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Lutz Schomburg - One of the best experts on this subject based on the ideXlab platform.
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selenium controls the sex specific immune Response and selenoprotein expression during the Acute Phase Response in mice
Biochemical Journal, 2010Co-Authors: Mette Stoedter, Kostja Renko, Lutz SchomburgAbstract:Selenium modifies inflammatory reactions in rodents and humans. The liver controls metabolism and transport of selenium via hepatically-derived SEPP (selenoprotein P). Intracellular SEPS (selenoprotein S) modifies endoplasmic-reticulum function and immune-cell activity. Polymorphisms in SEPS have been associated with cytokine levels and inflammatory diseases in a subset of clinical studies. In the present study, we hypothesized that sex and selenium represent decisive parameters controlling the immune Response and regulation of SEPS expression in vivo . Male and female mice fed a selenium-poor diet were supplemented or not with selenite for 3 days and injected with saline or LPS (lipopolysaccharide) 24 h before analysis. Selenium supplementation mitigated the LPS-induced rise in circulating cytokines in male mice. Serum SepP and selenium concentrations decreased in Response to LPS, whereas hepatic SepS was specifically up-regulated despite declining selenium concentrations in the liver. Hepatic SepS induction was mainly controlled by post-transcriptional mechanisms and attributed to hepatocytes by analysing transgenic mice. Notably, selenium supplementation was essential for an optimal SepS induction. We conclude that selenoprotein biosynthesis becomes redirected in hepatocytes during the Acute-Phase Response at the expense of dispensable selenoproteins (e.g. SepP) and in favour of SepS expression, thereby causing declining serum selenium and improving liver function. The selenium status and sex control SepS expression and modify cytokine Response patterns in serum, which might explain contradictory results on associations of SEPS genotype and inflammatory diseases in clinical studies.
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down regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the Acute Phase Response in mice
The FASEB Journal, 2009Co-Authors: Kostja Renko, Birgit Hollenbach, Josef Kohrle, Ulrich Schweizer, Peter J Hofmann, Mette Stoedter, Thomas Behrends, Lutz SchomburgAbstract:The Acute-Phase Response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed the expression of the central Se transport and storage protein selenoprotein P (Sepp1) during an APR in mice. Serum Se and Sepp1 concentrations declined in parallel after injection of lipopolysaccharide to 50 and 39% of control-injected littermates, respectively. This negative APR proceeded largely independent from hepatic Sepp1 transcript concentrations. Instead, we identified a set of hepatic transcripts involved in Se metabolism, which declined coordinately during the APR, including the selenocysteine-specific elongation factor (EFsec), selenophosphate-synthetase 2 (Sephs2), selenocysteine-tRNA[Ser]Sec synthase (SecS), and phosphoseryl-tRNA[Ser]Sec kinase (Pstk). Pstk reacted most strongly and qualified as a new limiting factor for Sepp1 biosynthesis in siRNA-mediated knockdown experiments in...
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down regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the Acute Phase Response in mice
The FASEB Journal, 2009Co-Authors: Kostja Renko, Birgit Hollenbach, Josef Kohrle, Ulrich Schweizer, Peter J Hofmann, Mette Stoedter, Thomas Behrends, Lutz SchomburgAbstract:The Acute-Phase Response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed the expression of the central Se transport and storage protein selenoprotein P (Sepp1) during an APR in mice. Serum Se and Sepp1 concentrations declined in parallel after injection of lipopolysaccharide to 50 and 39% of control-injected littermates, respectively. This negative APR proceeded largely independent from hepatic Sepp1 transcript concentrations. Instead, we identified a set of hepatic transcripts involved in Se metabolism, which declined coordinately during the APR, including the selenocysteine-specific elongation factor (EFsec), selenophosphate-synthetase 2 (Sephs2), selenocysteine-tRNA[Ser]Sec synthase (SecS), and phosphoseryl-tRNA[Ser]Sec kinase (Pstk). Pstk reacted most strongly and qualified as a new limiting factor for Sepp1 biosynthesis in siRNA-mediated knockdown experiments in hepatocytes in culture. Analogous experiments were performed with mice transgenic for hepatocyte-specific human Sepp1 cDNA to verify this hypothesis. Similar kinetics and effect sizes of Sepp1 expression were observed as before in wild-type mice. We conclude that hepatic translation of Sepp1 mRNA is specifically impaired during the APR. This deficit disrupts regular Se metabolism, transport, and supply to peripheral tissues and likely aggravates the pathological status.
Kostja Renko - One of the best experts on this subject based on the ideXlab platform.
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selenium controls the sex specific immune Response and selenoprotein expression during the Acute Phase Response in mice
Biochemical Journal, 2010Co-Authors: Mette Stoedter, Kostja Renko, Lutz SchomburgAbstract:Selenium modifies inflammatory reactions in rodents and humans. The liver controls metabolism and transport of selenium via hepatically-derived SEPP (selenoprotein P). Intracellular SEPS (selenoprotein S) modifies endoplasmic-reticulum function and immune-cell activity. Polymorphisms in SEPS have been associated with cytokine levels and inflammatory diseases in a subset of clinical studies. In the present study, we hypothesized that sex and selenium represent decisive parameters controlling the immune Response and regulation of SEPS expression in vivo . Male and female mice fed a selenium-poor diet were supplemented or not with selenite for 3 days and injected with saline or LPS (lipopolysaccharide) 24 h before analysis. Selenium supplementation mitigated the LPS-induced rise in circulating cytokines in male mice. Serum SepP and selenium concentrations decreased in Response to LPS, whereas hepatic SepS was specifically up-regulated despite declining selenium concentrations in the liver. Hepatic SepS induction was mainly controlled by post-transcriptional mechanisms and attributed to hepatocytes by analysing transgenic mice. Notably, selenium supplementation was essential for an optimal SepS induction. We conclude that selenoprotein biosynthesis becomes redirected in hepatocytes during the Acute-Phase Response at the expense of dispensable selenoproteins (e.g. SepP) and in favour of SepS expression, thereby causing declining serum selenium and improving liver function. The selenium status and sex control SepS expression and modify cytokine Response patterns in serum, which might explain contradictory results on associations of SEPS genotype and inflammatory diseases in clinical studies.
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down regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the Acute Phase Response in mice
The FASEB Journal, 2009Co-Authors: Kostja Renko, Birgit Hollenbach, Josef Kohrle, Ulrich Schweizer, Peter J Hofmann, Mette Stoedter, Thomas Behrends, Lutz SchomburgAbstract:The Acute-Phase Response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed the expression of the central Se transport and storage protein selenoprotein P (Sepp1) during an APR in mice. Serum Se and Sepp1 concentrations declined in parallel after injection of lipopolysaccharide to 50 and 39% of control-injected littermates, respectively. This negative APR proceeded largely independent from hepatic Sepp1 transcript concentrations. Instead, we identified a set of hepatic transcripts involved in Se metabolism, which declined coordinately during the APR, including the selenocysteine-specific elongation factor (EFsec), selenophosphate-synthetase 2 (Sephs2), selenocysteine-tRNA[Ser]Sec synthase (SecS), and phosphoseryl-tRNA[Ser]Sec kinase (Pstk). Pstk reacted most strongly and qualified as a new limiting factor for Sepp1 biosynthesis in siRNA-mediated knockdown experiments in...
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down regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the Acute Phase Response in mice
The FASEB Journal, 2009Co-Authors: Kostja Renko, Birgit Hollenbach, Josef Kohrle, Ulrich Schweizer, Peter J Hofmann, Mette Stoedter, Thomas Behrends, Lutz SchomburgAbstract:The Acute-Phase Response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed the expression of the central Se transport and storage protein selenoprotein P (Sepp1) during an APR in mice. Serum Se and Sepp1 concentrations declined in parallel after injection of lipopolysaccharide to 50 and 39% of control-injected littermates, respectively. This negative APR proceeded largely independent from hepatic Sepp1 transcript concentrations. Instead, we identified a set of hepatic transcripts involved in Se metabolism, which declined coordinately during the APR, including the selenocysteine-specific elongation factor (EFsec), selenophosphate-synthetase 2 (Sephs2), selenocysteine-tRNA[Ser]Sec synthase (SecS), and phosphoseryl-tRNA[Ser]Sec kinase (Pstk). Pstk reacted most strongly and qualified as a new limiting factor for Sepp1 biosynthesis in siRNA-mediated knockdown experiments in hepatocytes in culture. Analogous experiments were performed with mice transgenic for hepatocyte-specific human Sepp1 cDNA to verify this hypothesis. Similar kinetics and effect sizes of Sepp1 expression were observed as before in wild-type mice. We conclude that hepatic translation of Sepp1 mRNA is specifically impaired during the APR. This deficit disrupts regular Se metabolism, transport, and supply to peripheral tissues and likely aggravates the pathological status.
George A Kaysen - One of the best experts on this subject based on the ideXlab platform.
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the Acute Phase Response varies with time and predicts serum albumin levels in hemodialysis patients
Kidney International, 2000Co-Authors: George A Kaysen, Joel A Dubin, Hans G Muller, Laura RosalesAbstract:The Acute-Phase Response varies with time and predicts serum albumin levels in hemodialysis patients. Background Cross sectional studies have established that the serum albumin level is dependent on serum levels of Acute-Phase proteins (APPs) or cytokine levels in hemodialysis patients. While the Acute-Phase Response is generally associated with Acute inflammatory events, a cross sectional analysis relating laboratory values to outcomes assumes these values to be unchanging. The longitudinal relationship among laboratory measurements and how they vary over time in a population of patients are unknown. Methods Patients who were enrolled in the HEMO Study were recruited into an ancillary longitudinal study to establish the predictive effect of temporal variation in the levels of APPs and of temporal variation in normalized protein catabolic rate (nPCR) on the serum albumin concentration. nPCR was measured monthly using a double-pool method. The positive APPs—C-reactive protein (CRP), α1 acid glycoprotein (α1-AG), and ceruloplasmin—and the negative APP—transferrin (Trf)—were measured in serum obtained before each dialysis session for six weeks and then monthly in 37 hemodialysis patients. A random coefficient regression analysis was used to assess the association of serum albumin with other measured parameters at each time point, as well as fixed patient characteristics. Results The within-subject coefficients of variation of albumin (median, range of 25th to 75th percentiles; median, 0.0614; range, 0.0485 to 0.0690) were significantly less than that of APPs (CRP, median, 0.878; range, 0.595 to 1.314, P P P = 0.0014). nPCR also was a significant predictor for albumin levels ( P = 0.0440) after controlling for the effect of APPs, suggesting an effect of nPCR on serum albumin concentration irrespective of the Acute-Phase Response. Age and the presence of an arteriovenous graft were significant predictors that were associated with reduced albumin. Conclusions The Acute-Phase Response is intermittent and is not a continuous feature in individual dialysis patients. Levels of APPs are the most powerful predictors for the levels of albumin concentration in hemodialysis in a longitudinal setting. Since variations in albumin are small, measurement of variations in APPs may provide greater insight into the dynamics of clinically relevant processes.
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Acute Phase Response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients
American Journal of Kidney Diseases, 1999Co-Authors: Jennifer Gunnell, Jane Y Yeun, Thomas A Depner, George A KaysenAbstract:Abstract We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the Acute-Phase Response, assessed by the level of the Acute-Phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (Δ R 2 = 0.129; P R 2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (Δ R 2 = 0.205; P = 0.002) and ferritin levels (Δ R 2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (Δ R 2 = 0.105; P = 0.003) and ferritin levels (Δ R 2 = 0.051; P = 0.023) in HD patients and CRP level (Δ R 2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (Δ R 2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the Acute-Phase Response, not in iron deficiency. In well-dialyzed patients who were iron replete, the Acute-Phase Response was the most important predictor of EPO resistance.
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Acute Phase Response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients
American Journal of Kidney Diseases, 1999Co-Authors: Jennifer Gunnell, Jane Y Yeun, Thomas A Depner, George A KaysenAbstract:We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the Acute-Phase Response, assessed by the level of the Acute-Phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the Acute-Phase Response, not in iron deficiency. In well-dialyzed patients who were iron replete, the Acute-Phase Response was the most important predictor of EPO resistance.
Mette Stoedter - One of the best experts on this subject based on the ideXlab platform.
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selenium controls the sex specific immune Response and selenoprotein expression during the Acute Phase Response in mice
Biochemical Journal, 2010Co-Authors: Mette Stoedter, Kostja Renko, Lutz SchomburgAbstract:Selenium modifies inflammatory reactions in rodents and humans. The liver controls metabolism and transport of selenium via hepatically-derived SEPP (selenoprotein P). Intracellular SEPS (selenoprotein S) modifies endoplasmic-reticulum function and immune-cell activity. Polymorphisms in SEPS have been associated with cytokine levels and inflammatory diseases in a subset of clinical studies. In the present study, we hypothesized that sex and selenium represent decisive parameters controlling the immune Response and regulation of SEPS expression in vivo . Male and female mice fed a selenium-poor diet were supplemented or not with selenite for 3 days and injected with saline or LPS (lipopolysaccharide) 24 h before analysis. Selenium supplementation mitigated the LPS-induced rise in circulating cytokines in male mice. Serum SepP and selenium concentrations decreased in Response to LPS, whereas hepatic SepS was specifically up-regulated despite declining selenium concentrations in the liver. Hepatic SepS induction was mainly controlled by post-transcriptional mechanisms and attributed to hepatocytes by analysing transgenic mice. Notably, selenium supplementation was essential for an optimal SepS induction. We conclude that selenoprotein biosynthesis becomes redirected in hepatocytes during the Acute-Phase Response at the expense of dispensable selenoproteins (e.g. SepP) and in favour of SepS expression, thereby causing declining serum selenium and improving liver function. The selenium status and sex control SepS expression and modify cytokine Response patterns in serum, which might explain contradictory results on associations of SEPS genotype and inflammatory diseases in clinical studies.
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down regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the Acute Phase Response in mice
The FASEB Journal, 2009Co-Authors: Kostja Renko, Birgit Hollenbach, Josef Kohrle, Ulrich Schweizer, Peter J Hofmann, Mette Stoedter, Thomas Behrends, Lutz SchomburgAbstract:The Acute-Phase Response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed the expression of the central Se transport and storage protein selenoprotein P (Sepp1) during an APR in mice. Serum Se and Sepp1 concentrations declined in parallel after injection of lipopolysaccharide to 50 and 39% of control-injected littermates, respectively. This negative APR proceeded largely independent from hepatic Sepp1 transcript concentrations. Instead, we identified a set of hepatic transcripts involved in Se metabolism, which declined coordinately during the APR, including the selenocysteine-specific elongation factor (EFsec), selenophosphate-synthetase 2 (Sephs2), selenocysteine-tRNA[Ser]Sec synthase (SecS), and phosphoseryl-tRNA[Ser]Sec kinase (Pstk). Pstk reacted most strongly and qualified as a new limiting factor for Sepp1 biosynthesis in siRNA-mediated knockdown experiments in...
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down regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the Acute Phase Response in mice
The FASEB Journal, 2009Co-Authors: Kostja Renko, Birgit Hollenbach, Josef Kohrle, Ulrich Schweizer, Peter J Hofmann, Mette Stoedter, Thomas Behrends, Lutz SchomburgAbstract:The Acute-Phase Response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed the expression of the central Se transport and storage protein selenoprotein P (Sepp1) during an APR in mice. Serum Se and Sepp1 concentrations declined in parallel after injection of lipopolysaccharide to 50 and 39% of control-injected littermates, respectively. This negative APR proceeded largely independent from hepatic Sepp1 transcript concentrations. Instead, we identified a set of hepatic transcripts involved in Se metabolism, which declined coordinately during the APR, including the selenocysteine-specific elongation factor (EFsec), selenophosphate-synthetase 2 (Sephs2), selenocysteine-tRNA[Ser]Sec synthase (SecS), and phosphoseryl-tRNA[Ser]Sec kinase (Pstk). Pstk reacted most strongly and qualified as a new limiting factor for Sepp1 biosynthesis in siRNA-mediated knockdown experiments in hepatocytes in culture. Analogous experiments were performed with mice transgenic for hepatocyte-specific human Sepp1 cDNA to verify this hypothesis. Similar kinetics and effect sizes of Sepp1 expression were observed as before in wild-type mice. We conclude that hepatic translation of Sepp1 mRNA is specifically impaired during the APR. This deficit disrupts regular Se metabolism, transport, and supply to peripheral tissues and likely aggravates the pathological status.
Theunis Piersma - One of the best experts on this subject based on the ideXlab platform.
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limited access to food and physiological trade offs in a long distance migrant shorebird ii constitutive immune function and the Acute Phase Response
Physiological and Biochemical Zoology, 2009Co-Authors: Deborah M Buehler, Francisco Encinasviso, Magali Petit, Francois Vezina, Irene B Tieleman, Theunis PiersmaAbstract:In Response to unbalanced energy budgets, animals must allocate resources among competing physiological systems to maximize fitness. Constraints can be imposed on energy availability or energy expenditure, and adjustments can be made via changes in metabolism or trade-offs with competing demands such as body-mass maintenance and immune function. This study investigates changes in constitutive immune function and the Acute-Phase Response in shorebirds (red knots) faced with limited access time to food. We separated birds into two experimental groups receiving either 6 h or 22 h of food access and measured constitutive immune function. After 3 wk, we induced an Acute-Phase Response, and after 1 wk of recovery, we switched the groups to the opposite food treatment and measured constitutive immune function again. We found little effect of food treatment on constitutive immune function, which suggests that even under resource limitation, a baseline level of immune function is maintained. However, birds enduring limited access to food suppressed aspects of the Acute-Phase Response (decreased feeding and mass loss) to maintain energy intake, and they downregulated thermoregulatory adjustments to food treatment to maintain body temperature during simulated infection. Thus, under resource-limited conditions, birds save energy on the most costly aspects of immune defense.
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limited access to food and physiological trade offs in a long distance migrant shorebird ii constitutive immune function and the Acute Phase Response
Physiological and Biochemical Zoology, 2009Co-Authors: Deborah M Buehler, Francisco Encinasviso, Magali Petit, Francois Vezina, Irene B Tieleman, Theunis PiersmaAbstract:Abstract In Response to unbalanced energy budgets, animals must allocate resources among competing physiological systems to maximize fitness. Constraints can be imposed on energy availability or energy expenditure, and adjustments can be made via changes in metabolism or trade‐offs with competing demands such as body‐mass maintenance and immune function. This study investigates changes in constitutive immune function and the Acute‐Phase Response in shorebirds (red knots) faced with limited access time to food. We separated birds into two experimental groups receiving either 6 h or 22 h of food access and measured constitutive immune function. After 3 wk, we induced an Acute‐Phase Response, and after 1 wk of recovery, we switched the groups to the opposite food treatment and measured constitutive immune function again. We found little effect of food treatment on constitutive immune function, which suggests that even under resource limitation, a baseline level of immune function is maintained. However, bird...