citrate. Based on the results of a partial life cycle study (nominal [mean measured] concentrations ranged from 0.18 [0.11] to 18 [15.74] μg/L), a 284-d fish full life-cycle (FFLC) flow-through study was conducted using newly fertilized embryos (<24 h postfertilization) exposed to nominal (mean measured) concentrations of 14C-tamoxifen citrate that ranged from 0.01 (0.007) to 5.12 (4.08) μg/L. Triethylene glycol (2.0 μl/L) was used as a solvent carrier, with 17β-estradiol (E2) as a positive control (nominal 0.1 μg/L). Among the biomarkers measured, significant effects on VTG and gonad histology were observed, although these results required care in their interpretation. Among important population-relevant endpoints, no effects on reproduction were observed at nominal concentrations ≤5.12 μg/L. Effects on growth (length and weight) were observed in some treatments; however, some of these showed irregular concentration-response relationships, which made interpretation uncertain, or were deemed transient in nature (e.g., reduction in growth of F1 28-d posthatch larval fish at nominal concentrations of 0.08, 0.64, and 5.12 μg/L) and judged not to be biologically significant. Interpretation of results from fish chronic studies is challenging and frequently calls for scientific judgement about statistical and biological significance and what constitutes an adverse effect. Using the principles used in mammalian toxicology studies, data from partial and FFLC studies were evaluated from both statistical and biological perspectives in order to determine no-observed-adverse effect concentrations (expressed as adverseNOEC) for use in environmental risk assessment. Careful consideration of both biological and statistical outcomes from these studies suggested overall adverseNOEC concentration and lowest-observed-effect concentration (adverseLOEC) values for tamoxifen citrate of 5.12 μg/L and 5.6 μg/L, respectively.
Development of a daphnia magna DNA microarray for evaluating the toxicity of environmental chemicals
Authors: Watanabe Hajime , Takahashi Eri , Nakamura Yuko , Oda Shigeto , Tatarazako Norihisa , Iguchi Taisen
Published: June 2007

Toxic chemical contaminants have a variety of detrimental effects on various species, and the impact of pollutants on ecosystems has become an urgent issue. However, the majority of studies regarding the effects of chemical contaminants have focused on vertebrates. Among aquatic organisms, Daphnia magna has been used extensively to evaluate organism- and populationlevel responses of invertebrates to pollutants in acute toxicity or reproductive toxicity tests. Although these types of tests can provide information concerning hazardous concentrations of chemicals, they provide no information about their mode of action. Recent advances in molecular genetic techniques have provided tools to better understand the responses of aquatic organisms to pollutants. In the present study, we adapted some of the techniques of molecular genetics to develop new tools, which form the basis for an ecotoxicogenomic assessment of D. magna. Based on a Daphnia expressed sequence tag database, we developed an oligonucleotide-based DNA microarray with high reproducibility. The DNA microarray was used to evaluate gene expression profiles of neonatal daphnids exposed to several different chemicals: Copper sulfate, hydrogen peroxide, pentachlorophenol, or β-naphthoflavone. Exposure to these chemicals resulted in characteristic patterns of gene expression that were chemical-specific, indicating that the Daphnia DNA microarray can be used for classification of toxic chemicals and for development of a mechanistic understanding of chemical toxicity on a common freshwater organism.
The effects of three organic chemicals on the upper thermal tolerances of four freshwater fishes
Authors: Patra Ronald W. , Chapman John C. , Lim Richard P. , Gehrke Peter C.
Published: June 2007

The upper temperature tolerance limits of four freshwater fish species, silver perch Bidyanus bidyanus, eastern rainbowfish Melanotaenia duboulayi, western carp gudgeon Hypseleotris klunzingeri, and rainbow trout Oncorhynchus mykiss, were determined using the critical thermal maximum (CTMaximum) method. The CTMaximum tests were carried out with unexposed fish and fish exposed to sublethal concentrations of endosulfan, chlorpyrifos, and phenol to determine whether or not the CTMaximum was affected. The CTMaximum temperature of B. bidyanus decreased by 2.8, 3.8, and 0.3°C on exposure to endosulfan, chlorpyrifos, and phenol, respectively. Similarly, in M. duboulayi, the CTMaximum was decreased by 4.1, 2.5, and 0°C, while in H. klunzingeri it decreased by 3.1, 4.3, and 0.1°C, respectively, and in O. mykiss by 4.8, 5.9, and 0.7°C, respectively. Exposure to sublethal test concentrations of endosulfan and chlorpyrifos caused significant (p ≤ 0.0001) reductions in CTMaximum values for all fish species compared to that of unexposed fish. However, exposure to phenol did not cause any significant (p ≥ 0.05) change of CTMaximum temperatures.
Effect of carbon nanotubes on developing zebrafish (Danio Rerio) embryos
Authors: Cheng Jinping , Flahaut Emmanuel , Cheng Shuk Han
Published: June 2007

The impact of carbon nanotubes (CNTs) on the aquatic environment was investigated by examining the properties of raw CNTs under several environmental conditions and using developing zebrafish (Danio rerio) embryos. The agglomerate size for single-walled CNTs (SWCNTs) was significantly larger at pH 11 or greater and was stable at temperatures from 4 to 40°C and salinities from 0 to 30 ppt. Exposure to SWCNTs induced a significant hatching delay in zebrafish embryos between 52 to 72 h postfertilization (hpf) at concentrations of greater than 120 mg/L, but 99% of the exposed embryos hatched by 75 hpf. Double-walled CNTs also induced a hatching delay at concentrations of greater than 240 mg/L, but carbon black did not affect hatching at the concentrations tested. Molecular and cellular analysis showed that the embryonic development of the exposed embryos up to 96 hpf was not affected at SWCNT concentrations of up to 360 mg/L. Scanning-electron microscopic inspection showed that the size of the pores on the embryo chorion was nanoscaled and that the size of SWCNT agglomerates was microscaled or larger, indicating that the chorion of zebrafish embryos was an effective protective barrier to SWCNT agglomerates. The hatching delay observed in this study likely was induced by the Co and Ni catalysts used in the production of SWCNTs that remained at trace concentrations after purification. This study suggests that materials associated with raw SWCNTs (perhaps metal contaminants) have the potential to affect aquatic life when released into the aquatic environment.
Quantitative structure-activity relationship modeling on in vitro endocrine effects and metabolic stability involving 26 selected brominated flame retardants
Authors: Harju Mikael , Hamers Timo , Kamstra Jorke H. , Sonneveld Edwin , Boon Jan P. , Tysklind Mats , Andersson Patrik L.
Published: June 2007

In this work, quantitative structure—activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A, and hexabromocyclododecane, have been identified as potential endocrine disruptors. Quantitative structure—activity relationship models were built based on the in vitro potencies of 26 selected BFRs. The in vitro assays included interactions with, for example, androgen, progesterone, estrogen, and dioxin (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma carrier protein (transthyretin), inhibition of estradiol sulfation via sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a number of physicochemical parameters were calculated describing the electronic, lipophilic, and structural characteristics of the molecules. These include frontier molecular orbitals, molecular charges, polarities, log octanol/water partitioning coefficient, and two- and three-dimensional molecularproperties. Experimental properties were included and measured for PBDEs, such as their individual ultraviolet spectra (200–320 nm) and retention times on three different high-performance liquid chromatography columns and one nonpolar gas chromatography column. Quantitative structure—activity relationship models based on androgen antagonism and metabolic degradation rates generally gave similar results, suggesting that lower-brominated PBDEs with bromine substitutions in ortho positions and bromine-free meta- and para positions had the highest potencies and metabolic degradation rates. Predictions made for the constituents of the technical flame retardant Bromkal 70–5DE found BDE 17 to be a potent androgen antagonist and BDE 66, which is a relevant PBDE in environmental samples, to be only a weak antagonist.
Predicting metal uptake by wetland plants under aerobic and anaerobic conditions
Authors: van der Welle Marlies E.W. , Roelofs Jan G.M. , den Camp Huub J.M. Op , Lamers Leon P.M.
Published: June 2007

Metal pollution can be a serious threat to ecosystems at a global scale. Although the bioavailability of potentially toxic metals is determined by many biotic and abiotic factors, including pH and redox potential, total metal concentrations in the soil are used widely to assess or predict toxicity. In the present study we tested the effect of desiccation of soils differing in acidification potential and total heavy metal contamination on the growth and metal uptake of three typical, common wetland species: Caltha palustris, Juncus effusus, and Rumex hydrolapathum. We found that plant growth in wet soils mainly was determined by nutrient availability, though in dry soils the combined effects of acidification and increased metal availability prevailed. Metal uptake under anaerobic conditions was best predicted by the acidification potential (sediment S/[Ca + Mg] ratio), not by total metal concentrations. We propose that this is related to radial oxygen loss by wetland plant roots, which leads to acidification of the rhizosphere. Under aerobic conditions, plant metal uptake was best predicted by the amount of CaCl2-extractable metals. We conclude that total metal concentrations are not suitable for predicting bioavailability and that the above diagnostic parameters will provide insight into biogeochemical processes involved in toxicity assessment and soil policy.
Chlorophyll a fluorescence as a biomarker for rapid toxicity assessment
Authors: Fai Patricia Bi , Grant Alastair , Reid Brian
Published: June 2007

Algal growth assays are the most frequently used methods to detect herbicide toxicity in environmental samples; however, these require several days to detect reductions in growth rate with adequate precision. Hence, a need exists for more rapid assays. Two in vivo chlorophyll a fluorescence assays, one using pulse-amplitude modulation (PAM) fluorescence and another based on fluorescence at 684 and 735 nm, detect the effects of photosystem (PS) II inhibitors (atrazine, diuron, and isoproturon) on Selenastrum capricornutum Printz only after 1 h and 30 min, respectively, of incubation. The median growth inhibition (IC50) could be predicted reliably from effects on three PAM parameters—maximal PSII quantum yield (ϕm), operational quantum yield (ϕ'm), and nonphotochemical quenching—and from measurements of fluorescence at 684 and 735 nm. The effects of the PSI inhibitor paraquat dichloride, were smaller in magnitude and could be detected after a 24-h incubation. These two in vivo chlorophyll a fluorescence assays can thus provide reliable, rapid, and cost-effective tools to screen toxicity caused by PSII inhibitors. Neither of the two fluorescence assays could consistently predict the effects of nonphotosynthetic inhibitors (alachlor, metsulfuron methyl, and diclofop methyl).
Effects of proposed physical ballast tank treatments on aquatic invertebrate resting eggs
Authors: Raikow David F. , Reid David F. , Blatchley Ernest R. , Jacobs Gregory , Landrum Peter F.
Published: June 2007

Adaptations in aquatic invertebrate resting eggs that confer protection from natural catastrophic events also could confer protection from treatments applied to ballast water for biological invasion vector management. To evaluate the potential efficacy of physical ballast water treatment methods, the present study examined the acute toxicity of heat (flash and holding methods), ultraviolet (UV) radiation (254 nm), and deoxygenation (acute and chronic) on resting eggs of the freshwater cladoceran Daphnia mendotae and the marine brine shrimp Artemia sp. Both D. mendotae and Artemia sp. were similarly sensitive to flash exposures of heat (100% mortality at 70°C), but D. mendotae were much more sensitive to prolonged exposures. Exposure to 4,000 mJ/cm2 of UV radiation resulted in mortality rates of 59% in Artemia sp. and 91% in D. mendotae. Deoxygenation to an oxygen concentration of 1 mg/L was maximally toxic to both species. Deoxygenation suppressed hatching of D. mendotae resting eggs at oxygen concentrations of less than 5.5 mg/L and of Artemia sp. resting eggs at concentrations of less than 1 mg/L. Results suggest that UV radiation and deoxygenation are not viable treatment methods with respect to invertebrate resting eggs because of the impracticality of producing sufficient UV doses and the suppression of hatching at low oxygen concentrations. Results also suggest that the treatment temperatures required to kill resting eggs are much higher than those reported to be effective against other invertebrate life stages and species. The results, however, do not preclude the effectiveness of these treatments against other organisms or life stages. Nevertheless, if ballast tank treatment systems employing the tested methods are intended to include mitigation of viable resting eggs, then physical removal of large resting eggs and ephippia via filtration would be a necessary initial step.
Aqueous exposure to 4-nonylphenol and 17β-estradiol increases stress sensitivity and disrupts ion regulatory ability of juvenile Atlantic salmon
Authors: Lerner Darren T. , Björnsson Björn Thrandur , McCormick Stephen D.
Published: June 2007

Population declines of wild Atlantic salmon have been attributed to an array of anthropogenic disturbances, including dams, commercial and recreational fishing, habitat loss, and pollution. Environmental contaminants in particular, can act as environmental stressors on fish, typically causing disruption of ion homeostasis due to their close association with the aquatic environment. To examine the effects of the xenoestrogen 4-nonylphenol (NP) or 17β-estradiol (E2) on stress sensitivity and ion regulation, we exposed juvenile Atlantic salmon continuously for 21 d to either 10 or 100 μg/L NP (NP-L or NP-H), 2 μg/L E2 (positive control), or vehicle control during the parr-smolt transformation in April. After treatment, fish were sampled in freshwater (FW), transferred to 30‰ seawater (SW) for 24 h, or subjected to a handling stress. Estradiol and NP-H increased plasma vitellogenin in males and females, and E2 increased gonadosomatic index only in males. In FW, E2 reduced sodium potassium–activated adenosine triphosphatase activity as well as plasma levels of growth hormone, insulin-like growth factor I, and triiodothyronine. Both E2 and NP-H reduced plasma sodium in FW and increased plasma chloride in SW. Plasma Cortisol levels pre- and poststressor were significantly elevated by all treatments relative to controls, but only E2 increased plasma glucose before and after the stressor. These results indicate that exposure of anadromous salmonids to environmental estrogens heightens sensitivity to external stressors, impairs ion regulation in both FW and SW, and disrupts endocrine pathways critical for smolt development.
The effect of food rations on tissue-specific copper accumulation patterns of sublethal waterborne exposure in Cyprinus carpio
Authors: Hashemi Shodja , Blust Ronny , de Boeck Gudrun
Published: June 2007

Common carp (Cyprinus carpio) were fed to two different food rations, 0.5% body weight (low ration [LR]) and 5% body weight (high ration [HR]), and were exposed to sublethal (1 μM) copper levels for 28 d in softened Antwerp (Belgium) city tap water (Ca2+, 79.3 mg/L; Mg2+, 7.4 mg/L; Na+, 27.8 mg/L; pH 7.5–8.0). Copper accumulations in the liver, gills, kidney, anterior intestine, posterior intestine, and muscle were determined. Copper accumulation in the gills, liver, and kidney of LR fish was significantly higher than in HR fish. The only time copper uptake in HR fish was significantly higher than in LR fish was in the posterior intestine after two weeks of exposure. No difference was found between the two rations in the anterior intestine. Copper accumulation in the liver of both feeding treatments occurred in a time-dependent manner and did not reach steady state in any treatment. On the contrary, copper concentration in the gills reached a steady state for both HR and LR fish within the first week of exposure. No copper accumulation was found in muscle tissues of either treatment. Copper concentration dropped to control levels in all tissues, except liver tissue, two weeks after the exposure ended. Our studies indicated that copper uptake was influenced by the food ration in carp. The difference in copper accumulation probably is related to the amount of dietary NaCl and different rates of metallothionein synthesis. Low food availability provides less Na+ influx and leads to increased brachial uptake of Na+ and copper. In addition, it has been shown that starved animals show increased levels of metallothionein, possibly causing higher copper accumulation.