Trends in template/fragment-free protein structure prediction

Predicting the structure of a protein from its amino acid sequence is a long-standing unsolved problem in computational biology. Its solution would be of both fundamental and practical importance as the gap between the number of known sequences and the number of experimentally solved structures widens rapidly. Currently, the most successful approaches are based on fragment/template reassembly. Lacking progress in template-free structure prediction calls for novel ideas and approaches. This article reviews trends in the development of physical and specific knowledge-based energy functions as well as sampling techniques for fragment-free structure prediction. Recent physical- and knowledge-based studies demonstrated that it is possible to sample and predict highly accurate protein structures without borrowing native fragments from known protein structures. These emerging approaches with fully flexible sampling have the potential to move the field forward

Study design of DIACORE (DIAbetes COhoRtE) - a cohort study of patients with diabetes mellitus type 2

BACKGROUND: Diabetes mellitus type 2 (DM2) is highly associated with increased risk for chronic kidney disease (CKD), end stage renal disease (ESRD) and cardiovascular morbidity. Epidemiological and genetic studies generate hypotheses for innovative strategies in DM2 management by unravelling novel mechanisms of diabetes complications, which is essential for future intervention trials. We have thus initiated the DIAbetes COhoRtE study (DIACORE). METHODS: DIACORE is a prospective cohort study aiming to recruit 6000 patients of self-reported Caucasian ethnicity with prevalent DM2 for at least 10 years of follow-up. Study visits are performed in University-based recruiting clinics in Germany using standard operating procedures. All prevalent DM2 patients in outpatient clinics surrounding the recruiting centers are invited to participate. At baseline and at each 2-year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized online questionnaire and physical examination to determine incident micro- and macrovascular DM2 complications, malignancy and hospitalization, with a primary focus on renal events. Confirmatory outcome information is requested from patient records. Blood samples are obtained for a centrally analyzed standard laboratory panel and for biobanking of aliquots of serum, plasma, urine, mRNA and DNA for future scientific use. A subset of the cohort is subjected to extended phenotyping, e.g. sleep apnea screening, skin autofluorescence measurement, non-mydriatic retinal photography and non-invasive determination of arterial stiffness. DISCUSSION: DIACORE will enable the prospective evaluation of factors involved in DM2 complication pathogenesis using high-throughput technologies in biosamples and genetic epidemiological studies

N-terminal amino acid sequences of the major outer membrane proteins from a Neisseria meningitidis group B strain isolated in Brazil

The four dominant outer membrane proteins (46, 38, 33 and 28 kDa) were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in a semi-purified preparation of vesicle membranes of a Neisseria meningitidis (N44/89, B:4:P1.15:P5.5,7) strain isolated in Brazil. The N-terminal amino acid sequence for the 46 kDa and 28 kDa proteins matched that reported by others for class 1 and 5 proteins respectively, whereas the sequence (25 amino acids) for the 38 kDa (class 3) protein was similar to class 1 meningococcal proteins. The sequence for the 33 kDa (class 4) was unique and not homologous to any known protein

Inflammation as a Risk of Developing Chronic Kidney Disease in Rheumatoid Arthritis

The relationship between chronic inflammation and the incidence of chronic kidney disease (CKD) remained not-clear in patients with rheumatoid arthritis (RA). This study aims to examine the relationship between persistently high C-reactive protein (CRP), a marker of inflammation, and the incidence of CKD in RA.We retrospectively examined the relationship between the levels of CRP and incidence of CKD in 345 RA patients. The outcome of interest was incidence of CKD, defined as an estimated glomerular filtration rate (eGFR) 3.0 mg/L. On the basis of three measurements of CRP for 6-months period, patients were divided into three groups: group 1, including patients with no high CRP values; group 2, patients with transient high CRP values (once or twice) and group 3, patients with persistently high CRP values.During a median follow-up period of 89 months, 14% of all patients developed CKD. The cumulative incidence of CKD was 7% in group 1, 14% in group 2 and 22% in group 3 (P = 0.008, log-rank test). In a multivariate analysis, including classical risk factors for CKD, persistently high CRP was an independent predictor of the incidence of CKD (hazard ratio, 3.00; 95% confidence interval, 1.23-8.53; P = 0.01).Persistently high CRP was a significant risk factor for the incidence of CKD. Results suggest that persistent inflammation is a marker for the high risk of CKD in RA