bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and implementation of a right-to-know web site that presents estimated cancer risks for air emissions of large industrial facilities
Authors: Ragas Ad M.J. , Huijbregts Mark A.J. , van Kaathoven Eric H. , Wolsink Johan H. , Wemmenhove Jeroen 
Published: March 2010

Abstract
A publicly accessible web site was developed that provides environmental information on air emissions of local facilities in 3 regions in the Netherlands. Compared with other environmental right-to-know initiatives, the main innovative aspect of this web site is the presentation of emissions data in terms of estimated increased cancer risk. The basic idea is that this type of information will help people 1) to put the health effects of air emissions of the selected facilities into perspective and 2) to form a personal opinion about the acceptability of these risks. In the 1st 5 months, the web site was visited more than 77,000 times, with more than 33,000 visits in the 1st month (March 2004). The web site triggered a discussion on the accessibility and presentation of environmental risk information in The Netherlands, which even reached the Dutch parliament. To improve and maintain this type of right-to-know initiative, it is important that 1) responsible authorities establish and maintain a detailed and up-to-date database of national, regional, and local emissions data, 2) the initiative is implemented in a legal framework or adopted by an independent body, and 3) more knowledge becomes available about the understanding and effects of environmental risk information on the general public.
Animal use replacement, reduction, and refinement: Development of an integrated testing strategy for bioconcentration of chemicals in fish
Authors: de Wolf Watze , Comber Mike , Douben Peter , Gimeno Sylvia , Holt Martin , Léonard Marc , Lillicrap Adam , Sijm Dick , van Egmond Roger , Weisbrod Anne , Whale Graham 
Published: March 2010

Abstract
When addressing the use of fish for the environmental safety of chemicals and effluents, there are many opportunities for applying the principles of the 3Rs: Reduce, Refine, and Replace. The current environmental regulatory testing strategy for bioconcentration and secondary poisoning has been reviewed, and alternative approaches that provide useful information are described. Several approaches can be used to reduce the number of fish used in the Organization for Economic Cooperation and Development (OECD) Test Guideline 305, including alternative in vivo test methods such as the dietary accumulation test and the static exposure approach. The best replacement approach would seem to use read-across, chemical grouping, and quantitative structure-activity relationships with an assessment of the key processes in bioconcentration: Adsorption, distribution, metabolism, and excretion. Biomimetic extraction has particular usefulness in addressing bioavailable chemicals and is in some circumstances capable of predicting uptake. Use of alternative organisms such as invertebrates should also be considered. A single cut-off value for molecular weight and size beyond which no absorption will take place cannot be identified. Recommendations for their use in bioaccumulative (B) categorization schemes are provided. Assessment of biotransformation with in vitro assays and in silico approaches holds significant promise. Further research is needed to identify their variability and confidence limits and the ways to use this as a basis to estimate bioconcentration factors. A tiered bioconcentration testing strategy has been developed taking account of the alternatives discussed.
Predicting metal toxicity in sediments: A critique of current approaches
Authors: Simpson Stuart L , Batley Graeme E 
Published: March 2010

Abstract
The ability to predict metal toxicity in sediments based on measurements of simple chemical parameters is not possible using currently available sediment-quality guidelines (SQGs). Past evaluations of available SQGs for metals indicated little difference in their predictive abilities; however, the scientific understanding of cause-effect relationships is progressing rapidly. Today, it is clear that they can be protective of benthic ecosystem health, but single-value SQGs will be ineffective for predicting the toxicity of metals in sediments. Recent exposure-effects models and the sediment biotic ligand model both indicate that a better approach would be to have SQG concentrations, or ranges, that are applied to different sediment types. This review indicates that significant improvements in laboratory and field-based measurements, better recording of parameters that influence metal toxicity in sediments, as well as quantification of the metal exposure routes and the relative contribution of dissolved and particulate sources to toxic effects are needed to improve the power of predictive models and the overall effectiveness of SQGs for metals. Simply exposing benthic organisms to contaminated sediments and reporting effects concentrations or thresholds based on particulate metal concentrations will provide little information to aid future SQG development. For all tests, careful measurement and reporting of concentrations of particulate metal-binding phases (e.g., sulfide, organic carbon, and iron phases), metal partitioning between porewater and sediments, and porewater pH are considered as minimum data requirements. When using metal-spiked sediments, much better efforts are required to achieve sediment properties that resemble those of naturally contaminated sediments. Our current understanding of metal toxicity indicates that considerably greater information requirements will be needed to predict sublethal and chronic effects of metals, because the toxic, metabolically available concentration of metals within an organism will fluctuate over time. Based on the review of exposure and effects models, along with improved measurement of metal exposure-related parameters, the measurement of the short-term uptake rate of metals into organisms is likely to improve future models.
Application of risk assessment and decision analysis to aquatic nuisance species
Authors: Suedel Burton C , Bridges Todd S , Kim Jongbum , Payne Barry S , Miller Andrew C 
Published: March 2010

Abstract
The spread of nonindigenous (nonnative) species introduced into the United States is a significant and growing national problem and results in lost agricultural productivity, increased health problems, native species extinctions, and expensive prevention and eradication efforts. Thousands of nonindigenous species have either become established or spread, and introduction of aquatic nuisance species (ANS) into freshwater lakes threaten aquatic biodiversity. Expanding global trade is likely to increase the number of species that are spread across the globe, so the need to develop an approach to predict potential ANS invasions is great. Risk assessments currently being used to assess ANS risk rely on qualitative or semiquantitative information and expert opinion; thus, such approaches lack transparency and repeatability. A more quantitative approach is needed to augment the qualitative approaches currently in use. A quantitative approach with the use of the traditional ecological risk assessment (traditional ERA) framework combined with decision analysis tools was developed for assessing ANS risks in which the causative ecological risk agent is an organism rather than a chemical. This paper presents a systematic risk assessment framework that includes structured decision analysis to help organize and analyze pertinent data, state assumptions, address uncertainties in estimating the probability of an undesired ANS introduction, or spread and integrate these outputs with stakeholder values. This paper also describes when and how decision analysis tools can be used in such assessments for ANS. This framework and methodology will enable risk managers to systematically evaluate and compare alternatives and actions supporting ANS risk management and thus credibly prioritize resources.
Selenium effects: A weight-of-evidence approach
Authors: McDonald Blair G , Chapman Peter M 
Published: March 2010

Abstract
Selenium is increasingly an issue for a wide range of mining, industrial, and agricultural operations. Appropriate methods for evaluating the impacts of selenium in aquatic ecosystems are vigorously debated in the literature. Two common approaches include the use of tissue residue guidelines and reproductive toxicity testing using field-collected fish; however, each approach on its own does not provide sufficient evidence that wild fish populations are in fact impaired. The limitations of each method are discussed, and recommendations to improve the relevance of each line of evidence are provided. A 3rd line of evidence, field measurement of fish population dynamics, is proposed and also discussed. A framework, consistent with an ecological risk assessment methodology, for the design, application, and interpretation of selenium weight-of-evidence investigations is proposed.
Adjuvant effects of formalin‐inactivated HSV through activation of dendritic cells and inactivation of myeloid‐derived suppressor cells in cancer immunotherapy
Authors: Ohkusu‐Tsukada Kozo , Ohta Shigeki , Kawakami Yutaka , Toda Masahiro 
Published: March 2010

AbstractUse of adequate adjuvant is necessary for induction of effective antitumor immune responses. To develop an effective adjuvant for cancer immunotherapy, we selected formalin‐inactivated (f)‐HSV as an adjuvant component, and analyzed the mechanisms underlying its adjuvant effects. First, we found that f‐HSV can induce the tumor antigen‐specific CTLs by enhancing antigen cross‐presentation by dendritic cells (DCs), mainly through TLR2, but not TLR9. Next, f‐HSV was also found to prevent the accumulation of myeloid‐derived suppressor cells (MDSCs). We demonstrated that the expansion of MDSCs in the blood and spleen during tumor progression required B cells producing the inflammatory angiogenesis factors, vascular endothelial growth factor (VEGF)‐A and neuropilin‐1 (NRP‐1), a co‐receptor for VEGF receptor‐2 (VEGFR‐2). Interestingly, the transmembrane‐type NRP‐1 on B cells changed to soluble‐type NRP‐1 (sNRP‐1) by f‐HSV treatment. We further showed that the sNRP‐1 and VEGF‐A secreted from B cells by f‐HSV treatment could abrogate the immunosuppressive ability of MDSCs. These results suggest that f‐HSV can enhance antitumor immune responses as an adjuvant, not only through activation of DCs, but also inactivation of MDSCs via B cells.
Downregulation of the Rho GTPase signaling pathway is involved in the microRNA‐138‐mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma
Authors: Jiang Lu , Liu Xiqiang , Kolokythas Antonia , Yu Jinsheng , Wang Anxun , Heidbreder Caroline E. , Shi Fei , Zhou Xiaofeng 
Published: March 2010

AbstractTumor metastasis is the dominant cause of death in cancer patients, including patients with oral tongue squamous cell carcinoma (TSCC). Previously, we reported that reduced miR‐138 level is correlated with enhanced metastatic potential in TSCC cells. Here, we demonstrate that miR‐138 suppresses TSCC cell migration and invasion by regulating 2 key genes in the Rho GTPase signaling pathway: RhoC and ROCK2. Direct targeting of miR‐138 to specific sequences located in the 3′‐untranslated regions of both RhoC and ROCK2 mRNAs was confirmed using luciferase reporter gene assays. Ectopic transfection of miR‐138 reduced the expression of both RhoC and ROCK2 in TSCC cells. These reduced expressions, in consequence, led to the reorganization of the stress fibers and the subsequent cell morphology change to a round bleb‐like shape as well as the suppression of cell migration and invasion. In contrast, knockdown of miR‐138 in TSCC cells enhanced the expression of RhoC and ROCK2, which resulted in an altered, elongated cell morphology, enhanced cell stress fiber formation and accelerated cell migration and invasion. Taken together, our results suggest that miR‐138 plays an important role in TSCC cell migration and invasion by concurrently targeting RhoC and ROCK2, and miR‐138 may serve as a novel therapeutic target for TSCC patients at risk of metastatic disease.
Alfalfa production using saline drainage water
Authors: Ayars James E. , Soppe Richard W. , Shouse Peter 
Published: March 2010

AbstractA three‐year study investigated the use of saline (EC < 6 dS m−1) drainage water for irrigation of salt‐tolerant alfalfa in the presence of shallow saline groundwater. The irrigation treatments included: (1) irrigating twice between cuttings with nonsaline water, (2) irrigating twice with moderately saline water between cuttings, and(3) once between cuttings with moderately saline water. Yield data demonstrated an approximately 30% reduction in total yield over 3 years as a result of using the saline water for irrigation compared to irrigating with the nonsaline water. The overall alfalfa quality improved when irrigated with saline water compared to the non‐saline water. However, both boron and chloride progressively accumulated in alfalfa plant tissue during each growing season when irrigated with saline water. The plant tissue boron and chloride values returned to previously low levels by the start of the next growing season due to the influence of winter rainfall and irrigating with low‐salinity water at the break of dormancy. There was measurable accumulation of salt in the soil profile and in the shallow groundwater as a result of using saline drainage water for irrigation. A gradual decrease in depth to the shallow groundwater was observed as result of the lack of drainage capability. Electromagnetic induction proved adequate for characterizing root zone salinity with time. Published in 2010 John Wiley & Sons, Ltd.
Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overload
Authors: Rosón María I. , Della Penna Silvana L. , Cao Gabriel , Gorzalczany Susana , Pandolfo Marcela , Toblli Jorge E. , Fernández Belisario E. 
Published: March 2010

AbstractThe aim of this work was to study the role of local intrarenal angiotensin II (Ang II) and the oxidative stress in the up‐regulation of pro‐inflammatory cytokines expression observed in rats submitted to an acute sodium overload. Sprague–Dawley rats were infused for 2 h with isotonic saline solution (Control group) and with hypertonic saline solution alone (Na group), plus the AT1 receptor antagonist losartan (10 mg kg−1 in bolus) (Na–Los group), or plus the superoxide dismutase mimetic tempol (0.5 mg min−1 kg−1) (Na–Temp group). Mean arterial pressure, glomerular filtration rate, and fractional sodium excretion (FENa) were measured. Ang II, NF‐κB, hypoxia inducible factor‐1α (HIF‐1α), transforming growth factor β1 (TGF‐β1), smooth muscle actin (α‐SMA), endothelial nitric oxide synthase (eNOS), and RANTES renal expression was evaluated by immunohistochemistry. Ang II, NF‐κB, and TGF‐β1 and RANTES early inflammatory markers were overexpressed in Na group, accompanied by enhanced HIF‐1α immunostaining, lower eNOS expression, and unmodified α‐SMA. Losartan and tempol increased FENa in sodium overload group. Although losartan reduced Ang II and NF‐κB staining and increased eNOS expression, it did not restore HIF‐1α expression and did not prevent inflammation. Conversely, tempol increased eNOS and natriuresis, restored HIF‐1α expression, and prevented inflammation. Early inflammatory markers observed in rats with acute sodium overload is associated with the imbalance between HIF‐1α and eNOS expression. While both losartan and tempol increased natriuresis and eNOS expression, only tempol was effective in restoring HIF‐1α expression and down‐regulating TGF‐β1 and RANTES expression. The protective role of tempol, but not of losartan, in the inflammatory response may be associated with its greater antioxidant effects. J. Cell. Physiol. 224:41–48, 2010 © 2010 Wiley‐Liss, Inc.
Elucidation of the signaling pathways that underpin capacitation‐associated surface phosphotyrosine expression in mouse spermatozoa
Authors: Nixon Brett , Bielanowicz Amanda , Anderson Amanda L. , Walsh Andrew , Hall Tess , Mccloghry Andrea , Aitken R. John 
Published: March 2010

AbstractRecent studies from within our laboratory have demonstrated a causal relationship between capacitation‐associated surface phosphotyrosine expression and the ability of mouse spermatozoa to recognize the oocyte and engage in sperm–zona pellucida interaction. In the studies described herein we have sought to investigate the signaling pathways that underpin the tyrosine phosphorylation of sperm surface protein targets and validate the physiological significance of these pathways in relation to sperm–zona pellucida adhesion. Through selective pharmacological inhibition we have demonstrated that surface phosphotyrosine expression is unlikely to be mediated by the canonical cAMP‐dependent protein kinase A (PKA) signaling cascade that has been most widely studied in relation to sperm capacitation. Rather, it appears to be primarily driven by the extracellular signal‐regulated kinase (ERK) module of the mitogen‐activated protein kinase (MAPK) pathway. Consistent with this notion, the main components of the ERK module (RAS, RAF1, MEK, and ERK1/2) were localized to the periacrosomal region of the head of mature mouse spermatozoa and their phosphorylation status within this region of the cell was positively modulated by capacitation. Furthermore, inhibition of several elements of this pathway suppressed sperm surface phosphotyrosine expression and induced a concomitant reduction sperm–zona pellucida interaction. Collectively, these data highlight a previously unappreciated role of the ERK module in the modification of the sperm surface during capacitation to render these cells functionally competent to engage in the process of fertilization. J. Cell. Physiol. 224:71–83, 2010 © 2010 Wiley‐Liss, Inc.
Apoptosis induction by eIF5A1 involves activation of the intrinsic mitochondrial pathway
Authors: Sun Zhong , Cheng Zhenyu , Taylor Catherine A. , McConkey Brendan J. , Thompson John E. 
Published: March 2010

AbstractThe regulatory role of eukaryotic translation initiation factor 5A1 (eIF5A1) in apoptosis was examined using HT‐29 and HeLa S3 cells. eIF5A is the only known protein to contain the unusual amino acid, hypusine, and eIF5A1 is one of two human eIF5A family members. Two observations indicated that eIF5A1 is involved in apoptosis. First, siRNA‐mediated suppression of eIF5A1 resulted in inhibition of apoptosis induced by various apoptotic stimuli, and second, adenovirus‐mediated over‐expression of eIF5A1 strongly induced apoptotic cell death. A mutant of eIF5A1 incapable of being hypusinated also induced apoptosis when over‐expressed indicating that unhypusinated eIF5A1 is the pro‐apoptotic form of the protein. Over‐expression of eIF5A1 or of the mutant resulted in loss of mitochondrial transmembrane potential, translocation of Bax to the mitochondria, release of cytochrome c, caspase activation, up‐regulation of p53, and up‐regulation of Bim, a pro‐apoptotic BH3‐only Bcl‐2 family protein. In addition, BimL and BimS, the pro‐apoptotic alternative spliced forms of Bim, were induced in response to over‐expression of eIF5A1. Thus eIF5A1 appears to induce apoptosis by activating the mitochondrial apoptotic pathway. Proteomic analyses indicated that, of 1,899 proteins detected, 131 showed significant changes in expression (P ≤ 0.05, expression ratio ≥1.5) within 72 h of eIF5A1 up‐regulation. Among these are proteins involved in translation and protein folding, transcription factors, proteins mediating proteolysis, and a variety of proteins known to be directly involved in apoptosis. These observations collectively indicate that unhypusinated eIF5A1 plays a central role in the regulation of apoptosis. J. Cell. Physiol. 223:798–809, 2010. © 2010 Wiley‐Liss, Inc.
Impact of integrin–matrix interaction and signaling on insulin gene expression and the mesenchymal transition of human β‐cells
Authors: Kaido Thomas J. , Yebra Mayra , Kaneto Hideaki , Cirulli Vincenzo , Hayek Alberto , Montgomery Anthony M.P. 
Published: March 2010

AbstractA critical shortage of donor pancreata currently prevents the development of a universal cell‐based therapy for type I diabetes. The ex vivo expansion of insulin‐producing β‐cells offers a potential solution but is problematic due to the inherent tendency of these cells to transition into mesenchymal‐like cells that are devoid of function. Here, we demonstrate for the first time that exposure to elements of the extracellular matrix (ECM) directly potentiates the mesenchymal transition of cultured fetal β‐cells and causes associated declines in insulin gene expression. Individual ECM constituents varied in their ability to induce such responses, with collagen‐IV (C‐IV) and fibronectin inducing strong responses, whereas laminin‐1 had no significant effect. Mesenchymal transition and concomitant losses in insulin gene expression observed on C‐IV were found to be dependent on β1‐integrin ligation and were augmented in the presence of hepatocyte growth factor. Importantly, selective inhibition of c‐Src, c‐Jun N‐terminal kinase (JNK), and extracellular signal‐regulated kinase (ERK) prior to exposure to C‐IV prevented mesenchymal transition and effectively preserved insulin expression. Fetal β‐cells undergoing mesenchymal transition were found to acquire α1β1 expression, and ligation of this integrin then promotes declines in insulin gene expression and a marked increase in β‐cell motility. Inhibition of Src‐, ERK‐, or JNK‐dependent signaling combined with the selective regulation of matrix exposure may ultimately facilitate the development of more effective β‐cell expansion protocols. J. Cell. Physiol. 224:101–111, 2010 © 2010 Wiley‐Liss, Inc.
Meiotic cell cycle arrest in mammalian oocytes
Authors: Tripathi Anima , Kumar K.V. Prem , Chaube Shail K. 
Published: March 2010

AbstractMeiotic cell cycle in mammalian oocytes is a dynamic process that involves several stop/go channels. The cell cycle arrest in oocyte occurs at various stages such as diplotene, metaphase‐I (M‐I), metaphase‐II (M‐II), and so called metaphase‐like arrest (M‐III). Leutinizing hormone surge induces meiotic resumption from diplotene arrest in follicular microenvironment by overriding several factors responsible for the maintenance of meiotic arrest. The inhibitory factors are synthesized in oocyte or in the associated follicular somatic cells and transferred to the oocyte. The major factors include hypoxanthine, cyclic adenosine 3′, 5′‐monophosphate, cyclic guanosine 3′, 5′‐monophosphate, reactive oxygen species, protein kinase A, and protein kinase C. In the presence of active protein kinases, epidermal‐like growth factors are produced that activate mitogen‐activated protein kinase in cumulus granulosa cells. The maturation promoting factor, cytostatic factors, and spindle assembly checkpoint proteins are also involved in that maintenance of arrest at various stages of meiotic cell cycle in mammalian oocytes. In this review, we briefly summarize the role of these factors in the maintenance of meiotic cell cycle arrest in mammalian oocytes. J. Cell. Physiol. 223:592–600, 2010. © 2010 Wiley‐Liss, Inc.