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  1. Engineering Novel Proteins with Orthogonal tRNA: Artificial Causes that make a Difference.Janella Baxter - manuscript
    Model organisms, the use of green fluorescent proteins, and orthogonal transfer RNA are examples of artificial causes being used in biology. Recent work characterizing the research interests of biologists in terms of a common set of values has ruled out artificial causes as biologically interesting. For instance, Kenneth Waters argues that biologists are primarily interested in causes that actually obtain. Similarly, Marcel Weber argues that biologists are primarily concerned with biologically normal interventions. Both views express a widely received attitude about (...)
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  2. Causal Specificity, Biological Possibility and Non-parity about Genetic Causes.Marcel Weber - manuscript
    Several authors have used the notion of causal specificity in order to defend non-parity about genetic causes (Waters 2007, Woodward 2010, Weber 2017, forthcoming). Non-parity in this context is the idea that DNA and some other biomolecules that are often described as information-bearers by biologists play a unique role in life processes, an idea that has been challenged by Developmental Systems Theory (e.g., Oyama 2000). Indeed, it has proven to be quite difficult to state clearly what the alleged special role (...)
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  3. A Complementary Account of Scientific Modelling: Modelling Mechanisms in Cancer Immunology.Martin Zach - forthcoming - British Journal for the Philosophy of Science.
    According to a widely held view, scientific modelling consists in entertaining a set of model descriptions that specify a model. Rather than studying the phenomenon of interest directly, scientists investigate the phenomenon indirectly via a model in the hope of learning about some of the phenomenon’s features. I call this view the description-driven modelling (DDM) account. I argue that although an accurate description of much of scientific research, the DDM account is found wanting as regards the mechanistic modelling found in (...)
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  4. A Monist Proposal: Against Integrative Pluralism About Protein Structure.Agnes Bolinska - 2022 - Erkenntnis 1.
    Mitchell & Gronenborn propose that we account for the presence of multiple models of protein structure, each produced in different contexts, through the framework of integrative pluralism. I argue that two interpretations of this framework are available, neither of which captures the relationship between a model and the protein structure it represents or between multiple models of protein structure. Further, it inclines us toward concluding prematurely that models of protein structure are right in their contexts and makes extrapolation of findings (...)
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  5. SynBio 2.0, a new era for synthetic life: Neglected essential functions for resilience.Antoine Danchin & Jian Dong Huang - 2022 - Environmental Microbiology 25 (1):64-78.
    Synthetic biology (SynBio) covers two main areas: application engineering, exemplified by metabolic engi- neering, and the design of life from artificial building blocks. As the general public is often reluctant to embrace synthetic approaches, preferring nature to artifice, its immediate future will depend very much on the public’s reaction to the unmet needs created by the pervasive demands of sustainability. On the other hand, this reluctance should not have a negative impact on research that will now take into account the (...)
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  6. Thermal stability of solitons in protein α-helices.Danko D. Georgiev & James F. Glazebrook - 2022 - Chaos, Solitons and Fractals 155:111644.
    Protein α-helices provide an ordered biological environment that is conducive to soliton-assisted energy transport. The nonlinear interaction between amide I excitons and phonon deformations induced in the hydrogen-bonded lattice of peptide groups leads to self-trapping of the amide I energy, thereby creating a localized quasiparticle (soliton) that persists at zero temperature. The presence of thermal noise, however, could destabilize the protein soliton and dissipate its energy within a finite lifetime. In this work, we have computationally solved the system of stochastic (...)
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  7. Revisiting abstraction and idealization: how not to criticize mechanistic explanation in molecular biology.Martin Zach - 2022 - European Journal for Philosophy of Science 12 (1):1-20.
    Abstraction and idealization are the two notions that are most often discussed in the context of assumptions employed in the process of model building. These notions are also routinely used in philosophical debates such as that on the mechanistic account of explanation. Indeed, an objection to the mechanistic account has recently been formulated precisely on these grounds: mechanists cannot account for the common practice of idealizing difference-making factors in models in molecular biology. In this paper I revisit the debate and (...)
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  8. Beyond descriptive accuracy: The central dogma of molecular biology in scientific practice.M. Polo Camacho - 2021 - Studies in History and Philosophy of Science Part A 86 (C):20-26.
    There is no denying the Central Dogma’s impact on the biological sciences. Since the Dogma’s formulation by Francis Crick in 1958, however, many have debated the Dogma’s empirical adequacy. My aim is to move beyond these discussions, and instead consider the Central Dogma’s significance to contemporary biological practice. To do this, I consider four distinct approaches for determining the non-descriptive methodological significance of a scientific principle. I argue that these approaches fail to vindicate the Central Dogma, and that, under many (...)
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  9. The molecular vista: current perspectives on molecules and life in the twentieth century.Mathias Grote, Lisa Onaga, Angela N. H. Creager, Soraya de Chadarevian, Daniel Liu, Gina Surita & Sarah E. Tracy - 2021 - History and Philosophy of the Life Sciences 43 (1):1-18.
    This essay considers how scholarly approaches to the development of molecular biology have too often narrowed the historical aperture to genes, overlooking the ways in which other objects and processes contributed to the molecularization of life. From structural and dynamic studies of biomolecules to cellular membranes and organelles to metabolism and nutrition, new work by historians, philosophers, and STS scholars of the life sciences has revitalized older issues, such as the relationship of life to matter, or of physicochemical inquiries to (...)
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  10. Data science and molecular biology: prediction and mechanistic explanation.Ezequiel López-Rubio & Emanuele Ratti - 2021 - Synthese 198 (4):3131-3156.
    In the last few years, biologists and computer scientists have claimed that the introduction of data science techniques in molecular biology has changed the characteristics and the aims of typical outputs (i.e. models) of such a discipline. In this paper we will critically examine this claim. First, we identify the received view on models and their aims in molecular biology. Models in molecular biology are mechanistic and explanatory. Next, we identify the scope and aims of data science (machine learning in (...)
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  11. Causal Concepts in Biology: How Pathways Differ from Mechanisms and Why It Matters.Lauren N. Ross - 2021 - British Journal for the Philosophy of Science 72 (1):131-158.
    In the last two decades few topics in philosophy of science have received as much attention as mechanistic explanation. A significant motivation for these accounts is that scientists frequently use the term “mechanism” in their explanations of biological phenomena. While scientists appeal to a variety of causal concepts in their explanations, many philosophers argue or assume that all of these concepts are well understood with the single notion of mechanism. This reveals a significant problem with mainstream mechanistic accounts– although philosophers (...)
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  12. Synthetic biology as a technoscience: The case of minimal genomes and essential genes.Massimiliano Simons - 2021 - Studies in History and Philosophy of Science Part A 85:127-136.
    This article examines how minimal genome research mobilizes philosophical concepts such as minimality and essentiality. Following a historical approach the article aims to uncover what function this terminology plays and which problems are raised by them. Specifically, four historical moments are examined, linked to the work of Harold J. Morowitz, Mitsuhiro Itaya, Eugene Koonin and Arcady Mushegian, and J. Craig Venter. What this survey shows is a historical shift away from historical questions about life or descriptive questions about specific organisms (...)
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  13. Patrick Forterre. Microbes from Hell. Translated by Teresa Lavender Fagan. 288 pp., notes, bibl., index. Chicago/London: University of Chicago Press, 2016. $50 (cloth). ISBN 9780226265827. [REVIEW]Howard G. Barth - 2020 - Isis 111 (2):371-372.
  14. What’s all the fuss about? The inheritance of acquired traits is compatible with the Central Dogma.M. Polo Camacho - 2020 - History and Philosophy of the Life Sciences 42 (3):1-15.
    The Central Dogma of molecular biology, which holds that DNA makes protein and not the other way around, is as influential as it is controversial. Some believe the Dogma has outlived its usefulness, either because it fails to fully capture the ins-and-outs of protein synthesis (Griffiths and Stotz, 2013; Stotz, 2006), because it turns on a confused notion of information (Sarkar, 2004), or because it problematically assumes the unidirectional flow of information from DNA to protein (Gottlieb, 2001). This paper evaluates (...)
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  15. Launching of Davydov solitons in protein α-helix spines.Danko D. Georgiev & James F. Glazebrook - 2020 - Physica E: Low-Dimensional Systems and Nanostructures 124:114332.
    Biological order provided by α-helical secondary protein structures is an important resource exploitable by living organisms for increasing the efficiency of energy transport. In particular, self-trapping of amide I energy quanta by the induced phonon deformation of the hydrogen-bonded lattice of peptide groups is capable of generating either pinned or moving solitary waves following the Davydov quasiparticle/soliton model. The effect of applied in-phase Gaussian pulses of amide I energy, however, was found to be strongly dependent on the site of application. (...)
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  16. Quantum transport and utilization of free energy in protein α-helices.Danko D. Georgiev & James F. Glazebrook - 2020 - Advances in Quantum Chemistry 82:253-300.
    The essential biological processes that sustain life are catalyzed by protein nano-engines, which maintain living systems in far-from-equilibrium ordered states. To investigate energetic processes in proteins, we have analyzed the system of generalized Davydov equations that govern the quantum dynamics of multiple amide I exciton quanta propagating along the hydrogen-bonded peptide groups in α-helices. Computational simulations have confirmed the generation of moving Davydov solitons by applied pulses of amide I energy for protein α-helices of varying length. The stability and mobility (...)
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  17. Binding Specificity and Causal Selection in Drug Design.Oliver M. Lean - 2020 - Philosophy of Science 87 (1):70-90.
    Binding specificity is a centrally important concept in molecular biology, yet it has received little philosophical attention. Here I aim to remedy this by analyzing binding specificity as a causal property. I focus on the concept’s role in drug design, where it is highly prized and hence directly studied. From a causal perspective, understanding why binding specificity is a valuable property of drugs contributes to an understanding of causal selection—of how and why scientists distinguish between causes, not just causes from (...)
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  18. Mathias Grote. Membranes to Molecular Machines: Active Matter and the Remaking of Life. 286 pp., bibl., index. Chicago/London: University of Chicago Press, 2019. $45 (cloth). E-book available. [REVIEW]Ilana Löwy - 2020 - Isis 111 (3):692-693.
  19. Dynamical causes.Russell Meyer - 2020 - Biology and Philosophy 35 (5):1-21.
    Mechanistic explanations are often said to explain because they reveal the causal structure of the world. Conversely, dynamical models supposedly lack explanatory power because they do not describe causal structure. The only way for dynamical models to produce causal explanations is via the 3M criterion: the model must be mapped onto a mechanism. This framing of the situation has become the received view around the viability of dynamical explanation. In this paper, I argue against this position and show that dynamical (...)
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  20. What kind of novelties can machine learning possibly generate? The case of genomics.Emanuele Ratti - 2020 - Studies in History and Philosophy of Science Part A 83:86-96.
    Machine learning (ML) has been praised as a tool that can advance science and knowledge in radical ways. However, it is not clear exactly how radical are the novelties that ML generates. In this article, I argue that this question can only be answered contextually, because outputs generated by ML have to be evaluated on the basis of the theory of the science to which ML is applied. In particular, I analyze the problem of novelty of ML outputs in the (...)
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  21. Onur Erdur. Die epistemologischen Jahre: Philosophie und Biologie in Frankreich, 1960–1980. (Interferenzen, 24.) 391 pp., bibl., illus., index. Zurich: Chronos, 2018. €48 (cloth). ISBN 9783034013826. [REVIEW]Hans-Jörg Rheinberger - 2020 - Isis 111 (2):438-439.
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  22. Philosophy of immunology.Bartlomiej Swiatczak & Alfred I. Tauber - 2020 - Stanford Encyclopedia of Philosophy 2020.
    Philosophy of immunology is a subfield of philosophy of biology dealing with ontological and epistemological issues related to the studies of the immune system. While speculative investigations and abstract analyses have always been part of immune theorizing, until recently philosophers have largely ignored immunology. Yet the implications for understanding the philosophical basis of organismal functions framed by immunity offer new perspectives on fundamental questions of biology and medicine. Developed in the context of history of medicine, theoretical biology, and medical anthropology, (...)
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  23. Indispensability and Effectiveness of Diagrams in Molecular Biology.Javier Anta - 2019 - Quaderns de Filosofia 6 (1):29-46.
    In this paper I aim to defend a twofold thesis. On one hand, I will sup-port, against Perini [7], the indispensability of diagrams when structurally complex biomolecules are concerned, since it is not possible to satisfactorily use linguistic-sentential representations at that domain. On the other hand, even when diagrams are dispensable I will defend than they will generally be more effective than other representations in encoding biomolecular knowledge, relying on Kulvicki-Shimojima’s diagrammatic effectiveness thesis. Finally, I will ground many epistemic virtues (...)
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  24. Developing Gamified Instructional Materials in Genetics for Grade 12 STEM.Aaron Funa & Jhonner Ricafort - 2019 - International Journal of Engineering Science and Computing 9 (3):20597-20600.
    As technology advances, the demand for innovative instructional materials also increases. As a result, the Department of Education urges teachers to develop instructional materials. This study was conducted at Bulusan National High School, Bulusan, Sorsogon, Philippines SY 2018-2019 which was aimed to develop gamified instructional materials in genetics that would aid in teaching and learning process of grade 12 STEM students. The developed gamified materials were collectively called the GIM in Genetics which is comprised of two parts; namely, Student’s Portfolio (...)
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  25. Chemical arbitrariness and the causal role of molecular adapters.Oliver M. Lean - 2019 - Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences 78:101180.
    Jacques Monod (1971) argued that certain molecular processes rely critically on the property of chemical arbitrariness, which he claimed allows those processes to “transcend the laws of chemistry”. It seems natural, as some philosophers have done, to interpret this in modal terms: a biological relationship is chemically arbitrary if it is possible, within the constraints of chemical “law”, for that relationship to have been otherwise than it is. But while modality is certainly important for understanding chemical arbitrariness, understanding its biological (...)
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  26. Is “Wolf‐Pack” Predation by Antimicrobial Bacteria Cooperative? Cell Behaviour and Predatory Mechanisms Indicate Profound Selfishness, Even when Working Alongside Kin.Rupert C. Marshall & David E. Whitworth - 2019 - Bioessays 41 (4):1800247.
    For decades, myxobacteria have been spotlighted as exemplars of social “wolf‐pack” predation, communally secreting antimicrobial substances into the shared public milieu. This behavior has been described as cooperative, becoming more efficient if performed by more cells. However, laboratory evidence for cooperativity is limited and of little relevance to predation in a natural setting. In contrast, there is accumulating evidence for predatory mechanisms promoting “selfish” behavior during predation, which together with conflicting definitions of cooperativity, casts doubt on whether microbial “wolf‐pack” predation (...)
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  27. Phronesis and Automated Science: The Case of Machine Learning and Biology.Emanuele Ratti - 2019 - In Fabio Sterpetti & M. Bertolaso (eds.), Will Science Remain Human? Springer.
    The applications of machine learning and deep learning to the natural sciences has fostered the idea that the automated nature of algorithmic analysis will gradually dispense human beings from scientific work. In this paper, I will show that this view is problematic, at least when ML is applied to biology. In particular, I will claim that ML is not independent of human beings and cannot form the basis of automated science. Computer scientists conceive their work as being a case of (...)
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  28. Gravity Constraints Drive Biological Systems Toward Specific Organization Patterns.Mariano Bizzarri, Maria Grazia Masiello, Alessandro Giuliani & Alessandra Cucina - 2018 - Bioessays 40 (1):1700138.
    Different cell lineages growing in microgravity undergo a spontaneous transition leading to the emergence of two distinct phenotypes. By returning these populations in a normal gravitational field, the two phenotypes collapse, recovering their original configuration. In this review, we hypothesize that, once the gravitational constraint is removed, the system freely explores its phenotypic space, while, when in a gravitational field, cells are “constrained” to adopt only one favored configuration. We suggest that the genome allows for a wide range of “possibilities” (...)
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  29. Synthetic versus analytic approaches to protein and DNA structure determination.Agnes Bolinska - 2018 - Biology and Philosophy 33 (3-4):26.
    The structures of protein and DNA were discovered primarily by means of synthesizing component-level information about bond types, lengths, and angles, rather than analyzing X-ray diffraction photographs of these molecules. In this paper, I consider the synthetic and analytic approaches to exemplify alternative heuristics for approaching mid-twentieth-century macromolecular structure determination. I argue that the former was, all else being equal, likeliest to generate the correct structure in the shortest period of time. I begin by characterizing problem solving in these cases (...)
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  30. Molecular pathways and the contextual explanation of molecular functions.Giovanni Boniolo & Raffaella Campaner - 2018 - Biology and Philosophy 33 (3-4):24.
    Much of the recent philosophical debate on causation and causal explanation in the biological and biomedical sciences has focused on the notion of mechanism. Mechanisms, their nature and epistemic roles have been tackled by a range of so-called neo-mechanistic theories, and widely discussed. Without denying the merits of this approach, our paper aims to show how lately it has failed to give proper credit to processes, which are central to the field, especially of contemporary molecular biology. Processes can be summed (...)
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  31. Are There Really Too Many Eukaryote LGTs? A Reply To William Martin.Luis Boto - 2018 - Bioessays 40 (3):1800001.
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  32. Demarcation of Viral Shelters Results in Destruction by Membranolytic GTPases: Antiviral Function of Autophagy Proteins and Interferon‐Inducible GTPases.Hailey M. Brown, Scott B. Biering, Allen Zhu, Jayoung Choi & Seungmin Hwang - 2018 - Bioessays 40 (6):1700231.
    A hallmark of positive‐sense RNA viruses is the formation of membranous shelters for safe replication in the cytoplasm. Once considered invisible to the immune system, these viral shelters are now found to be antagonized through the cooperation of autophagy proteins and anti‐microbial GTPases. This coordinated effort of autophagy proteins guiding GTPases functions against not only the shelters of viruses but also cytoplasmic vacuoles containing bacteria or protozoa, suggesting a broad immune‐defense mechanism against disparate vacuolar pathogens. Fundamental questions regarding this process (...)
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  33. BET‐ting on Nrf2: How Nrf2 Signaling can Influence the Therapeutic Activities of BET Protein Inhibitors.Nirmalya Chatterjee & Dirk Bohmann - 2018 - Bioessays 40 (5):1800007.
    BET proteins such as Brd3 and Brd4 are chromatin‐associated factors, which control gene expression programs that promote inflammation and cancer. The Nrf2 transcription factor is a master regulator of genes that protect the organism against xenobiotic attack and oxidative stress. Nrf2 has demonstrated anti‐inflammatory activity and can support cancer cell malignancy. This review describes the discovery, mechanism and biomedical implications of the regulatory interplay between Nrf2 and BET proteins. Both Nrf2 and BET proteins are established drug targets. Small molecules that (...)
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  34. Anthropocene: The philosophy of Biotechnology.Valentin Cheshko, Glazko Valery & Ivanitskaya Lida - 2018 - Moscow, Russia: Kurs INFRA-M.
    The theory of evolution of complex, including the humans system and algorithm for its constructing are a synthesis of evolutionary epistemology, philosophical anthropology and concrete scientific empirical basis in modern science,. In other words, natural philosophy is regaining the status bar element theoretical science in the era of technology-driven evolution. The co-evolutionary concept of 3-modal stable evolutionary strategy of Homo sapiens is developed. The concept based on the principle of evolutionary complementarity of anthropogenesis: value of evolutionary risk and evolutionary path (...)
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  35. Surviving Starvation: AMPK Protects Germ Cell Integrity by Targeting Multiple Epigenetic Effectors.Emilie Demoinet & Richard Roy - 2018 - Bioessays 40 (3):1700095.
    Acute starvation can have long-term consequences that are mediated through epigenetic change. Some of these changes are affected by the activity of AMP-activated protein kinase, a master regulator of cellular energy homeostasis. In Caenorhabditis elegans, the absence of AMPK during a period of starvation in an early larval stage results in developmental defects following their recovery on food, while many of them become sterile. Moreover, the loss of AMPK during this quiescent period results in transgenerational phenotypes that can become progressively (...)
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  36. Human Endogenous Formaldehyde as an Anticancer Metabolite: Its Oxidation Downregulation May Be a Means of Improving Therapy.Yuri L. Dorokhov, Ekaterina V. Sheshukova, Tatiana E. Bialik & Tatiana V. Komarova - 2018 - Bioessays 40 (12):1800136.
    Malignant cells are characterized by an increased content of endogenous formaldehyde formed as a by‐product of biosynthetic processes. Accumulation of formaldehyde in cancer cells is combined with activation of the processes of cellular formaldehyde clearance. These mechanisms include increased ALDH and suppressed ADH5/FDH activity, which oncologists consider poor and favorable prognostic markers, respectively. Here, the sources and regulation of formaldehyde metabolism in cancer cells are reviewed. The authors also analyze the participation of oncoproteins such as fibulins, FGFR1, HER2/neu, FBI‐1, and (...)
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  37. DNA Repair: The Search for Homology.James E. Haber - 2018 - Bioessays 40 (5):1700229.
    The repair of chromosomal double‐strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51‐mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms.
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  38. The Origins of Life: The Managed-Metabolism Hypothesis.John E. Stewart - 2018 - Foundations of Science:1-25.
    The ‘managed-metabolism’ hypothesis suggests that a ‘cooperation barrier’ must be overcome if self-producing chemical organizations are to undergo the transition from non-life to life. This dynamical barrier prevents un-managed autocatalytic networks of molecular species from individuating into complex, cooperative organizations. The barrier arises because molecular species that could otherwise make significant cooperative contributions to the success of an organization will often not be supported within the organization, and because side reactions and other ‘free-riding’ processes will undermine cooperation. As a result, (...)
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  39. Creating Lineage Trajectory Maps Via Integration of Single‐Cell RNA‐Sequencing and Lineage Tracing.Russell B. Fletcher, Diya Das & John Ngai - 2018 - Bioessays 40 (8):1800056.
    Mapping the paths that stem and progenitor cells take en route to differentiate and elucidating the underlying molecular controls are key goals in developmental and stem cell biology. However, with population level analyses it is difficult − if not impossible − to define the transition states and lineage trajectory branch points within complex developmental lineages. Single‐cell RNA‐sequencing analysis can discriminate heterogeneity in a population of cells and even identify rare or transient intermediates. In this review, we propose that using these (...)
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  40. Lipoprotein Transport: Greasing the Machines of Outer Membrane Biogenesis.Marcin Grabowicz - 2018 - Bioessays 40 (4):1700187.
    The Gram-negative outer membrane is a potent permeability barrier against antibiotics, limiting clinical options amid mounting rates of resistance. The Lol transport pathway delivers lipoproteins to the OM. All the OM assembly machines require one or more OM lipoprotein to function, making the Lol pathway central for all aspects of OM biogenesis. The Lol pathways of many medically important species clearly deviate from the Escherichia coli paradigm, perhaps with implications for efforts to develop novel antibiotics. Moreover, recent work reveals the (...)
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  41. We're Stressed Out: BET‐Ting on Oxidative Stress?Steven G. Gray - 2018 - Bioessays 40 (5):1800049.
  42. PROTACs: An Emerging Targeting Technique for Protein Degradation in Drug Discovery.Shanshan Gu, Danrui Cui, Xiaoyu Chen, Xiufang Xiong & Yongchao Zhao - 2018 - Bioessays 40 (4):1700247.
    Proteolysis-targeting chimeric molecules represent an emerging technique that is receiving much attention for therapeutic intervention. The mechanism is based on the inhibition of protein function by hijacking a ubiquitin E3 ligase for protein degradation. The hetero-bifunctional PROTACs contain a ligand for recruiting an E3 ligase, a linker, and another ligand to bind with the protein targeted for degradation. Thus, PROTACs have profound potential to eliminate “undruggable” protein targets, such as transcription factors and non-enzymatic proteins, which are not limited to physiological (...)
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  43. Glycogen at the Crossroad of Stress Resistance, Energy Maintenance, and Pathophysiology of Aging.Ivan Gusarov & Evgeny Nudler - 2018 - Bioessays 40 (9):1800033.
    Glycogen is synthesized and stored to maintain postprandial blood glucose homeostasis and to ensure an uninterrupted energy supply between meals. Although the regulation of glycogen turnover has been well studied, the effects of glycogen on aging and disease development have been largely unexplored. In Caenorhabditis elegans fed a high sugar diet, glycogen potentiates resistance to oxidants, but paradoxically, shortens lifespan. Depletion of glycogen by oxidants or inhibition of glycogen synthesis extends the lifespan of worms by an AMPK‐dependent mechanism. Thus, glycogen (...)
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  44. Transmembrane Signal Transduction in Two-Component Systems: Piston, Scissoring, or Helical Rotation?Ivan Gushchin & Valentin Gordeliy - 2018 - Bioessays 40 (2):1700197.
    Allosteric and transmembrane signaling are among the major questions of structural biology. Here, we review and discuss signal transduction in four-helical TM bundles, focusing on histidine kinases and chemoreceptors found in two-component systems. Previously, piston, scissors, and helical rotation have been proposed as the mechanisms of TM signaling. We discuss theoretically possible conformational changes and examine the available experimental data, including the recent crystallographic structures of nitrate/nitrite sensor histidine kinase NarQ and phototaxis system NpSRII:NpHtrII. We show that TM helices can (...)
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  45. Membrane Transport at an Organelle Interface in the Early Secretory Pathway: Take Your Coat Off and Stay a While.Michael G. Hanna, Jennifer L. Peotter, E. B. Frankel & Anjon Audhya - 2018 - Bioessays 40 (7):1800004.
    Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum‐Golgi intermediate compartment (ERGIC). These membranous vesicular‐tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII‐coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI‐dependent transport on to the cis‐Golgi. The mechanisms underlying formation and (...)
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  46. Epigenetic Modifications of Cytosine: Biophysical Properties, Regulation, and Function in Mammalian DNA.Jack S. Hardwick, Andrew N. Lane & Tom Brown - 2018 - Bioessays 40 (3):1700199.
    To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome – 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine – a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical changes (...)
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  47. Developmental Roles and Evolutionary Significance of AMPA‐Type Glutamate Receptors.Shinobu Hirai, Kohji Hotta & Haruo Okado - 2018 - Bioessays 40 (9):1800028.
    Organogenesis and metamorphosis require the intricate orchestration of multiple types of cellular interactions and signaling pathways. Glutamate (Glu) is an excitatory extracellular signaling molecule in the nervous system, while Ca2+ is a major intracellular signaling molecule. The first Glu receptors to be cloned are Ca2+‐permeable receptors in mammalian brains. Although recent studies have focused on Glu signaling in synaptic mechanisms of the mammalian central nervous system, it is unclear how this signaling functions in development. Our recent article demonstrated that Ca2+‐permeable (...)
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  48. Primary Cilia Reconsidered in the Context of Ciliopathies: Extraciliary and Ciliary Functions of Cilia Proteins Converge on a Polarity theme?Kiet Hua & Russell J. Ferland - 2018 - Bioessays 40 (8):1700132.
    Once dismissed as vestigial organelles, primary cilia have garnered the interest of scientists, given their importance in development/signaling, and for their implication in a new disease category known as ciliopathies. However, many, if not all, “cilia” proteins also have locations/functions outside of the primary cilium. These extraciliary functions can complicate the interpretation of a particular ciliopathy phenotype: it may be a result of defects at the cilium and/or at extraciliary locations, and it could be broadly related to a unifying cellular (...)
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  49. Microtubule Inner Proteins: A Meshwork of Luminal Proteins Stabilizing the Doublet Microtubule.Muneyoshi Ichikawa & Khanh Huy Bui - 2018 - Bioessays 40 (3):1700209.
    Motile eukaryotic cilia and flagella are hair-like organelles responsible for cell motility and mucociliary clearance. Using cryo-electron tomography, it has been shown that the doublet microtubule, the cytoskeleton core of the cilia and flagella, has microtubule inner protein structures binding periodically inside its lumen. More recently, single-particle cryo-electron microscopy analyses of isolated doublet microtubules have shown that microtubule inner proteins form a meshwork inside the doublet microtubule. High-resolution structures revealed new types of interactions between the microtubule inner proteins and the (...)
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  50. Loss and Rebirth of the Animal Microtubule Organizing Center: How Maternal Expression of Centrosomal Proteins Cooperates with the Sperm Centriole in Zygotic Centrosome Reformation.Daigo Inoue, Joachim Wittbrodt & Oliver J. Gruss - 2018 - Bioessays 40 (4):1700135.
    Centrosomes are the main microtubule organizing centers in animal cells. In particular during embryogenesis, they ensure faithful spindle formation and proper cell divisions. As metazoan centrosomes are eliminated during oogenesis, they have to be reassembled upon fertilization. Most metazoans use the sperm centrioles as templates for new centrosome biogenesis while the egg's cytoplasm re-prepares all components for on-going centrosome duplication in rapidly dividing embryonic cells. We discuss our knowledge and the experimental challenges to analyze zygotic centrosome reformation, which requires genetic (...)
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