bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diclofenac: New data on chronic toxicity and bioconcentration in fish
Authors: Memmert Ulrich , Peither Armin , Burri Roland , Weber Klaus , Schmidt Thomas , Sumpter John P. , Hartmann Andreas 
Published: January 2013

Abstract
Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug that is regularly detected in surface waters. To support a robust aquatic risk assessment, two early life stage (ELS) tests, compliant with the Organisation for Economic Co-operation and Development (OECD) test guideline 210, were conducted in rainbow trout and in zebrafish. Population relevant endpoints, such as hatching, growth, and survival, and in the trout study, histopathological effects in potential target organs, were examined. The bioconcentration of DCF in rainbow trout was measured in a separate study according to OECD test guideline 305. The bioconcentration factor (BCF) in rainbow trout remained below 10, demonstrating no relevant bioconcentration of DCF in fish. In the rainbow trout ELS test, the no observed effect concentration (NOEC) including histopathology was 320 µg/L. The effect of DCF on zebrafish growth was less clear, and the NOEC can be interpreted as 10 µg/L. However, for a number of reasons, the authors consider the moderately reduced growth of zebrafish exposed to concentrations of up to 320 µg/L not a repeatable, treatment-related effect of DCF. This leads us to a conclusion that DCF has, with high probability, no adverse effect on both fish species up to 320 µg/L. This NOEC indicates a sufficient safety margin for fish populations, because concentrations of DCF in European rivers are in the range of ng/L to low µg/L. Environ. Toxicol. Chem. 2013;32:442–452. © 2013 SETAC
Ruxolitinib: JAK2 inhibitor for treatment of myelofibrosis
Authors: Mead Adam 
Published: January 2013

AbstractRuxolitinib is an orally administered JAK2 inhibitor for the treatment of disease‐related splenomegaly or symptoms in primary myelofibrosis or myelofibrosis due to polycythaemia vera or essential thrombocythaemia. In our Drug profile Dr Adam Mead presents the clinical data relating to its efficacy and adverse events and comments on its place in therapy. Copyright © 2013 John Wiley & Sons, Ltd.
Dexmedetomidine: a unique clinical profile in ICU sedation
Authors: Chaplin Steve 
Published: January 2013

AbstractDexmedetomidine is a sedating agent with a pharmacological and therapeutic profile that is unlike those of the most commonly used sedative agents (midazolam and propofol). In this article, we provide an over view of dexmedetomidine in terms of its pharmacokinetics and pharmacodynamics, and describe its place in the management of patients in intensive care. Copyright © 2013 John Wiley & Sons, Ltd.
The astrocyte in multiple sclerosis revisited
Authors: Brosnan Celia F. , Raine Cedric S. 
Published: January 2013

AbstractAmong the constituent cell types of the multiple sclerosis (MS) plaque, the astrocyte has been the least considered as a player in the pathogenesis of the lesion. Traditionally, it has been assigned a secondary scarring role with little or no role in lesion formation or repair. However, the recent upsurge of interest in the demyelinating condition neuromyelitis optica (NMO) has resulted in NMO being identified as the first disease of myelin in which primary damage to astrocytes, resulting from a humoral immune response that forms against the water channel aquaporin‐4, has been documented. This finding in NMO prompted us to re‐examine data and material from cases of MS displaying active lesions. Our reappraisal revealed unambiguous early damage to perivascular astrocyte end‐feet and to hypertrophic astrocytes in the adjacent parenchyma, but whether this was a primary event was difficult to evaluate due to concomitant edema and inflammation in these acute lesions. The astrocyte damage was long‐lasting since resolving lesions displaying remyelination also showed defects in the integrity of the astrocytic covering around blood vessels. Analysis of our findings and of the astrocytic literature supports multiple roles for the astrocyte in the evolution of changes encountered in MS depending upon lesion stage and lesion topography. At variance with the somewhat inhibitory role of the astrocyte is the abundant and growing evidence for this cell to actively participate in both lesion development and repair. We propose that the unequivocal selective early involvement of the astrocyte in MS lesions may have therapeutic relevance. © 2013 Wiley Periodicals, Inc.
Sulfatide decrease in myelin influences formation of the paranodal axo‐glial junction and conduction velocity in the sciatic nerve
Authors: Hayashi Akiko , Kaneko Naoki , Tomihira Chiaki , Baba Hiroko 
Published: January 2013

AbstractCerebroside sulfotransferase (CST) catalyzes the production of sulfatide, which is one of the major glycolipids in myelin. Homozygous CST knockout mice were shown to be completely deficient in sulfatide. They were born healthy but began to display progressive neurological deficits from 6 weeks of age. Severe abnormalities of paranodal regions and changes in axonal ion channel distribution were prominent in both the central and peripheral nervous systems. But whether partial decreases in myelin sulfatide levels influence paranodal formation, as well as nerve conduction velocity (NCV), is largely unknown. To determine the functional significance of sulfatide content in myelin, we performed electrophysiological, morphological, and biochemical analyses using heterozygote, homozygote, and wild‐type mouse peripheral nerves and compared the results with individual sulfatide content. NCVs were significantly reduced in homozygote animals compared with wild‐type mice. In contrast, these values were markedly varied in individual heterozygote mice. On the basis of NCV values, we divided heterozygous mice into two groups: mice with mild but significant reduction of NCV and those with normal NCV. Teased nerve fibers obtained from individual mouse sciatic nerves were immunostained, and Na+ channel and Caspr cluster lengths were measured to determine abnormal levels of junctional formation at the paranode. Furthermore, sulfatide content in each sciatic nerve was examined by thin layer chromatography. The results demonstrated significant correlations among sulfatide level, severity of paranodal abnormality, and reduction of NCV. Thus, the fine regulation of myelin sulfatide content by CST is important for normal function of myelinated axons. © 2013 Wiley Periodicals, Inc.
A comparative study of glial and non‐neural cell properties for transplant‐mediated repair of the injured spinal cord
Authors: Toft Andrew , Tome Mercedes , Barnett Susan C. , Riddell John S. 
Published: January 2013

AbstractCell transplantation is one strategy for encouraging regeneration after spinal cord injury and a range of cell types have been investigated for their repair potential. However, variations in study design complicate determination of which cells are most effective. In this study we have carried out a direct comparison of the regenerative and integrative properties of several cell preparations following transplantation into the lesioned rat spinal cord. Transplants included: (i) purified olfactory ensheathing cells (OECs) and (ii) fibroblast‐like cells, from olfactory bulb (OBFB‐L), (iii) a 50:50 mixture of (i) and (ii) (OEC/OBFB‐L), (iv) dissociated nasal mucosa (OM), (v) purified peripheral nerve Schwann cells (SCs), (vi) peripheral nerve fibroblasts, and (vii) skin fibroblasts (SF). All transplants supported axonal regeneration: OECs and SCs promoted the greatest regeneration while OBFB‐like cells were least efficient and mixed cell populations were less effective than purified populations. Tract‐tracing experiments demonstrated that none of the cell types promoted regeneration beyond the lesion. Although all cell types prevented cavity formation, the extent of astrocytic hypertrophy [GFAP immunoreactivity (IR) at the transplant/lesion site] differed markedly. OECs and SCs were associated with the least GFAP‐IR, fibroblasts and fibroblast‐like cells resulted in greater GFAP‐IR while hypertrophy surrounding transplants of OM was most extensive. These differences in host‐transplant reactivity were confirmed by transplanting cells into normal spinal cord where the cellular interaction is not complicated by injury. Thus, purified glial cells have advantages for transplant‐mediated repair, combining maximal support for axonal regeneration with a minimal astrocytic reaction around the transplant site. © 2013 Wiley Periodicals, Inc.
MAT2B-GIT1 interplay activates MEK1/ERK 1 and 2 to induce growth in human liver and colon cancer
Authors: Peng Hui , Dara Lily , Li Tony W.H. , Zheng Yuhua , Yang Heping , Tomasi Maria Lauda , Tomasi Ivan , Giordano Pasquale , Mato Jose M. , Lu Shelly C. 
Published: January 2013

Abstract

Methionine adenosyltransferase 2B (MAT2B) encodes for two variant proteins (V1 and V2) that promote cell growth. Using in-solution proteomics, GIT1 (G Protein Coupled Receptor Kinase Interacting ArfGAP 1) was identified as a potential interacting partner of MAT2B. Here, we examined the functional significance of this interplay. Coimmunoprecipitation experiments examined protein interactions. Tissue expression levels of proteins were examined using immunohistochemistry and western blotting. Expression levels of proteins were varied using transient knockdown or overexpression to observe the effect of alterations in each protein on the entire complex. Direct interaction among individual proteins was further verified using

in vitro

translated and recombinant proteins. We found both MAT2B variants interact with GIT1. Overexpression of V1, V2, or GIT1 activated mitogen-activated protein kinase kinase 1 (MEK1) and extracellular signal-regulated kinase (ERK), raised cyclin D1 protein level, and increased growth, whereas the opposite occurred when V1, V2, or GIT1 was knocked down. MAT2B and GIT1 require each other to activate MEK1/ERK and increase growth. MAT2B directly interacts with MEK1, GIT1, and ERK2. Expression level of V1, V2, or GIT1 directly influenced recruitment of GIT1 or MAT2B and ERK2 to MEK1, respectively. In pull-down assays, MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens. Increased expression of V1, V2, or GIT1 promoted growth in an orthotopic liver cancer model, whereas increased expression of either V1 or V2 with GIT1 further enhanced growth and lung metastasis.

Conclusion:

MAT2B and GIT1 form a scaffold, which recruits and activates MEK and ERK to promote growth and tumorigenesis. This novel MAT2B/GIT1 complex may provide a potential therapeutic gateway in human liver and colon cancer.
Gene expression profiling in the cerebral cortex of patients with cirrhosis with and without hepatic encephalopathy
Authors: Görg Boris , Bidmon Hans-Jürgen , Häussinger Dieter 
Published: January 2013

Abstract

Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis and is seen as the clinical manifestation of a low-grade cerebral edema associated with oxidative-nitrosative stress. However, comprehensive data on HE-associated molecular derangements in the human brain are lacking. In the present study, we used a whole human genome microarray approach for gene expression profiling in

post mortem

brain samples from patients with cirrhosis with or without HE and controls without cirrhosis. Altered expression levels were found for a total of 1,012 genes in liver cirrhosis patients without and with HE, and HE-characteristic gene expression changes were identified. Genes with altered expression pattern in HE were related to oxidative stress, microglia activation, receptor signaling, inflammatory pathways, cell proliferation, and apoptosis. Despite an up-regulation of genes associated with microglia activation,

pro

-inflammatory cytokine messenger RNA profiles remained unchanged in the brains of patients with liver cirrhosis and HE compared with controls. Interestingly, many genes counteracting

pro

-inflammatory signaling and inflammatory cytokine expression were up-regulated in the cerebral cortex of patients with liver cirrhosis and HE.

Conclusion

: Pathogenetic mechanisms of HE deduced from cell culture and animal experiments, such as oxidative stress, altered Zn2+ homeostasis and microglia activation also apply to human brain from patients with liver cirrhosis and HE. The study also revealed a not-yet recognized increased expression of genes antagonizing proinflammatory signaling and inflammatory cytokine expression.
BTB/POZ domain-containing protein 7: Epithelial-mesenchymal transition promoter and prognostic biomarker of hepatocellular carcinoma
Authors: Tao Yi-Ming , Huang Jin-Lin , Zeng Shan , Zhang Sai , Fan Xue-Gong , Wang Zhi-Ming , Yang Hui-Xiang , Yuan Xiao-Hua , Wang Pu , Wu Fan , Luo Jia , Zeng De-Yu , Shen Hong 
Published: January 2013

Abstract

Epithelial-mesenchymal transition (EMT) is a critical step in the metastasis of hepatocellular carcinoma (HCC). BTB/POZ domain-containing protein 7 (BTBD7) regulates EMT-associated proteins implicated in HCC progression. However, the role(s) of BTBD7 in HCC have not been identified. Using highly metastatic HCC HCCLM3 cells, immortalized L02 hepatocytes, metastatic HCC animal models, and three independent cohorts of HCC patient specimens, we aimed to determine the involvement of BTBD7 in HCC metastasis. We show that BTBD7 messenger RNA and protein was highly expressed in HCC cells and tumor tissues, with such expression being associated with: enhanced cell motility, venous invasion, and poor prognosis. BTBD7 promoted HCC angiogenesis and metastasis

in vitro

and

in vivo

, but did not influence cell proliferation or colony formation. BTBD7 enhancement of HCC invasion and EMT phenotype occurred through activation of a RhoC-Rock2-FAK-signaling pathway, resulting in matrix metalloproteinase-2/9 production and microvessel formation. Applying a predictive risk score model, Cox regression analysis revealed that high BTBD7 expression integrated with high microvessel density was a powerful independent predictive factor of HCC clinical outcome.

Conclusion

: The present study identifies BTBD7 as a novel candidate prognostic factor and a potential therapeutic target of HCC.
Nitrate dynamics in a rural headwater catchment: measurements and modelling
Authors: Smethurst Philip J. , Petrone Kevin C. , Langergraber Günter , Baillie Craig C. , Worledge Dale , Nash David 
Published: January 2013

AbstractThis study was designed to improve our understanding of, and mechanistically simulate, nitrate (NO3) dynamics in a steep 9.8 ha rural headwater catchment, including its production in soil and delivery to a stream via surface and subsurface processes. A two‐dimensional modelling approach was evaluated for (1) integrating these processes at a hillslope scale annually and within storms, (2) estimating denitrification, and (3) running virtual experiments to generate insights and hypotheses about using trees in streamside management zones (SMZs) to mitigate NO3 delivery to streams. Total flow was mathematically separated into quick‐ and slow‐flow components; the latter was routed through the HYDRUS software with a nitrogen module designed for constructed wetlands. Flow was monitored for two years. High surface‐soil NO3 concentrations started to be delivered to the stream via preferential subsurface flow within two days of the storm commencing. Groundwater NO3‐N concentrations decreased from 1.0 to less than 0.1 mg l−1 from up‐slope to down‐slope water tables, respectively, which was attributed to denitrification. Measurements were consistent with the flushing of NO3 mainly laterally from surface soil during and following each storm. The model accurately accounted for NO3 turnover, leading to the hypotheses that denitrification was a minor flux (<3 kg N ha−1) compared to uptake (98−127 kg N ha−1), and that SMZ trees would reduce denitrification if they lowered the water table. This research provides an example of the measurement and modelling of NO3 dynamics at a small‐catchment scale with high spatial and temporal resolution. Copyright © 2013 John Wiley & Sons, Ltd.
Hydrological response of a humid agroforestry catchment at different time scales
Authors: Palleiro L. , Rodríguez‐Blanco M. L. , Taboada‐Castro M. M. , Taboada‐Castro M. T. 
Published: January 2013

AbstractUsing data collected at the Mero catchment during three hydrological years (2005/06–2007/08), an analysis of rainfall–runoff relationships was performed at annual, seasonal, monthly, and event scales. At annual scale, the catchment showed low runoff coefficients (23–35%), due to high water storage capacity soils as well as high runoff inter‐annual variability. Rainfall variability was the main responsible for the differences in the inter‐annual runoff. At seasonal and monthly scales, there was no simple relationship between rainfall and runoff. Seasonal dynamics of rainfall and potential evapotranspiration in conjunction with different rainfall distribution during the study years could be the key factors explaining the complex relationship between rainfall and runoff at monthly and seasonal scale. At the event scale, the results revealed that the hydrological response was highly dependent on initial conditions and, to a lesser extent, on rainfall amount. The shapes of the different hydrographs, regardless of the magnitude, presented similar characteristics: a moderate rise and a prolonged recession, suggesting that subsurface flow was the dominant process in direct runoff. Moreover, all rainfall–runoff events had a higher proportion of baseflow than of direct runoff. A cluster‐type analysis discriminated three types of events differentiated mainly by rainfall amount and antecedent rainfall conditions. The study highlights the role of the antecedent rainfall and the need for caution in extrapolating relationships between rainfall amount and hydrological response of the catchment. Copyright © 2013 John Wiley & Sons, Ltd.
Investigating the influence of minor hydraulic structures on modeling flood events in lowland areas
Authors: Hailemariam Freegzi Mehari , Brandimarte Luigia , Dottori Francesco 
Published: January 2013

AbstractFlood inundation models have been recognized to be a valuable tool to reproduce flow dynamics in a given area and support decision‐making processes on flood management measures. In many cases, in the simulation of flood events, only the main river channel and the associated structures are represented within the model. However, during flood events involving lowland areas, the minor drainage network – and the associated hydraulic structures – may have an important role in conveying flow and determining which areas will be flooded. The objective of this study is to investigate whether – and to what extent – small hydraulic structures in drainage networks have an influence in flooding on lowland areas.The case study for this research is the 1990 flood event which occurred in the lowland plain of the Reno River, in Northern Italy. The study area is mainly used for agricultural purposes and has a drainage system with several small bridges and culverts.The influence of the minor hydraulic structures on flood dynamics was analyzed through a combined use of one‐dimensional (1D) and two‐dimensional (2D) hydraulic models. First, a number of detailed and simplified approaches to represent hydraulic structures in the computational grids were analyzed by means of the HECRAS 1D model. Second, these approaches were implemented and tested in several 2D simulations of the flood event. The simulated inundation extents and flood levels were then compared with the observed data and with each other. The analysis of results showed that simplified schematizations were sufficient to obtain good model predictions of peak inundation extent and flood levels, at least for the present case study. Moreover, the influence of the structures on the peak flood inundation extent and flood levels was found to be limited, whereas it showed to be more significant during the drainage phase of the flood. Copyright © 2013 John Wiley & Sons, Ltd.
Water balance analysis for the Tonle Sap Lake–floodplain system
Authors: Kummu M. , Tes S. , Yin S. , Adamson P. , Józsa J. , Koponen J. , Richey J. , Sarkkula J. 
Published: January 2013

AbstractThe Tonle Sap Lake of Cambodia is the largest freshwater body of Southeast Asia, forming an important part of the Mekong River system. The lake has an extremely productive ecosystem and operates as a natural floodwater reservoir for the lower Mekong Basin, offering flood protection and assuring the dry season flow to the Mekong Delta. In light of the accelerating pace of water resources development within the Mekong Basin and the anticipation of potentially significant hydrological impacts, it is critical to understand the overall hydrologic regime of Tonle Sap Lake. We present here a detailed water balance model based on observed data of discharges from the lake's tributaries, discharge between Mekong and the lake through the Tonle Sap River, precipitation, and evaporation. The overland flow between the Mekong and lake was modelled with the EIA 3D hydrodynamic model. We found that majority (53.5%) of the water originates from the Mekong mainstream, but the lake's tributaries also play an important role contributing 34% of the annual flow, while 12.5% is derived from precipitation. The water level in the lake is mainly controlled by the water level in the Mekong mainstream. The Tonle Sap system is hence very vulnerable, from a water quantity point of view, to possible changes in the Mekong mainstream and thus, development activities in the whole Mekong basin. From a biogeochemical point of view, the possible changes in the lake's own catchment are equally important, together with the changes in the whole Mekong Basin. Based on our findings, we recommend of continuing the monitoring programmes in lake's tributaries and urgently starting of groundwater measurement campaign within the floodplain, and including the groundwater modelling to be part of the hydrodynamic models applied for the lake. Copyright © 2013 John Wiley & Sons, Ltd.