526 research outputs found

    Unsupervised Discovery of Toxoplasma gondii Motility Phenotypes

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    Toxoplasma gondii is a parasitic protozoan that causes dis- seminated toxoplasmosis, a disease that afflicts roughly a third of the worlds population. Its virulence is predicated on its motility and ability to enter and exit nucleated cells; therefore, studies elucidating its mechanism of motility and in particular, its motility patterns in the context of its lytic cycle, are critical to the eventual development of therapeutic strate- gies. Here, we present an end-to-end computational pipeline for identifying T. gondii motility phenotypes in a completely unsupervised, data-driven way. We track the parasites before and after addition of extracellular Ca2+ to study its effects on the parasite motility patterns and use this information to parameterize the motion and group it according to similarity of spatiotemporal dynamics.Comment: 4 pages, Accepted to 2018 IEEE International Symposium on Biomedical Imagin

    Modulating carbohydrate–protein interactions through glycoengineering of monoclonal antibodies to impact cancer physiology

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    Diverse glycans on proteins help impact cell and organism physiology along with drug activity. Since many protein-based biotherapeutics are glycosylated and these glycans have biological activity, there is a desire to engineer glycosylation for recombinant protein-based biotherapeutics. Engineered glycosylation can impact the recombinant protein efficacy and also influence many cell pathways by first changing glycan-protein interactions and consequently modulating disease physiologies. However, its complexity is enormous. Due to recent advances in glycoengineering, modulating protein-glycan interactions become more amenable to therapeutic approaches. Here, we discuss how engineered glycans contribute to therapeutic monoclonal antibodies (mAbs) in the treatment of cancers, how these glycoengineered therapeutic mAbs affect the transformed phenotypes and downstream cell pathways, and how systems biology can help in the next generation mAb glycoengineering process by aiding in data analysis and guiding engineering efforts to tailor mAb glycan and ultimately drug efficacy, safety and affordability

    The metabolic syndrome is not associated with homocysteinemia: The Persian Gulf Healthy Heart Study

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    Background: It is uncertain whether homocysteine and the metabolic syndrome or its components are related in the general population, as studies investigating the association between homocysteine levels and insulin resistance have shown conflicting results. Methods: In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of Iranian men and women aged ≥25 yr, a random sample of 1754 subjects were evaluated for the association of plasma homocysteine levels and the metabolic syndrome using National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria. Total homocysteine levels and high sensitivity C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assays. Results: Subjects with lower HDL-cholesterol and higher blood pressure showed significantly higher homocysteine levels (p=0.001 and p<0.0001; respectively). There was no significant difference in serum levels of homocysteine between subjects with and without the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome did not show a significant association with serum homocysteine levels after adjusting for sex, age, smoking, fruit and vegetable intake pattern, body mass index, and physical inactivity. Concurrent elevated CRP levels and the metabolic syndrome also did not show a significant association with serum homocysteine levels after adjusting for sex, age, and lifestyle cardiovascular risk factors. Conclusions: There was no association between the metabolic syndrome using NCEP-ATPIII criteria and homocysteinemia in this study. These data refute the hypothesis that homocysteine levels are influenced by the metabolic syndrome, at least in general healthy population

    High ultra-processed food consumption is associated with elevated psychological distress as an indicator of depression in adults from the Melbourne Collaborative Cohort Study

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    Background: Few studies have tested longitudinal associations between ultra-processed food consumption and depressive outcomes. As such, further investigation and replication are necessary. The aim of this study is to examine associations of ultra-processed food intake with elevated psychological distress as an indicator of depression after 15 years. Method: Data from the Melbourne Collaborative Cohort Study (MCCS) were analysed (n = 23,299). We applied the NOVA food classification system to a food frequency questionnaire (FFQ) to determine ultra-processed food intake at baseline. We categorised energy-adjusted ultra-processed food consumption into quartiles by using the distribution of the dataset. Psychological distress was measured by the ten-item Kessler Psychological Distress Scale (K10). We fitted unadjusted and adjusted logistic regression models to assess the association of ultra-processed food consumption (exposure) with elevated psychological distress (outcome and defined as K10 ≥ 20). We fitted additional logistic regression models to determine whether these associations were modified by sex, age and body mass index. Results: After adjusting for sociodemographic characteristics and lifestyle and health-related behaviours, participants with the highest relative intake of ultra-processed food were at increased odds of elevated psychological distress compared to participants with the lowest intake (aOR: 1.23; 95%CI: 1.10, 1.38, p for trend = 0.001). We found no evidence for an interaction of sex, age and body mass index with ultra-processed food intake. Conclusion: Higher ultra-processed food intake at baseline was associated with subsequent elevated psychological distress as an indicator of depression at follow-up. Further prospective and intervention studies are necessary to identify possible underlying pathways, specify the precise attributes of ultra-processed food that confer harm, and optimise nutrition-related and public health strategies for common mental disorders

    Constraints on Randall-Sundrum model from top-antitop production at the LHC

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    We study the top pair production cross section at the LHC in the context of Randall-Sundrum model including the Kaluza-Klein (KK) excited gravitons. It is shown that the recent measurement of the cross section of this process at the LHC restricts the parameter space in Randall-Sundrum (RS) model considerably. We show that the coupling parameter (kMˉpl\frac{k}{\bar{M}_{pl}}) is excluded by this measurement from 0.03 to 0.22 depending on the mass of first KK excited graviton (m1m_1). We also study the effect of KK excitations on the spin correlation of the top pairs. It is shown that the spin asymmetry in ttˉt\bar{t} events is sensitive to the RS model parameters with a reasonable choice of model parameters.Comment: 17 pages, 6 figure
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