This book reveals a stunning thread of scientific data that points the way to the natural anabolic state a biochemical condition wherein body fat is metabolized, muscle tissue is built, strength and speed are increased, mental acuity is enhanced, and the mind and body perform at top efficiency. This inspirational book is a must-read for athletes and coaches in every sport, students and teachers at every level, people of faith, people seeking faith, and anyone competing for success. Readers will learn (...) how one simple thought altered the blood chemistry of students taking the GRE and raised test scores and how that same thought increased athletic performance in multiple sports. Readers will also come to understand why honesty, gratitude, humility, self-discipline, assertiveness, love, faith, and playing-to-win induce an empowering anabolic blood chemistry. If you read this book, you will meet Jenny (the girl who achieved a seemingly impossible goal), Susie (the most aggressive infielder I ve ever seen), Hank (the shortstop who experienced his worst nightmare), John Doe (the guy who experienced all five types of stress before leaving his driveway), Attila the Hun (an example of humility), and several more unforgettable characters. If you read this book, I promise you that, by the time you finish the third chapter, you will fervently wish you'd read it earlier in your life. (shrink)

George Will, the well-known pundit, once observed: “A society's recreation is charged with moral significance. Sport—and a society that takes it seriously—would be debased if it did not strictly forbid things that blur the distinction between the triumph of character and the triumph of chemistry.” In opposition, Dan Duchaine, the highly publicized “steroid guru” and counter-culture columnist, declared: “There comes a time for many in competitive athletics where winning is more important than those initial goals of health, recreation, and relaxation.” (...) The parallels of these two philosophies to life in general are patent simply by substituting “sports” and “winning” for “career” and “success,” respectively.This paper will review the basis for banning anabolic steroids in athletics, and consider especially the recent medical findings that support this prohibition. This survey leads into a discussion of the available deterrents, and the secondary, but essential, role of random drug testing as a final safeguard. (shrink)

The purposes of this study are twofold. First, it investigates how the digital media discursively react against the use of anabolic-androgenic steroids. Second, it examines how Thailand is portrayed as a venue for steroid holiday among recreational bodybuilders from the Western countries. Adhering to the principle of theoretical triangulation, the study employs two frameworks including Reisigl and Wodak’s discursive strategies and Van Dijk’s ideological structures. The methodology undertaken is a corpus-assisted discourse analysis. The corpus contains 100 articles published on various (...) websites between the period of 2014 and 2019 with the total number of 107,116 words. Main findings indicate that, regarding the first purpose, the media portray AAS as the ‘outgroup’ by employing various negative lexical items while attempting to dilute any claimed benefits. Concerning the second purpose, Thailand is represented as a venue in which AAS are easily available coupled with corrupt dealers and lax regulations. (shrink)

Salivary testosterone levels were measured in a population of New World indigenous adult hunter-gatherer males in order to compare circulating levels of free unbound bioactive steroid with those previously reported among Boston and nonwestern males. The study population consisted of adult Aché hunter-gatherer males (n=45) living in eastern Paraguay. Morning and evening salivary testosterone levels (TsalA.M.; TsalP.M.) among the Aché were considerably lower than western values (Boston) and even lower than other previously reported nonwestern populations (Efe, Lese, Nepalese). No association (...) was observed between height, weight, or age and salivary testosterone levels within the Aché group, although older men (ages>40) were poorly represented in the study sample. Nevertheless, a mild correlation was observed between Aché TsalA.M. levels and BMI (r=0.133,p=0.0725). Comparison of Aché values with those for other populations confirms the prevalence of significant interpopulational variation in testosterone levels among adult males. Interpopulational variation in male testosterone is not as great, however, as has been documented for ovarian steroids among females, nor is it likely that such variation reflects differences in male fecundity. Nevertheless, such interpopulational variation in salivary testosterone levels may have a functional significance in the regulation of protein anabolism in skeletal muscle, thereby affecting the overall energy budget of the organism. It is suggested that relative suppression of average testosterone may be adaptive under conditions of chronic energy shortage. (shrink)

Molecular imprints of organisms serving as both the agents and the products of the underlying sign activities are quantum mechanical in their origins. In particular, molecules in any reaction networks constituting a biological organism are semiotic or context-dependent in the sense that their activities reside within the proper coordination of the entire networks. The origin of life could have been related to a specific aspect of molecular semiotics, especially in the transition from molecules as the physical symbols of material units (...) to molecules as the semiotic signs having the capacity of pointing to something else other than the molecules themselves. Quantum mechanical underpinning of the molecular imprints leading to the emergence of life is in the appraisal of the material capacities of both coherent assimilation and decoherent dissociation already latent in the imprints. One empirical evidence suggesting the likelihood of both coherent assimilation and decoherent dissociation in prebiotic settings could have been found in synthetic chemical reactions running in hydrothermal circulation of seawater through hot vents in the Haedean ocean on the primitive Earth. (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)

The origin of the eukaryotic cell nucleus and the selective forces that drove its evolution remain unknown and are a matter of controversy. Autogenous models state that both the nucleus and endoplasmic reticulum (ER) derived from the invagination of the plasma membrane, but most of them do not advance clear selective forces for this process. Alternative models proposing an endosymbiotic origin of the nucleus fail to provide a pathway fully compatible with our knowledge of cell biology. We propose here an (...) evolutionary scenario that reconciles both an ancestral endosymbiotic origin of the eukaryotic nucleus (endosymbiosis of a methanogenic archaeon within a fermentative myxobacterium) with an autogenous generation of the contemporary nuclear membrane and ER from the bacterial membrane. We specifically state two selective forces that operated sequentially during its evolution: (1) metabolic compartmentation to avoid deleterious co‐existence of anabolic (autotrophic synthesis by the methanogen) and catabolic (fermentation by the myxobacterium) pathways in the cell, and (2) avoidance of aberrant protein synthesis due to intron spreading in the ancient archaeal genome following mitochondrial acquisition and loss of methanogenesis. BioEssays 28: 525–533, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

There is a long history and growing evidence base that the use of drugs, such as anabolic-androgenic steroids, to enhance human performance is common amongst armed forces, including in Australia. We should not be surprised that this might have occurred for it has long been predicted by observers. It is a commonplace of many recent discussion of the future of warfare and future military technology to proclaim the imminent arrival of Super Soldiers, whose capacities are modified via drugs, digital technology (...) and genetic engineering, in ways that increase their performance exponentially. This is what some observers have referred to as the “Gladiator Model” wherein the aim is to create soldiers able to perform feats of which ordinary citizens are not capable. One key aspect of this “gladiator project” is the use of illicit drugs to enhance performance. Could we use drugs, such as steroids or amphetamines, to enhance performance? Should we use such drugs? In this paper we explore the ethics of creating Super Soldiers, and raise issues of consent, coercion and the extent to which such use is permitted or condemned by just war theory. We conclude that much will depend on the extent to which such use is harmful to the soldiers themselves and this is still an open question. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Notes on Hesiod's Works and Days, 383-828E. F. BeallErrata: In E. F. Beall's "Notes on Hesiod's Works and Days, 383- 828," AJP 122.2 (June 2001):155-71, the references to the works of Hoekstra and Solmsen were inadvertently switched in proofs to cite the wrong work of each author. Page 156, notes 5 and 9 should have referred to Hoekstra's "Hésiode, Les Travaux et les jours..."; page 158, note 14 should (...) have referred to Solmsen's Hesiodi: Theogonia, Opera et Dies, Scutum. We regret the error. [End Page 154]In the interests of stimulating critical attention to the works and days proper of the Works and Days, lines 383-828, I offer some remarks on selected problems of the text.11. The poem's addressee will need(405-6)West2 and others suspect 406,3 mostly becfause Aristotle does not observe it and sees the gunē as a wife (Oec. 1343a, Pol. 1252b),4 but several critics beginning with Scaliger (sixteenth century) have noted that this is no [End Page 155] basis for doubt. Although some merely impugn the philosopher's memory without evidence, Lanzi in his 1808 commentary and Erbse (1993, 24) make a substantive point: marriage upon starting farming (prōtista) is inconsistent with Hesiod's advice to wait until age thirty at 696-97.5 One can respond that Aristotle may have different recensions from ours here (one without 406 and 695-705) and elsewhere.6 But if the issue is whose recensions are best, then despite any feeling that Aristotle is "closer" to the originals, other epic citations hurt the case for his texts. For example,7 we read today that trembling (tromos) seized (hele) Hector upon meeting Achilles (Il. 22.136), and he fled for a time (to 22.225); yet Aristotle says (EE 1230a) that what seized (heile) him at the encounter was shame (aidōs), making him brave and able to face the danger. At first sight this conflates the actual line with an earlier one, 22.105 (= 6.442): Hector is ashamed (aideomai) for urging battle at another time.8 But possibly Aristotle has, rather, a version of the Iliad without character development, where Hector and Achilles get right to their contest. If so, our version is superior: the temporary flight allows introduction of a wealth of detail; see Richardson 1993, 121-32. With Hesiod, Metaphysics 984b omits Theogony 118, to make Gaea/Earth support not just all the gods of Olympus but simply "all," a role few would now agree the poem could intend for her. Lesser concerns about 406 being easily met,9 it may be kept in the text bequeathed to us. [End Page 156]2.10(410-13)Etōsioergos is often construed as "lazy" or the like. Thus West explains the word as the man's neglect of his ergon rendering it etōsios, "useless." But as Lehrs says against Voss's equivalent, "säumiger," etōsio-ergos is really frustra-laborans: acting uselessly, that is, without purpose; it is not causing uselessness via inaction.11 Thus, for example, Tandy and Neale: "works at vain tasks." Etōsioergos should be different from anaballomenos in 412, given ou... oude, contra West's forced interpretation of hendiadys. The "lazy" construal may stem from belief that gar indicates explanation of anaballesthai in 410, but this particle's causal thrust is inherently loose. Moreover, it can govern more than a clause or sentence (de Jong), and it is natural to take the entire segment 411-13 as the quasi-explanation of 410.12 In short, 411 and 412 single out two distinct modes of avoiding serious work, puttering and putting off, rather than simply attack the avoidance in broad strokes twice. It is also possible that 413 adds yet a third mode: Amboliergos might be "working sporadically" rather than delaying the required labor all at once. Anabolē in its sense of "thrown upward" can refer to an intermittent process (as a boiling liquid makes bubbles; Arist., Pr. 936b), so that the delay of any entity to which it was prefixed might be thought fragmented. [End Page 157... (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)

Traditionally the doping debate has been dominated by those who want to see doping forbidden (the prohibitionist view) and those who want to see it permitted (the ban abolitionist view). In this article, the authors analyse a third position starting from the assertion that doping use is a symptom of the paradigm of highly competitive elite sports, in the same way as addictions reflect current social paradigms in wider society. Based upon a conceptual distinction between occasional use, habitual use and (...) addiction, and focusing on the physical and/or mental dependency caused by the addictive use of a certain drug, we argue that marihuana, stimulants and anabolic steroid abuse—the most frequently detected substances in doping tests—satisfies at least one, often both, of these conditions. A conclusion to be drawn from the authors' arguments is that the prohibitionist view is inappropriate for dealing with doping, as the severe sanctions attached to it will cut the doper off her/his social and professional environment, thereby risking reinforcing her/his addictive conduct. But the ban abolitionist view seems inappropriate as well. At first sight, it seems neither rational nor humane not to intervene when confronted with conduct which is highly harmful for the individual and upon which she has reduced or no control whatsoever. Instead the authors' proposal will be to contextualise dopers' conduct within sport healthcare and see it strictly in relation to each athlete's personal background. Developing preventive programmes—implemented through person-tailored counselling and eventually treatment, rather than severe sanctions or the mere lifting of the ban—seems to be a more reasonable, and probably more efficient, way of conducting ‘the war against doping’. (shrink)

Observed biological growth curves generally are sigmoid in appearance. It is common practice to fit such data with either a Verhulst logistic or a Gompertz curve. This paper critically considers the conceptual bases underlying these descriptive models.The logistic model was developed by Verhulst to accommodate the common sense observation that populations cannot keep growing indefinitely. A justification for using the same equation to describe the growth of individuals, based on considerations from chemical kinetics (autocatalysis of a monomolecular reaction), was put (...) forward by Richardson, but met with heavy criticism as a result of his erroneous derivation of the basic equation (Snell, 1929). It errs on the side of over-simplicity (Priestley & Pearsall, 1922). Von Bertalanffy (1957) subsequently based a justification on the assumption that, as a first approximation, the rates of catabolism and anabolism may be assumed to be proportional to weight and power (still vacant places, between the maximal possible and the already accumulated population sizes. This point of view was fiercely challenged by Nicholson (1933), Milne (1962), Smith (1954) and Rubinov (1973). And indeed, what is meant by vacant places has never become entirely clear. Finally Lotka (1925) devised a third leading approach by just truncating a Taylor expansion around zero of the differential law for autonomous growth after the second degree term. (shrink)

Ecology shows that living beings, with all their diversity, make up a homogenous system on the earth's surface, with rules that are no less exacting than those applicable to gravitational astronomy (celestial mechanics). The physical energy coming from the sun in the form of radiation is attracted by green plant-life, be it vegetation growing on the land or microscopic algae floating on the surface of the ocean; this energy is then transformed into chemical energy, with, incidentally, a modest yield, due (...) to the process of chlorophyllian synthesis. This stage is the only one to include a productive process—an anabolism. Other sorts of living beings derive their energy and the elements necessary for their sustenance and multiplication from organic matter devised in this way. Some vegetarian animals feed on them and are in their turn prey to predators which are themselves devoured by other predators. Food chains, grouped in bunches or network systems, are thus established on the principle of a complex pyramid. Each consumer occupies a place at a trophic level, which is clearly defined, where he guarantees the conveyance of matter and energy which are degraded in accordance with the laws of thermodynamics. These biological mechanisms entail numerous species, ranging from the most elementary forms of life to birds and mammals. Decomposition agents then recycle the mineral elements and make them available to plants. In any given area, the inert chemical elements and the community of living beings (embracing all species) together constitute a biological entity or ecosystem, this is a kind of supraspecific organism which functions with a certain flexibility, and yet is ordered down to the last detail. Just as a man consists of a heart, lungs, a liver, so a natural community consists of “organs” which are each made up of one of the various constituent species. These ecosystems are the fundamental units of the living world and they are relatively independent of one another, although exchanges do occur between them. They all come together to form a balanced system which encompasses the whole complex of living beings. This is the biosphere, a gigantic mechanism with innumerable cogs and gears which have evolved in harmony with each other throughout the whole of history, going as far back as the first trace of life on earth. (shrink)

Variations in life history define key comparative and evolutionary biological questions, important for understanding the mechanisms of mammalian evolutionary divergence, developmental adaptability and plasticity. In this regard, the differences among predominantly altricial and precocial species represent a particularly significant, if still poorly understood and contested case. Here, it will be shown how the classical analysis of such ontogenetic variations, going back to the semantic biology of A. Portmann, can be expanded and synthesized with comparative physiological approaches, based on the negentropic (...) theory of ontogeny by I. A. Arshavsky and his school. In this little received but pioneering tradition, extensive comparative and experimental investigations were carried out on the role of musculoskeletal systems and stressors in driving life history variations, particularly in the altricial-precocial spectrum. As shown by Arshavsky and co-workers, by focusing on general allometric regularities, the approximations based on the classical energy rules of surface and mass offer valuable benchmarks, but also predictions that are frequently violated by the variability of physiological and metabolic scaling relationships among altricials and precocials, and thus, a complex and historical approach is needed to describe their local physiological mechanisms and systemic regularities. This paper shows how Arshavsky’s findings and framework can play an integrative role in this context, potentially helping to bridge the mainly descriptive approach of semantic morphology, as developed by Portmann’s school, with the more functional explanations predominating current ecology and life history theory. These problems can be important for biosemiotics by highlighting the contingent, activity-dependent, and surplus anabolic stress mechanisms underlying diversification in eutherian developmental systems and possibly, the epigenetic evolution of pace-of-life syndromes. (shrink)

This article considers the war against terror in relation to classical tragedy. It uses Heidegger's analysis of Sophocles's play Antigone to argue that human beings are essentially `homeless' and yet our destiny lies in the continual attempt to overcome this homelessness by establishing foundational principles that might bring our journeying to an end. The tragedy of this situation is that the search for foundations and a search for a home invariably bring differing worlds in conflict with each other as their (...) paths to truth collide. Lucien Goldmann's analysis of the tragedy of refusal is also considered in relation to a non-foundational politics that may permit us not only to endure, but actually to affirm our homelessness as an attempt to resist the terror and anabolic militarism that marks the current age. (shrink)

AMP‐activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti‐diabetic drugs, exerts its actions by AMPK activation. However, while the functions of (...) AMPK as a metabolic regulator are fairly well understood, its actions in neuronal cells only recently gained attention. This review will discuss newly emerged functions of AMPK in neuroprotection and neurodegeneration. Additionally, recent views on the role of AMPK in autophagy, an important catabolic process that is also involved in neurodegeneration and cancer, will be highlighted. (shrink)

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe symptoms of (...) autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (shrink)

Before a cell divides into two daughter cells, it typically doubles not only its DNA, but also its mass. Numerous studies in cells ranging from yeast to mammals have shown that cellular growth, stimulated by nutrients and/or growth factor signaling, is a prerequisite for cell cycle progression in most types of cells. The textbook view of growth‐regulated cell cycles is that growth signaling activates the transcription of G1 Cyclin genes to induce cell proliferation, and also stimulates anabolic metabolism and cell (...) growth in parallel. However, genetic knockout tests in model organisms indicate that this is not the whole story, and new studies show that additional, “smarter” mechanisms help to coordinate the cell cycle with growth itself. Here we summarize recent advances in this field, and discuss current models in which growth signaling regulates cell proliferation by targeting core cell cycle regulators via non‐transcriptional mechanisms. (shrink)

To the Editor. A correction is necessary with respect to one of the articles in the Fall 1994 issue of the journal. In the article by Robert Fuentes et al., “Sentinel Effect of Drug Testing for Anabolic Steroid Abuse,” at page 228, the authors say, “…on May 2, 1994, the United States Supreme Court ruled that random drug tests violated the privacy rights of [various people] at the University of Colorado at Boulder…. The Court further stated….” No footnote is given, (...) and thus no citation to the case. The superscripted note at the end of the previous sentence is to an article in the NCAA News, “Court Rules Against Colorado Drug Policy.” The Supreme Court of the United States decided no such thing as what the authors state. If the reference is to a denial of review, the authors should have said something like, “The Supreme Court denied review to … leaving in place a ruling that….” A denial of review is not the Supreme Court ruling anything beyond the announcement that it will not hear a case; inferences can be drawn from the denial, but that is not what happened here: a flat statement—and an erroneous one—was made. Prof. Stephen L. Wasby Dept. of Political Science SUNY at Albany Ed. The authors cite the NCAA News accurately, and the reference refers to both courts; however, the NCAA News article in question fails to make the necessary distinction that Professor Wasby correctly points out. Our thanks to Professor Wasby for his remarks. (shrink)

It is not clear why cancer cells choose to disrupt their circadian clock rhythms, and whether such disruption governs a selective fitness and a survival advantage. In this review, I focus on understanding the impacts of clock gene disruption on a simpler model, such as the unicellular cyanobacterium, in order to explain how cancer cells may alter the circadian rhythm to reprogram their metabolism based on their needs and status. It appears to be that the activation of the oxidative pentose (...) phosphate pathway (OPPP) and production of NADPH, the preferred molecule for detoxification of reactive oxygen species, is a critical process for night survival in unicellular organisms. The circadian clock acts as a gatekeeper that controls how the organism will utilize its sugar, shifting sugar influx between glycolysis and OPPP. The circadian clock can thus act as a gatekeeper between an anabolic, proliferative mode and a homeostatic, survival mode. (shrink)

The enhancement of athletic performance using procedures that increase physical ability, such as anabolic steroids, is a familiar phenomenon. Yet recent years have also witnessed the rise of direct interventions into the brain, referred to as “neuro-doping”, that promise to also enhance sports performance. This paper discusses one potential objection to neuro-doping, based on the contribution to athletic achievement, particularly within endurance sports, of effortfully overcoming inner challenges. After introducing the practice of neuro-doping, and the controversies surrounding it, I describe (...) two major mechanisms some have proposed to explain how it might produce its putative performance-enhancing effects. I then clarify the notion of effort, and its relationship to neuro-doping. I also briefly address common concerns about access and safety. My central argument invokes considerations of effort to maintain that we have at least a significant reason for prohibiting the use of neuro-doping in officially regulated endurance competitions – though only conditional upon a specific set of empirical assumptions. I consider three possible objections: that neuro-doping is no different from widely accepted enhancement methods, that it can make athletic competition fairer, and that a broader range of factors can compensate for a reduced scope for effort than I recognize. I ultimately conclude that these objections do not refute the argument from effort, while stressing nonetheless that this argument applies more clearly to hypothetical improved forms of neuro-doping than to existing ones, and is not meant to offer a final overall verdict on how neuro-doping should be regulated. (shrink)

Sarcopenia is a process of progressive aging‐associated loss of skeletal muscle mass (SMM) recognized as a serious global health issue contributing to frailty and increased all‐cause mortality. Exercise and nutritional interventions (particularly intake of dairy products and milk) demonstrate good efficacy, safety, and broad applicability. Here, we propose that at least some of the well‐documented favorable effects of milk and milk‐derived protein supplements on SMM might be mediated by D‐galactose, a monosaccharide present in large quantities in milk in the form (...) of disaccharide lactose (milk sugar). We suggest that ingestion of dairy products results in exposure to D‐galactose in concentrations metabolized primarily via the Leloir pathway with the potential to (i) promote anabolic signaling via maintenance of growth factor (e.g., insulin‐like growth factor 1 [IGF‐1]) receptor mature glycosylation patterns; and (ii) provide extracellular (liver glycogen) and intracellular substrates for short (muscle glycolysis) and long‐term (muscle glycogen, intramyocellular lipids) energy availability. Additionally, D‐galactose might optimize the metabolic function of skeletal muscles by increasing mitochondrial content and stimulating glucose and fatty acid utilization. The proposed potential of D‐galactose to promote the accretion of SMM is discussed in the context of its therapeutic potential in sarcopenia. (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 tricarboxylic acid (TCA) or Krebs cycle, which takes place in prokaryotic cells and in the mitochondria of eukaryotic cells, is central to life on Earth and participates in key events such as energy production and anabolic processes. Despite its relevance, it is not perceived as tightly regulated compared to other key metabolisms such as glycolysis/gluconeogenesis. A better understanding of the functioning of the TCA cycle is crucial due to mitochondrial function impairment in several diseases, especially those that occur with (...) neurodegeneration. This article revisits what is known about the regulation of the Krebs cycle and hypothesizes the need for large‐scale, rapid regulation of TCA cycle enzyme activity. Evidence of mitochondrial enzyme activity regulation by activation/deactivation of protein kinases and phosphatases exists in the literature. Apart from indirect regulation via G protein‐coupled receptors (GPCRs) at the cell surface, signaling upon activation of GPCRs in mitochondrial membranes may lead to a direct regulation of the enzymes of the Krebs cycle. Hormonal‐like regulation by posttranscriptional events mediated by activable kinases and phosphatases deserve proper assessment using isolated mitochondria. Also see the video abstract here: https://youtu.be/aBpDSWiMQyI. (shrink)

One of the consequences of global warming is reduced final body sizes in animals of different orders, mainly in aquatic ectotherms like fish or water-breathing invertebrates. In this article, we identify August Pütter (1879–1929) as the originator of what is now called the “temperature–size rule” and as the first physiologist to develop a mechanistic explanation for this phenomenon. While Pütter’s growth model was indirectly influential through its adaptation by Ludwig von Bertalanffy (1901–1972), his explanation of the influence of temperature on (...) growth remained either unknown or misunderstood. In this contribution, we reconstruct the theoretical framework of his model and compare it to recent critiques of mechanistic models on growth and temperature. As we argue, Pütter’s theory of “similarities of growth” provides explanations for observed temperature–size patterns trends that avoid later accounts of underlying “biological laws.” While recent findings suggest that some aspects of Pütter’s model need revision—for example, the proposed exponents of the anabolic and catabolic terms in his growth equation—we argue that his mechanistic model was designed in a way that could account for the multiple apparent exceptions to the temperature–size rule that were recently found. (shrink)

Controversy over the use of performance–enhancing drugs in athletics has involved sometimes rather complex technological advances (e.g. ‘designer steroids’ in track, and anabolic steroids in...