Further evidence that naloxone acts as an inverse opiate agonist: Implications for drug dependence and withdrawaL

To test if naloxone behaved as an inverse agonist rather than as an antagonist we evaluated its responses in guinea-pig ilea with and without morphine (480 nM, 24 h). In control ilea, naloxone (100 nM) had no effect. In morphine-treated ilea, naloxone as a bolus, but not as an infusion, elicited an abstinence response. Preadministration of naloxone blocked the response to subsequent administrations. Similarly, naloxone failed to produce an abstinence response in ilea pretreated with kappa compounds (bremazocine, U50488 or xorphanol 100 nM) or with kinase inhibitors (H7 or H8 30 μM). These findings can be interpreted in the light of the two-state receptor model if naloxone behaves as an inverse agonist: Incubation with morphine increased the active state of receptors making them susceptible to the inverse agonist (naloxone); exposure to naloxone favored the inactive conformation making them insensitive to further administration of naloxone; kappa compounds behaved as antagonists preventing the response to naloxone; and kinase inhibitors interfered with the active conformation making the system insensitive to naloxone. According to this model, dependence can be viewed as an overexpression of the active receptors and withdrawal as an abrupt change from the active to the inactive state.     

The leaf-clipping display: A newly-discovered expressive gesture in wild chimpanzees

Chimpanzees of the Mahale Mountains, Tanzania were discovered to show an expressive gesture using leaves, termed as “leaf-clipping display”. This behavioural signal is directed by an adult male to an estrous female as a possessive behaviour, or by an adolescent male as a courtship display, or by an estrous female to an adolescent male also as a solicitation of copulation. The signal also is used toward human observers as a signal of food-demanding. This behaviour pattern might originate in a displacement tool-making behaviour in conflict situations. The leaf-clipping display has not been observed in any other chimpanzee populations studied, and may probably be one example of the tradition drift in wild chimpanzees.     

Strigolactones as small molecule communicators

Originally identified as an allelochemical involved in plant host-parasite interactions, strigolactones have more recently been shown to have much broader communication roles. Strigolactones function as a symbiotic communicator in plants and mycorrhizal fungi interactions and have also been shown to have hormonal roles in higher plants. This ability to act as both an exogenous and an endogenous signal has interesting implications with respect to the constraints on strigolactone structures. Probing the hormonal function of strigolactones using chemical biology and genetics is beginning to provide clues as to how strigolactones were co-opted as an allelochemical signal by parasitic plants.     

Spatial Imprint of Food Consumption: A Historical Analysis for Sweden, 1870–2000

Depending on quantity and composition of food as well as on production conditions and techniques, the space needed to sustain an individual’s nourishment varies. The amount of space needed also depends on the use of resources such as energy, water, and fertilizers, as well as potential land degradation and water pollution. Our study focuses on the changing spatial imprint of an average inhabitant of an expanding Swedish city, Linköping, from 1870 to 2000 taking into account both shifts in consumption as well as agricultural productivity and practices. Despite the distinctly larger amount of animal food products, such as meat and fish, consumed in 2000, we calculate the area needed to sustain an individual’s annual food consumption could be less than one fourth of that needed in 1870. However, if the import of various globally produced foods is included in our calculations, the land needed to sustain the consumption of an inhabitant of Linköping in 2000 doubles. We also argue that an examination of this regional imprint can be used to explore and evaluate possibilities for regional development.     

Deciding with dignity: The account of human dignity as an attitude and its implications for assisted suicide

Discussions about assisted suicide have hitherto been based on accounts of dignity conceived only as an inherent value or as a status; accounts of dignity in which it appears as a (contingent) attitude, by contrast, have been neglected. Yet there are two good reasons to consider dignity to be an attitude. First, this concept of dignity best allows us to grasp a crucial aspect of everyday language: people often express fears of losing their dignity—and it is not possible to explain this with an account in which dignity is inherent. Second, such a concept allows us to adduce new argumentation where the argument based on status ends. Dignity considered as a status provides grounds to argue for the moral permissibility of assisted suicide, in the sense that in such an account individuals possess the normative power to waive their right to life. But the question then remains of how to decide what counts as a good reason for assisted suicide—and this is where an argument based on dignity as an attitude can provide illumination.     

Evolutionary stable sets in mixed-strategist models

Evolutionary stable sets are used as an extension of the concept of an evolutionarily stable strategy (ESS). They have, as sets, essentially the same properties as ordinary ESSs. Here, ES sets are applied to the characterization of what will happen in an asexual population of mixed-strategists under frequency-dependent selection. Such a population will tend to establish some state, usually not a unique one, that belongs to an ES set. For an important class of widely used mixed-strategist models, ES sets are found to comprise just those population states that allow the possible behavioural acts to be equally successful, or, to put it more precisely, that establish an evolutionarily stable population strategy.     

The fitness consequences of the autotomous blue tail in lizards: an empirical test of predator response using clay models

Numerous vertebrates employ one or more autotomous body parts as an anti-predation mechanism. Many lizards possess an autotomous tail that is brightly colored blue, which has been suggested to either serve as a decoy mechanism to divert predator attention to the autotomous body part, as an interspecific signal, or as an aposematic signal to predators that it is distasteful or dangerous. While theoretical studies suggest that a conspicuous autotomous body part that increases the probability of escape while not increasing the rate of detection will be favorable over a completely cryptic form, there is little empirical evidence supporting the adaptive benefit of an autotomous blue tail. We used in situ clay models of a scincid lizard to test the fitness consequences of blue coloration. Lizard models with a dark base color and blue decoy coloration experienced no measurable difference in avian predation relative to an all-dark model, which suggests that blue coloration neither serves as an aposematic signal nor increases the conspicuousness of the lizard model. Despite statistically similar attack rates, avian attacks on models with blue coloration were indeed focused on body sections that were colored blue. Our results suggest that the blue tail in lizards serves as an effective decoy, and that avian predation has possibly played a role in the evolution of the blue tail.     

Acting to Let Someone Die

This paper examines the recent prominent view in medical ethics that withdrawing life‐sustaining treatment (LST) is an act of killing. I trace this view to the rejection of the traditional claim that withdrawing LST is an omission rather than an act. Although that traditional claim is not as problematic as this recent prominent view suggests, my main claim is that even if we accepted that withdrawing LST should be classified as an act rather than as an omission, it could still be classified as letting die rather than killing. Even though omissions are contrasted with acts, letting die need not be, for one can let die by means of acts. The remainder of the paper is devoted to establishing this claim and addresses certain objections to it.     

The competitive ability of stem cells from mice with Hertwig's anemia

Mice homozygous for the gene, an, have a macrocytic, normochromic anemia. In this report, attempts have been made to cure Hertwig's anemia (an/an) by injecting genetically normal (+/+) stem cells. The anemia of unirradiated an/an mice was alleviated but not completely cured by injection of as many as 3 X 10(7) +/+ bone marrow cells. Lethal irradiation of the an/an recipients was necessary before injections of 10(7) +/+ marrow cells were effective in normalizing the blood parameters. The inability to achieve normal blood values without first destroying the host's own stem cells suggested that the indigenous an/an cells compete effectively with injected +/+ cells. This hypothesis was tested by injecting varying numbers of stem cells from C57BL/6J-+/+ mice, together with stem cells from either WBB6F1-an/an or, as controls, from their WBB6F1-+/+ littermates, into lethally irradiated hosts. The C57BL/6J and WBB6F1 mice have electrophoretically distinguishable hemoglobins. The an/an cells are able to compete in the repopulation of the host hematopoietic tissue as shown by the presence of WBB6F1 hemoglobin in the recipients. The cells from mice with Hertwig's anemia, however, do not compete as effectively as do the same number of cells from the +/+ littermates. These results indicate that the pluripotent hematopoietic stem cells of an/an mice are reduced in number, seeding capacity, or proliferative potential.     

Metaphors of glaucoma

In a phenomenological study of glaucoma as an illness, 31 patients were interviewed. The goal of the study was an explication of the meanings of the experience of glaucoma, in a twofold sense: (1) the face, the role, or the self of the patient that responds to the illness; (2) the visage that the illness presents to the patient. This twofold explication was achieved by generating a classification of the interviews in terms of the dominant metaphor that emerged in each interview. The following basic metaphors are presented through case material: glaucoma as an accompaniment of aging, as blindness, as pressure, as an abstraction (and a weapon), and as fate. Variations on these themes demonstrate the necessity, in such work and for enhanced communication with patients, of paying attention to both the face that the illness presents and to the self that responds.     

Targeting telomerase-expressing cancer cells

The role of telomeres and telomerase as a target for cancer therapeutics is an area of continuing interest. This review is intended to provide an update on the field, pointing to areas in which our knowledge remains deficient and exploring the details of the most promising areas being advanced into clinical trials. Topics that will be covered include the role of dysfunctional telomeres in cellular aging and how replicative senescence provides an initial barrier to the emergence of immortalized cells, a hallmark of cancer. As an important translational theme, this review will consider possibilities for selectively targeting telomeres and telomerase to enhance cancer therapy. The role of telomerase as an immunotherapy, as a gene therapy approach using telomerase promoter driven oncolytic viruses and as a small oligonucleotide targeted therapy (Imetelstat) will be discussed.     

Ethical challenges at the science-policy interface: an ethical risk assessment and proposition of an ethical infrastructure

Developing an interface between knowledge holders, stakeholders and decision makers on biodiversity issues, just as any science-policy interface, will face many challenges. In the crucial endeavour to tackle all those challenges, determining an ethical course of actions will be essential to the prestige and credibility of such an interface. The paper identifies and assesses potential ethical risks that may arise in interactions between science, society and policy and uses the Network of Knowledge (NoK) process as an example to show how an ethical infrastructure could be developed for minimizing the ethical risks and their potential consequences. Indeed, when various actors from different spheres (politics, academia, lobbyism, media, etc.) are called upon to interact within one process as complex as the NoK, the integrity and credibility of the latter are at high risk of being compromised if the ethical risks are not adequately addressed. In order to limit those risks, which science-policy interfaces such as IPCC and IPBES have already encountered, we propose to set up an ethical governance infrastructure that will guide (and regulate) interactions among internal actors of the NoK (knowledge coordination body, secretariat, expert working groups, etc.) as well as with external actors (requesters, stakeholders, etc.). A thorough evaluation of the interaction between the actors for every step of the process is carried out and potential ethical risks are identified. Suggestions as to how the risks can be handled and prevented are presented and integrated as part of an ethical infrastructure. The main objective of the paper is to address how a science-policy interface and the scientific community as a whole would benefit from implementing ethical measures and instruments to help prevent sensitive issues and undesired consequences undermining credibility and legitimacy.     

Homeostasis: a plea for a unified approach

Accompanying the progressive erosion of a coherent sense of physiology as an intellectual discipline, there has been a tendency to lose sight of the homeostatic principles that underpin physiological science, and to teach them in an oversimplified form. When (as is increasingly the case) these principles are rediscovered, they are often treated as something both novel and distinct from homeostasis, fragmenting what is best understood and taught as a unified whole. This article urges a more unitary approach to homeostasis, and attempts to show how such an approach can be presented.     

Seimatoantlerium tepuiense gen. nov., a unique epiphytic fungus producing taxol from the Venezuelan Guyana.

Seimatoantlerium gen. nov., type species, S. tepuiense sp. nov. is proposed for an acervular fungus producing 4-septate, holoblastic conidia with 6-8 unbranched, apical appendages that dehisce as an appendage apparatus and also commonly possessing one or two exogenous basal appendages as well as a pedicel. It is compared with Seimatosporium, Seimatosporiopsis, and other genera. It is epiphytic on Maguireothamnus speciosus, a rubiaceous plant endemic to the tepuis of southeastern Venezuela. It produces the anti-oomycetous anticancer compound, taxol, as shown by immunological and spectroscopic methods. Taxol production is discussed relative to the ability of this fungus to exist in an extremely moist ecosystem, as well as to its relationship to other plant associated fungi.     

A Novel Microfluidic Device-Based Neurite Outgrowth Inhibition Assay Reveals the Neurite Outgrowth-Promoting Activity of Tropomyosin Tpm3.1 in Hippocampal Neurons

Overcoming neurite inhibition is integral for restoring neuronal connectivity after CNS injury. Actin dynamics are critical for neurite growth cone formation and extension. The tropomyosin family of proteins is a regarded as master regulator of actin dynamics. This study investigates tropomyosin isoform 3.1 (Tpm3.1) as a potential candidate for overcoming an inhibitory substrate, as it is known to influence neurite branching and outgrowth. We designed a microfluidic device that enables neurons to be grown adjacent to an inhibitory substrate, Nogo-66. Results show that neurons, overexpressing hTpm3.1, have an increased propensity to overcome Nogo-66 inhibition. We propose Tpm3.1 as a potential target for promoting neurite growth in an inhibitory environment in the central nervous system.     

Human tissue for in vitro research as an alternative to animal experiments: a charitable "honest broker" model to fulfil ethical and legal regulations and to protect research participants

Research with human tissue offers the possibility not only of improving preclinical pharmaceutical research and safety assessment, but also of the substitution of some animal experiments. Surgically removed human tissue is discarded after pathological evaluation. This tissue would be of enormous value for research, especially in the pharmaceutical branch, if it were readily available in an ethically and legally approved manner. But there are public concerns about the use of human tissue, especially for "commercial" purposes, such as in the pharmaceutical industry. The question is whether the ethical boundaries are sufficiently respected in the course of striving for industrial profit. To overcome this problem, a clear procedure for tissue donation, collection, supply and allocation must be established, which is guaranteed to be independent of special interests. The persisting problem seems to be the lack of an authority which asks for informed consent, coordinates tissue as well as blinded data collection, and supplies research facilities with tissue samples in a transparent manner. Therefore, a charitable, state-controlled foundation acting as an "honest broker" was initiated, to cover the ethical and legal aspects, as well as to protect the research participants in their use of human tissue as an alternative to animal experiments.     

Le « Mégalosaure » (Dinosauria,Sauropoda) de Saint-Agnant (Charente-Maritime,France) : description et origine stratigraphique

The “Megalosaur” remains from Saint-Agnant (Charente-Maritime, France), reported as early as 1881 by Boissellier, are here described and figured for the first time. These bones, as well as a few additional specimens from the nearby locality of Soubise, belong in fact to an indeterminate sauropod. The stratigraphical position of these remains unambiguously indicates an infra-Cenomanian age. However, the presence in this area of continental deposits with Purbeckian and Wealden facies does not allow to decide between an earliest or late Early Cretaceous age.     

The intramolecular chaperone-mediated protein folding

Some proteins have evolved to contain a specific sequence as an intramolecular chaperone, which is essential for protein folding but not required for protein function, as it is removed after the protein is folded by autoprocessing or by an exogenous protease. To date, a large number of sequences encoded as N-terminal or C-terminal extensions have been identified to function as intramolecular chaperones. An increasing amount of evidence has revealed that these intramolecular chaperones play an important role in protein folding both in vivo and in vitro. Here, we summarize recent studies on intramolecular chaperone-assisted protein folding and discuss the mechanisms as to how intramolecular chaperones play roles in protein folding.     

Oligosaccharides in molecular recognition

The development, organization and growth of complex organisms as well as their interactions with the environment involve an intricate array of molecular recognition events. There is an increased awareness of the involvement of oligosaccharides in many of these processes. In this article, studies of oligosaccharide antigenicity, and the way these have been interpreted with respect to oligosaccharide function will be discussed. In addition, examples of oligosaccharides as receptor, first, as receptors and determinants of susceptibility to an exogenous infective agent and secondly, as recognition structures possibly involved in endogenous interactions, will be described. This will be followed by a discussion of the recent hypothesis in which oligosaccharides are envisaged as recognition structures and integral components of cell growth-regulating networks. Finally, an outline of new strategies for decoding the information content in glycoprotein oligosaccharides will be given.