Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

New data on the intraindividual variation of cystatin C.

BACKGROUND: Cystatin C is a new interesting marker of glomerular filtration rate (GFR). However, data regarding its biological variance are scarce and conflicting. The ability of cystatin C to longitudinally follow renal function in patients therefore remains questionable. METHODS: 12 healthy subjects (6 men and 6 women) were included in the final statistical analysis. Serum creatinine, plasma cystatin C and GFR were measured twice after a 1-week interval on the same day, at the same time, and under the same preanalytical and analytical conditions. GFR was measured with an iohexol method. Serum creatinine was measured with a compensated Jaffe and an enzymatic method. Plasma cystatin C was measured by a particle-enhanced immunonephelometric method. Analytical (CV(A)) and within-subject (CV(I)) variances were classically calculated. RESULTS: CV(A) for creatinine (Jaffe and enzymatic methods) and cystatin C was 2.5, 0.97 and 1.29%, respectively. CV(I) was 5.8, 5 and 4.5% for the Jaffe creatinine, enzymatic creatinine and cystatin C determinations, respectively. CONCLUSION: Our study confirms that intraindividual variation of cystatin C and creatinine are similar. Therefore, from a biological point of view, cystatin C seems as accurate as creatinine for the longitudinal follow-up of renal function in daily clinical practice

Should hamstring muscles be stretched by flexing the hip while keeping the knee extended or by flexing the hip with a flexed knee and then extending the knee?

peer reviewedaudience: researcher, professional, studen

Dynamic biofilm architecture confers individual and collective mechanisms of viral protection

In nature, bacteria primarily live in surface-attached, multicellular communities, termed biofilms 1-6 . In medical settings, biofilms cause devastating damage during chronic and acute infections; indeed, bacteria are often viewed as agents of human disease 7 . However, bacteria themselves suffer from diseases, most notably in the form of viral pathogens termed bacteriophages 8-12 , which are the most abundant replicating entities on Earth. Phage-biofilm encounters are undoubtedly common in the environment, but the mechanisms that determine the outcome of these encounters are unknown. Using Escherichia coli biofilms and the lytic phage T7 as models, we discovered that an amyloid fibre network of CsgA (curli polymer) protects biofilms against phage attack via two separate mechanisms. First, collective cell protection results from inhibition of phage transport into the biofilm, which we demonstrate in vivo and in vitro. Second, CsgA fibres protect cells individually by coating their surface and binding phage particles, thereby preventing their attachment to the cell exterior. These insights into biofilm-phage interactions have broad-ranging implications for the design of phage applications in biotechnology, phage therapy and the evolutionary dynamics of phages with their bacterial hosts