Calcineurin immunoreactivity in striatonigral degeneration
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In a soil bioassay, adult Deroceras reticulatum (Stylommatophora: Limacidae) and three different weight-classes of young Arion lusitanicus (Stylommatophora: Arionidae) were exposed to a single dosage (170 dauer larvae per g of soil) of the nematode Phasmarhabditis hermaphrodita monoxenically associated with the bacterium Moraxella osloensis. Groups of 10 slugs were continuously exposed to nematodes for 4 days, and then transferred individually to Petri-dishes containing a disc of Chinese cabbage as food. Food consumption—measured by image analysis—and slug mortality were recorded daily for 10 days. Food consumption was inhibited in both slug species tested. D. reticulatum stopped feeding 6 days after the start of nematode treatment, while all A. lusitanicus continued to feed. However, in the three weight-classes of A. lusitanicus (0.15 g, 0.24 g, 0.45 g), food consumption was reduced by at least 50 %. The greatest reduction in feeding, nearly 90 %, was noted in the smallest A. lusitanicus. The nematodes successfully killed D. reticulatum but were less efficient at killing young A. lusitanicus. At the end of the experiment, mortality was highest in D. reticultatum (98 %) and the smallest weight-class of A. lusitanicus (47 %). There was almost no mortality in the largest weight-class of A. lusitanicus treated with nematodes. P. hermaphrodita associated with M. osloensis can thus be considered as a biological control agent for young stages of A. lusitanicus for its effect as a feeding inhibitor, rather than for its ability to kill the slugs.
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In response to DNA damage, p53 undergoes post-translational modifications (including acetylation) that are critical for its transcriptional activity. However, the mechanism by which p53 acetylation is regulated is still unclear. Here, we describe an essential role for HLA-B-associated transcript 3 (Bat3)/Scythe in controlling the acetylation of p53 required for DNA damage responses. Depletion of Bat3 from human and mouse cells markedly impairs p53-mediated transactivation of its target genes Puma and p21 . Although DNA damage-induced phosphorylation, stabilization, and nuclear accumulation of p53 are not significantly affected by Bat3 depletion, p53 acetylation is almost completely abolished. Bat3 forms a complex with p300, and an increased amount of Bat3 enhances the recruitment of p53 to p300 and facilitates subsequent p53 acetylation. In contrast, Bat3-depleted cells show reduced p53–p300 complex formation and decreased p53 acetylation. Furthermore, consistent with our in vitro findings, thymocytes from Bat3-deficient mice exhibit reduced induction of puma and p21, and are resistant to DNA damage-induced apoptosis in vivo. Our data indicate that Bat3 is a novel and essential regulator of p53-mediated responses to genotoxic stress, and that Bat3 controls DNA damage-induced acetylation of p53.
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In the present study, several multivariate analyses were carried out to assess the taxonomic relationships among European species of the genus Anthoxanthum. A total of 1787 Anthoxanthum specimens representing all European taxa were analyzed. Thirty macro-morphological (13 quantitative and 17 qualitative) and 29 micro-morphological (7 quantitative and 22 qualitative) characters were considered. First, resemblances between specimens were established independently for macro- and micro-morphological characters using Gower's similarity coefficient, and were represented by means of principal coordinates and cluster analyses. Subsequently, different multivariate analyses were applied to quantitative and qualitative macromorphological data to determine the most discriminant characters and the accuracy of the present taxonomic structure of the genus. Finally, dissimilarities among groups of individuals -species and populations- were estimated using the information radius measure and then represented in different dendrograms. Within annuals, Anthoxanthum gracile is clearly differentiated morphologically, yet no compelling morphological differentiation can be found between Anthoxanthum aristatum and Anthoxanthum ovatum. Moreover, the definition of subspecies in the annual taxa is not supported by our results. Then, within perennials, although the morphological relationships among Anthoxanthum amarum, Anthoxanthum odoratum and Anthoxanthum alpinum have also been resolved, further research is needed to assess the taxonomic position of the Macaronesian endemic Anthoxanthum maderense.
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Previous studies have demonstrated that activation of calcineurin induces pathological cardiac hypertrophy (CH). In these studies, loss‐of‐function was mostly achieved by systemic administration of the calcineurin inhibitor cyclosporin A. The lack of conditional knockout models for calcineurin function has impeded progress toward defining the role of this protein during the onset and the development of CH in adults. Here, we exploited a mouse model of CH based on the infusion of a hypertensive dose of angiotensin II (Ang II ) to model the role of calcineurin in CH in adulthood. Ang II ‐induced CH in adult mice was reduced by treatment with cyclosporin A, without affecting the associated increase in blood pressure, and also by induction of calcineurin deletion in adult mouse cardiomyocytes, indicating that cardiomyocyte calcineurin is required for Ang II ‐induced CH. Surprisingly, cardiac‐specific deletion of calcineurin, but not treatment of mice with cyclosporin A, significantly reduced Ang II ‐induced cardiac fibrosis and apoptosis. Analysis of profibrotic genes revealed that Ang II ‐induced expression of Tgfβ family members and Lox was not inhibited by cyclosporin A but was markedly reduced by cardiac‐specific calcineurin deletion. These results show that Ang II induces a direct, calcineurin‐dependent prohypertrophic effect in cardiomyocytes, as well as a systemic hypertensive effect that is independent of calcineurin activity.
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Calcium Signaling
Calcium in biology
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To the Editor: The calcineurin pathway has been proposed to mediate left ventricular hypertrophy, particularly its initiation. 1 However, evidence has been scant. Braun et al 2 designed a very interesting experimental protocol and investigated whether calcineurin expression was up-regulated at the initial stage of left ventricular hypertrophy. Unfortunately, they failed to detect calcineurin overexpression. There are a couple of problems with the methodology they employed in the study. First, it appears that they homogenized the whole heart instead of the left ventricle only, which may dilute calcineurin expression. Second, calcineurin upregulation represents both increased calcineurin expression and increased calcineurin activity. Apparently, the activity was not measured in the study, as the assay for calcineurin has not been perfected. 3,4 As such, it remains unclear whether calcineurin plays an important role at an early stage in isoproterenol-induced cardiac hypertrophy. 5 Isuzu Yamori, MD
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Holcus lanatus
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SUMMARY A hitherto unrecorded virus having flexible rod‐shaped particles about 740–760 × 13 nm was isolated from Anthoxanthum odoratwn L. It was transmitted by sap inoculation, but not by several species of insect, seed or soil to 18 species of Gramineae including wheat, oats and barley. In susceptible species the virus normally produced a mosaic mottling of the leaves which was sometimes followed by a necrotic streaking or striping.
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HLA-B-associated transcript 3 (BAT3) was originally identified as one of the genes located within human major histocompatibility complex. It encodes a large proline-rich protein with unknown function. In this study, we found that a fragment of the BAT3 gene product interacts with a candidate tumor suppressor, DAN, in the yeast-based two-hybrid system. We cloned the full-length rat BAT3 cDNA from a fibroblast 3Y1 cDNA library. Our sequence analysis has demonstrated that rat BAT3 cDNA is 3617 nucleotides in length and encodes a full-length BAT3 (1098 amino acids) with an estimated molecular mass of 114,801 daltons, which displays an 87.4% identity with human BAT3. The deletion experiment revealed that the N-terminal region (amino acid residues 1-80) of DAN was required for the interaction with BAT3. Green fluorescent protein-tagged BAT3 was largely localized in the cytoplasm of COS cells. Northern hybridization showed that BAT3 mRNA was expressed in all the adult rat tissues examined but predominantly in testis. In addition, the level of BAT3 mRNA expression was more downregulated in some of the transformed cells, including v-mos- and v-Ha-ras-transformed 3Y1 cells, than in the parental cells.
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The objective of this pharmacodynamic study was to longitudinally assess the activity of calcineurin during the first 2 years after lung transplantation. From March 2004 to October 2008, 107 patients were prospectively enrolled and their follow-up was performed until 2009. Calcineurin activity was measured in peripheral blood mononuclear cells. We report that calcineurin activity was linked to both acute and chronic rejection. An optimal activity for calcineurin with two thresholds was defined, and we found that the risk of rejection was higher when the enzyme activity was above the upper threshold of 102 pmol/mg/min or below the lower threshold of 12 pmol/mg/min. In addition, we report that the occurrence of malignancies and viral infections was significantly higher in patients displaying very low levels of calcineurin activity. Taken together, these findings suggest that the measurement of calcineurin activity may provide useful information for the management of the prevention therapy of patients receiving lung transplantation.
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