Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

[Q]: Inflammation triggered by infection or injury is tightly controlled by glucocorticoid hormones which signal via a dedicated transcription factor, the Glucocorticoid Receptor (GR), to regulate hundreds of genes. However, the hierarchy of transcriptional responses to GR activation and the molecular basis of their oftentimes non-linear dynamics are not understood.', 'We investigated early glucocorticoid-driven transcriptional events in macrophages, a cell type highly responsive to both pro- and anti-inflammatory stimuli. Using whole transcriptome analyses in resting and acutely lipopolysaccharide (LPS)-stimulated macrophages, we show that early GR target genes form dense networks with the majority of control nodes represented by transcription factors. The expression dynamics of several glucocorticoid-responsive genes are consistent with feed forward loops (FFL) and coincide with rapid GR recruitment. Notably, GR binding sites in genes encoding members of the KLF transcription factor family colocalize with KLF binding sites. Moreover, our gene expression, transcription factor binding and computational data are consistent with the existence of the GR-KLF9-KLF2 incoherent FFL. Analysis of LPS-downregulated genes revealed striking enrichment in multimerized Zn-fingers- and KRAB domain-containing proteins known to bind nucleic acids and repress transcription by propagating heterochromatin. This raises an intriguing possibility that an increase in chromatin accessibility in inflammatory macrophages results from broad downregulation of negative chromatin remodelers.
[A]: 0


[Q]: SUMO-specific protease 1 (SENP1) removes SUMO from proteins and plays important roles in the regulation of multiple cellular signalling pathways. However, little is known about the role of SENP1 in coronary heart disease. In this study, we tested the hypothesis that SENP1 protects against myocardial ischaemia/reperfusion (I/R) injury and investigated the underlying molecular mechanisms involved.', 'First, we found that SENP1 levels increased after I/R in human and mouse myocardium in vivo and in rat cardiomyocytes in vitro. We then performed coronary artery ligation to induce I/R injury in wild-type (WT) and heterozygous SENP1-knockdown (SENP1(+/-)) mice. Compared with WT mice, SENP1(+/-) mice had normal cardiac function at baseline but lower systolic function after I/R. Post-I/R myocardial infarction sizes were larger in SENP1(+/-) mice. Furthermore, we demonstrated that SENP1 regulates the expression of hypoxia-inducible factor 1 α (HIF1α), a critical protective factor during I/R, in vivo and in vitro. Overexpression of HIF1α reversed the deteriorating effect of SENP1 knockdown on cellular death.
[A]: 1


[Q]: Progressive loss of skeletal muscle mass with aging (sarcopenia) forms a global health concern. It has been suggested that an impaired capacity to increase muscle protein synthesis rates in response to protein intake is a key contributor to sarcopenia. We assessed whether differences in post-absorptive and/or post-prandial muscle protein synthesis rates exist between large cohorts of healthy young and older men.', 'We performed a cross-sectional, retrospective study comparing in vivo post-absorptive muscle protein synthesis rates determined with stable isotope methodologies between 34 healthy young (22±1 y) and 72 older (75±1 y) men, and post-prandial muscle protein synthesis rates between 35 healthy young (22±1 y) and 40 older (74±1 y) men.', 'Post-absorptive muscle protein synthesis rates did not differ significantly between the young and older group. Post-prandial muscle protein synthesis rates were 16% lower in the older subjects when compared with the young. Muscle protein synthesis rates were >3 fold more responsive to dietary protein ingestion in the young. Irrespective of age, there was a strong negative correlation between post-absorptive muscle protein synthesis rates and the increase in muscle protein synthesis rate following protein ingestion.
[A]:
1