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1.
This study evaluates causal relationships between chronic exposure of fish to metals and effects at different levels of biological organization based on a weight-of-evidence approach. Criteria for evaluation of causality were strength, consistency, and specificity of the association, as well as biological gradient and plausibility. Field sampling was conducted three times between 1998 and 2000, in Furnas Stream, impacted by an abandoned lead mine, and in three other locations, including two reference and one impacted sites. Levels of Pb, Zn, Cd, and Ag in sediments from the Furnas Stream exceeded background levels, and their concentrations were above sediment quality guidelines. Residual levels of metals in fish tissue were high enough to indicate reduced growth, reproduction and/or survival according to toxicological benchmarks. Lead-induced biochemical changes (ALA-D activity depletion) were observed in two species of siluriform catfish. The condition factor of a predatory catfish was reduced, and the percentage of prey generalists was higher in Furnas than at the noncontaminated sites. Reduction in fish community diversity and density was observed. Integration of data provided supporting evidence that observed effects on fish from the Furnas Stream resulted from long-term exposure to metals, however influences from other stressors cannot be ruled out. 相似文献
2.
A Rauch R A Pfeiffer G Leipold H Singer M Tigges M Hofbeck 《American journal of human genetics》1999,64(2):659-666
3.
Microphotometric measurements of fast reacting protein thiols (PSHr) and proteins were performed on freshly frozen sections of samples from normal skin (26 cases as controls) and from 45 basal cell epitheliomas (basalioma; BCE). The intensity of the staining (E/micron2) for both proteins and PSHr was significantly higher in normal epidermis than in the adjacent dermis. The values of QE (quotient of values observed in the epidermis divided by those observed in the dermis) were calculated to be 3.48 for proteins (QE, Prot) and 4.62 for PSHr (QE, PSHr). In cases of BCE, significantly lower QE values were found: QE, Prot = 2.16 and QE, PSHr = 1.72. The decrease of QE, PSHr was due to a decrease in the staining intensity observed in the BCEs, whereas practically no changes occurred in the adjacent dermis. The decrease of QE, Prot was mainly caused by a decrease in the staining intensity in the BCE (by 68%) as well as in the adjacent dermis (by 36%). By dividing the mean extinction value (E/micron2) for PSHr by the E/micron2 for proteins, a new quotient, PSHr/Prot, is obtained which can serve as a quantitative measure of the content of the tissue proteins of PSHr. The proteins of normal epidermis contained more PSHr than dermal proteins. The proteins of BCEs also contained more PSHr than those of the adjacent dermis, but the PSHr/Prot values of both tissues were 1.5 to 1.6 times greater than the corresponding values for normal epidermis and dermis, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
The binding of cardiac glycosides to the E2 conformation of Na, K ATPase suggests that this conformation may represent a potential regulatory site for an endogenous ligand. To examine this hypothesis, delipidated and desalted, ethanolic extracts were prepared from plasma. Plasma extracts produced displacement of 3H-ouabain from Type I and II high affinity binding sites that was parallel to the displacement by cold ouabain. Plasma extracts shifted the binding curve of 3H-ouabain to the right indicating a competitive and reversible displacement. Extracts also produced a dose-dependent inhibition of Na, K ATPase and K-stimulated, p-nitrophenyl phosphatase activity. These results indicate that this ligand may function as an endogenous ligand to the E2 conformation of the Na, K ATPase molecule and be involved in its regulation. 相似文献
5.
肺癌在中国恶性肿瘤的发病率位居第一,随着低剂量薄层CT在肺癌筛查中的广泛应用,临床发现更多表现为非完全实性结节的肺腺癌,目前众多研究使CT影像学特征和肺腺癌病理的关系得到更进一步的认知,虽然CT能对部分非完全实性结节做出定性和定位诊断,但仍有部分非完全实性结节诊断困难,PET-CT结合了病灶的代谢信息和精确的定位信息,从而提高对肺部结节诊断的敏感性、特异性、准确性,综合多个文献PET-CT在非完全实性结节中的诊断分期价值较CT无明显提升,却在评估预后和制定合适手术方案上可以起到一定的作用,本文就PET-CT在SSN中的应用价值进行阐述。 相似文献
6.
Paratscha Roman Von Der Thannen Magdalena Smutny Roman Lampalzer Thomas Strauss Alfred Rauch Hans Peter 《The International Journal of Life Cycle Assessment》2019,24(11):2035-2053
The International Journal of Life Cycle Assessment - This study emerged from a research project that aimed to develop a Life Cycle Assessment (LCA) model for torrent control structures. This... 相似文献
7.
Lauren A. Demers Elizabeth A. Olson David J. Crowley Scott L. Rauch Isabelle M. Rosso 《PloS one》2015,10(10)
Alexithymia, or “no words for feelings”, is highly prevalent in samples with childhood maltreatment and posttraumatic stress disorder (PTSD). The dorsal anterior cingulate cortex (dACC) has been identified as a key region involved in alexithymia, early life trauma, and PTSD. Functional alterations in the dACC also have been associated with alexithymia in PTSD. This study examined whether dACC morphology is a neural correlate of alexithymia in child maltreatment-related PTSD. Sixteen adults with PTSD and a history of childhood sexual abuse, physical abuse, or exposure to domestic violence, and 24 healthy controls (HC) completed the Toronto Alexithymia Scale 20 (TAS–20) and underwent magnetic resonance imaging. Cortical thickness of the dACC was measured using FreeSurfer, and values were correlated with TAS–20 scores, controlling for sex and age, in both groups. Average TAS–20 score was significantly higher in the PTSD than the HC group. TAS–20 scores were significantly positively associated with dACC thickness only in the PTSD group. This association was strongest in the left hemisphere and for TAS–20 subscales that assess difficulty identifying and describing feelings. We found that increasing dACC gray matter thickness is a neural correlate of greater alexithymia in the context of PTSD with childhood maltreatment. While findings are correlational, they motivate further inquiry into the relationships between childhood adversity, emotional awareness and expression, and dACC morphologic development in trauma-related psychopathology. 相似文献
8.
Chia-Chun Yu Shih-Ping Liu Jui-Ling Hsu John TA Hsu Konstantin V Kudryavtsev Jih-Hwa Guh 《Journal of biomedical science》2015,22(1)
Background
Hormone-refractory prostate cancer (HRPC), which is resistant to hormone therapy, is a major obstacle in clinical treatment. An approach to inhibit HRPC growth and ultimately to kill cancers is highly demanded.Results
KUD773 induced the anti-proliferative effect and subsequent apoptosis in PC-3 and DU-145 (two HRPC cell lines); whereas, it showed less active in normal prostate cells. Further examination showed that KUD773 inhibited tubulin polymerization and induced an increase of mitotic phosphoproteins and polo-like kinase 1 (PLK1) phosphorylation, indicating a mitotic arrest of the cell cycle through an anti-tubulin action. The kinase assay demonstrated that KUD773 inhibited Aurora A activity. KUD773 induced an increase of Cdk1 phosphorylation at Thr161 (a stimulatory phosphorylation site) and a decrease of phosphorylation at Tyr15 (an inhibitory phosphorylation site), suggesting the activation of Cdk1. The data were substantiated by an up-regulation of cyclin B1 (a Cdk1 partner). Furthermore, KUD773 induced the phosphorylation and subsequent down-regulation of Bcl-2 and activation of caspase cascades.Conclusions
The data suggest that KUD773 induces apoptotic signaling in a sequential manner. It inhibits tubulin polymerization associated with an anti-Aurora A activity, leading to Cdk1 activation and mitotic arrest of the cell cycle that in turn induces Bcl-2 degradation and a subsequent caspase activation in HRPCs. 相似文献9.
Roberto Mendoza-Londono Somayyeh Fahiminiya Jacek Majewski CareRare Canada Consortium Martine Tétreault Javad Nadaf Peter Kannu Etienne Sochett Andrew Howard Jennifer Stimec Lucie Dupuis Paul Roschger Klaus Klaushofer Telma Palomo Jean Ouellet Hadil Al-Jallad John?S. Mort Pierre Moffatt Sergei Boudko Hans-Peter B?chinger Frank Rauch 《American journal of human genetics》2015,96(6):979-985
Secreted protein, acidic, cysteine-rich (SPARC) is a glycoprotein that binds to collagen type I and other proteins in the extracellular matrix. Using whole-exome sequencing to identify the molecular defect in two unrelated girls with severe bone fragility and a clinical diagnosis of osteogenesis imperfecta type IV, we identified two homozygous variants in SPARC (GenBank: ; c.497G>A [p.Arg166His] in individual 1; c.787G>A [p.Glu263Lys] in individual 2). Published modeling and site-directed mutagenesis studies had previously shown that the residues substituted by these mutations form an intramolecular salt bridge in SPARC and are essential for the binding of SPARC to collagen type I. The amount of SPARC secreted by skin fibroblasts was reduced in individual 1 but appeared normal in individual 2. The migration of collagen type I alpha chains produced by these fibroblasts was mildly delayed on SDS-PAGE gel, suggesting some overmodification of collagen during triple helical formation. Pulse-chase experiments showed that collagen type I secretion was mildly delayed in skin fibroblasts from both individuals. Analysis of an iliac bone sample from individual 2 showed that trabecular bone was hypermineralized on the material level. In conclusion, these observations show that homozygous mutations in SPARC can give rise to severe bone fragility in humans. NM_003118.3相似文献
10.
Sarah N. Fontaine Jennifer N. Rauch Bryce A. Nordhues Victoria A. Assimon Andrew R. Stothert Umesh K. Jinwal Jonathan J. Sabbagh Lyra Chang Stanley M. Stevens Jr. Erik R. P. Zuiderweg Jason E. Gestwicki Chad A. Dickey 《The Journal of biological chemistry》2015,290(21):13115-13127
The constitutively expressed heat shock protein 70 kDa (Hsc70) is a major chaperone protein responsible for maintaining proteostasis, yet how its structure translates into functional decisions regarding client fate is still unclear. We previously showed that Hsc70 preserved aberrant Tau, but it remained unknown if selective inhibition of the activity of this Hsp70 isoform could facilitate Tau clearance. Using single point mutations in the nucleotide binding domain, we assessed the effect of several mutations on the functions of human Hsc70. Biochemical characterization revealed that one mutation abolished both Hsc70 ATPase and refolding activities. This variant resembled the ADP-bound conformer at all times yet remained able to interact with cofactors, nucleotides, and substrates appropriately, resembling a dominant negative Hsc70 (DN-Hsc70). We then assessed the effects of this DN-Hsc70 on its client Tau. DN-Hsc70 potently facilitated Tau clearance via the proteasome in cells and brain tissue, in contrast to wild type Hsc70 that stabilized Tau. Thus, DN-Hsc70 mimics the action of small molecule pan Hsp70 inhibitors with regard to Tau metabolism. This shift in Hsc70 function by a single point mutation was the result of a change in the chaperome associated with Hsc70 such that DN-Hsc70 associated more with Hsp90 and DnaJ proteins, whereas wild type Hsc70 was more associated with other Hsp70 isoforms. Thus, isoform-selective targeting of Hsc70 could be a viable therapeutic strategy for tauopathies and possibly lead to new insights in chaperone complex biology. 相似文献