Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor-á, and interleukin-6 levels in rheumatoid arthritis. Longitudinal evaluation during methotrexate and azathioprine therapy

Contains fulltext : 4749.pdf (publisher's version ) (Open Access

Burden-driven feedback control of gene expression

Cells use feedback regulation to ensure robust growth despite fluctuating demands for resources and differing environmental conditions. However, the expression of foreign proteins from engineered constructs is an unnatural burden that cells are not adapted for. Here we combined RNA-seq with an in vivo assay to identify the major transcriptional changes that occur in Escherichia coli when inducible synthetic constructs are expressed. We observed that native promoters related to the heat-shock response activated expression rapidly in response to synthetic expression, regardless of the construct. Using these promoters, we built a dCas9-based feedback-regulation system that automatically adjusts the expression of a synthetic construct in response to burden. Cells equipped with this general-use controller maintained their capacity for native gene expression to ensure robust growth and thus outperformed unregulated cells in terms of protein yield in batch production. This engineered feedback is to our knowledge the first example of a universal, burden-based biomolecular control system and is modular, tunable and portable

Urinary prostaglandin and prostaglandin metabolite excretion in patients with essential hypertension or hypertension with renal artery stenosis

Contains fulltext : 21439___.PDF (publisher's version ) (Open Access

Clinical and biochemical criteria in the detection of renal artery stenosis

Contains fulltext : 23517___.PDF (publisher's version ) (Open Access

Sodium-blood pressure interrelationship in pregnancy

Item does not contain fulltex

Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia

Background: Raised plasma lipoprotein(a) (Lp(a)) is associated with increased risk of cardiovascular disease. It is unknown whether increased Lp(a) is an additional risk factor for coronary artery disease in familial hypercholesterolaemia (FH) or whether statin treatment can reduce Lp(a) concentrations in the long term. Objective: To investigate Lp(a) concentrations in relation to statin treatment and the progression of atherosclerosis in a large cohort of FH patients. Design: A two year, randomised, double blind trial (the ASAP trial). Patients: 325 heterozygous FH patients. Intervention: Treatment with 80 mg atorvastatin or 40 mg simvastatin. Main outcome measure: Change in Lp(a) concentrations and intima-media thickness of carotid artery segments at one year and two years. Results: At baseline, median Lp(a) concentrations were 327 mg/l and 531 mg/l in the atorvastatin and simvastatin arms, respectively (p = 0.03). In the atorvastatin arm, Lp(a) concentrations decreased to 243 mg/l after one year (p <0.001) and to 263 mg/l after two years (p <0.001). In the simvastatin arm, Lp(a) concentrations decreased to 437 mg/l after one year (p <0.001) and to 417 mg/l after two years (p <0.001). The difference in Lp(a) reduction between the two treatment arms was significant after one year (p = 0.004), but not after two years (p = 0.086). Lp(a) concentrations at baseline were not related to cardiovascular events at baseline. There was no correlation between baseline Lp(a) concentrations and low density lipoprotein cholesterol concentrations or intima-media thickness at baseline. Change in Lp(a) concentrations was not correlated with change in intima-media thickness after one or two years. Conclusions: Long term statin treatment significantly lowers Lp(a) in FH patients. However, this reduction was unrelated to changes in intima-media thickness and casts doubt on the importance of Lp(a) in the progression of atherosclerotic disease in these patient