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)

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.

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)

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)

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)

The systems view on life and its emergence from complex chemistry has remarkably increased the scientific attention on metabolism in the last two decades. However, during this time there has not been much theoretical discussion on what constitutes a metabolism and what role it actually played in biogenesis. A critical and updated review on the topic is here offered, including some references to classical models from last century, but focusing more on current and future research. Metabolism is (...) considered as intrinsically related to the living but not necessarily equivalent to it. More precisely, the idea of “minimal metabolism”, in contrast to previous, top‐down conceptions, is formulated as a heuristic construct, halfway between chemistry and biology. Thus, rather than providing a complete or final characterization of metabolism, our aim is to encourage further investigations on it, particularly in the context of life's origin, for which some concrete methodological suggestions are provided. Also see the video abstract here:https://youtu.be/DP7VMKk2qpA. (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)

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)

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)

The gut microbiota is an important component of the human body and its immune‐modulating and metabolic activities are critical to maintain good health. Gut microbes, however, are sensitive to changes in diet, exposure to antibiotics, or infections, all of which cause transient disruptions in the microbial composition, a phenomenon known as dysbiosis. It is now recognized that microbial dysbiosis is at the root of many gastrointestinal disorders. However, the mechanisms through which bacterial dysbiosis initiates disease are not fully understood. Microbially‐derived (...) metabolites and their role in disease have also attracted significant attention. Identification of cancer‐associated bacteria and understanding the contributions of microbial metabolism in health and disease are exciting but challenging areas that will allow defining microbial biomarkers for predicting gastrointestinal disorders. Understanding the complex interactions between gut microbiota, diet, host immune system and host genetics will be critical to developing more personalized therapies and approaches to treat disease. (shrink)

At Discorsi II.20, Machiavelli defines auxiliary arms as those, “whom a prince or a republic send captained and already paid for, for your aid.” My contention is that Machiavelli’s treatment of auxiliary arms is much more nuanced than it may seem at first glance. Throughout his works, Machiavelli articulates this type of force from the standpoint of the prince but also, surprisingly, from the standpoint of the people. In their princely employment, auxiliary arms act instrumentally as means for the projection (...) of power. However, analyzed from the standpoint of the people, auxiliary force exposes the projects of the state to the radically aleatory. Acknowledging the aspectival function played by the definition of auxiliaries in Machiavelli’s texts offers a new vantage point for re-reading Machiavelli on the nature of authority, power and the conflict of the umori. (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)

We provide a mathematical study of a model of energy metabolism and hemodynamics of glioma allowing a better understanding of metabolic modifications leading to anaplastic transformation from low grade glioma.This mathematical analysis allows ultimately to unveil the solution to a viability problem which seems quite pertinent for applications to medecine.

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)

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)

Metabolomics, including lipidomics, is emerging as a quantitative biology approach for the assessment of energy flow through metabolism and information flow through metabolic signaling; thus, providing novel insights into metabolism and its regulation, in health, healthy ageing and disease. In this forward‐looking review we provide an overview on the origins of metabolomics, on its role in this postgenomic era of biochemistry and its application to investigate metabolite role and (bio)activity, from model systems to human population studies. We present (...) the challenges inherent to this analytical science, and approaches and modes of analysis that are used to resolve, characterize and measure the infinite chemical diversity contained in the metabolome (including lipidome) of complex biological matrices. In the current outbreak of metabolic diseases such as cardiometabolic disorders, cancer and neurodegenerative diseases, metabolomics appears to be ideally situated for the investigation of disease pathophysiology from a metabolite perspective. (shrink)

T cells develop in the thymus by expressing a diverse repertoire of either αβ‐ or γδ‐T cell receptors (TCR). While many studies have elucidated how TCR signaling and gene expression control T cell ontogeny, the role of nutrient metabolism is just emerging. Here, we discuss how metabolic reprogramming and nutrient availability impact the fate of developing thymic T cells. We focus on how the PI3K/mTOR signaling mediates various extracellular inputs and how this signaling pathway controls metabolic rewiring during highly (...) proliferative and anabolic developmental stages. We highlight the role of the hexosamine biosynthetic pathway that generates metabolites that are utilized for N‐ and O‐linked glycosylation of proteins and how it impacts TCR expression during T cell ontogeny. We consider the dichotomy in metabolic needs during αβ‐ versus γδ‐T cell lineage commitment as well as how metabolism is also coupled to molecular signaling that controls cell fate. (shrink)

This article views capitalism not only as a mode of production, but also as a mediation of the reproduction of life, following the concept of ‘social metabolism’ that Marx employs to analyze the interaction between the individuals composing a society and their natural environment. Insofar as the ‘value-form’ is the distinctive social relation of capitalism, it appears necessary to ask whether the metabolic process of reproduction can be fully subsumed under this form. Marx takes for granted the idea that (...) the reproduction of labor-power consists only in the consumption of commodities resulting from abstract labor, thus omitting the appropriation of unpaid domestic work, mostly performed by women. Feminist criticism clarifies how capitalism always depends on some reproductive work being appropriated for the accumulation of surplus-value without being integrated in the value-form. Following Jason W. Moore, I attempt to indicate that the same logic is at work for the reproduction... (shrink)

The hypothalamus is a specialized area in the brain that integrates the control of energy homeostasis. More than 70 years ago, it was proposed that the central nervous system sensed circulating levels of metabolites such as glucose, lipids and amino acids and modified feeding according to the levels of those molecules. This led to the formulation of the Glucostatic, Lipostatic and Aminostatic Hypotheses. It has taken almost that much time to demonstrate that circulating long‐chain fatty acids act as signals of (...) nutrient surplus in the hypothalamus. Moreover, pharmacological and/or genetic inhibition of fatty acid synthase, AMP‐activated protein kinase and carnitine palmitoyltransferase 1 results in profound decrease in feeding and body weight in rodents. The molecular mechanism behind these actions depends on changes in the cellular pool of malonyl‐CoA and fatty acyl‐CoAs. Current evidence also suggests that this pathway may play a major role in the physiological regulation of feeding, by integrating hormonal and nutrient‐derived signals in the hypothalamus. Here, we summarize what is known about hypothalamic fatty acid metabolism and feeding control and provide future directions for research. Understanding these molecular mechanisms could provide new targets for the treatment of obesity and related disorders. BioEssays 29: 248–261, 2007. © 2007 Wiley Periodicals, Inc. (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)

We address three fundamental questions: What does it mean for an entity to be living? What is the role of inter-organismic collaboration in evolution? What is a biological individual? Our central argument is that life arises when lineage-forming entities collaborate in metabolism. By conceiving of metabolism as a collaborative process performed by functional wholes, which are associations of a variety of lineage-forming entities, we avoid the standard tension between reproduction and metabolism in discussions of life – a (...) tension particularly evident in discussions of whether viruses are alive. Our perspective assumes no sharp distinction between life and non-life, and does not equate life exclusively with cellular or organismal status. We reach this conclusion through an analysis of the capabilities of a spectrum of biological entities, in which we include the pivotal case of viruses as well as prions, plasmids, organelles, intracellular and extracellular symbionts, unicellular and multicellular life-forms. The usual criterion for classifying many of the entities of our continuum as non-living is autonomy. This emphasis on autonomy is problematic, however, because even paradigmatic biological individuals, such as large animals, are dependent on symbiotic associations with many other organisms. These composite individuals constitute the metabolic wholes on which selection acts. Finally, our account treats cooperation and competition not as polar opposites but as points on a continuum of collaboration. We suggest that competitive relations are a transitional state, with multi-lineage metabolic wholes eventually outcompeting selfish competitors, and that this process sometimes leads to the emergence of new types or levels of wholes. Our view of life as a continuum of variably structured collaborative systems leaves open the possibility that a variety of forms of organized matter – from chemical systems to ecosystems – might be usefully understood as living entities. (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)

Over the past several years, discoveries from mouse genetics have had direct impact on our understanding of vitamin A metabolism. Although the metabolism of vitamin A in the mouse does have some special features (for example very large stores of liver and pulmonary retinyl esters), the ability to construct knockout and transgenic mouse models has yielded an impressive amount of information directly relevant to understanding the general principles of vitamin A transport, storage and degradation. We discuss below the (...) metabolism of vitamin A through a number of genetically engineered mouse strains with alterations in genes that affect this metabolism. The novelty of this experimental approach is evidenced by the fact that the oldest of these strains was first reported only eight years ago.1) BioEssays 23:409–419, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

In this paper, we aim at rethinking the concept of obesity in a way that better captures the connection between underlying medical aspects, on the one hand, and an individual’s developmental history, on the other. Our proposal rests on the idea that obesity is not to be understood as a phenotypic trait or character; rather, obesity represents one of the many possible states of a more complex phenotypic trait that we call ‘energy metabolism.’ We argue that this apparently simple (...) conceptual shift can help solve important theoretical misconceptions regarding the genetics, epigenetics, and development of obesity. In addition, we show that our proposal can be fruitfully paired with the concept of developmental channeling of a trait, which connects to the study of the plasticity and canalization of complex traits. Finally, we discuss the potential impact of our approach on the assessment, treatment, and social narratives of obesity. (shrink)

Intermediary metabolism molecules are orchestrated into logical pathways stemming from history (L-amino acids, D-sugars) and dynamic constraints (hydrolysis of pyrophosphate or amide groups is the driving force of anabolism). Beside essential metabolites, numerous variants derive from programmed or accidental changes. Broken down, variants enter standard pathways, producing further variants. Macromolecule modification alters enzyme reactions specificity. Metabolism conform thermodynamic laws, precluding strict accuracy. Hence, for each regular pathway, a wealth of variants inputs and produces metabolites that are similar to (...) but not the exact replicas of core metabolites. As corollary, a shadow, paralogous metabolism, is associated to standard metabolism. We focus on a logic of paralogous metabolism based on diversion of the core metabolic mimics into pathways where they are modified to minimize their input in the core pathways where they create havoc. We propose that a significant proportion of paralogues of well-characterized enzymes have evolved as the natural way to cope with paralogous metabolites. A second type of denouement uses a process where protecting/deprotecting unwanted metabolites - conceptually similar to the procedure used in the laboratory of an organic chemist - is used to enter a completely new catabolic pathway. (shrink)

K L Kahlbaum published in 1874 the first recorded description of catatonia. Akinetic catatonia is now defined as a neuropsychiatric syndrome principally characterised by akinesia, mutism, stupor, and catalepsy. 1 Even if some advances have been made in the recognition of catatonia, in particular by the development of different rating scales, 1 the pathophysiology of this syndrome is not clearly established. A right handed 14 year old girl presented with akinetic catatonia during an episode of depression in the context of (...) a bipolar type I disorder. Her catatonic status was characterised by akinesia with brief episodic spontaneous stereotyped movements, mutism, no spontaneous oral intake, catalepsy, waxy flexibility, and stupor with brief occasional eye contacts. This corresponded to a total score of 19 on the Northoff Catatonia Scale.1 Electroencephalogram performed one day after onset of symptoms showed diffuse theta activity with sporadic diffuse delta activity. Cerebral magnetic resonance imaging was normal. Brain positron emission tomographies (PET) were obtained on a CTI-Siemens HR+ tomograph. A first PET (PET1) using (18F(- fluorodeoxyglucose (FDG) was performed on day 2 in a drug free state. Thereafter, intramuscular injection of 2 mg of lorazepam induced rapid clinical remission of the akinetic phase. Oral lorazepam was then given (3.75 mg/day) during five days. On day 8, a second PET with FDG was performed while the patient was treated by olanzapine (15 mg/day) and presented hyperactivity, logorrhoea, and disinhibition characterised by uncontrolled social interactions and physical contacts. Neuropsychological testing performed some days after remission revealed no apraxia or language disturbances but dysfunction of executive tasks manifested in the revised Wisconsin card sorting, the Tower of London, Stroop, and Trailmaking tests. Voxel based analyses comparing patient’s cerebral glucose metabolism with that of 29 right handed healthy controls (16 women and 13 men, mean age 32) were performed using Statistical Parametric Mapping (SPM99) (Wellcome Department of Cognitive Neurology, London, UK).. (shrink)

Non‐invasive microanalytical methods have been devised to study the energy metabolism of single human preimplantation embryos. Psyruvate, which is added routinely to all media used to culture human embryos, is consumed throughout the preimplantation period, with glucose assuming an increasing role at embryo compaction and blastocyst formation. All of the glucose consumed may be accounted for by the appearance of lactate in the incubation medium. The enzyme hexokinase my be involved in regulating this aerobic glycolysis. There is cosiderable indirect (...) evidence for the utilisation of endogenous as opposed to exogenous energy substrates, the most likely candidate being protein. Information on early human embryo metabolismis likely to find application in a number of areas: these include the improvement of techniques for assisted human conception, notably in the selection of embryos for transfer following In Vitro Fertilisation; the diagnosis of gentic defects at the preimplantation stage; increased undersding of the causes of implantation failure and miscarriage, and the development of novel post‐coital contraceptives. (shrink)

Citrate, an organic trivalent anion, is a major substrate for generation of energy in most cells. It is produced in mitochondria and used either in the Krebs' cycle or released into cytoplasm through a specific mitochondrial carriers. Citrate can also be taken up from blood through different plasma membrane transporters. In the cytoplasm, citrate can be used ultimately for fatty acid synthesis, which is increased in cancer cells. Here, we review the ways in which citrate can be transported and discuss (...) the changes in transport and metabolism that occur in cancer cells. The primary focus is on the prostate gland, which is known to produce and release large amounts of citrate during its normal secretory function. The significant changes that occur in citrate‐related metabolism and transport in prostate cancer are the second focus. This review strives to relate these mechanisms to molecular biology on the one hand and to clinical applications on the other. (shrink)

In eukaryotes, folate metabolism is compartmentalized between the cytoplasm and organelles. The folate pathways of mitochondria are adapted to serve the metabolism of the organism. In yeast, mitochondria support cytoplasmic purine synthesis through the generation of formate. This pathway is important but not essential for survival, consistent with the flexibility of yeast metabolism. In plants, the mitochondrial pathways support photorespiration by generating serine from glycine. This pathway is essential under photosynthetic conditions and the enzyme expression varies with (...) photosynthetic activity. In mammals, the expression of the mitochondrial enzymes varies in tissues and during development. In embryos, mitochondria supply formate and glycine for purine synthesis, a process essential for survival; in adult tissues, flux through mitochondria can favor serine production. The differences in the folate pathways of mitochondria depending on species, tissues and developmental stages, profoundly alter the nature of their metabolic contribution. BioEssays 28: 595–605, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Dysregulation of lipid metabolism is a commonly observed feature associated with metabolic syndrome and leads to the development of negative health outcomes such as obesity, diabetes mellitus, non‐alcoholic fatty liver disease, or atherosclerosis. Time‐restricted feeding/eating (TRF/TRE), an emerging dietary intervention, has been shown to promote pleiotropic health benefits including the alteration of diurnal expression of genes associated with lipid metabolism, as well as levels of lipid species. Although TRF likely induces a response in multiple organs leading to the (...) modulation of lipid metabolism, a majority of the studies related to TRF effects on lipids have focused only on individual tissues, and furthermore there is a lack of insight into potential underlying mechanisms. In this review, we summarize the current insights regarding TRF effects on lipid metabolism and the potential mechanisms in adipose tissue, liver, skeletal muscle, and heart, and conclude by outlining possible avenues for future exploration. (shrink)

In recent years, there has been a growing interest in the relation between Marxism and the Soviet productivist economy. While historical scholarship rarely explores the intellectual context in which the Soviet experiment unfolded, ecomarxists tend to describe the Soviet Union’s mistaken path as a result of the loss of ‘metabolic’ thinkers following the rise of Stalin. This article challenges the neat, purported divide between a ‘metabolic’ and ‘productivist’ Marxism by analysing the energy-economic thinking of Gleb M. Krzhizhanovskii, a Bolshevik engineer (...) and old friend of Lenin. As chairman of both the electrification commission (GOELRO) and the State Planning Commission (Gosplan), Krzhizhanovskii conceptualised the energy economy as something embedded in the metabolism of nature and society and as the technical-economic basis of the socialist economy. This argument drew its strength from his idea that production is part of the general, ongoing life-process, and the hope that large-scale electrification and electro-chemistry could help govern the metabolism between nature and society more rationally – both arguments commonly found among contemporary natural scientists. Any ecomarxist attempt to recover the concept of metabolism today has to come to terms with its productivist and technocratic history. (shrink)

This article develops a new way of understanding the integration of emotions in practical life and the practical appraisal of emotions, drawing on insights from both J-P. Sartre and R. G. Collingwo...

When the existing order cannot offer a solution, the solution to climate crisis must come from the radical left, and this is precisely why Karl Marx’s idea of ecosocialism is more important than ever. In this context, it is worth revisiting not only the legacy of István Mészáros’s theory of ‘social metabolism’ and that of his successors – who can be categorised as comprising the ‘metabolic rift school’, which includes John Bellamy Foster, Paul Burkett, and Brett Clark –, but (...) also Karl Marx’s own theory of metabolism. In order to highlight the contemporary importance of Marx’s theory of metabolism after its long suppression in the twentieth century, this paper aims at classifying the three different levels of Marx’s concept of ‘metabolic rift’, which also entails clarifying three different levels of ‘metabolic shift’ as the theoretical foundation for updating Marx’s theory of postcapitalism in the age of global ecological crisis. (shrink)

Defects in man in four steps of 4‐aminobutyric acid (GABA) metabolism may interefere with the function of this major inhibitory neurotransmitter. Glutamic acid decarboxylase, 4‐aminobutyric acid aminotransferase, succinic semialdehyde dehydrogenase, and homocarnosinase are closely identified with the brain, but two of these enzymes are expressed in cultured peripheral cells, which may permit novel approaches to the study of the metabolism and regulation of GABA.

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.

The fate of eukaryotic proteins, from their synthesis to destruction, is supervised by the ubiquitin–proteasome system (UPS). The UPS is the primary pathway responsible for selective proteolysis of intracellular proteins, which is guided by covalent attachment of ubiquitin to target proteins by E1 (activating), E2 (conjugating), and E3 (ligating) enzymes in a process known as ubiquitylation. The UPS can also regulate protein synthesis by influencing multiple steps of RNA (ribonucleic acid) metabolism. Here, recent publications concerning the interplay between the (...) UPS and different types of RNA are reviewed. This interplay mainly involves specific RNA‐binding E3 ligases that link RNA‐dependent processes with protein ubiquitylation. The emerging understanding of their modes of RNA binding, their RNA targets, and their molecular and cellular functions are primarily focused on. It is discussed how the UPS adapted to interact with different types of RNA and how RNA molecules influence the ubiquitin signaling components. (shrink)

Several recently discovered small proteins of less than 100 amino acids control important, but sometimes surprising, steps in the metabolism of cyanobacteria. There is mounting evidence that a large number of small protein genes have also been overlooked in the genome annotation of many other microorganisms. Although too short for enzymatic activity, their functional characterization has frequently revealed the involvement in processes such as signaling and sensing, interspecies communication, stress responses, metabolism, regulation of transcription and translation, and in (...) the formation of multisubunit protein complexes. Cyanobacteria are the only prokaryotes that perform oxygenic photosynthesis. They thrive under a wide variety of conditions as long as there is light and must cope with dynamic changes in the environment. To acclimate to these fluctuations, frequently small regulatory proteins become expressed that target key enzymes and metabolic processes. The consequences of their actions are profound and can even impact the surrounding microbiome. This review highlights the diverse functions of recently discovered small proteins that control cyanobacterial metabolism. It also addresses why many of these proteins have been overlooked so far and explores the potential for implementing metabolic engineering strategies to improve the use of cyanobacteria in biotechnological applications. (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)