Alterations In The Achilles Tendon After Inflammation In Surrounding Tissue

Objective: To analyze the characteristics of the Achilles tendon of rats after induction of localized inflammation in the rat paw. Methods: In our study three groups were used: inflamed group with carrageenan in rat paw (G1); saline group (G2) and control group (G3). After 4 hours the animals were euthanized and the Achilles tendon removed. Results: No significant differences were observed in the analysis of non-collagenous proteins, glycosaminoglycans and hydroxyproline in the groups but a tendency of reduction was verified in G1. As regards the organization of collagen molecules, no differences were observed between groups. With respect to MMPs activity, a stronger presence of the active isoform of MMP-2 in G1 was observed, suggesting that the remodeling was occurring. Conclusion: Thus, we conclude that the inflammatory process in rat paw may affect the remodeling of tendons located near the inflamed site.205266269Maffulli, N., Kader, D., Tendinopathy of tendo Achillis (2002) J Bone Joint Surg Br, 84 (1), pp. 1-8Maffulli, N., Rupture of the Achilles tendon (1999) J Bone Joint Surg Am, 81 (7), pp. 1019-1036Järvinen, T.A., Kannus, P., Maffulli, N., Khan, K.M., Achilles tendon disorders: etiology and epidemiology (2005) Foot Ankle Clin, 10 (2), pp. 255-266Oliveira, F.S., Pinfildi, C.E., Parizoto, N.A., Liebano, R.E., Bossini, P.S., Garcia, E.B., Effect of low level laser therapy (830 nm) with different therapyregimes on the process of tissue repair in partial lesion calcaneous tendon (2009) Lasers Surg Med, 41 (4), pp. 271-276Karousou, E., Ronga, M., Vigetti, D., Passi, A., Maffulli, N., Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human Achilles tendon rupture (2008) Clin Orthop Relat Res, 466 (7), pp. 1577-1582Riley, G., Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology (2002) Matrix Biol, 21 (2), pp. 185-195Dario, B.E., Barquilha, G., Marques, R.M., Lesões esportivas: um estudo com atletas de basquetebol Bauruense (2010) Rev Bras Cienc Esporte, 31 (3), pp. 205-215Vieira, C.P., Aro, A.A., Almeida, M.S., de Mello, G.C., Antunes, E., Pimentel, E.R., Effects of acute inflammation induced in the rat paw on the deep digital flexor tendon (2012) Connect Tissue Res, 53 (2), pp. 160-168Tillander, B., Franzén, L.E., Nilsson, E., Norlin, R., Carrageenan-induced subacromial bursitis caused changes in the rat's rotator cuff (2001) J Orthop Res, 19 (3), pp. 441-447Winter, C.A., Risley, E.A., Nuss, G.W., Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs (1962) Proc Soc Exp Biol Med, 111, pp. 544-547Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Farndale, R.W., Buttle, D.J., Barrett, A.J., Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue (1986) Biochim Biophys Acta, 883 (2), pp. 173-177Marqueti, R.C., Parizotto, N.A., Chriguer, R.S., Perez, S.E., Selistre-de-Araujo, H.S.A., ndrogenic-anabolic steroids associated with mechanical loading inhibit matrix metallopeptidase activity and affect the remodeling of the achilles tendon in rats (2006) Am J Sports Med, 34 (8), pp. 1274-1280Vidal, B.C., Mello, M.L., Supramolecular order following binding of the dichroic birefringent sulfonic dye Ponceau SS to collagen fibers (2005) Biopolymers, 78 (3), pp. 121-128Riley, G., Tendinopathy:from basic science to treatment (2008) Nat Clin Pract Rheumatol, 4 (2), pp. 82-89Szabo, K.A., Ablin, R.J., Singhingh, G., Matrix metalloproteinases and the immune response (2004) Clin Appl Immun Rev, 4, pp. 295-319Chakraborti, S., Mandal, M., Das, S., Mandal, A., Chakraborti, T., Regulation of matrix metalloproteinases: an overview (2003) Mol Cell Biochem, 253 (1-2), pp. 269-285Magra, M., Maffulli, N., Matrix metalloproteases: a role in overuse tendinopathies (2005) Br J Sports Med, 39 (11), pp. 789-791Clutterbuck, A.L., Harris, P., Allaway, D., Mobasheri, A., Matrix metalloproteinases in inflammatory pathologies of the horse (2010) Vet J, 183 (1), pp. 27-38Marsolais, D., Duchesne, E., Côté, C.H., Frenette, J., Inflammatory cells do not decrease the ultimate tensile strength of intact tendons in vivo and in vitro: protective role of mechanical loading (2007) J Appl Physiol, 102 (1), pp. 11-1

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Maternal high fat diet compromises survival and modulates lung development of offspring, and impairs lung function of dams (female mice)

© 2019 The Author(s). Published in Respiratory Research. Background: Epidemiological studies have identified strong relationships between maternal obesity and offspring respiratory dysfunction; however, the causal direction is not known. We tested whether maternal obesity alters respiratory function of offspring in early life. Methods: Female C57Bl/6 J mice were fed a high or low fat diet prior to and during two rounds of mating and resulting pregnancies with offspring lung function assessed at 2 weeks of age. The lung function of dams was measured at 33 weeks of age. Results: A high fat diet caused significant weight gain prior to conception with dams exhibiting elevated fasting glucose, and glucose intolerance. The number of surviving litters was significantly less for dams fed a high fat diet, and surviving offspring weighed more, were longer and had larger lung volumes than those born to dams fed a low fat diet. The larger lung volumes significantly correlated in a linear fashion with body length. Pups born from the second pregnancy had reduced tissue elastance compared to pups born from the first pregnancy, regardless of the dam's diet. As there was reduced offspring survival born to dams fed a high fat diet, the statistical power of lung function measures of offspring was limited. There were signs of increased inflammation in the bronchoalveolar lavage fluid of dams (but not offspring) fed a high fat diet, with more tumour necrosis factor-α, interleukin(IL)-5, IL-33 and leptin detected. Dams that were fed a high fat diet and became pregnant twice had reduced fasting glucose immediately prior to the second mating, and lower levels of IL-33 and leptin in bronchoalveolar lavage fluid. Conclusions: While maternal high fat diet compromised litter survival, it also promoted somatic and lung growth (increased lung volume) in the offspring. Further studies are required to examine downstream effects of this enhanced lung volume on respiratory function in disease settings

Incorporating field wind data to improve crop evapotranspiration parameterization in heterogeneous regions

Accurate parameterization of reference evapotranspiration ( ET0) is necessary for optimizing irrigation scheduling and avoiding costs associated with over-irrigation (water expense, loss of water productivity, energy costs, and pollution) or with under-irrigation (crop stress and suboptimal yields or quality). ET0 is often estimated using the FAO-56 method with meteorological data gathered over a reference surface, usually short grass. However, the density of suitable ET0 stations is often low relative to the microclimatic variability of many arid and semi-arid regions, leading to a potentially inaccurate ET0 for irrigation scheduling. In this study, we investigated multiple ET0 products from six meteorological stations, a satellite ET0 product, and integration (merger) of two stations’ data in Southern California, USA. We evaluated ET0 against lysimetric ET observations from two lysimeter systems (weighing and volumetric) and two crops (wine grapes and Jerusalem artichoke) by calculating crop ET ( ETc) using crop coefficients for the lysimetric crops with the different ET0. ETc calculated with ET0 products that incorporated field-specific wind speed had closer agreement with lysimetric ET, with RMSE reduced by 36 and 45% for grape and Jerusalem artichoke, respectively, with on-field anemometer data compared to wind data from the nearest station. The results indicate the potential importance of on-site meteorological sensors for ET0 parameterization; particularly where microclimates are highly variable and/or irrigation water is expensive or scarce

Mastermind Mutations Generate a Unique Constellation of Midline Cells within the Drosophila CNS

Background: The Notch pathway functions repeatedly during the development of the central nervous system in metazoan organisms to control cell fate and regulate cell proliferation and asymmetric cell divisions. Within the Drosophila midline cell lineage, which bisects the two symmetrical halves of the central nervous system, Notch is required for initial cell specification and subsequent differentiation of many midline lineages. Methodology/Principal Findings: Here, we provide the first description of the role of the Notch co-factor, mastermind, in the central nervous system midline of Drosophila. Overall, zygotic mastermind mutations cause an increase in midline cell number and decrease in midline cell diversity. Compared to mutations in other components of the Notch signaling pathway, such as Notch itself and Delta, zygotic mutations in mastermind cause the production of a unique constellation of midline cell types. The major difference is that midline glia form normally in zygotic mastermind mutants, but not in Notch and Delta mutants. Moreover, during late embryogenesis, extra anterior midline glia survive in zygotic mastermind mutants compared to wild type embryos. Conclusions/Significance: This is an example of a mutation in a signaling pathway cofactor producing a distinct centra

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions

Monkeypox virus (MPV) is a zoonotic Orthopoxvirus and a potential biothreat agent that causes human disease with varying morbidity and mortality. Members of the Orthopoxvirus genus have been shown to suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes and virus-targeted host networks during infection is lacking. To better understand viral strategies adopted in manipulating routine host biology on global scale, we investigated the effect of MPV infection on Macaca mulatta kidney epithelial cells (MK2) using GeneChip rhesus macaque genome microarrays. Functional analysis of genes differentially expressed at 3 and 7 hours post infection showed distinctive regulation of canonical pathways and networks. While the majority of modulated histone-encoding genes exhibited sharp copy number increases, many of its transcription regulators were substantially suppressed; suggesting involvement of unknown viral factors in host histone expression. In agreement with known viral dependence on actin in motility, egress, and infection of adjacent cells, our results showed extensive regulation of genes usually involved in controlling actin expression dynamics. Similarly, a substantial ratio of genes contributing to cell cycle checkpoints exhibited concerted regulation that favors cell cycle progression in G1, S, G2 phases, but arrest cells in G2 phase and inhibits entry into mitosis. Moreover, the data showed that large number of infection-regulated genes is involved in molecular mechanisms characteristic of cancer canonical pathways. Interestingly, ten ion channels and transporters showed progressive suppression during the course of infection. Although the outcome of this unusual channel expression on cell osmotic homeostasis remains unknown, instability of cell osmotic balance and membrane potential has been implicated in intracellular pathogens egress. Our results highlight the role of histones, actin, cell cycle regulators, and ion channels in MPV infection, and propose these host functions as attractive research focal points in identifying novel drug intervention sites

A Genetically Hard-Wired Metabolic Transcriptome in Plasmodium falciparum Fails to Mount Protective Responses to Lethal Antifolates

Genome sequences of Plasmodium falciparum allow for global analysis of drug responses to antimalarial agents. It was of interest to learn how DNA microarrays may be used to study drug action in malaria parasites. In one large, tightly controlled study involving 123 microarray hybridizations between cDNA from isogenic drug-sensitive and drug-resistant parasites, a lethal antifolate (WR99210) failed to over-produce RNA for the genetically proven principal target, dihydrofolate reductase-thymidylate synthase (DHFR-TS). This transcriptional rigidity carried over to metabolically related RNA encoding folate and pyrimidine biosynthesis, as well as to the rest of the parasite genome. No genes were reproducibly up-regulated by more than 2-fold until 24 h after initial drug exposure, even though clonal viability decreased by 50% within 6 h. We predicted and showed that while the parasites do not mount protective transcriptional responses to antifolates in real time, P. falciparum cells transfected with human DHFR gene, and adapted to long-term WR99210 exposure, adjusted the hard-wired transcriptome itself to thrive in the presence of the drug. A system-wide incapacity for changing RNA levels in response to specific metabolic perturbations may contribute to selective vulnerabilities of Plasmodium falciparum to lethal antimetabolites. In addition, such regulation affects how DNA microarrays are used to understand the mode of action of antimetabolites

Identification of Novel Functional Inhibitors of Acid Sphingomyelinase

We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression, radiation- and chemotherapy-induced apoptosis and endotoxic shock syndrome. Residual activity of ASM measured in the presence of 10 µM drug concentration shows a bimodal distribution; thus the tested drugs can be classified into two groups with lower and higher inhibitory activity. All FIASMAs share distinct physicochemical properties in showing lipophilic and weakly basic properties. Hierarchical clustering of Tanimoto coefficients revealed that FIASMAs occur among drugs of various chemical scaffolds. Moreover, FIASMAs more frequently violate Lipinski's Rule-of-Five than compounds without effect on ASM. Inhibition of ASM appears to be associated with good permeability across the blood-brain barrier. In the present investigation, we developed a novel structure-property-activity relationship by using a random forest-based binary classification learner. Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans