Bloodsucking parasites such as ticks have evolved a wide variety of immunomodulatory proteins that are secreted in their saliva, allowing them to feed for long periods of time without being detected by the host immune system. One possible strategy used by ticks to evade the host immune response is to produce proteins that selectively bind and neutralize the chemokines that normally recruit cells of the innate immune system that protect the host from parasites. We have identified distinct cDNAs encoding novel chemokine binding proteins (CHPBs), which we have termed Evasins, using an expression cloning approach. These CHBPs have unusually stringent chemokine selectivity, differentiating them from broader spectrum viral CHBPs. Evasin-1 binds to CCL3, CCL4, and CCL18; Evasin-3 binds to CXCL8 and CXCL1; and Evasin-4 binds to CCL5 and CCL11. We report the characterization of Evasin-1 and -3, which are unrelated in primary sequence and tertiary structure, and reveal novel folds. Administration of recombinant Evasin-1 and -3 in animal models of disease demonstrates that they have potent antiinflammatory properties. These novel CHBPs designed by nature are even smaller than the recently described single-domain antibodies (Hollinger, P., and P.J. Hudson. 2005. Nat. Biotechnol. 23:1126–1136), and may be therapeutically useful as novel antiinflammatory agents in the future.

Objectives: To culturally adapt the Falls Efficacy Scale -International (FES-I) and assess its psychometric properties in a sample of community-dwelling elderly Brazilians. Methods: The instrument was translated into Brazilian Portuguese and culturally adapted to the Brazilian population (FES-I-Brazil) as recommended by the Prevention of Falls Network Europe. FES-I-Brazil was applied to 163 elderly people (73.44±5.51 years), and the demographic data and history of falls were also collected. From this group, 58 participants were randomly distributed to evaluate reliability. The reliability was analyzed using the intraclass correlation coefficient (ICC) and the internal consistency, using Cronbach's alpha coefficient (α). The internal structure of FES-I-Brazil was evaluated by means of exploratory factor analysis. The logistic regression model was used to determine which tasks on the scale were more relevant for discriminating falls. To analyze the sensitivity and specificity of FES-I-Brazil, the receiver operating characteristic (ROC) curve was used. Results: The internal consistency of FES-I-Brazil was α=0.93, and the intra-and inter-examiner reliability were ICC=0.84 and 0.91, respectively. Factor analysis suggested two factors: concern about falling during social activities and activities of daily living (basic and instrumental), and postural control tasks. FES-I-Brazil scores ≥23 suggested an association with a previous history of sporadic falls, whereas scores ≥31 suggested an association with recurrent falls. Conclusions: FES-I-Brazil was shown to be semantically, linguistically and psychometrically appropriate to evaluate the fear of falling in the community-dwelling Brazilian elderly population. ResumoObjetivos: Adaptar culturalmente a Falls Efficacy Scale-International (FES-I) e avaliar suas propriedades psicométricas em uma amostra de idosos brasileiros da comunidade. Métodos: Conforme recomendações da Rede Européia de prevenção às quedas, o instrumento foi traduzido para o português do Brasil e adaptado culturalmente para a população brasileira (FES-I-Brasil). A FES-I-Brasil foi aplicada em 163 idosos (73,44±5,51 anos), e foram coletados dados demográficos e relacionados à história de quedas. Dentre esses idosos, 58 foram distribuídos aleatoriamente para avaliação da confiabilidade. A confiabilidade foi analisada pelo Índice de Correlação Intraclasse (ICC) e a consistência interna pelo α de Cronbach. A estrutura interna foi da FES-I-Brasil foi avaliada pela análise fatorial exploratória. O modelo de regressão logística foi utilizado para identificar quais tarefas da escala eram mais relevantes para discriminar quedas. Para análise de sensibilidade e especificidade da FES-I-Brasil, empregou-se a curva Receiving Operator Characteristic (ROC). Resultados: A consistência interna da FES-I-Brasil foi α=0,93, e a confiabilidade foi ICC=0,84 e 0,91 (intra e interexaminadores, respectivamente). A análise fatorial sugeriu dois fatores que verificavam preocupação em cair durante atividades de socialização e de vid...

Ticks are blood-feeding parasites that secrete a number of immuno-modulatory factors to evade the host immune response. Saliva isolated from different species of ticks has recently been shown to contain chemokine neutralizing activity. To characterize this activity, we constructed a cDNA library from the salivary glands of the common brown dog tick, Rhipicephalus sanguineus. Pools of cDNA clones from the library were transfected into HEK293 cells, and the conditioned media from the transfected cells were tested for chemokine binding activity by chemical cross-linking to radiolabeled CCL3 followed by SDS-PAGE. By de-convolution of a single positive pool of 270 clones, we identified a full-length cDNA encoding a protein of 114 amino acids, which after signal peptide cleavage was predicted to yield a mature protein of 94 amino acids that we called Evasin-1. Recombinant Evasin-1 was produced in HEK293 cells and in insect cells. Using surface plasmon resonance we were able to show that Evasin-1 was exquisitely selective for 3 CC chemokines, CCL3 and CCL4 and the closely related chemokine CCL18, with K(D) values of 0.16, 0.81, and 3.21 nm, respectively. The affinities for CCL3 and CCL4 were confirmed in competition receptor binding assays. Analysis by size exclusion chromatography demonstrated that Evasin-1 was monomeric and formed a 1:1 complex with CCL3. Thus, unlike the other chemokine-binding proteins identified to date from viruses and from the parasitic worm Schistosoma mansoni, Evasin-1 is highly specific for a subgroup of CC chemokines, which may reflect a specific role for these chemokines in host defense against parasites.

The Pilates method did not improve functionality and pain in patients who have low back pain when compared with control and lumbar stabilization exercise groups.

BackgroundChemokines are a subset of cytokines responsible for controlling the cellular migration of inflammatory cells through interaction with seven transmembrane G protein-coupled receptors. The blocking of a chemokine-receptor interaction results in a reduced inflammatory response, and represents a possible anti-inflammatory strategy, a strategy that is already employed by some virus and parasites. Anti-chemokine activity has been described in the extracts of tick salivary glands, and we have recently described the cloning and characterization of such chemokine binding proteins from the salivary glands, which we have named Evasins.Methodology/Principal FindingsWe have solved the structure of Evasin-1, a very small and highly selective chemokine-binding protein, by x-ray crystallography and report that the structure is novel, with no obvious similarity to the previously described structures of viral chemokine binding proteins. Moreover it does not possess a known fold. We have also solved the structure of the complex of Evasin-1 and its high affinity ligand, CCL3. The complex is a 1∶1 heterodimer in which the N-terminal region of CCL3 forms numerous contacts with Evasin-1, including prominent π-π interactions between residues Trp89 and Phe14 of the binding protein and Phe29 and Phe13 of the chemokine.Conclusions/SignificanceHowever, these interactions do not appear to be crucial for the selectivity of the binding protein, since these residues are found in CCL5, which is not a ligand for Evasin-1. The selectivity of the interaction would appear to lie in the N-terminal residues of the chemokine, which form the “address” whereas the hydrophobic interactions in the rest of the complex would serve primarily to stabilize the complex. A thorough understanding of the binding mode of this small protein, and its other family members, could be very informative in the design of potent neutralizing molecules of pro-inflammatory mediators of the immune system, such as chemokines.

BackgroundSarcopenic obesity is associated with disability in older people, especially in women. Resistance exercises are recommended for this population, but their efficacy is not clear.ObjectiveTo evaluate the effects of a progressive resistance exercise program with high-speed component on the physical function of older women with sarcopenic obesity.MethodTwenty-eight women 65 to 80 years old, with a body mass index ≥30kg/m2 and handgrip strength ≤21kg were randomly allocated to two groups. The experimental group underwent a 10-week resistance exercise program designed to improve strength, power, and endurance of lower-limb muscles, with open chain and closed chain exercises. The control group had their health status monitored through telephone calls. The primary outcomes were lower limb muscle performance measured by knee extensor strength, power and fatigue by isokinetic dynamometry, and mobility measured by the Short Physical Performance Battery and by gait velocity. The secondary outcome was health-related quality of life assessed by the SF-36 Questionnaire.ResultsThe average rate of adherence was 85%, with few mild adverse effects. There were no significant between-group differences for any of the outcomes.ConclusionIn this study, a progressive resistance exercise program with high-speed component was not effective for improving the physical function of older women with sarcopenic obesity.

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