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Munz C, Boya P, Santambrogio L, Debnath J, Melendez A, Galluzzi L, Jaattela M, Ballabio A, Simon HU, Gewirtz DA, Bravo-San Pedro JM, Harper JW, Murphy LO, Tavernarakis N, Chu CT, Kroemer G, Deretic V, Dikic I, Fulda S, Martens S, Cuervo AM, Reggiori F, Green DR, Kimmelman AC, Levine B, Cecconi F, Penninger JM, Johansen T, Piacentini M, Codogno P, Choi AM, Madeo F, Lopez-Otin C, Simon AK, Juhasz G, Colombo MI, Fimia GM, Martinez J, Kraft C, Ryan KM, Yue Z, Hansen M, Zhong Q, Mizushima N, Simonsen A, Baehrecke EH, Ktistakis NT, Rubinsztein DC, Scorrano L, Tooze SA, Yoshimori T, Eskelinen EL, Yuan J, Kumar S
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EMBO J,
2017]
Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research.
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Ann N Y Acad Sci,
2006]
During the last three decades the soil nematode C. elegans has become a prominent model organism for studying aging. Initially research in the C. elegans aging field was focused on the genetics of aging and single gene mutations that dramatically increased the life span of the worm. Undoubtedly, the existence of such mutations is one of the main reasons for the popularity of the worm as model system for studying aging. However, today many different approaches are being used in the C. elegans aging field in addition to genetic manipulations that influence life span. For example, environmental manipulations such as caloric restriction and hormetic treatments, evolutionary studies, population studies, models of age-related diseases, and drug screening for compounds that extend life span are now being investigated using this nematode. This review will focus on the most recent developments in C. elegans aging research with the aim of illustrating the diversity of the field.
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Prog Mol Biol Transl Sci,
2014]
Mechanobiology is an emerging field that investigates how living cells sense and respond to their physical surroundings. Recent interest in the field has been sparked by the finding that stem cells differentiate along different lineages based on the stiffness of the cell surroundings (Engler et al., 2006), and that metastatic behavior of cancer cells is strongly influenced by the mechanical properties of the surrounding tissue (Kumar and Weaver, 2009). Many questions remain about how cells convert mechanical information, such as viscosity, stiffness of the substrate, or stretch state of the cells, into the biochemical signals that control tissue function. Caenorhabditis elegans researchers are making significant contributions to the understanding of mechanotransduction in vivo. This review summarizes recent insights into the role of mechanical forces in morphogenesis and tissue function. Examples of mechanical regulation across length scales, from the single-celled zygote, to the intercellular coordination that enables cohesive tissue function, to the mechanical influences between tissues, are considered. The power of the C. elegans system as a gene discovery and in vivo quantitative bioimaging platform is enabling an important discoveries in this exciting field.
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Cell Metab,
2017]
Nutrition is paramount in shaping all aspects of animal biology. In addition, the influence of the intestinal microbiota on physiology is now widely recognized. Given that dietalso shapes the intestinal microbiota, this raises the question of how the nutritional environment and microbial assemblages together influence animal physiology. This research field constitutes a new frontier in the field of organismal biology that needs to be addressed. Here we review recent studies using animal models and humans and propose an integrative framework within which to define the study of the diet-physiology-microbiota systems and ultimately link it to human health. Nutritional Geometry sits centrally in the proposed framework and offers means to define diet compositions that are optimal for individuals and populations.
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Toxicon,
2001]
Diphtheria toxin is one of the most extensively studied and well understood bacterial toxins. Ever since its discovery in the late 1800's this toxin has occupied a central focus in the field of toxinology. In this review, I present a chronology of major discoveries that led to our current understanding of the structure and activity of diphtheria toxin.
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Environ Mol Mutagen,
2018]
The roundworm Caenorhabitis elegans has been an established model organism for the study of genetics and developmental biology, including studies of transcriptional regulation, since the 1970s. This model organism has continued to be used as a classical model system as the field of transcriptional regulation has expanded to include scientific advances in epigenetics and chromatin biology. In the last several decades, C. elegans has emerged as a powerful model for environmental toxicology, particularly for the study of chemical genotoxicity. Here, we outline the utility and applicability of C. elegans as a powerful model organism for mechanistic studies of environmental influences on the epigenome. Our goal in this article is to inform the field of environmental epigenetics of the strengths and limitations of the well-established C. elegans model organism as an emerging model for medium-throughput, in vivo exploration of the role of exogenous chemical stimuli in transcriptional regulation, developmental epigenetic reprogramming, and epigenetic memory and inheritance. As the field of environmental epigenetics matures, and research begins to map mechanisms underlying observed associations, new toolkits and model systems, particularly manipulable, scalable in vivo systems that accurately model human transcriptional regulatory circuits, will provide an essential experimental bridge between in vitro biochemical experiments and mammalian model systems. Environ. Mol. Mutagen., 2018. 2018 Wiley Periodicals, Inc.
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Integr Comp Biol,
2014]
When a bubble oscillates in an acoustically driven pressure field, its oscillations result in an attractive force on micro-sized objects in the near field. At the same time, the objects are subject to a viscous drag force due to the streaming flow that is generated by the oscillating bubble. Based on these secondary effects, oscillating bubbles have recently been implemented in biological applications to control and manipulate micron-sized objects. These objects include live microorganisms, such as Caenorhabditis elegans and Daphnia (water flea), as well as cells and vesicles. Oscillating bubbles are also used in delivering drugs or genes inside human blood vessels. In this review paper, we explain the underlying physical mechanism behind oscillating bubbles and discuss some of their key applications in biology, with the focus on the manipulation of microorganisms and cells.
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Trends Cell Biol,
2001]
Research performed over the past decade has transformed apoptosis from a distinctive form of cell death known only by its characteristic morphology and genomic destruction to an increasingly well understood cellular disassembly pathway remarkable for its complex and multifaceted regulation. Here, we summarize current understanding of apoptotic events, note recent advances in this field and identify questions that might help guide research in the coming years.
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Genes Dev,
1989]
The rapid growth of the Caenorhabditis elegans field in recent years reflects the remarkable utility of this nematode for study of diverse biological problems. This organism has many natural attributes. Its anatomy is simple and relatively invariant. Its ease of cultivation, large brood size, and rapid generation of time facilitate genetic analysis; its small genome size facilitates molecular analysis. Although these features have been important to the expansion of this field of study, the deliberate accumulation of basic biological knowledge and techniques-the complete cell lineage and anatomy of wild type, extensive genetic and physical maps, and methods for gene isolation, DNA transformation, and genetic mosaic analysis-has provided the foundation for further progress. The magnitude of this progress was evident at the 1989 Cold Spring Harbor Laboratory C. elegans meeting. In this review, due to limited space, we describe only some of this progress.
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Annu Rev Biochem,
2010]
The discovery of RNA interference (RNAi) is among the most significant biomedical breakthroughs in recent history. Multiple classes of small RNA, including small-interfering RNA (siRNA), micro-RNA (miRNA), and piwi-interacting RNA (piRNA), play important roles in many fundamental biological and disease processes. Collective studies in multiple organisms, including plants, Drosophila, Caenorhabditis elegans, and mammals indicate that these pathways are highly conserved throughout evolution. Thus, scientists across disciplines have found novel pathways to unravel, new insights in probing pathology, and nascent technologies to develop. The field of RNAi also provides a clear framework for understanding fundamental principles of biochemistry. The current review highlights elegant, reason-based experimentation in discovering RNA-directed biological phenomena and the importance of robust assay development in translating these observations into mechanistic understanding. This biochemical template also provides a conceptual framework for overcoming emerging challenges in the field and for understanding an expanding small RNA world.