Utility of synovial biopsy

Synovial biopsies, gained either by blind needle biopsy or minimally invasive arthroscopy, offer additional information in certain clinical situations where routine assessment has not permitted a certain diagnosis. In research settings, synovial histology and modern applications of molecular biology increase our insight into pathogenesis and enable responses to treatment with new therapeutic agents to be assessed directly at the pathophysiological level. This review focuses on the diagnostic usefulness of synovial biopsies in the light of actual developments.     

Prion protein and Alzheimer disease

Alzheimer and prion diseases are neurodegenerative disorders characterised by the abnormal processing of amyloid-β (Aβ) peptide and prion protein (PrP^C), respectively. Recent evidence indicates that PrP^C may play a critical role in the pathogenesis of Alzheimer disease. PrP^C interacts with and inhibits the β-secretase BACE1, the rate-limiting enzyme in the production of Aβ. More recently PrP^C was identified as a receptor for Aβ oligomers and the expression of PrP^C appears to be controlled by the amyloid intracellular domain (AICD). Here we review these observations and propose a feedback loop in the normal brain where PrP^C exerts an inhibitory effect on BACE1 to decrease both Aβ and AICD production. In turn, the AICD upregulates PrP^C expression, thus maintaining the inhibitory effect of PrP^C on BACE1. In Alzheimer disease, this feedback loop is disrupted, and the increased level of Aβ oligomers bind to PrP^C and prevent it from regulating BACE1 activity.Key words: alzheimer disease, amyloid-β, Aβ oligomers, amyloid intracellular domain, BACE1, presenilin, prion protein     

Segmentation of liver,its vessels and lesions from CT images for surgical planning

Background  

Cancer treatments are complex and involve different actions, which include many times a surgical procedure. Medical imaging provides important information for surgical planning, and it usually demands a proper segmentation, i.e., the identification of meaningful objects, such as organs and lesions. This study proposes a methodology to segment the liver, its vessels and nodules from computer tomography images for surgical planning.     

Reappraisal of the diagnostic and prognostic value of morning stiffness in arthralgia and early arthritis: results from the Groningen EARC,Leiden EARC,ESPOIR, Leiden EAC and REACH

IntroductionMorning stiffness is assessed daily in the diagnostic process of arthralgia and arthritis, but large-scale studies on the discriminative ability are absent. This study explored the diagnostic value of morning stiffness in 5,202 arthralgia and arthritis patients and the prognostic value in early rheumatoid arthritis (RA).MethodsIn arthralgia patients referred to the Early Arthritis Recognition Clinics (EARC) of Leiden (n = 807) and Groningen (n = 481) or included in the Rotterdam Early Arthritis Cohort (REACH) study (n = 353), the associations (cross-sectional analyses) between morning stiffness and presence of arthritis at physical examination were studied. In early arthritis patients, included in the Leiden Early Arthritis Clinic (EAC) (n = 2,748) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n = 813), associations with fulfilling the 2010-RA criteria after one year were assessed. In 2010-RA patients included in the EAC (n = 1,140) and ESPOIR (n = 677), association with the long-term outcomes of disease-modifying antirheumatic drug (DMARD)-free sustained remission and radiological progression were determined. Morning stiffness was defined as a duration ≥60 minutes; sensitivity analyses were performed for other definitions.ResultsIn arthralgia, morning stiffness (≥60 minutes) associated with the presence of arthritis; Leiden EARC odds ratio (OR) 1.49 (95% CI 1.001 to 2.20), Groningen EARC OR 2.21 (1.33 to 3.69) and REACH OR 1.55 (0.97 to 2.47) but the areas under the receiver operating characteristic curve (AUCs) were low (0.52, 0.57, 0.54). In early arthritis, morning stiffness was associated with 2010-RA independent of other predictors (Leiden EAC OR 1.72 (95% CI 1.31 to 2.25, AUC 0.68), ESPOIR OR 1.68 (1.03 to 2.74, AUC 0.64)). Duration of ≥30 minutes provided optimal discrimination for RA in early arthritis. Morning stiffness was not associated with radiological progression or DMARD-free sustained remission.ConclusionsMorning stiffness in arthralgia and early arthritis is associated with arthritis and RA respectively. This supports the incorporation of morning stiffness in the diagnostic process.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0616-3) contains supplementary material, which is available to authorized users.     

Interaction between RNA polymerase and a ribosomal RNA promoter of E. coli.

The interaction between RNA polymerase and the E. coli ribosomal (r) RNA promoter(s) of the rrnE operon has been studied by the filter-binding method. The extent of complex formation between RNA polymerase and rrnE promoter(s) is salt-dependent; ppGpp specifically inhibits interaction of RNA polymerase with the rrnE promoter(s). A tentative model is proposed for the molecular events in the early steps of rRNA initiation: a transition of the primarily formed, labile RNA polymerase-rRNA promoter complex to a more stable form is the determining step. This step is salt-sensitive; ppGpp acts on this "isomerization".     

Caryoscope: An Open Source Java application for viewing microarray data in a genomic context

Background  

Microarray-based comparative genome hybridization experiments generate data that can be mapped onto the genome. These data are interpreted more easily when represented graphically in a genomic context.     

The high resolution NMR structure of the third SH3 domain of CD2AP

CD2 associated protein (CD2AP) is an adaptor protein that plays an important role in cell to cell union needed for the kidney function. CD2AP interacts, as an adaptor protein, with different natural targets, such as CD2, nefrin, c-Cbl and podocin. These proteins are believed to interact to one of the three SH3 domains that are positioned in the N-terminal region of CD2AP. To understand the network of interactions between the natural targets and the three SH3 domains (SH3-A, B and C), we have started to determine the structures of the individual SH3 domains. Here we present the high-resolution structure of the SH3-C domain derived from NMR data. Full backbone and side-chain assignments were obtained from triple-resonance spectra. The structure was determined from distance restraints derived from high-resolution 600 and 800 MHz NOESY spectra, together with phi and psi torsion angle restraints based on the analysis of ¹HN, ¹⁵N, ¹Hα, ¹³Cα, ¹³CO and ¹³Cβ chemical shifts. Structures were calculated using CYANA and refined in water using RECOORD. The three-dimensional structure of CD2AP SH3-C contains all the features that are typically found in other SH3 domains, including the general binding site for the recognition of polyproline sequences.