The emerging field of synthetic biology aims to engineer novel biological entities. The envisioned future bio-based economy builds largely on “cell factories”: organisms that have been metabolically engineered to sustainably produce substances for human ends. In this paper, we argue that synthetic biology’s goal of creating efficient production vessels for industrial applications implies a set of ontological assumptions according to which living organisms are machines. Traditionally, a machine is understood as a technological, isolated and controllable production unit consisting of parts. (...) But modified organisms, or hybrids, require us to think beyond the machine paradigm and its associated dichotomies between artificial and natural, organisms and artefacts. We ask: How may we conceptualise hybrids beyond limiting ontological categories? Our main claim is that the hybrids created by synthetic biology should be considered not as machines but as metabolic systems. We shall show how the philosophical account of metabolism can inform an ontology of hybrids that moves beyond what we call the “machine ontology”, considering that metabolism enables thinking beyond the dominant dichotomies and allows us to understand and design lifeforms in a bio-based economy. Thus, the aim of this paper is twofold: first, to develop the philosophical ontology of hybrids, and second, to move synthetic biology beyond the problematically limiting view of hybrids. (shrink)

The human brain makes up just 2% of body mass but consumes closer to 20% of the body’s energy. Nonetheless, it is significantly more energy-efficient than most modern computers. Although these facts are well-known, models of cognitive capacities rarely account for metabolic factors. In this paper, we argue that metabolic considerations should be integrated into cognitive models. We distinguish two uses of metabolic considerations in modeling. First, metabolic considerations can be used to evaluate models. Evaluative metabolic considerations function as explanatory (...) constraints. Metabolism limits which types of computation are possible in biological brains. Further, it structures and guides the flow of information in neural systems. Second, metabolic considerations can be used to generate new models. They provide: a starting point for inquiry into the relation between brain structure and information processing, a proof-of-concept that metabolic knowledge is relevant to cognitive modeling, and potential explanations of how a particular type of computation is implemented. Evaluative metabolic considerations allow researchers to prune and partition the space of possible models for a given cognitive capacity or neural system, while generative considerations populate that space with new models. Our account suggests cognitive models should be consistent with the brain’s metabolic limits, and modelers should assess how their models fit within these bounds. Our account offers fresh insights into the role of metabolism for cognitive models of mental effort, philosophical views of multiple realization and medium independence, and the comparison of biological and artificial computational systems. (shrink)

Haueis and Colaço's central distinction—between evaluative and generative metabolic considerations—appears less theoretically secure than they suggest. First, the generative examples may ultimately reduce to evaluative reasoning applied earlier in the modeling process. Second, the principal generative examples do not clearly show metabolic considerations functioning within a cognitive model.

Metabolism is a criterion of life. Three senses are distinguished. The weakest allows strong A-Life: virtual creatures having physical existence in computer electronics, but not bodies, are classes as 'alive'. The second excludes strong A-Life but allows that some non-biochemical A-Life robots could be classed as alive. The third, which stresses the body's self-production by energy budgeting and self-equilibrating energy exchanges of some (necessary) complexity, excludes both strong A-Life and living non-biochemical robots.

Haueis and Colaço leave unanswered whether metabolic considerations are merely one neglected type of biological detail that constrains cognitive models, or a distinctive kind uniquely poised to do so. Their examples give little reason to think the latter. If the former, a methodology built around metabolic considerations specifically—rather than neuroscientific facts generally—is unjustified unless embedded within resource-rational analysis.

The definition of metabolic syndrome (MetS) has been, and still is, extremely controversial. My purpose is not to give a solution to the associated debate but to argue that the controversy is at least partially due to the different ‘causal content’ of the various definitions: their theoretical validity and practical utility can be evaluated by reconstructing or making explicit the underlying causal structure. I will therefore propose to distinguish the alternative definitions according to the kinds of causal content they carry: (...) (1) definitions grounded on associations, (2) definitions presupposing a causal model built upon statistical associations, and (3) definitions grounded on underlying mechanisms. I suggest that analysing definitions according to their causal content can be helpful in evaluating alternative definitions of some diseases. I want to show how the controversy over MetS suggests a distinction among three kinds of definitions based on how explicitly they characterise the syndrome in causal terms, and on the type of causality involved. I will call ‘type 1 definitions’ those definitions that are purely associative; ‘type 2 definitions’ the definitions based on statistical associations, plus generic medical and causal knowledge; and ‘type 3 definitions’ the definitions based on (hypotheses about) mechanisms. These kinds of definitions, although different, can be related to each other. A definition with more specific causal content may be useful in the evaluation of definitions characterised by a lower degree of causal specificity. Moreover, the identification of the type of causality involved is of help to constitute a good criterion for choosing among different definitions of a pathological entity. In section (1) I introduce the controversy about MetS, in section (2) I propose some remarks about medical definitions and their ‘causal import’, and in section (3) I suggest that the different attitudes towards the definition of MetS are relevant to evaluate their explicative power. (shrink)

This paper applies concepts of elemental media and metabolisms to the case of cosmic and planetary ecologies that emerge from the interaction between Earth and Sun, manifesting in photosynthesis or carbon isotope chemistry. In doing so, it expands on registers of media theory and environmental studies and prompts the reader to consider the medial and archival affordances of the light-based interactions, and further processes they give rise to. The main aim of the paper is to use these observations to speculate (...) about the human condition in the Anthropocene, characterised by the experience of human mediality. The paper addresses human mediality mainly in the dimension of affective qualities this condition may prompt, and the resulting narrative model of selfhood – the metabolic self. The paper develops its conceptual contribution in close proximity with several artistic examples, especially Eduardo Navarro’s performance In Collaboration with the Sun (2017–2019). The paper is positioned as a contribution to studies of multispecies cohabitation and more-than-human communication, while also developing a narrative strategy for talking about the decentred position of human species in the more-than-human world-making. (shrink)

Cancer cells exhibit reprogrammed metabolic pathways to sustain aggressive phenotypes, including continuous cell division, stemness, invasion, and metastasis. Emerging evidence suggests that these metabolic adaptations profoundly impact DNA repair pathways, which contribute to the responses to therapy and influence overall outcomes. Metabolic processes such as the Warburg effect, nicotinamide adenine dinucleotide (NAD) metabolism, glutamine metabolism, and one‐carbon metabolism support DNA repair by expanding the metabolite pool and facilitating post‐translational modifications. Conversely, oncometabolites impair DNA repair pathways through epigenetic (...) reprogramming, thereby promoting genomic instability. This review highlights recent discoveries that elucidate the intricate connections between metabolic hallmarks in cancer cells and DNA repair mechanisms, offering insights into potential therapeutic targets for future cancer treatments. (shrink)

When an agent can not recognize, immediately, the implausible part of new information received, she will usually first expand her belief state by the new information, and then she may encounter some belief conflicts, and find the implausible information based on her criteria to consolidate her belief state. This process indicates a new kind of non-prioritized multiple revision, called metabolic revision. I give some axiomatic postulates for metabolic revision and propose two functional constructions for it, namely kernel metabolic revision and (...) partial meet metabolic revision, with respect to which the representation theorems are proved. I also compare metabolic revision with some related works in the literature, including semi-revision, merging with integrity constraints, evaluation, and evaluative multiple revision. (shrink)

The prevalence of obesity, metabolic syndrome, and the associated long-term chronic diseases (cardiovascular disease, type II diabetes, cancer, Alzheimer’s disease, depression) have reached epidemic levels in the United States and Western nations. In response to this public health calamity, the author of this paper presents and defends a novel bioethical argument: the consistency argument for outlawing SSBs (sugar-sweetened beverages) for child consumption (the “consistency argument”). This argument’s radical conclusion states that the government is justified in outlawing SSBs consumption for child (...) consumption. The reasoning is as follows: if one accepts that the physical harm caused by chronic alcohol consumption justifies the government outlawing alcoholic beverages for child consumption, and there is strong evidence that comparable physical harms result from chronic SSBs consumption, then, mutatis mutandis, the government is also justified in outlawing child consumption of SSBs. To support this argument, the author provides extensive evidence based on epidemiological observational studies, interventional studies, controlled trials, large meta-analyses, and the pathophysiology and biological mechanisms of action behind SSBs and chronic disease. Chronic consumption of large doses of SSBs and alcoholic beverages both drive the same diseases: obesity and insulin resistance, cardiovascular disease, hypertension, and cancer. Chronic SSB consumption carries the additional risk of Alzheimer’s disease, dementia, and depression. The author concludes this paper by considering prominent objections to the consistency argument, and then demonstrating that each objection is unsound. (shrink)

The reprogramming of metabolism has been identified as one of the hallmarks of cancer. It is becoming more and more frequent to connect other diseases with metabolic reprogramming. This article aims to argue that metabolic reprogramming is not driven by disease but instead is the main hallmark of metabolism, based on its dynamic behavior that allows it to continuously adapt to changes in the internal and external conditions.

Recent advances in research on iron metabolism have revealed the identity of a number of genes, signal transduction pathways, and proteins involved in iron regulation in mammals. The emerging paradigm is a coordination of homeostasis within a network of classical iron metabolic pathways and other cellular processes such as cell differentiation, growth, inflammation, immunity, and a host of physiologic and pathologic conditions. Iron, immunity, and infection are intricately linked and their regulation is fundamental to the survival of mammals. The (...) mutual dependence on iron by the host and invading pathogenic organisms elicits competition for the element during infection. While the host maintains mechanisms to utilize iron for its own metabolism exclusively, pathogenic organisms are armed with a myriad of strategies to circumvent these measures. This review explores iron metabolism in mammalian host, defense mechanisms against pathogenic microbes and the competitive devices of microbes for access to iron. (shrink)

Computational approaches in systems biology have become a powerful tool for understanding the fundamental mechanisms of cellular metabolism and regulation. However, the interplay between the regulatory and the metabolic system is still poorly understood. In particular, there is a need for formal mathematical frameworks that allow analyzing metabolism together with dynamic enzyme resources and regulatory events. Here, we introduce a metabolic-regulatory network model that allows integrating metabolism with transcriptional regulation, macromolecule production and enzyme resources. Using this model, (...) we show that the dynamic interplay between these different cellular processes can be formalized by a hybrid automaton, combining continuous dynamics and discrete control. (shrink)

In larger animals a considerable part of the total body mass (e.g. body water, dissolved substances, mineral and organic deposits) does not consume significant amounts of oxygen. These materials can be considered to form a metabolically inert infrastructure which mainly serves three functions: (1) structural support to the organism, (2) storage of nutrients (building material and energy stores) and (3) transport and distribution of these materials. Considering the transport and support function of the metabolically inert structures and their interconnections it (...) is likely that the infrastructure will basically show some tree-like, branching building plan. The weight of the metabolically inert infrastructure of an organism, can be given by bW/(c+W), in which W=body weight, b and c are constants. With increasing size the weight of the metabolic inert infrastructure increases disproportionably. Experimental data concerning basic metabolic rate (M) in relation to body weight (W) better fit the equation M=a W(1-bW)/(c+W), (a=constant) than the conventional power law. (shrink)

Whipple disease is a rare, infectious, disease first described from a single case by Whipple in 1907. As well as characterising the clinical and pathological features of the condition, Whipple made two suggestions regarding its aetiology. These were either than the disease was caused by an infectious agent, or that it was of metabolic origin. As the disease is now thought to be caused by infection with the bacterium Tropheryma whipplei, historical reviews of the history of the disease typically mention (...) only the first of these suggestions. In this paper, we therefore revisit Whipple’s other theory. We argue that a diverse and often successful research programme was developed around this mechanism of disease causation which gave rise to many useful findings on the condition. In the later parts of this article, we then turn to discuss the surprising neglect of this period of Whipple disease research in the current literature, and conclude by offering a brief reconstruction of this early history suitable for use in a technical context. (shrink)

Various lipid transfer proteins (LTPs) mediate the inter‐organelle transport of lipids. By working at membrane contact zones between donor and acceptor organelles, LTPs achieve rapid and accurate inter‐organelle transfer of lipids. This article will describe the emerging paradigm that the action of LTPs at organelle contact zones generates metabolic channeling events in lipid metabolism, mainly referring to how ceramide synthesized in the endoplasmic reticulum is preferentially metabolized to sphingomyelin in the distal Golgi region, how cholesterol and phospholipids receive specific (...) metabolic reactions in mitochondria, and how the hijacking of host LTPs by intracellular pathogens may generate new channeling‐like events. In addition, the article will discuss how the function of LTPs is regulated, exemplified by a few representative LTP systems, and will briefly touch on experiments that will be necessary to establish the paradigm that LTP‐mediated inter‐organelle transport of lipids is one of the mechanisms of compartmentalization‐based metabolic channeling events. (shrink)

The Fukushima catastrophe has led to important practical and conceptual shifts in contemporary Japanese architecture which in turn has led to a re-evaluation of the influential 1960s Japanese modern architecture movement, Metabolism. The Metabolists had the ambition to create a new Japanese society through techno-utopian city planning. The new generation of Japanese architects, after the Fukushima event, no longer seek evolutionally social change; rather, the disaster has made them re-consider what architecture is and what architects can do for people (...) who had everything snatched from them by technology (nuclear power station) and nature (earthquake and tsunami). Drawing on the architectural projects of Tange Kenzo and Metabolists in the 1960s and Ito Toyo’s ‘Home-for-All project’ in 2011, the paper explores this major paradigm shift in Japanese architectural theory and practices. (shrink)

Lymphangiogenesis is an important developmental process that is critical to regulation of fluid homeostasis, immune surveillance and response as well as pathogenesis of a number of diseases, among them cancer, inflammation, and heart failure. Specification, formation, and maturation of lymphatic blood vessels involves an interplay between a series of events orchestrated by various transcription factors that determine expression of key genes involved in lymphangiogenesis. These are traditionally thought to be under control of several key growth factors including vascular growth factor‐C (...) (VEGF‐C) and fibroblast growth factors (FGFs). Recent insights into VEGF and FGF signaling point to their role in control of endothelial metabolic processes such as glycolysis and fatty acid oxidation that, in turn, play a major role in regulation of lymphangiogenesis. These advances have significantly increased our understanding of lymphatic biology and opened new therapeutic vistas. Here we review our current understanding of metabolic controls in the lymphatic vasculature. (shrink)

Bone‐marrow mesenchymal stem cell (BM‐MSC) proliferation and lineage commitment are under the coordinated control of metabolism and epigenetics; the MSC niche contains low oxygen, which is an important determinant of the cellular metabolic state. In turn, metabolism drives stem cell fate decisions via alterations of the chromatin landscape. Due to the fundamental role of BM‐MSCs in the development of adipose tissue, bones and cartilage, age‐associated changes in metabolism and the epigenome perturb the balance between stem cell proliferation (...) and differentiation leading to stem cell depletion, fat accumulation and bone‐quality related diseases. Therefore, understanding the dynamics of the metabolism‐chromatin interplay is crucial for maintaining the stem cell pool and delaying the development and progression of ageing. This review summarizes the current knowledge on the role of metabolism in stem cell identity and highlights the impact of the metabolic inputs on the epigenome, with regards to stemness and pluripotency. (shrink)

We recently examined gene expression during Xenopus tadpole tail appendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to (...) promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon.Also watch the Video Abstract. (shrink)

The search for a systems‐level picture of metabolism as a web of molecular interactions provides a paradigmatic example of how the methods used to characterize a system can bias the interpretation of its functional meaning. Metabolic maps have been analyzed using novel techniques from network theory, revealing some non‐trivial, functionally relevant properties. These include a small‐world structure and hierarchical modularity. However, as discussed here, some of these properties might actually result from an inappropriate way of defining network interactions. Starting (...) from the so‐called bipartite organization of metabolism, where the two meaningful subsets (reactions and metabolites) are considered, most current works use only one of the subsets by means of so‐called graph projections. Unfortunately, projected graphs often ignore relevant biological and chemical constraints, thus leading to statistical artifacts. Some of these drawbacks and alternative approaches need to be properly addressed. (shrink)

I consider the case of the “simplest” living beings—bacteria—and examine how their embodied activity constitutes an organism/environment interaction, out of which emerges the possibility of learning from an environment. I suggest that this mutual co-emergence of organism and environment implies a panbiotic educational interaction that is at once the condition for, and achievement of, all living beings. Learning and being learned from are entangled in varied ways throughout the biosphere. Education is not an exclusively human project, it is part of (...) the ancient evolutionary process of elaborating and diversifying the relational possibilities inherent in metabolism that has brought forth our diverse and flourishing world.ed from context, “education” appears as a set of ways in which humans actively engage and take responsibility for the learning outcomes of relationships with each other. Insofar as we consider this distinction absolute rather than a performed construct to be assessed by its consequences, we blind ourselves to the educative dimension of other species as well as our many miseducative engagements with them. If learning processes are inherent and constitutive of ecological communities, education theorists should devote their pedagogical sensitivities and insights to the crucial challenge of developing educative sustainable human–nature relations. (shrink)

The point of departure of this article is the trend towards hybridisation in new technology development, which makes classical dichotomies between machines, human life and the environment obsolete and leads to the post-human world we live in today. We critically reflect on the post-human concept of the hybrid world. Although we agree with post-humanists that human life can no longer be opposed to machines but appears as a decentralized human-technology relation, alliance or network that constitutes a hybrid world, we ask (...) for a limit to hybridisation. After rejecting the concept of metabolism as such a limit, we explore the concept of the responsive conativity of material entities. The principle of conativity of material entities provides a materialist perspective on metabolism, which enables us to conceive material entities as self-assertive material entities that are differentiated from the environment. The principle of responsivity of material entities provides a materialist perspective on the post-human world in which material entities are responsive to each other and form alliances and networks. We propose to differentiate between the conativity and responsivity of material entities and propose the conativity of matter as a limit to hybridisation in the post-human world. (shrink)

In this paper I explore how the limitations of sociological and economic approaches to the gift can be exposed not only through deconstructive analysis, such as Jacques Derrida pursues in Given Time, vols. I & II, but also through the philological resources and biological conceptuality of ‘metabolism’. By bridging Derrida’s textual conception of survival with neurobiological and phenomenological approaches to life, I argue that what ‘gift’ names is nothing distinctly human but, rather, a possibility at the origin of any (...) economization of differences, be they ‘textual’ or ‘biological’ in nature. (shrink)

In the flowering of Red-Green Thought over the past two decades, metabolic rift thinking is surely one of its most colorful varieties. The metabolic rift has captured the imagination of critical environmental scholars, becoming a shorthand for capitalism’s troubled relations in the web of life. This article pursues an entwined critique and reconstruction: of metabolic rift thinking and the possibilities for a post-Cartesian perspective on historical change, the world-ecology conversation. Far from dismissing metabolic rift thinking, my intention is to affirm (...) its dialectical core. At stake is not merely the mode of explanation within environmental sociology. The impasse of metabolic rift thinking is suggestive of wider problems across the environmental social sciences, now confronted by a double challenge. One of course is the widespread—and reasonable—sense of urgency to evolve modes of thought appropriate to an era of deepening biospheric instability. The second is the widely recognized—but inadequately internalized—understanding that humans are part of nature. (shrink)

Metabolism of propionate in human subjects was studied using bolus administration of l- 13 C-propionate i.v. or orally. The study population consisted of five patients with propionic acidemia, eight with methylmalonic acidemia, one each with multiple carboxylase deficiency and transcobalamin-II deficiency, and five healthy volunteers. Concentrations of l- 13 C-propionate were measured in blood in three patients with PA, two with MMA, and two controls. Breath samples were obtained at intervals during 3 h after the dose, isotopic enrichment of (...) 13 C0 2 was measured, and the cumulative percentage of recovery of 13 C was calculated from the individual’s predicted resting energy expenditure. Recovery of 13 C0 2 and half-time of l- 13 C-propionate in PA were significantly less than normal. The same parameters in MMA were below normal, but significantly greater than in PA. Recovery of 13 C0 2 was well correlated with clinical severity in PA, but did not correlate in MMA. Differences between MMA and PA may indicate different distribution of propionate pools, differences in inducibility of residual enzyme activities, or an alternate pathway for decarboxylation of propionate available in MMA but not PA. Only one patient with PA demonstrated increased 13 C0 2 production during biotin treatment. In a B 12 -responsive MMA patient, no differences were noted within 2 d of initiating treatment with B 12, but there was an increase in 13 C0 2 production after 4 mo. Recovery of 13 C0 2 was normal in the patient with transcobalamin-II deficiency before and after treatment with vitamin B 12. In the patient with multiple carboxylase deficiency, 13 C0 2 generation was nearly normal while he was receiving his maintenance dose of biotin, and was not significantly changed after 3 and 7 d without biotin treatment, despite a decrease of 30% in lymphocyte propionyl-CoA carboxylase activity. © 1991 International Pediatric Research Foundation, Inc. (shrink)

Metabolic systems are complicated and contain very large numbers of interacting reactions and many internal regulatory mechanisms. This does not prevent the genetic composition of an organism from influencing its behavior, however, nor does it preclude the possibility that some aspects of its behavior may be amenable to simple explanations.

We propose a discrete, stage-dependent model for metabolic scaling grounded in approximately geometric growth across successive developmental steps, using Fibonacci recursion as an archetype. In contrast to continuous fractal models such as the West-Brown-Enquist (WBE) theory, our framework treats metabolism as the cumulative activity of structures formed in prior stages. The scaling exponent b(n) emerges from a logarithmic relation between consecutive stages and varies with the growth stage n. A refined logarithmic expression improves descriptive agreement with empirical mammalian data (...) relative to the WBE baseline. Across nine species, model-based b(n) values are on average closer (mean deviation $$<\!9\%$$, with improvements up to $$\sim \!12\%$$ ) to intraspecific estimates. The stage index n is inferred deterministically as $$n=\log _{\phi }(M(n)/M_0)$$, where $$\phi =(1+\sqrt{5})/2$$ is the golden ratio, from reported birth mass $$M_0$$ and mass at stage n, M(n). The model is intended for moderate developmental stages under basal conditions and complements classical 2/3 and 3/4 baselines by capturing systematic, stage-specific departures from a single constant exponent. This discrete perspective clarifies when and why deviations from classical allometries arise and offers a compact mechanism linking recursive growth to metabolic scaling. (shrink)

The point of departure of this article is the trend towards hybridisation in new technology development, which makes classical dichotomies between machines, human life and the environment obsolete and leads to the post-human world we live in today. We critically reflect on the post-human concept of the hybrid world. Although we agree with post-humanists that human life can no longer be opposed to machines but appears as a decentralized human-technology relation, alliance or network that constitutes a hybrid world, we ask (...) for a limit to hybridisation. After rejecting the concept of metabolism as such a limit, we explore the concept of the responsive conativity of material entities. The principle of conativity of material entities provides a materialist perspective on metabolism, which enables us to conceive material entities as self-assertive material entities that are differentiated from the environment. The principle of responsivity of material entities provides a materialist perspective on the post-human world in which material entities are responsive to each other and form alliances and networks. We propose to differentiate between the conativity and responsivity of material entities and propose the conativity of matter as a limit to hybridisation in the post-human world. (shrink)

Bacterial conjugation, wherein DNA is transferred between cells through direct contact, is highly prevalent in complex microbial communities and is responsible for spreading myriad genes related to human and environmental health. Despite their importance, much remains unknown regarding the mechanisms driving the spread and persistence of these plasmids in situ. Studies have demonstrated that transferring, acquiring, and maintaining a plasmid imposes a significant metabolic burden on the host. Simultaneously, emerging evidence suggests that the presence of a conjugative plasmid can also (...) provide both obvious and unexpected benefits to their host and local community. Combined, this highlights a continuous cost‐benefit tradeoff at the population level, likely contributing to overall plasmid abundance and long‐term persistence. Yet, while the metabolic burdens of plasmid conjugation, and their causes, are widely studied, their attendant potential advantages are less clear. Here, we summarize current perspectives on conjugative plasmids’ metabolic burden and then highlight the lesser‐appreciated yet critical benefits that plasmid‐mediated metabolic burdens may provide. We argue that this largely unexplored tradeoff is critical to both a fundamental theory of microbial populations and engineering applications and therefore warrants further detailed study. (shrink)

ABSTRACT16p11.2 deletion syndrome is a severe genetic disorder associated with the deletion of 27 genes from a Copy Number Variant region on human chromosome 16. Symptoms associated include cognitive impairment, language and motor delay, epilepsy or seizures, psychiatric disorders, autism spectrum disorder (ASD), changes in head size and body weight, and dysmorphic features, with a crucial need to define genes and mechanisms responsible for symptomatology. In this review, we analyze the clinical associations and biological pathways of 16p11.2 locus genes and (...) identify that a majority of 16p11.2 genes relate to metabolic processes. We present a hypothesis in which changes in the dosage of 16p11.2 metabolic genes contribute to pathology through direct or indirect alterations in pathways that include amino acids or proteins, DNA, RNA, catabolism, lipid, energy (carbohydrate). This hypothesis suggests that research into the specific roles of each metabolic gene will help identify useful therapeutic targets. (shrink)

Understanding terrestrial carbon metabolism is critical because terrestrial ecosystems play a major role in the global carbon cycle. Furthermore, humans have severely disrupted the carbon cycle in ways that will alter the climate system and directly affect terrestrial metabolism. Changes in terrestrial metabolism may well be as important an indicator of global change as the changing temperature signal. Improving our understanding of the carbon cycle at various spatial and temporal scales will require the integration of multiple, complementary (...) and independent methods that are used by different research communities. Tools such as air sampling networks, inverse numerical methods, and satellite data allow us to study the strength and location of the global- and continental-scale carbon sources and sinks. Bottom-up studies provide estimates of carbon fluxes at finer spatial scales and examine the mechanisms that control fluxes at the ecosystem, landscape, and regional scales. Bottom-up approaches include comparative and process studies that provide the necessary mechanistic information to develop and validate terrestrial biospheric models. An iteration and reiteration of top-down and bottom-up approaches will be necessary to help constrain measurements at various scales. We propose a major international effort to coordinate and lead research programs of global scope of the carbon cycle. (shrink)

More-than-human metabolic processes increasingly constitute the locus of contemporary biopower, often responding to industrially-altered biogeochemical cycles. We conceptualise ‘metabolo-politics’ to examine the targeting of bodies and populations via interventions in the biochemical surroundings and ecologies that shape them; and simultaneously, the administration and modulation of materials in the environment via interventions in the bodies and populations that ingest, digest, and excrete them. Focusing on the governance of environmental crises related to carbon and nitrogen pollution, particularly in livestock sectors in the (...) Global North, we offer three analytics for theorising metabolo-politics as a form of governance oscillating between bio-politics and anatomo-politics. They are: the dispositive, which grapples with the relations of matter and discourse that shape emergent problematisations of metabolism; the milieu, which is the more-than-human scene of intervention; and technologies, which are the diverse means through which power is operationalised metabolically and through which bodies, populations, and environments are governed. (shrink)

This paper examines the historical split of microbiology into the fields of medicine and ecology from a feminist perspective, using Helen Longino’s contextual empiricism and her onto-epistemic view of interactions. Examining microbial interactions is interesting for two reasons, one is ontological as microbial metabolic interactions constitute the bio-geo-chemical cycles that are the driving force of life on Earth. The second reason is epistemic, involving our conceptual challenges in understanding microbial traits and classification, as their activities and ability to evolve are, (...) for the most part, driven by their interactions. I follow the work and methodology of Sergei Vinogradskii (1856–1953) and Robert Koch (1843–1910), as two main founders each of a different microbiology field. Koch focused on medicine, developing pure mass cultures and the Koch postulates. Vinogradskii focused on soil microbiology and ecosystem ecology, developing the elective culture technique, and is known for the Winogradsky Column. I use contextual empiricism to discuss their methodological differences in classification and cultivation and reflect on their position regarding microbial individuality and interactions. For instance, Vinogradskii’s research focused on metabolic interactions and microbial life cycles, considering individual microbes as part of their environment and never in isolation. This view emphasizes the individual, the interactions, and the environment as equally focal in causal explanations. Thus, in his view, the individual should be studied as part of its milieu and never in isolation. Based on Longino’s ontology of interactions, I elaborate on this view of the microbial individual in a given state of interdependence with changing levels of autonomy. This onto-epistemic understanding of the microbial phenomena is empirically consistent with today’s microbiome studies and discussions on host-holobiont definitions in microbiology, ecology, and medicine. (shrink)

I discuss the bearing on the mind-body problem of some general characteristics of living systems, including the physical basis of metabolism and the relation between living activity and cognitive capacities in simple organisms. I then attempt to describe stages in the history of animal life important to the evolution of subjective experience. Features of the biological basis of cognition are used to criticize arguments against materialism that draw on the conceivability of a separation between mental and physical. I also (...) argue against commonly held views about the "multiple realizability" of mental states of the kind seen in humans. The aim of the paper is to reconfigure and narrow the "explanatory gap" between mental and physical. (shrink)

Kohei Saito is an eco-Marxist thinker who mobilizes the concept of metabolism to propose an alternative socio-economic trajectory for the Anthropocene. However, a systematic study of his conception of metabolism is lacking. To address this gap, I apply a framework of critical concept analysis to his major works. The analysis identifies three conceptual strata in Saito’s metabolism concept: criticism of the modern lifestyle, structural elaboration of the capitalist accumulation–alienation–externalization paradigm, and material description of the metabolic rift. These (...) strata cohere with the problems of overcoming the Anthropocene and recovering Marx, but the fundamental question traversing Saito’s metabolism is normative: How ought the non-capitalist society organize its metabolism and habits? Rejecting social constructivism and speculative philosophy, Saito posits an original unity between humanity and nature that degrowth communism must recover from capitalist deviation. I argue that the presupposition of natural law underpinning this normative position requires further critical reflection. (shrink)

During the transition to calving, dairy ruminants undergo physiological changes affecting several metabolic functions, including feeding behavior, nutrient flux and redistribution, hormonal patterns, and immune responses. Failure in those adaptations often induces a physiological imbalance condition, predisposing animals to developing several metabolic and infectious disorders at the onset of lactation.The immune system exerts a pivotal role in allowing a proper adaptation of dairy ruminants to the transition period, as immune dysfunctions and chronic inflammatory conditions contribute to increasing the development of (...) physiological imbalance condition. Several managerial practices could be adopted to improve dairy ruminants’ adaptation to the transition period through improving the immune system function and mainly mitigating the inflammatory conditions. This chapter is aimed at (1) exploring physiological adaptations affecting metabolic functions of dairy ruminants while approaching calving, (2) understanding metabolic processes that are more likely affected by a physiological imbalance condition, (3) highlighting the role of the immune system in affecting a successful adaptation to the transition period, and (4) listing possible intervention aimed at improving such adaptation, mainly through modulating inflammation. (shrink)

Here, we analyze how the set of nucleotides in the cell is equilibrated and how this generates simple rules that help the cell to organize itself via maintenance of a stable non‐equilibrium state. A major mechanism operating to achieve this state is thermodynamic buffering via high activities of equilibrating enzymes such as adenylate kinase. Under stable non‐equilibrium, the ratios of free and Mg‐bound adenylates, Mg2+ and membrane potentials are interdependent and can be computed. The adenylate status is balanced with the (...) levels of reduced and oxidized pyridine nucleotides through regulated uncoupling of the pyridine nucleotide pool from ATP production in mitochondria, and through oxidation of substrates non‐coupled to NAD+ reduction in peroxisomes. The set of adenylates and pyridine nucleotides constitutes a generalized cell energy status and determines rates of major metabolic fluxes. As the result, fluxes of energy and information become organized spatially and temporally, providing conditions for self‐maintenance of metabolism. (shrink)

Stewart and Korol (“De-Signing Fat,” International Journal of Applied Philosophy 23.2 [2009]) contend that obesity is benign. In support of their position they have focussed on selected papers that do not take into consideration key realities. Their attempt to minimise the impact of obesity appears to centre on how difficult it can be to lose weight by diet alone (and its risks) and problems with measurements of obesity, while failing to acknowledge the specific and well-documented impact of deleterious biochemical alterations (...) arising from central obesity. Stewart and Korol also do not point out the considerable controversy with the fat but fit (metabolically healthy obesity [MHO]) concept. Whether looping from above or below, nothing changes the biochemical realities of central obesity. Above all, Stewart and Korol never once mention the benefits of obesity prevention, rather focussing on the difficulties of losing weight. Thus, respectfully, a word of caution is put forward on the views of Stewart and Korol regarding obesity. (shrink)

Many kinds of multifunctional regulatory proteins have been identified that perform distinct biochemical functions in the nucleus, the cytoplasm, or both. Here we describe the recent discovery by Hall et al. (2004)1 of a new type of multifunctional protein: a metabolic enzyme that doubles as a transcription factor. This enzyme, Arg5,6, functions as a catalytic enzyme in ornithine biosynthesis and also binds and regulates the promoters of nuclear and mitochondrial genes. It may also regulate precursor mRNA metabolism. We discuss (...) how proteins that serve as both metabolic enzymes and transcription factors might have evolved. BioEssays 27:467–471, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Reproduction places severe demands on the energy metabolism in human females. When physical work entails higher energy expenditure, not enough energy will be left for the support of the reproductive processes and temporal suppression of the reproductive function is expected. While energy needed for reproduction may be obtained by increases in energy intake, utilization of fat reserves, or reallocation of energy from basal metabolism, several environmental or physiological constraints render such solutions unlikely. For human ancestors increases in energy (...) intake were limited by availability of food, by labor of food preparation and by metabolic ceilings to energy assimilation. Energy stored as fat may support only a fraction of the requirements for reproduction (especially lactation). Effects of intense physical activity on basal metabolism may also interfere with fat accumulation during pregnancy. Finally, the female physiology may experience demands on increasing the basal metabolism as a consequence of physical activity and, at the same time, on decreasing the basal metabolism, when energy to support the ongoing pregnancy or lactation is inadequate. The resulting metabolic dilemmas could constitute a plausible cause for the occurrence of reproductive suppression in response to physical activity. It is, therefore, likely that allocating enough energy to the reproductive processes during periods when energy expenditure rises may be difficult due to physiological and bioenergetic constraints. Females attempting pregnancy in such conditions may compromise their lifetime reproductive output. A reproductive suppression occurring in low energy availability situations may thus represent an adaptive rather then a pathological response. (shrink)

A variety of herbicides act by inhibiting the branched chain amino‐acid biosynthetic enzyme, acetolactate synthase (EC 4.1.3.18). The initial consequences of this event are 2‐ketoacid accumulation and amino‐acid starvation. Recent studies demonstrate that 2‐ketoacid imbalances play a significant role in the action of these herbicides; such imbalances may also be important in certain inborn errors of human metabolism.

Hematopoiesis unfolds within the bone marrow niche where hematopoietic stem cells (HSCs) play a central role in continually replenishing blood cells. The hypoxic bone marrow environment imparts peculiar metabolic characteristics to hematopoietic processes. Here, we discuss the internal metabolism of HSCs and describe external influences exerted on HSC metabolism by the bone marrow niche environment. Importantly, we suggest that the metabolic environment and metabolic cues are intertwined with HSC cell fate, and are crucial for hematopoietic processes. Metabolic dysregulation (...) within the bone marrow niche during acute stress, inflammation, and chronic inflammatory conditions can lead to reduced HSC vitality. Additionally, we raise questions regarding metabolic stresses imposed on HSCs during implementation of stem cell protocols such as allo‐SCT and gene therapy, and the potential ramifications. Enhancing our comprehension of metabolic influences on HSCs will expand our understanding of pathophysiology in the bone marrow and improve the application of stem cell therapies. (shrink)

Substrate cycles are ubiquitous structures of the cellular metabolism (e.g. Krebs cycle, fatty acids -oxydation cycles, etc... ). Moiety-conserved cycles (e.g. adenine nucleotides and NADH/NAD, etc...) are also important.The role played by such cycles in the metabolism and its regulation is not clearly understood so far. However, it was shown that these cycles can generate multistationarity (bistability), irreversible transitions, enhancement of sensitivity, temporal oscillations and chaotic motions (Hervagault & Canu, 1987; Hervagault & Cimino, 1989; Reich & Sel'kov, 1981; (...) Ricard & Soulié, 1982). Fig. 1: Scheme of the open binary substrate cycle under study. The substrate S is converted into P with a net rate v2. Substrate P is converted in turn into S with a net rate v3. Step v2 is inhibited by excess of the substrate, S. In addition, the cycle operates under open conditions, that is zero-order input of S at rates \ga0(v1) and first order outputs of S and P at rates \gaS and \gaP(v4), respectively. (shrink)

The goal of synthetic biology is to create artificial organisms. To achieve this it is essential to understand what life is. Metabolism-replacement systems, or (M, R)-systems, constitute a theory of life developed by Robert Rosen, characterized in the statement that organisms are closed to efficient causation, which means that they must themselves produce all the catalysts they need. This theory overlaps in part with other current theories, including autopoiesis, the chemoton, and autocatalytic sets, all of them invoking some idea (...) of closure. A simple model of an (M, R)-system has been implemented in the computer, and behaves in ways that may shed light on the requirements for a prebiotic self-organizing system. In addition to a trivial steady state in which nothing happens, it can establish a non-trivial steady state in which all intermediates have finite concentrations, with their rates of degradation balanced by their rates of synthesis. The system can be regenerated from the set of food components plus a single intermediate, and maintain itself in that state indefinitely, despite continuous degradation. At the very low compartment volumes that may have existed in prebiotic conditions, for example in cavities in minerals, or in micelles formed by simple amphiphiles, statistical fluctuations in the numbers of molecules need to be taken into account. With the stochastic approach there is no non-trivial steady state in strict mathematical terms, because the system will always collapse to the trivial state after sufficient time. However, the average time before collapse is so long for volumes greater than $10^{-19}\;{\textsc{l}}$ (much smaller than the volume of the order of $10^{-15}\;{\textsc{l}}$ for a typical bacterial cell) that for practical purposes the self-maintaining state of non-null concentrations becomes significant, recalling the situation of bistability that is observed in deterministic analysis. In turn, there exists a minimum size below which the self-organizing system cannot maintain itself on chemically relevant time scales. The value of the critical volume depends on the particular concentrations and rate constants assumed, but the principle could apply generally. (shrink)

This article explores the metabolic lives of whey powder, the most popular form of protein supplement in what has become a multibillion-dollar industry during the past two decades. Faced with the slippery and elusive properties latent to this multiplicitous substance, our approach is to follow whey powder from its mid-20th century emergence as a noxious byproduct of industrial dairy production, through the human and animal bodies unevenly tasked with its processing, and out into waterways, where its nitrogen density rematerializes as (...) a pollutant. We show how whey powder emerged as a solution to the environmental damage posed by whey pollution, how such damage is an effect of the systematic overproduction endemic to agrofood industries and how whey’s toxicity persists through processes of metabolism and consumption, despite attempts to process and profit from its vital capacities. Throughout, we argue that whey exemplifies ecological embodiment, understood as the co-constitutive relations between bodily matter and ecological life, and their entanglement with processes of commodification. (shrink)

In this article, we propose some fundamental requirements for the appearance of adaptivity. We argue that a basic metabolic organization, taken in its minimal sense, may provide the conceptual framework for naturalizing the origin of teleology and normative functionality as it appears in living systems. However, adaptivity also requires the emergence of a regulatory subsystem, which implies a certain form of dynamic decoupling within a globally integrated, autonomous system. Thus, we analyze several forms of minimal adaptivity, including the special case (...) of motility. We go on to explain how an open-ended complexity growth of motility-based adaptive agency, namely, behavior, requires the appearance of the nervous system. Finally, we discuss some implications of these ideas for embodied robotics. (shrink)