481 research outputs found

    Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology

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    The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a “middle-out” strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from “-omics” signatures are identified as key elements of a successful systems biology modeling approach in nutrition research—one that integrates physiological mechanisms and data at multiple space and time scales

    Predicting consumer biomass, size-structure, production, catch potential, responses to fishing and associated uncertainties in the world's marine ecosystems

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    Existing estimates of fish and consumer biomass in the world’s oceans are disparate. This creates uncertainty about the roles of fish and other consumers in biogeochemical cycles and ecosystem processes, the extent of human and environmental impacts and fishery potential. We develop and use a size-based macroecological model to assess the effects of parameter uncertainty on predicted consumer biomass, production and distribution. Resulting uncertainty is large (e.g. median global biomass 4.9 billion tonnes for consumers weighing 1 g to 1000 kg; 50% uncertainty intervals of 2 to 10.4 billion tonnes; 90% uncertainty intervals of 0.3 to 26.1 billion tonnes) and driven primarily by uncertainty in trophic transfer efficiency and its relationship with predator-prey body mass ratios. Even the upper uncertainty intervals for global predictions of consumer biomass demonstrate the remarkable scarcity of marine consumers, with less than one part in 30 million by volume of the global oceans comprising tissue of macroscopic animals. Thus the apparently high densities of marine life seen in surface and coastal waters and frequently visited abundance hotspots will likely give many in society a false impression of the abundance of marine animals. Unexploited baseline biomass predictions from the simple macroecological model were used to calibrate a more complex size- and trait-based model to estimate fisheries yield and impacts. Yields are highly dependent on baseline biomass and fisheries selectivity. Predicted global sustainable fisheries yield increases ≈4 fold when smaller individuals (< 20 cm from species of maximum mass < 1kg) are targeted in all oceans, but the predicted yields would rarely be accessible in practice and this fishing strategy leads to the collapse of larger species if fishing mortality rates on different size classes cannot be decoupled. Our analyses show that models with minimal parameter demands that are based on a few established ecological principles can support equitable analysis and comparison of diverse ecosystems. The analyses provide insights into the effects of parameter uncertainty on global biomass and production estimates, which have yet to be achieved with complex models, and will therefore help to highlight priorities for future research and data collection. However, the focus on simple model structures and global processes means that non-phytoplankton primary production and several groups, structures and processes of ecological and conservation interest are not represented. Consequently, our simple models become increasingly less useful than more complex alternatives when addressing questions about food web structure and function, biodiversity, resilience and human impacts at smaller scales and for areas closer to coasts

    Pull-out and push-in tests of bonded steel strands

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    Martí Vargas, JR. (2013). Pull-out and push-in tests of bonded steel strands. Magazine of Concrete Research. 65(18):1128-1131. doi:10.1680/macr.13.00061S112811316518Balázs LG .Bond Model with Non-Linear Bond-Slip Law, 1987, Politecnico di Milano, Italy, 395–430, Studi e Ricerche, Post-Graduate Course for Reinforced Concrete Structures, V.8/86.Balazs, G. L. (1992). Transfer Control of Prestressing Strands. PCI Journal, 37(6), 60-71. doi:10.15554/pcij.11011992.60.71Balazs, G. L. (1993). Transfer Length of Prestressing Strand as a Function of Draw-In and Initial Prestress. PCI Journal, 38(2), 86-93. doi:10.15554/pcij.03011993.86.93Balázs, G. L. (2007). Connecting Reinforcement to Concrete by Bond. Beton- und Stahlbetonbau, 102(S1), 46-50. doi:10.1002/best.200710109Carmo RNF .Ancoragem de Armaduras Pré-Esforçadas por Pré-Tensão. MSc thesis, 1999, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, Portugal, (in Portuguese).Faria, D. M. V., Lúcio, V. J. G., & Pinho Ramos, A. (2011). Pull-out and push-in tests of bonded steel strands. Magazine of Concrete Research, 63(9), 689-705. doi:10.1680/macr.2011.63.9.689Faria, D. M. V., Lúcio, V. J. G., & Ramos, A. P. (2011). Strengthening of flat slabs with post-tensioning using anchorages by bonding. Engineering Structures, 33(6), 2025-2043. doi:10.1016/j.engstruct.2011.02.039Faria, D. M. V., Lúcio, V. J. G., & Pinho Ramos, A. (2012). Post-punching behaviour of flat slabs strengthened with a new technique using post-tensioning. Engineering Structures, 40, 383-397. doi:10.1016/j.engstruct.2012.03.014Laldji S .Bond Characteristics of Prestressing Strand in Grout. MPhil thesis, 1987, University of Leicester, UK.Laldji, S., & Young, A. G. (1988). Bond between steel strand and cement grout in ground anchorages. Magazine of Concrete Research, 40(143), 90-98. doi:10.1680/macr.1988.40.143.90Lopes, S. M. R., & do Carmo, R. N. F. (2002). Bond of prestressed strands to concrete: transfer rate and relationship between transmission length and tendon draw-in. Structural Concrete, 3(3), 117-126. doi:10.1680/stco.2002.3.3.117Martí-Vargas, J. R., Serna-Ros, P., Fernández-Prada, M. A., Miguel-Sosa, P. F., & Arbeláez, C. A. (2006). Test method for determination of the transmission and anchorage lengths in prestressed reinforcement. Magazine of Concrete Research, 58(1), 21-29. doi:10.1680/macr.2006.58.1.21Marti-Vargas, J. R., Arbelaez, C. A., Serna-Ros, P., Navarro-Gregori, J., & Pallares-Rubio, L. (2007). Analytical model for transfer length prediction of 13 mm prestressing strand. Structural Engineering and Mechanics, 26(2), 211-229. doi:10.12989/sem.2007.26.2.211Palmer, K. D., & Schultz, A. E. (2011). Experimental investigation of the web-shear strength of deep hollow-core units. PCI Journal, 56(4), 83-104. doi:10.15554/pcij.09012011.83.10

    The UBA-UIM Domains of the USP25 Regulate the Enzyme Ubiquitination State and Modulate Substrate Recognition

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    USP25m is the muscle isoform of the deubiquitinating (DUB) enzyme USP25. Similarly to most DUBs, data on USP25 regulation and substrate recognition is scarce. In silico analysis predicted three ubiquitin binding domains (UBDs) at the N-terminus: one ubiquitin-associated domain (UBA) and two ubiquitin-interacting motifs (UIMs), whereas no clear structural homology at the extended C-terminal region outside the catalytic domains were detected. In order to asses the contribution of the UBDs and the C-terminus to the regulation of USP25m catalytic activity, ubiquitination state and substrate interaction, serial and combinatorial deletions were generated. Our results showed that USP25m catalytic activity did not strictly depend on the UBDs, but required a coiled-coil stretch between amino acids 679 to 769. USP25 oligomerized but this interaction did not require either the UBDs or the C-terminus. Besides, USP25 was monoubiquitinated and able to autodeubiquitinate in a possible loop of autoregulation. UBDs favored the monoubiquitination of USP25m at the preferential site lysine 99 (K99). This residue had been previously shown to be a target for SUMO and this modification inhibited USP25 activity. We showed that mutation of K99 clearly diminished USP25-dependent rescue of the specific substrate MyBPC1 from proteasome degradation, thereby supporting a new mechanistic model, in which USP25m is regulated through alternative conjugation of ubiquitin (activating) or SUMO (inhibiting) to the same lysine residue (K99), which may promote the interaction with distinct intramolecular regulatory domains

    Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response

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    <p>Abstract</p> <p>Background</p> <p>Resveratrol (RES), a natural phytoalexin found at high levels in grapes and red wine, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are at present only partially understood.</p> <p>Method</p> <p>The effects of RES on activation of unfolded protein responses (UPR) were evaluated using Western blotting, semi-quantitative and real-time RT-PCR. Cell death was evaluated using Annexin V/PI staining and subsequent FACS.</p> <p>Results</p> <p>Similar as tunicamycin, treatment with RES lead to the activation of all 3 branches of the UPR, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2α consistent with ER resident kinase (PERK) activation, activating transcription factor 6 (ATF6) splicing, and increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines. RES was shown to induce cell death, which could be attenuated by thwarting upregulation of CHOP.</p> <p>Conclusions</p> <p>Our data suggest that activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells.</p
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