224 research outputs found

    Infrapatellar fat pad gene expression and protein production in patients with and without osteoarthritis

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    Osteoarthritis (OA) is one of the most common joint disorders. Evidence suggests that the infrapatellar fat pad (IFP) is directly involved in OA pathology. However, a comparison between OA versus non-OA IFP is still missing. Thus, the aim of this study was to compare IFP molecular, adipocytes and extracellular matrix characteristics of patients affected by OA, and patients undergoing anterior cruciate ligament (ACL) reconstruction. We hypothesized that not only inflammation but also changes in adipocytes and extracellular matrix (ECM) composition might be involved in OA pathogenesis. Fifty-three patients were enrolled. IFP biopsies were obtained, evaluating: (a) lymphocytic infiltration and vascularization; (b) adipocytes area and number; (c) adipo-cytokines and extracellular matrix gene expression levels; (d) IL-6 and VEGF protein production; (e) collagen fibers distribution. OA IFP was more inflamed and vascularized compared to ACL IFP. OA IFP adipocytes were larger and numerically lower (1.3-fold) than ACL IFP adipocytes. An increase of gene expression of typical white adipose tissue genes was observed in OA compared to ACL IFP. Collagen-types distribution was different in the OA IFP group compared to controls, possibly explaining the change of the biomechanical characteristics found in OA IFP. Statistical linear models revealed that the adipocyte area correlated with BMI in the OA group. In conclusion, inflammation and fibrotic changes of OA IFP could represent novel therapeutic targets to counteract OA

    Impact assessment for the improved four boundary conditions (at bed, free-surface, land-boundary and offshore-boundary) on coastal hydrodynamics and particulate transport

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    The FIELD_AC project aims at providing an improved operational service for coastal areas and at generating added value for shelf and regional scale predictions. Coastal-zone oceanographic predictions seldom appraise the land discharge as a boundary condition. River fluxes are sometimes considered, but neglecting their 3D character, while the "distributed" continental run-off is not taken into consideration. Moreover, many coastal scale processes, particularly those relevant in geographically restricted domains (coast with harbors or river mouth areas), are not well parametrized in present simulations.Work package 3 dedicated to Boundary Fluxes aims to establish and use the best possible boundary conditions for coastal water quality modelling. On this scale, all boundaries become important. For the land boundary side the needed products are distributed and point wise run-off both quantitatively and qualitatively. For the offshore boundary condition, 3D current, water quality field, and wave spectra will be used. For the atmospheric boundary, products from local scale meteorological models (wind, atmospheric pressure and rainfall) are needed. For the seabed, boundary information on sediment composition, bedforms and bathymetry and bio-geo-chemical parameters is essential.This report addresses the impact assessment for improvements in the four boundary conditions (boundary fluxes from land, free-surface boundary condition, seabed boundary condition and open boundary fluxes) on coastal hydrodynamics and particulate transport. The description of the improved four boundary conditions is followed by examples of concrete impact assessment of the theory into the Catalan coast, Liverpool Bay, German Bight and Gulf of Venice

    Structural insight into molecular mechanism of poly (ethylene terephthalate) degradation

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    Plastics, including poly(ethylene terephthalate) (PET), possess many desirable characteristics and thus are widely used in daily life. However, non-biodegradability, once thought to be an advantage offered by plastics, is causing major environmental problem. Recently, a PET-degrading bacterium, Ideonella sakaiensis, was identified and suggested for possible use in degradation and/or recycling of PET. However, the molecular mechanism of PET degradation is not known. Here we report the crystal structure of I. sakaiensis PETase (IsPETase) at 1.5 angstrom resolution. IsPETase has a Ser-His-Asp catalytic triad at its active site and contains an optimal substrate binding site to accommodate four monohydroxyethyl terephthalate (MHET) moieties of PET. Based on structural and site-directed mutagenesis experiments, the detailed process of PET degradation into MHET, terephthalic acid, and ethylene glycol is suggested. Moreover, other PETase candidates potentially having high PET-degrading activities are suggested based on phylogenetic tree analysis of 69 PETase-like proteins

    Cardiac Alpha-Myosin (MYH6) Is the Predominant Sarcomeric Disease Gene for Familial Atrial Septal Defects

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    Secundum-type atrial septal defects (ASDII) account for approximately 10% of all congenital heart defects (CHD) and are associated with a familial risk. Mutations in transcription factors represent a genetic source for ASDII. Yet, little is known about the role of mutations in sarcomeric genes in ASDII etiology. To assess the role of sarcomeric genes in patients with inherited ASDII, we analyzed 13 sarcomeric genes (MYH7, MYBPC3, TNNT2, TCAP, TNNI3, MYH6, TPM1, MYL2, CSRP3, ACTC1, MYL3, TNNC1, and TTN kinase region) in 31 patients with familial ASDII using array-based resequencing. Genotyping of family relatives and control subjects as well as structural and homology analyses were used to evaluate the pathogenic impact of novel non-synonymous gene variants. Three novel missense mutations were found in the MYH6 gene encoding alpha-myosin heavy chain (R17H, C539R, and K543R). These mutations co-segregated with CHD in the families and were absent in 370 control alleles. Interestingly, all three MYH6 mutations are located in a highly conserved region of the alpha-myosin motor domain, which is involved in myosin-actin interaction. In addition, the cardiomyopathy related MYH6-A1004S and the MYBPC3-A833T mutations were also found in one and two unrelated subjects with ASDII, respectively. No mutations were found in the 11 other sarcomeric genes analyzed. The study indicates that sarcomeric gene mutations may represent a so far underestimated genetic source for familial recurrence of ASDII. In particular, perturbations in the MYH6 head domain seem to play a major role in the genetic origin of familial ASDII

    Rehabilitation and release of confiscated songbirds into the wild: A pilot study

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    Songbirds are currently the most prevalent animals in illegal trafficking in Brazil and other countries, so they are often confiscated, and this poses legal, ethical, and conservation challenges. Returning them to nature requires complex and expensive management, a topic that is sparingly addressed in the literature. Here, we described the processes and costs associated with an attempt to rehabilitate and release confiscated songbirds into the wild. A total of 1,721 songbirds of several species were quarantined, rehabilitated, and released, primarily on two farms located within their typical geographical distribution. Health assessments were performed on samples from 370 birds. Serology revealed no antibodies against Newcastle disease, and Salmonella spp. cultures were negative. Real-time polymerase chain reactions detected M. gallisepticum in samples from seven birds. Atoxoplasma spp. and Acuaria spp. infections, sepsis, and trauma were the top causes of bird death. About 6% of the released birds were recaptured, within an average period of 249 days after release, and at a mean distance of 2,397 meters from the release sites. The majority of these birds were found with free-living mates within or close to fragments of transitional ecoregions with native or cultivated grasslands, and native groves/forests, and shrublands. However, eucalyptus plantations with rich understory regeneration provided a suitable environment for the released forest species to settle, since they were recaptured during the defense of these sites. Over half of the recaptured birds presented behavioral profiles with both dominant and tame traits. Birds with dominant traits are more likely to settle in habitats and face the live decoys during fieldwork, whereas birds with tame characteristics tend to accept close contact with humans. Ultramarine grosbeak (Cyanoloxia brissonii), the least common species among those released, at the release sites showed an almost 2-fold recapture rate in the shortest mean distances from the release sites. This suggests less territory competition, perhaps a major factor of bird re-establishment here. The total per-bird cost was USD 57. Our findings suggested suitable survival and re-establishment of confiscated songbirds in the wild, when managed as we describe

    The impact of maternal HIV infection on cord blood lymphocyte subsets and cytokine profile in exposed non-infected newborns

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    <p>Abstract</p> <p>Background</p> <p>Children born to HIV+ mothers are exposed intra-utero to several drugs and cytokines that can modify the developing immune system, and influence the newborn's immune response to infections and vaccines. We analyzed the relation between the distribution of cord blood lymphocyte subsets and cytokine profile in term newborns of HIV+ mothers using HAART during pregnancy and compared them to normal newborns.</p> <p>Methods</p> <p>In a prospective, controlled study, 36 mother-child pairs from HIV+ mothers and 15 HIV-uninfected mothers were studied. Hematological features and cytokine profiles of mothers at 35 weeks of pregnancy were examined. Maternal and cord lymphocyte subsets as well as B-cell maturation in cord blood were analyzed by flow cytometry. The non-stimulated, as well as BCG- and PHA-stimulated production of IL2, IL4, IL7, IL10, IL12, IFN-γ and TNF-alpha in mononuclear cell cultures from mothers and infants were quantified using ELISA.</p> <p>Results</p> <p>After one year follow-up none of the exposed infants became seropositive for HIV. An increase in B lymphocytes, especially the CD19/CD5+ ones, was observed in cord blood of HIV-exposed newborns. Children of HIV+ hard drug using mothers had also an increase of immature B-cells. Cord blood mononuclear cells of HIV-exposed newborns produced less IL-4 and IL-7 and more IL-10 and IFN-γ in culture than those of uninfected mothers. Cytokine values in supernatants were similar in infants and their mothers except for IFN-γ and TNF-alpha that were higher in HIV+ mothers, especially in drug abusing ones. Cord blood CD19/CD5+ lymphocytes showed a positive correlation with cord IL-7 and IL-10. A higher maternal age and smoking was associated with a decrease of cord blood CD4+ cells.</p> <p>Conclusions</p> <p>in uninfected infants born to HIV+ women, several immunological abnormalities were found, related to the residual maternal immune changes induced by the HIV infection and those associated with antiretroviral treatment. Maternal smoking was associated to changes in cord CD3/CD4 lymphocytes and maternal hard drug abuse was associated with more pronounced changes in the cord B cell line.</p

    Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization

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    Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD8+CD161+ T cell clusters were significantly lower in colonized than in non-colonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide-specific and total plasmablasts in blood. Moreover, increased responses of blood mucosal associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell population

    Heavy and light roles: myosin in the morphogenesis of the heart

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    Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin lightchain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed

    Non-invasive imaging in the diagnosis of acute viral myocarditis

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    Autopsy series of consecutive cases have demonstrated an incidence of myocarditis at approximately 1–10%; on the contrary, myocarditis is seriously underdiagnosed clinically. In a traditional view, the gold standard has been myocardial biopsy. However, it is generally specific but invasive and less sensitive, mostly because of the focal nature of the disease. Thus, non-invasive approaches to detect myocarditis are necessary. The traditional diagnostic tools are electrocardiography, laboratory values, especially troponin T or I, creatine kinase and echocardiography. For a long period, nuclear technique with indium-111 antimyosin antibody has been used as a diagnostic approach. In the last years, the use of this technique has declined because of radiation exposure and 48-h delay in obtaining imaging after injection to prevent blood pool effect. Thus, a non-invasive diagnostic approach without radiation and online image availability has been awaited. Cardiac magnetic resonance imaging has these promising characteristics. With this technique, it is possible to analyse inflammation, oedema and necrosis in addition to functional parameters such as left ventricular function, regional wall motion and dimensions. Thus, cardiovascular magnetic resonance imaging has emerged as the most important imaging tool in the diagnostic procedure and the review focus on this field. But there are also advances in echocardiography and computer tomography, which are described in detail
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