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Journal articles on the topic 'Mechanistic Approaches'

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Published: 10 December 2022
Last updated: 28 January 2023

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1

Frazier, J. M. "Predictive toxicodynamics: Empirical/mechanistic approaches." Toxicology in Vitro 11, no. 5 (October 1997): 465–72. http://dx.doi.org/10.1016/s0887-2333(97)00073-8.

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2

Gries, Stefan Th. "Mechanistic formal approaches to language acquisition." Epistemological issue with keynote article “A Formalist Perspective on Language Acquisition” by Charles Yang 8, no. 6 (November 26, 2018): 733–37. http://dx.doi.org/10.1075/lab.18050.gri.

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3

Denny, Mark, and Lisandro Benedetti-Cecchi. "Scaling Up in Ecology: Mechanistic Approaches." Annual Review of Ecology, Evolution, and Systematics 43, no. 1 (December 2012): 1–22. http://dx.doi.org/10.1146/annurev-ecolsys-102710-145103.

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4

Betarbet, Ranjita, Todd B. Sherer, Donato A. Di, and J. Timothy Greenamyre. "Mechanistic Approaches to Parkinson's Disease Pathogenesis." Brain Pathology 12, no. 4 (April 5, 2006): 499–510. http://dx.doi.org/10.1111/j.1750-3639.2002.tb00468.x.

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5

Denny, M. "Biophysics, bioenergetics and mechanistic approaches to ecology." Journal of Experimental Biology 215, no. 6 (February 22, 2012): 871. http://dx.doi.org/10.1242/jeb.069575.

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6

Knight, K. "BIOPHYSICS, BIOENERGETICS AND MECHANISTIC APPROACHES TO ECOLOGY." Journal of Experimental Biology 215, no. 6 (February 22, 2012): i—iii. http://dx.doi.org/10.1242/jeb.071027.

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7

Links, Jonathan M., Thomas W. Kensler, and John D. Groopman. "Biomarkers and Mechanistic Approaches in Environmental Epidemiology." Annual Review of Public Health 16, no. 1 (May 1995): 83–103. http://dx.doi.org/10.1146/annurev.pu.16.050195.000503.

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8

Huang, Weili, Sau Lawrence Lee, and Lawrence X. Yu. "Mechanistic Approaches to Predicting Oral Drug Absorption." AAPS Journal 11, no. 2 (April 21, 2009): 217–24. http://dx.doi.org/10.1208/s12248-009-9098-z.

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9

Steele, Vernon E. "Current Mechanistic Approaches to the Chemoprevention of Cancer." BMB Reports 36, no. 1 (January 31, 2003): 78–81. http://dx.doi.org/10.5483/bmbrep.2003.36.1.078.

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10

Araujo, Leandro C., Patricia M. Santos, Daniel Rodriguez, José Ricardo M. Pezzopane, Patricia P. A. Oliveira, and Pedro G. Cruz. "Simulating Guinea Grass Production: Empirical and Mechanistic Approaches." Agronomy Journal 105, no. 1 (January 2013): 61–69. http://dx.doi.org/10.2134/agronj2012.0245.

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11

SCHOENER, THOMAS W. "Mechanistic Approaches to Community Ecology: A New Reductionism." American Zoologist 26, no. 1 (February 1986): 81–106. http://dx.doi.org/10.1093/icb/26.1.81.

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12

Ferguson, Lynnette R., Giorgio Bronzetti, and Silvio De Flora. "Mechanistic approaches to chemoprevention of mutation and cancer." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 591, no. 1-2 (December 2005): 3–7. http://dx.doi.org/10.1016/j.mrfmmm.2005.05.017.

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13

Kalkunte, Satyan, Zhongbin Lai, Wendy E. Norris, Linda A. Pietras, Neetu Tewari, Roland Boij, Stefan Neubeck, Udo R. Markert, and Surendra Sharma. "Novel approaches for mechanistic understanding and predicting preeclampsia." Journal of Reproductive Immunology 83, no. 1-2 (December 2009): 134–38. http://dx.doi.org/10.1016/j.jri.2009.08.006.

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14

Bhattacharya, S. S., and K. A. Padmanabhan. "Phenomenological and Mechanistic Approaches to Optimal Structural Superplasticity." Key Engineering Materials 97-98 (January 1995): 141–50. http://dx.doi.org/10.4028/www.scientific.net/kem.97-98.141.

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15

Jensen, Katrina H., and Matthew S. Sigman. "Mechanistic approaches to palladium-catalyzed alkene difunctionalization reactions." Organic & Biomolecular Chemistry 6, no. 22 (2008): 4083. http://dx.doi.org/10.1039/b813246a.

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16

Khan, Luqman, Nisar Ul Khaliq, Asad Ullah, Naseem Rafiq, and Mujib Ullah. "COVID-19 pandemic: Mechanistic approaches and gender vulnerabilities." Saudi Pharmaceutical Journal 28, no. 12 (December 2020): 1874–76. http://dx.doi.org/10.1016/j.jsps.2020.11.014.

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17

Kikuchi, Takashi, and Koji Tanaka. "Mechanistic Approaches to Molecular Catalysts for Water Oxidation." European Journal of Inorganic Chemistry 2014, no. 4 (August 29, 2013): 607–18. http://dx.doi.org/10.1002/ejic.201300716.

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18

Elham Alshammari. "Semi-mechanistic modelling of neutropenia." International Journal of Research in Pharmaceutical Sciences 10, no. 2 (April 14, 2019): 1157–60. http://dx.doi.org/10.26452/ijrps.v10i2.397.

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Population pharmacokinetics and pharmacodynamics PKPD modelling of chemotherapy-induced neutropenia can help with efficacy optimization and toxicity prevention in cancer patients. These medications focus on the fast-growing cells within the body and destroy them. Most of the fast-growing cells in the body are usually cancer cells, but there is an increased chance that certain healthy cells, such as white blood cells could be killed during chemotherapy. Several approaches have been identified for different drugs. Both empirical and mechanist approaches are discussed in this paper. Further, the author identified the pharmacokinetic-pharmacodynamic profile described by Friberg et al. (2003) as the most commonly used. This model consists of five sectors that represent proliferation, maturation, as well as elimination from the circulation of the neutrophils or leucocytes. This review covers these aspects and promotes a full understanding of dose prediction using semi-mechanistic modelling.
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19

SAITOH, SHU-ICHI, YASUCHIKA TAKEISHI, and YUKIO MARUYAMA. "MECHANISTIC INSIGHTS OF CORONARY VASOSPASM AND NEW THERAPEUTIC APPROACHES." FUKUSHIMA JOURNAL OF MEDICAL SCIENCE 61, no. 1 (2015): 1–12. http://dx.doi.org/10.5387/fms.2015-2.

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20

Bauer, Matthias, Jamie Cadge, David Davies, Derek J. Durand, Odile Eisenstein, Daniel Ess, Natalie Fey, et al. "Computational and theoretical approaches for mechanistic understanding: general discussion." Faraday Discussions 220 (2019): 464–88. http://dx.doi.org/10.1039/c9fd90073j.

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21

Steele, Vernon E., and Gary J. Kelloff. "Development of cancer chemopreventive drugs based on mechanistic approaches." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 591, no. 1-2 (December 2005): 16–23. http://dx.doi.org/10.1016/j.mrfmmm.2005.04.018.

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22

Desta, T. Zerihun, A. Van Brecht, J. Meyers, M. Baelmans, and D. Berckmans. "Combining CFD and data-based mechanistic (DBM) modelling approaches." Energy and Buildings 36, no. 6 (June 2004): 535–42. http://dx.doi.org/10.1016/j.enbuild.2003.12.015.

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23

Ho, N. F. H., J. S. Day, C. L. Barsuhn, P. S. Burton, and T. J. Raub. "Biophysical model approaches to mechanistic transepithelial studies of peptides." Journal of Controlled Release 11, no. 1-3 (January 1990): 3–24. http://dx.doi.org/10.1016/0168-3659(90)90117-c.

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24

Thompson, D. P., N. F. H. Ho, S. M. Sims, and T. G. Geary. "Mechanistic approaches to quantitate anthelmintic absorption by gastrointestinal nematodes." Parasitology Today 9, no. 1 (January 1993): 31–35. http://dx.doi.org/10.1016/0169-4758(93)90162-9.

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25

O’Brien, J. J., J. K. Hiers, J. M. Varner, C. M. Hoffman, M. B. Dickinson, S. T. Michaletz, E. L. Loudermilk, and B. W. Butler. "Advances in Mechanistic Approaches to Quantifying Biophysical Fire Effects." Current Forestry Reports 4, no. 4 (September 15, 2018): 161–77. http://dx.doi.org/10.1007/s40725-018-0082-7.

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26

Kandula, Sasikiran, Teresa Yamana, Sen Pei, Wan Yang, Haruka Morita, and Jeffrey Shaman. "Evaluation of mechanistic and statistical methods in forecasting influenza-like illness." Journal of The Royal Society Interface 15, no. 144 (July 2018): 20180174. http://dx.doi.org/10.1098/rsif.2018.0174.

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A variety of mechanistic and statistical methods to forecast seasonal influenza have been proposed and are in use; however, the effects of various data issues and design choices (statistical versus mechanistic methods, for example) on the accuracy of these approaches have not been thoroughly assessed. Here, we compare the accuracy of three forecasting approaches—a mechanistic method, a weighted average of two statistical methods and a super-ensemble of eight statistical and mechanistic models—in predicting seven outbreak characteristics of seasonal influenza during the 2016–2017 season at the national and 10 regional levels in the USA. For each of these approaches, we report the effects of real time under- and over-reporting in surveillance systems, use of non-surveillance proxies of influenza activity and manual override of model predictions on forecast quality. Our results suggest that a meta-ensemble of statistical and mechanistic methods has better overall accuracy than the individual methods. Supplementing surveillance data with proxy estimates generally improves the quality of forecasts and transient reporting errors degrade the performance of all three approaches considerably. The improvement in quality from ad hoc and post-forecast changes suggests that domain experts continue to possess information that is not being sufficiently captured by current forecasting approaches.
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27

Quackenbush, J. "Section 7: Bioinformatics: Computational Approaches to Analysis of DNA Microarray Data." Yearbook of Medical Informatics 15, no. 01 (August 2006): 91–103. http://dx.doi.org/10.1055/s-0038-1638484.

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SummaryTo review the current state of the art in computational methods for the analysis of DNA microarray data.The review considers methods of microarray data collection, transformation and representation, comparisons and predictions of gene expression from the data, their mechanistic analysis, related systems biology, and the application of clustering techniques.Functional genomics approaches have greatly increased the rate at which data on biological systems is generated, leading to corresponding challenges in analyzing the data through advanced computational techniques . The paper compares and contrasts the application of computational clustering for discovery, comparison, and prediction of gene expression classes, together with their evaluation and relation to mechanistic analyses of biological systems.Methods for assaying gene expression levels by DNA microarray experiments produce considerably more data than other techniques, and require a wide variety of computational techniques for identifying patterns of expression that may be biologically significant. These will have to be verified and validated by comparison to results from other methods, integrated with other systems data, and provide the feedback for further experimentation for testing mechanistic or other biological hypotheses.
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28

Kaupp, Gerd. "Solid-state photochemistry: new approaches based on new mechanistic insights." International Journal of Photoenergy 3, no. 2 (2001): 55–62. http://dx.doi.org/10.1155/s1110662x01000071.

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The application of atomic force microscopy (AFM) to solid-state photodimerizations revealed previously unexpected long-range molecular movements in the initial stages (phase rebuilding) and in the final stages (phase transformation and disintegration) of reaction. The consequences for the new understanding of solid-state photochemistry are discussed. The 4.2 Å criterion of organic topochemistry lacks a real basis and is not applicable to regular photolyses, even under tail irradiation conditions for instance ofα-cinnamic acid or inE/Z-isomerizations in the crystal bulk. The experimental observation of molecular movements in reacting crystals requires more elaborate use of X-ray structural data by invoking the molecular packing. If a crystal keeps its outer form upon photolysis this does not necessarily indicate a topotactic transformation, and submicroscopically resolved AFM investigations are in order. The applications of molecular movements or non-photoreactivities due to the prevention of movements by 3D-interlocked packing have numerous applications. Thus, amorphous solids or inclusion compounds may enable the movements in these cases. Hitherto puzzlingE/Z-photoisomerizations in the crystalline state can now be mechanistically understood. In some cases even rotational mechanisms can be modelled in combination with the movements. In others the space saving twist mechanism is the only choice. The benefits of the new solid-state mechanisms for crystal engineering, photochromism, mixed crystals, absolute asymmetric syntheses, and preparative photochemistry derive from its experimental basis. Numerous presumed puzzles from the postulate of minimal atomic and molecular movement vanish in a straightforward manner.
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29

Balls, M. "Mechanistic approaches and the development of alternative toxicity test methods." Environmental Health Perspectives 106, suppl 2 (April 1998): 453–57. http://dx.doi.org/10.1289/ehp.98106453.

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30

Bartolo, P. J., and E. Lenz. "Computer simulation of stereolithographic curing reactions: phenomenological versus mechanistic approaches." CIRP Annals 55, no. 1 (2006): 221–25. http://dx.doi.org/10.1016/s0007-8506(07)60403-x.

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31

Sommer, J. "Activation of small alkanes on strong solid acids: mechanistic approaches." Catalysis Today 38, no. 3 (November 17, 1997): 309–19. http://dx.doi.org/10.1016/s0920-5861(97)81501-3.

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32

Sahni, Ekneet Kaur, and Bodhisattwa Chaudhuri. "Contact drying: A review of experimental and mechanistic modeling approaches." International Journal of Pharmaceutics 434, no. 1-2 (September 2012): 334–48. http://dx.doi.org/10.1016/j.ijpharm.2012.06.010.

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33

Dean, Antony M., and Joseph W. Thornton. "Mechanistic approaches to the study of evolution: the functional synthesis." Nature Reviews Genetics 8, no. 9 (September 2007): 675–88. http://dx.doi.org/10.1038/nrg2160.

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34

Berg, Hermann. "Mechanistic Approaches to Interactions of Electromagnetic Fields with Living Systems." Journal of Electroanalytical Chemistry 342, no. 2 (April 1992): 239–40. http://dx.doi.org/10.1016/0022-0728(92)85056-9.

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35

Berg, Hermann. "Mechanistic Approaches to Interactions of Electromagnetic Fields with Living Systems." Bioelectrochemistry and Bioenergetics 27, no. 2 (April 1992): 239–40. http://dx.doi.org/10.1016/0302-4598(92)87049-z.

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36

Cutler, Corey S., John Koreth, and Jerome Ritz. "Mechanistic approaches for the prevention and treatment of chronic GVHD." Blood 129, no. 1 (January 5, 2017): 22–29. http://dx.doi.org/10.1182/blood-2016-08-686659.

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Abstract Clinical outcomes for patients undergoing allogeneic hematopoietic stem cell transplantation continue to improve, but chronic graft-versus-host disease (GVHD) remains a common toxicity and major cause of nonrelapse morbidity and mortality. Treatment of chronic GVHD has previously relied primarily on corticosteroids and other broadly immune suppressive agents. However, conventional immune suppressive agents have limited clinical efficacy in chronic GVHD, and prolonged immune suppressive treatments result in additional toxicities that further limit clinical recovery from transplant and return to normal daily function. Recent advances in our understanding of the immune pathology of chronic GVHD offer the possibility that new therapeutic approaches can be directed in more precise ways to target specific immunologic mechanisms and pathways. In this review, we briefly summarize current standard treatment options and present new therapeutic approaches that are supported by preclinical studies and early-phase clinical trials suggesting that these approaches may have clinical utility for treatment or prevention of chronic GVHD. Further evaluation of these new therapeutic options in well-designed prospective multicenter trials are needed to identify the most effective new agents and improve outcomes for patients with chronic GVHD.
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37

Rodgers, Trudy, and Malcolm Rowland. "Mechanistic Approaches to Volume of Distribution Predictions: Understanding the Processes." Pharmaceutical Research 24, no. 5 (March 20, 2007): 918–33. http://dx.doi.org/10.1007/s11095-006-9210-3.

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38

Kikuchi, Takashi, and Koji Tanaka. "ChemInform Abstract: Mechanistic Approaches to Molecular Catalysts for Water Oxidation." ChemInform 45, no. 12 (March 6, 2014): no. http://dx.doi.org/10.1002/chin.201412234.

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39

von Sonntag, C. "Advanced oxidation processes: mechanistic aspects." Water Science and Technology 58, no. 5 (September 1, 2008): 1015–21. http://dx.doi.org/10.2166/wst.2008.467.

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The reactive intermediate in Advanced Oxidation Processes (AOPs) is the •OH radical. It may be generated by various approaches such as the Fenton reaction (Fe2 + /H2O2), photo-Fenton reaction (Fe3 + /H2O2/hν), UV/H2O2, peroxone reaction (O3/H2O2), O3/UV, O3/activated carbon, O3/dissolved organic carbon (DOC) of water matrix, ionizing radiation, vacuum UV, and ultrasound. The underlying reactions and •OH formation efficiencies are discussed. The key reactions of •OH radicals also addressed in this review.
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40

Agadullina, E. R. "Dehumanization: Approaches to Indirect Prejudice." Social Psychology and Society 12, no. 2 (2021): 5–22. http://dx.doi.org/10.17759/sps.2021120201.

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Objective. The presented review aims to describe and critically analyze the two most popular approaches to understanding and operationalizing the concepts of “humanity” and “dehumanization” (Infrahumanization theory and Two-dimensional model of humanness). Background. The studies of prejudice has identified two key problems. The first problem is associated with the limitations of existing theories in understanding the nature of prejudices, and the second — with a low efficiency of assessing blatant prejudice since an increasing spread of egalitarian attitudes in the world changes the intergroup relations and contributes to a transformation of explicit prejudices into indirect forms. The theories and models of dehumanization has become the response to these problems since they offer a new conceptual framework for the analysis of intergroup and interpersonal relationships, and new methods for assessing indirect prejudice that are independent of a social desirability. Conclusions. The results of a theoretical analysis showed that in psychological studies, “humanity” is operationalized either through the unique human emotions and traits, the negation of which leads to the association between certain individuals or groups with animals and the emergence of animalistic dehumanization, or through a description of the “human” prototype, the discrepancy to which is associated with mechanistic dehumanization. Animalistic dehumanization is more common in the context of intergroup relations, and mechanistic dehumanization is more related to the processes of self-perception. Despite the contradictions between different approaches to understanding humanity and dehumanization, as well as some methodological problems within each of them, dehumanization is recognized as an important phenomenon which significantly enriches psychological knowledge and understanding of a process of social cognition and interaction.
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41

Haga, Masatoshi, and Mariko Okada. "Systems approaches to investigate the role of NF-κB signaling in aging." Biochemical Journal 479, no. 2 (January 28, 2022): 161–83. http://dx.doi.org/10.1042/bcj20210547.

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The nuclear factor-κB (NF-κB) signaling pathway is one of the most well-studied pathways related to inflammation, and its involvement in aging has attracted considerable attention. As aging is a complex phenomenon and is the result of a multi-step process, the involvement of the NF-κB pathway in aging remains unclear. To elucidate the role of NF-κB in the regulation of aging, different systems biology approaches have been employed. A multi-omics data-driven approach can be used to interpret and clarify unknown mechanisms but cannot generate mechanistic regulatory structures alone. In contrast, combining this approach with a mathematical modeling approach can identify the mechanistics of the phenomena of interest. The development of single-cell technologies has also helped clarify the heterogeneity of the NF-κB response and underlying mechanisms. Here, we review advances in the understanding of the regulation of aging by NF-κB by focusing on omics approaches, single-cell analysis, and mathematical modeling of the NF-κB network.
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42

Nabity, Mary B., Joseph W. Polli, Vishal Vaidya, Andrzej Krolewski, and Warren E. Glaab. "New Frontiers: Approaches to Understand the Mechanistic Basis of Renal Toxicity." Toxicologic Pathology 46, no. 8 (September 6, 2018): 1002–5. http://dx.doi.org/10.1177/0192623318798599.

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A scientific session entitled “New Frontiers: Approaches to Understand the Mechanistic Basis of Renal Toxicity” focused on novel biomarkers to monitor kidney injury both preclinically and clinically, as well as providing mechanistic insight of the induced injury. Further, the role and impact of kidney membrane transporters in drug-induced kidney toxicity provided additional considerations when understanding kidney injury and the complex role of drug transporters in either sensitivity or resistance to drug-induced injury. The onset of nephropathy in diabetic patients was also presented, focusing on the quest to discover novel biomarkers that would differentiate diabetic populations more susceptible to nephropathy and renal failure. The session highlighted exciting new research areas and novel biomarkers that will enhance our understanding of kidney injury and provide tools for ensuring patient safety clinically.
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43

McMahon, Stephen J., and Kevin M. Prise. "Mechanistic Modelling of Radiation Responses." Cancers 11, no. 2 (February 10, 2019): 205. http://dx.doi.org/10.3390/cancers11020205.

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Radiobiological modelling has been a key part of radiation biology and therapy for many decades, and many aspects of clinical practice are guided by tools such as the linear-quadratic model. However, most of the models in regular clinical use are abstract and empirical, and do not provide significant scope for mechanistic interpretation or making predictions in novel cell lines or therapies. In this review, we will discuss the key areas of ongoing mechanistic research in radiation biology, including physical, chemical, and biological steps, and review a range of mechanistic modelling approaches which are being applied in each area, highlighting the possible opportunities and challenges presented by these techniques.
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44

Han, Jiyeon, Hyuck Jin Lee, Kyu Yeon Kim, Geewoo Nam, Junghyun Chae, and Mi Hee Lim. "Mechanistic approaches for chemically modifying the coordination sphere of copper–amyloid-β complexes." Proceedings of the National Academy of Sciences 117, no. 10 (February 26, 2020): 5160–67. http://dx.doi.org/10.1073/pnas.1916944117.

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Neurotoxic implications of the interactions between Cu(I/II) and amyloid-β (Aβ) indicate a connection between amyloid cascade hypothesis and metal ion hypothesis with respect to the neurodegeneration associated with Alzheimer’s disease (AD). Herein, we report a mechanistic strategy for modifying the first coordination sphere of Cu(II) bound to Aβ utilizing a rationally designed peptide modifier, L1. Upon reacting with L1, a metal-binding histidine (His) residue, His14, in Cu(II)–Aβ was modified through either covalent adduct formation, oxidation, or both. Consequently, the reactivity of L1 with Cu(II)–Aβ was able to disrupt binding of Cu(II) to Aβ and result in chemically modified Aβ with altered aggregation and toxicity profiles. Our molecular-level mechanistic studies revealed that such L1-mediated modifications toward Cu(II)–Aβ could stem from the molecule’s ability to 1) interact with Cu(II)–Aβ and 2) foster copper–O2 chemistry. Collectively, our work demonstrates the development of an effective approach to modify Cu(II)–Aβ at a metal-binding amino acid residue and consequently alter Aβ’s coordination to copper, aggregation, and toxicity, supplemented with an in-depth mechanistic perspective regarding such reactivity.
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45

Leitão, Emília P. T. "Chalcones: Retrospective Synthetic Approaches and Mechanistic Aspects of a Privileged Scaffold." Current Pharmaceutical Design 26, no. 24 (July 21, 2020): 2843–58. http://dx.doi.org/10.2174/1381612826666200403124259.

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This review summarizes the synthetic methodologies used in the last 25 years for the synthesis of chalcones, which are a class of flavonoids having a 1,3-diphenyl-2-propene-1-one backbone. These compounds are considered a hot topic in the field of medicinal chemistry, due to their pharmacological activity and because they are important precursors for the synthesis of heterocyclic compounds with therapeutic applications such as: flavones, flavanones, isoxazolines, benzothiazepines, pyrimidines and pyrazolines derivatives.
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46

Sakamoto, Yasuaki, Matt Jones, and Bradley C. Love. "Putting the psychology back into psychological models: Mechanistic versus rational approaches." Memory & Cognition 36, no. 6 (September 2008): 1057–65. http://dx.doi.org/10.3758/mc.36.6.1057.

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47

Boer, Geke Aline, and Jens Juul Holst. "Incretin Hormones and Type 2 Diabetes—Mechanistic Insights and Therapeutic Approaches." Biology 9, no. 12 (December 16, 2020): 473. http://dx.doi.org/10.3390/biology9120473.

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Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.
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48

Balls, Michael. "Commentary: Mechanistic Approaches and the Development of Alternative Toxicity Test Methods." Environmental Health Perspectives 106 (April 1998): 453. http://dx.doi.org/10.2307/3433794.

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49

Michmerhuizen, Nicole L., Jeffery M. Klco, and Charles G. Mullighan. "Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies." Blood 136, no. 20 (November 12, 2020): 2275–89. http://dx.doi.org/10.1182/blood.2020007093.

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Abstract Nucleoporin 98 (NUP98) fusion oncoproteins are observed in a spectrum of hematologic malignancies, particularly pediatric leukemias with poor patient outcomes. Although wild-type full-length NUP98 is a member of the nuclear pore complex, the chromosomal translocations leading to NUP98 gene fusions involve the intrinsically disordered and N-terminal region of NUP98 with over 30 partner genes. Fusion partners include several genes bearing homeodomains or having known roles in transcriptional or epigenetic regulation. Based on data in both experimental models and patient samples, NUP98 fusion oncoprotein–driven leukemogenesis is mediated by changes in chromatin structure and gene expression. Multiple cofactors associate with NUP98 fusion oncoproteins to mediate transcriptional changes possibly via phase separation, in a manner likely dependent on the fusion partner. NUP98 gene fusions co-occur with a set of additional mutations, including FLT3–internal tandem duplication and other events contributing to increased proliferation. To improve the currently dire outcomes for patients with NUP98-rearranged malignancies, therapeutic strategies have been considered that target transcriptional and epigenetic machinery, cooperating alterations, and signaling or cell-cycle pathways. With the development of more faithful experimental systems and continued study, we anticipate great strides in our understanding of the molecular mechanisms and therapeutic vulnerabilities at play in NUP98-rearranged models. Taken together, these studies should lead to improved clinical outcomes for NUP98-rearranged leukemia.
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Béchaux, Camille, and Jean-Lou C. M. Dorne. "Mechanistic approaches for human and ecological risk assessment of chemical mixtures." Toxicology Letters 229 (September 2014): S18. http://dx.doi.org/10.1016/j.toxlet.2014.06.098.

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