Improved serological detection of rheumatoid arthritis: a highly antigenic mimotope of carbonic anhydrase III selected in a murine model by phage display

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects around 1 % of the human population worldwide. RA diagnosis can be difficult as there is no definitive test for its detection. Therefore, the aim of this study was to identify biomarkers that could be used for RA diagnosis.MethodsSera from a collagen-induced arthritis mouse model were used to select potential biomarkers for RA diagnosis by phage display technology. In silico and in vitro analyses were performed to characterize and validate the selected peptides. Samples were classified into three groups: RA; two other immune-mediated rheumatic diseases (systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS)); and healthy controls (HC). Enzyme-linked immunosorbent assay (ELISA) was carried out to determine antibody levels, and diagnostic parameters were determined by constructing receiver operating characteristic curves. Mass spectrometry and Western blot were performed to identify the putative autoantigen that was mimicked by a highly reactive mimotope.ResultsAfter three rounds of selection, 14 clones were obtained and tested for immunoreactivity analysis against sera from RA and HC groups. The phage-fused peptide with the highest immunoreactivity (M12) was synthesized, and was able to efficiently discriminate RA patients from SLE, AS and HCs (p < 0.0001) by ELISA. The specificity and sensitivity of anti-M12 antibodies for RA diagnosis were 91 % and 84.3 %, respectively. The M12 peptide was identified as one that mimics a predicted antigenic site of the carbonic anhydrase III (CAIII) protein, a ubiquitous biomarker that has been identified in patients with other diseases.ConclusionM12 is the first peptide associated with the CAIII protein that may be used as an antigen for antibody detection to aid in RA diagnosis with high sensitivity and specificity.     

Muscular co-contraction during walking and landing from a jump: comparison between genders and influence of activity level.

BACKGROUND: Women have higher rates of knee ligament injury than men. Co-contraction of knee muscles is proposed to be an important mechanism to protect the joint from injuries. HYPOTHESIS: Females have lower co-contraction levels when compared to males. STUDY DESIGN: Exploratory, cross-sectional design. METHODS: Thirty-six men and women equally divided into four groups according to gender and activity level (sedentary and athletic) were compared in relation to vastus lateralis and biceps femoris co-contraction before heel strike during level walking and before floor contact during landing from a jump. Muscular co-contraction was assessed by surface electromyography. Correlations between co-contraction and ligament laxity, extensor and flexor work, and flexion/extension torque ratio were also analyzed. RESULTS: No differences between genders were found in the studied situations (p0.381). During walking, co-contraction was greater in sedentary women compared to athletic women (p=0.002). A moderate inverse correlation was found between co-contraction during walking and women extensor (r=-0.613; p=0.007) and flexor (r=-0.575; p=0.012) work. During landing from a jump, no variables correlated to co-contraction in any of the groups tested (r0.477; p0.061). CONCLUSION: Co-contraction levels were not different between genders. Results suggest that women compensate strength deficits by means of increasing activation levels, possibly to generate adequate joint stiffness to meet stabilization demands. However, this is not evident in a more stressful activity like landing from a jump. CLINICAL RELEVANCE: This study contributes to a better understanding of the factors related to joint protection in females, who are at a greater risk of ligament injuries.     

Morphological and anatomical changes in soybean roots subjected to indole-3-acetic acid and tryptophol: indole compounds present in plant auxin metabolism

The auxin metabolism is practically elucidated, and the compounds that are part of the biosynthesis are well characterized, but the indole-3-ethanol or tryptophol, a molecule that has a regulatory position in the indole-3-acetic acid biosynthesis, still represents a gap in the understanding of this pathway. We examined the hypothesis that tryptophol present the function of plant growth regulation on soybean root development. We evaluated two doses of auxin and two doses of tryptophol (100 e 200 mg L^??1), respectively, beside a control treatment (water), via leaf application, in soybean plants under V1–V2 phonological stages. After 18 days of application, the roots were collected for their volume and area measurement, thereafter small segments (0.5 cm of length), were collected at 1 cm below the root-collar, for anatomical analysis. We observed that the control showed greater area and root volume, but using 200 mg L^??1 auxin and 100 mg L^??1 tryptophol led to a radial increase of roots with significant increases in width radius vascular and cortical parenchyma. These results suggest that the application of both compounds had a potential of modify the vascular and ground tissues in soybean roots, which may be beneficial for the development of plants.