Hydra are remarkable because they are immortal. Much of immortality can be ascribed to the asexual mode of reproduction by budding, which requires a tissue consisting of stem cells with continuous self‐renewal capacity. Emerging novel technologies and the availability of genomic resources enable for the first time to analyse these cells in vivo. Stem cell differentiation in Hydra is governed through the coordinated actions of conserved signaling pathways. Studies of stem cells in Hydra, therefore, promise critical insights of general relevance (...) into stem cell biology including cellular senescence, lineage programming and reprogramming, the role of extrinsic signals in fate determination and tissue homeostasis, and the evolutionary origin of these cells. With these new facts as a backdrop, this review traces the history of studying stem cells in Hydra and offers a view of what the future may hold. (shrink)

Current work in experimental biology revolves around a handful of animal species. Studying only a few organisms limits science to the answers that those organisms can provide. Nature has given us an overwhelming diversity of animals to study, and recent technological advances have greatly accelerated the ability to generate genetic and genomic tools to develop model organisms for research on host–microbe interactions. With the help of such models the authors therefore hope to construct a more complete picture of the mechanisms (...) that underlie crucial interactions in a given metaorganism (entity consisting of a eukaryotic host with all its associated microbial partners). As reviewed here, new knowledge of the diversity of host–microbe interactions found across the animal kingdom will provide new insights into how animals develop, evolve, and succumb to the disease. (shrink)

Peptides serve as important signalling molecules in development and differentiation in the simple metazoan Hydra. A systematic approach (The Hydra Peptide Project) has revealed that Hydra contains several hundreds of peptide signalling molecules, some of which are neuropeptides and others emanate from epithelial cells. These peptides control biological processes as diverse as muscle contraction, neuron differentiation, and the positional value gradient. Signal peptides cause changes in cell behaviour by controlling target genes such as matrix metalloproteases. The abundance of peptides in (...) Hydra raises the question of whether, in early metazoan evolution, cell–cell communication was based mainly on these small molecules rather than on the growth‐factor‐like cytokines that control differentiation and development in higher animals. BioEssays 23:420–427, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Ecological developmental biology (eco‐devo) explores the mechanistic relationships between the processes of individual development and environmental factors. Recent studies imply that some of these relationships have deep evolutionary origins, and may even pre‐date the divergences of the simplest extant animals, including cnidarians and sponges. Development of these early diverging metazoans is often sensitive to environmental factors, and these interactions occur in the context of conserved signaling pathways and mechanisms of tissue homeostasis whose detailed molecular logic remain elusive. Efficient methods for (...) transgenesis in cnidarians together with the ease of experimental manipulation in cnidarians and sponges make them ideal models for understanding causal relationships between environmental factors and developmental mechanisms. Here, we identify major questions at the interface between animal evolution and development and outline a road map for research aimed at identifying the mechanisms that link environmental factors to developmental mechanisms in early diverging metazoans.Also watch the Video Abstract. (shrink)

Cover Photograph: Transgenic Hydra provide insights of general relevance into stem cell biology. The image shows a mass culture of transgenic Hydra expressing EGFP in all of their ectodermal epithelial cells. See article by Thomas C. G. Bosch pp. 478–486.

Graphical AbstractCIFAR's Humans & the Microbiome program is a multidisciplinary group of biological, clinical, and social scientists who explore the links between microbiome biology and sociocultural, historical, evolutionary, and environmental aspects of human existence that may impact the microbiome or be impacted by it. In this focus issue, members of the program focus on topics ranging from decoding the link between nutrition, the microbiome and human developmental, metabolic, and immune health and aging, to understanding past changes in the environment and (...) microbiome. The image depicts a population of bacteria (green) in association with the epithelia tissues (magenta and blue), perhaps the most common type of symbiosis in humans and other animals. Image contribution: Tara Essock-Burns. DOI: 10.1002/bies.201900130. (shrink)

Cells in the basal metazoan phylum Cnidaria are characterized by remarkable plasticity in their differentiation capacity. The mechanism controlling asymmetric cell divisions is not understood in cnidarians or in any other animal group. PIWI proteins recently have been shown to be involved in maintaining the self‐renewal capacity of stem cells in organisms as diverse as ciliates, flies, worms and mammals. Seipel et al.1 find that, in the cnidarian Podocoryne carnea, the Piwi homolog Cniwi is transcriptionally upregulated when the polyp generates (...) buds, which will develop into medusae. Since transdifferentiation of striated muscle cells to smooth muscle cells also activated Cniwi expression, Cniwi appears to play a crucial role in differentiation events. The discovery should facilitate elucidation of the poorly understood factors that control asymmetric cell divisions at the beginning of animal evolution. BioEssays 26:929–931, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Here we evaluate our current understanding of the function of the nervous system in Hydra, a non‐bilaterian animal which is among the first metazoans that contain neurons. We highlight growing evidence that the nervous system, with its rich repertoire of neuropeptides, is involved in controlling resident beneficial microbes. We also review observations that indicate that microbes affect the animal's behavior by directly interfering with neuronal receptors. These findings provide new insight into the original role of the nervous system, and suggest (...) that it emerged to orchestrate multiple functions including host‐microbiome interactions. The excitement of future research in the Hydra model now relies on uncovering the common rules and principles that govern the interaction between neurons and microbes and the extent to which such laws might apply to other and more complex organisms. (shrink)

While largely studied because of their harmful effects on human health, there is growing appreciation that bacteria are important partners for invertebrates and vertebrates, including man. Epithelia in metazoans do not only select their microbiota; a coevolved consortium of microbes enables both invertebrates and vertebrates to expand the range of diet supply, to shape the complex immune system and to control pathogenic bacteria. Microbes in zebrafish and mice regulate gut epithelial homeostasis. In a squid, microbes control the development of the (...) symbiotic light organ. These discoveries point to a key role for bacteria in any metazoan existence, and imply that beneficial bacteria‐host interactions should be considered an integral part of development and evolution. (shrink)

The conference explored an extraordinary diversity of aging strategies in organisms ranging from short‐lived species to “immortal” animals and plants. Research on the biological processes of aging is at the brink of a revolution with respect to our understanding of its underlying mechanisms as well as our ability to prevent and cure a wide variety of age‐related pathologies.

Humans’ indigenous microbes strongly influence organ functions in an age‐ and diet‐dependent manner, adding an important dimension to aging biology that remains poorly understood. Although age‐related differences in the gut microbiota composition correlate with age‐related loss of organ function and diseases, including inflammation and frailty, variation exists among the elderly, especially centenarians and people living in areas of extreme longevity. Studies using short‐lived as well as nonsenescent model organisms provide surprising functional insights into factors affecting aging and implicate attenuating effects (...) of microbes as well as a crucial role for certain transcription factors like forkhead box O. The unexpected beneficial effects of microbes on aged animals imply an even more complex interplay between the gut microbiome and the host. The microbiome constitutes the major interface between humans and the environment, is influenced by biosocial stressors and behaviors, and mediates effects on health and aging processes, while being moderated by sex and developmental stages. (shrink)

The microbiome of human hair follicles (HFs) has emerged as an important player in different HF and skin pathologies, yet awaits in‐depth exploration. This raises questions regarding the tightly linked interactions between host environment, nutrient dependency of host‐associated microbes, microbial metabolism, microbe‐microbe interactions and host immunity. The use of simple model systems facilitates addressing generally important questions and testing overarching, therapeutically relevant principles that likely transcend obvious interspecies differences. Here, we evaluate the potential of the freshwater polyp Hydra, to dissect (...) fundamental principles of microbiome regulation by the host, that is the human HF. In particular, we focus on therapeutically targetable host‐microbiome interactions, such as nutrient dependency, microbial interactions and host defence. Offering a new lens into the study of HF – microbiota interactions, we argue that general principles of how Hydra manages its microbiota can inform the development of novel, microbiome‐targeting therapeutic interventions in human skin disease. (shrink)

There are two possible positions with regard to the Mycenaean hegemony: that it existed or that it did not. Modern scholars who accept its existence appear to be more vocal in arguing their position than are those who question the existence of Mycenaean unity. Desborough, for example, states forcibly:I am firmly convinced that there was one ruler over the whole Mycenaean territory, with his capital at Mycenae, although the tablets are of no assistance one way or the other in this (...) matter, and although the overlordship of Agamemnon clearly envisaged by Homer can perhaps be explained simply as a military leadership for the purpose of waging war against Troy. The burden of proof must therefore depend on other evidence, the archaeological material taken in conjunction with the fairly frequent mention by the Hittites, in the fourteenth and much of the thirteenth centuries, of the king of a land called Ahhiyawa, which I believe to represent the entire Mycenaean orbit.The opposite position is represented largely through hints given in a larger context. Stubbings, for example, writes of ‘the Mycenaean Greeks of the mainland and the Mycenaean rulers of Cnossus’ and of ‘the mainland kingdoms’. Catling speaks of ‘metropolitan Greeks grown jealous of the wealth and power which their Knossian relatives had built up’. This emphasis on plurality, it seems to me, is the best way not only to view the events of the Mycenaean Greek world but also to understand the nature and degree of change in Greece during the Dark Age period. (shrink)

Anecdotal reports obtained from three individuals with prosopagnosia, all of whom have participated in an investigation, capture the essence of their impairment. This article focuses on the contrast between two prominent forms of prosopagnosia, one of which results from an acquired brain insult in an otherwise premorbidly normal individual and a second which appears to be lifelong and occurs in the absence of any obvious brain damage, at least as evident on conventional brain imaging. It reviews two central issues: the (...) first concerns the similarities and differences in the psychological representations of faces in acquired prosopagnosia and congenital prosopagnosia, and the second concerns the nature of the underlying neural representations of faces in these two populations. Some well-established overlapping behavioral characteristics are identified. (shrink)

J. G. Taylor advances an empirically testable local neural network model to understand the neural correlates of phenomenal experience. Taylor's model is better able to explain the presence and unity of phenomenal consciousness which support the idea that consciousness is coherent, undivided, and centered. However, Taylor fails to offer a satisfactory explanation of the nonlinear relationship between local and global neural systems. In addition, the ontological assumptions that PE is immediate, intrinsic, and incorrigible limit an understanding of the different experiential (...) forms consciousness takes during neurobehavioral development. Recent studies suggest that neurobehavioral development is discontinuous and that judgment emerges under conditions of uncertainty to render feeling and perception in equivalent terms of energy and behavior. Approaching the problem of phenomenal experience from a developmental perspective may help resolve the paradox of feeling infinitely close as well as distant from one's self. (shrink)

Descartes is not simply our iconic modern philosopher, mathematician or scientist. He stands as the cultural symbol for modernity itself. This title offers insights into the relationship between Descartes and the Modern, and the very meaning and status of Modernity itself.

: In her recent paper, “How to Escape Indictment for Impiety: Teaching as Punishment in the Euthyphro,” G. Fay Edwards argues that if Socrates were to become Euthyphro’s student, this should count as the appropriate punishment for Socrates’ alleged crime. In this paper, we show that the interpretation Edwards has proposed conflicts with what Socrates has to say about the functional role of punishment in the Apology, and that the account Socrates gives in the Apology, properly understood, also provides the (...) correct interpretation of what Socrates says in the Euthyphro about the role of instruction for wrongdoers. (shrink)

Analyses of the height variation of 16-year-old members of the British National Child Development Study revealed a number of biological and social variables which associated with stature. After multiple regression analyses only eight variables, namely social class, family size, tenure , crowding status, number of children sleeping in the bed, region of the country, sex of child, and pubic hair rating, remained significant. The total variation explained by these biosocial variables was 37·5%.

Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equivalent in importance to natural selection. Here, we subject NCT to critical evaluation, in (...) the form of a collaboration between one prominent advocate of NCT, and a team of skeptics. We discuss whether niche construction is an evolutionary process, whether NCT obscures or clarifies how natural selection leads to organismal adaptation, and whether niche construction and natural selection are of equivalent explanatory importance. We also consider whether the literature that promotes NCT overstates the significance of niche construction, whether it is internally coherent, and whether it accurately portrays standard evolutionary theory. Our disagreements reflect a wider dispute within evolutionary theory over whether the neo-Darwinian synthesis is in need of reformulation, as well as different usages of some key terms (e.g., evolutionary process). (shrink)

J. G. Taylor advances an empirically testable local neural network model to understand the neural correlates of phenomenal experience. Taylor's model is better able to explain the presence (i.e., persistence, latency, and seamlessness) and unity of phenomenal consciousness which support the idea that consciousness is coherent, undivided, and centered. However, Taylor fails to offer a satisfactory explanation of the nonlinear relationship between local and global neural systems. In addition, the ontological assumptions that PE is immediate, intrinsic, and incorrigible limit an (...) understanding of the different experiential forms consciousness takes during neurobehavioral development. Recent studies suggest that neurobehavioral development is discontinuous and that judgment emerges under conditions of uncertainty to render feeling and perception in equivalent terms of energy and behavior. Approaching the problem of phenomenal experience from a developmental perspective may help resolve the paradox of feeling infinitely close as well as distant from one's self. (shrink)

Despite external environmental changes in walking, such as manipulating gait speed, previous studies have shown that the underlying muscle synergy structures (synergy weights or vectors) rarely vary. The purpose of this study is to examine if external environmental changes to the walking task influence muscle synergies in children with cerebral palsy (CP) and/or typical development (TD). To identify muscle synergies, we extracted muscle synergies from eight children with CP and eight age-matched TD in three treadmill walking conditions, e.g., baseline (adjusted (...) to individual comfortable walking speed), variable speed (VS), or restricted foot width (RW). Then, we grouped similar muscle synergies using k-mean clustering and discriminant analyses from all datasets of individual synergy structures. Proportion tests exhibited six clusters of muscle synergies predominantly arising from children with CP and four clusters from children with TD. Also, the proportion of muscle synergies was significantly different in four of the CP-preferred clusters across conditions. Specifically, the proportion of the baseline condition was significantly different from VS and RW conditions in one and two clusters, respectively. The proportion was significantly different between VS and RW conditions in four clusters. Cadence and step lengths differed across conditions but not groups which makes the group differences in proportion even more notable. In contrast, step width, while significantly lower in CP, did not differ across conditions. Our findings demonstrate that muscle synergies in children with CP are more sensitive to changes in the external walking environment than in typically developing children. (shrink)

Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the molecular mechanism (...) of action of the p53 Ser46 phospho‐isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferroptosis still await exploration. In this essay, the current body of evidence on the molecular function of this deadly p53 mark, its evolutionary conservation, and the regulation of the key players of this response, the p53 Serine 46 kinases, are reviewed and dissected. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Criminal Law, Pain Relief, and Physician Aid in DyingFaye Girsh, Ed.D., Executive DirectorMadam:The article by Cantor and Thomas on “Pain Relief, Acceleration of Death, and Criminal Law” (KIEJ, June 1996) was a tortured attempt to develop criteria for the humane and compassionate physician who tries to serve the needs of a patient in unremitting pain. There are three areas that merit comment.The authors dealt with pain medications that (...) might have the undesirable side effect of causing death. They did not mention tolerance, which usually occurs in a patient with chronic pain and which would require exceedingly high doses to be effective. They did not mention barbiturates, which are preferable to opiates in causing death and which are used increasingly by compassionate physicians to answer the pleas of their suffering patients, but for which there is no excuse about alleviating pain. Would the criminal law just call the prescription of a lethal dose of barbiturates a reckless act and require conviction? Fortunately, juries, as the authors point out, do not balance these formulas on the head of a pin. When they see the circumstances under which these doctors do help their patients, they choose to nullify the law and would ignore the suggestions made in this article.The authors refer to the “consent” of the patient. They do not mention that these doctors are operating with more than consent; they are administering these medications because suffering patients are begging them to put them out of their pain and the indignities of the dying process. The article discusses the process as though it were the same as consent to elective surgery. These patients—with AIDS, cancer, and hopeless neurological degeneration—are not simply agreeing to a procedure; they are desperately seeking a way out. If the criminal law were to develop criteria for physician aid in dying, certainly one of them should be the active, witnessed, repeated request of such a patient for a certain, quick, painless, gentle death.The third point is that physicians do not face prosecution when administering no treatment to a patient whose life could be saved with treatment but who chooses not to receive it. This has been upheld by the U.S. Supreme Court; no criteria for suffering, alternatives, terminality, justifiability, or unbearability are required. The doctor can stand by while the patient dies what may be a protracted, difficult death, but it is within the law. What matters in this situation is the decision of the patient to refuse treatment, and that is absolute. How ironic that the patient who cannot refuse treatment must, with his or her doctor, jump through all these hoops to achieve a peaceful death.One worries that the physician who must balance the risk of “risky pain relief” against the accusation of recklessness will err in the direction of allowing [End Page 103] the patient to bear the pain rather than help with a dose of analgesics that might be considered beyond the stipulated “risk.”Why don’t we just be honest about it? Allow dying or hopelessly ill patients to make the decision about what they want by passing a carefully defined law allowing euthanasia rather than balancing the risk and trying to determine the “purpose” of the physician’s ministrations. We protect some patients from themselves while allowing others almost complete autonomy to make the choice of ending their lives. The authors were right in saying that proponents of rational laws consider this sheer hypocrisy.Faye Girsh, Executive DirectorHemlock Society U.S.A. Denver, COFaye Girsh misconceives our article’s objective as an “attempt to develop criteria” for the humane physician. Our goal in writing the paper was to analyze the current criminal law framework in the hope of sharpening debate and engendering normative critiques. We readily acknowledge tensions in the current legal framework and would support changes in that framework.Copyright © 1997 The Johns Hopkins University Press... (shrink)

Scholars and professional organizations in bioethics describe various approaches to “quality assessment” in clinical ethics. Although much of this work represents significant contributions to the literature, it is not clear that there is a robust and shared understanding of what constitutes “quality” in clinical ethics, what activities should be measured when tracking clinical ethics work, and what metrics should be used when measuring those activities. Further, even the most robust quality assessment efforts to date are idiosyncratic, in that they represent (...) evaluation of single activities or domains of clinical ethics activities, or a range of activities at a single hospital or healthcare system. Countering this trend, in this article we propose a framework for moving beyond our current ways of understanding clinical ethics quality, toward comprehensive quality assessment. We first describe a way to conceptualize quality assessment as a process of measuring disparate, isolated work activities; then, we describe quality assessment in terms of tracking interconnected work activities holistically, across different levels of assessment. We conclude by inviting future efforts in quality improvement to adopt a comprehensive approach to quality assessment into their improvement practices, and offer recommendations for how the field might move in this direction. (shrink)

The publication of Mr. R. S. Bluck's stimulating Phaedo prompts me to ask the following questions concerning the traditional interpretation of the cosmographical passage beginning 108 e. Do the terms of 108 e-109 a in combination with 110 b 5 ff. and Timaeus 40 b-c and 62 d ff. prove conclusively that in the Phaedo Plato thinks of the earth as a spherical body? Granted that he does, need his description of the earth, as a setting for his eschatological myth, (...) conform with the spherical theory? (shrink)

The publication of Mr. R. S. Bluck's stimulating Phaedo prompts me to ask the following questions concerning the traditional interpretation of the cosmographical passage beginning 108 e. Do the terms of 108 e-109 a in combination with 110 b 5 ff. and Timaeus 40 b-c and 62 d ff. prove conclusively that in the Phaedo Plato thinks of the earth as a spherical body? Granted that he does, need his description of the earth, as a setting for his eschatological myth, (...) conform with the spherical theory? (shrink)