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1.
The arsenic ambient water quality criterion (AWQC) for protection of human health via ingestion of aquatic organisms is currently 0.14 μ g/L. This AWQC is derived using a bioconcentration factor (BCF) of 44, which is a consumption-weighted average based on two data points for oysters and fish that was proposed by the U.S. Environmental Protection Agency in 1980 for broad application to freshwater and marine environments. This BCF is based on the assumption that bioaccumulation is a simple linear function of the exposure concentration. In the nearly quarter of a century since this BCF was promulgated, there have been additions to the arsenic bioaccumulation database and a broader scientific understanding of bioaccumulation mechanisms and how they can be applied to estimating tissue concentrations in aquatic organisms. From this database, we identified 12 studies of arsenic bioaccumulation in freshwater fishes in order to explore differences in laboratory-generated BCFs and field-generated bioaccumulation factors (BAFs) and to assess their relationship to arsenic concentrations in water. Our analysis indicates that arsenic concentrations in tissue and arsenic BAFs may be power functions of arsenic concentration in water. A power function indicates that the highest BCF values may occur at low background levels and may decrease as environmental concentrations increase above the ambient range. 相似文献
2.
Factor IXPortland: a nonsense mutation (CGA to TGA) resulting in hemophilia B 总被引:5,自引:0,他引:5
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S H Chen C R Scott J Schoof E W Lovrien K Kurachi 《American journal of human genetics》1989,44(4):567-569
Male siblings with severe hemophilia b were studied for the molecular defect responsible for their disorder. To define the precise DNA alteration, a 362-bp fragment in the first part of exon VIII of the factor IX gene was amplified and sequenced. A single-base-pair substitution of C----T at the nucleotide sequence 30875 was found which resulted in a nonsense mutation (TGA) and terminated the protein synthesis of factor IX at amino acid residue 252. The single-base change occurred as a classic CG dinucleotide alteration to TG (or CA), a common mechanism for point mutations in mammals. 相似文献
3.
1. Coincidental preparation of the intramuscular vascular bed and the plexus myentericus (Auerbach) of the cat's large intestine by India-ink method and silverimpregnation allowed to demonstrate independent vascularisation of ganglia and nerve-branches of the plexus Auerbach. 2. Each ganglion is surrounded by a capillary network widely independently existing of the intramuscular capillary bed. The preferred innervated terminal arterioles and especially the sphincteric capillaries opening into the periganglionic capillary network and the numerous arterio-venous short-circuits in its marginal area suggest to conclude a differentiated regulation of blood supply. 相似文献
4.
5.
Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献6.
Intervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune
diseases. A new report by Schurgers and colleagues in a previous issue of Arthritis Research & Therapy sheds novel mechanistic insight into the pathways employed by MSCs to suppress T-cell proliferation in vitro, but, at the same time, indicates that MSCs do not influence T-cell reactivity and the disease course in an in vivo arthritis model. Such discrepancies between the in vitro and in vivo effects of potent cellular immune modulators should spark further research and should be interpreted as a sign of caution
for the in vitro design of MSC-derived interventions in the setting of human autoimmune diseases. 相似文献
7.
Adam P Schoof J Hartmann M Schwarz S Puppe B Ott M Rosenwald A Ott G Muller-Hermelink HK 《Cytogenetic and genome research》2007,118(2-4):328-336
Follicular lymphoma (FL) constitutes the neoplastic equivalent of germinal center B-cells. Like its physiological counterpart, FL grows in (atypical) follicular structures, the formation of which is as yet poorly understood. Recent data indicate that in early tumour stages, neoplastic FL cells home to and colonise reactive germinal centers. Laser microdissection (LMD) and micromanipulation techniques now allow for the molecular genetic analysis of single cell mutation patterns in FL. The purpose of the present study was the analysis of the sequence and order of somatic mutations in FL, i.e. the influence of the germinal center microenvironment on the clonal evolution in different grades of FL. By generating phylogenetic trees as calculated from tumour cell sequences, the clonal evolution from a putative progenitor cell was elucidated and finally, the tumour cell migration pattern in disease progression was assessed by analyzing biopsies at different time points in relapsed tumours. Four patients suffering from FL were included in the study. A primary FL grade 1 showed clustering of genetically related subclones in distinct follicles. A moderate interfollicular exchange of tumour cells was detected. Three cases of FL grade 2 were found to show decreased subclonal clustering in follicles and an increase in the interfollicular migration. Accumulations of replacement mutations in antigen binding domains (CDR) and silent mutations in non-antigen binding domains (FR), respectively, indicating antigen influence on hypermutation were only found in the case of FL grade 1. Our conclusion is that the microenvironment in germinal centers exercises influence on clonal evolution and tumour cell distribution patterns in FL. With increasing histologic grade during disease progression, a reduced intraclonal diversity and selection of subclones also occurs outside the setting of transformation to high-grade lymphoma. Antigen-dependent hypermutations were only seen in FL grade 1, while in progressed FL, random mutation patterns and a decrease of clonal diversity were found. 相似文献
8.
Bahareh Honarparvar Sachin A Pawar Cláudio Nahum Alves Jer?nimo Lameira Glenn EM Maguire José Rogério A Silva Thavendran Govender Hendrik G Kruger 《Journal of biomedical science》2015,22(1)
Background
Novel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC50 values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC50) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.Results
The PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC50 = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC50 = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆Gsolv) were also considered.Conclusions
A general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC50 data.Electronic supplementary material
The online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users. 相似文献9.
Nadine Kraemer Ethiraj Ravindran Sami Zaqout Gerda Neubert Detlev Schindler Olaf Ninnemann Ralph Gr?f Andrea EM Seiler Angela M Kaindl 《Cell cycle (Georgetown, Tex.)》2015,14(13):2044-2057
Biallelic mutations in the gene encoding centrosomal CDK5RAP2 lead to autosomal recessive primary microcephaly (MCPH), a disorder characterized by pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. The current model for the microcephaly phenotype in MCPH invokes a premature shift from symmetric to asymmetric neural progenitor-cell divisions with a subsequent depletion of the progenitor pool. The isolated neural phenotype, despite the ubiquitous expression of CDK5RAP2, and reports of progressive microcephaly in individual MCPH cases prompted us to investigate neural and non-neural differentiation of Cdk5rap2-depleted and control murine embryonic stem cells (mESC). We demonstrate an accumulating proliferation defect of neurally differentiating Cdk5rap2-depleted mESC and cell death of proliferative and early postmitotic cells. A similar effect does not occur in non-neural differentiation into beating cardiomyocytes, which is in line with the lack of non-central nervous system features in MCPH patients. Our data suggest that MCPH is not only caused by premature differentiation of progenitors, but also by reduced propagation and survival of neural progenitors. 相似文献
10.
Suurmond J Dorjée AL Boon MR Knol EF Huizinga TW Toes RE Schuerwegh AJ 《Arthritis research & therapy》2011,13(5):R150