Pain, paradox, and value

The author argues that "as soon as one begins to study the understanding and management of pain in science, human medicine, and veterinary medicine, one begins to encounter a variety of apparent paradoxes." He contends that these paradoxes, ten of which he identifies and discusses in this essay, are based on flawed philosophical and valuational assumptions underlying science and medicine. Rollins concludes that, as social morality increasingly has an impact on science, a new ideology will evolve that is more receptive to the moral universe and more capable of a "coherent vision of pain, one which acknowledges that the medical notion of adequacy of anaesthesia is as much a moral as a scientific one."     

Cadmium transport, resistance, and toxicity in bacteria, algae, and fungi

Cadmium is an important environmental pollutant and a potent toxicant to bacteria, algae, and fungi. Mechanisms of Cd toxicity and resistance are variable, depending on the organism. It is very clear that the form of the metal and the environment it is studied in, play an important role in how Cd exerts its effect and how the organism(s) responds. A wide range of Cd concentrations have been used to designate resistance in organisms. To date, no concentration has been specified that is applicable to all species studied under standardized conditions. Cadmium exerts its toxic effect(s) over a wide range of concentrations. In most cases, algae and cyanobacteria are the most sensitive organisms, whereas bacteria and fungi appear to be more resistant. In some bacteria, plasmid-encoded resistance can lead to reduced Cd2+ uptake. However, some Gram-negative bacteria without plasmids are just as resistant to Cd as are bacteria containing plasmids encoding for Cd resistance. According to Silver and Misra (1984), there is no evidence for enzymatic or chemical transformations associated with Cd resistance. Insufficient information is available on the genetics of Cd uptake and resistance in cyanobacteria and algae. Mechanisms remain largely unknown at this point in time. Cadmium is toxic to these organisms, causing severe inhibition of such physiological processes as growth, photosynthesis, and nitrogen fixation at concentrations less than 2 ppm, and often in the ppb range (Tables 2 and 3). Cadmium also causes pronounced morphological aberrations in these organisms, which are probably related to deleterious effects on cell division. This may be direct or indirect, as a result of Cd effects on protein synthesis and cellular organelles such as mitochondria and chloroplasts. Cadmium is accumulated internally in algae (Table 4) as a result of a two-phase uptake process. The first phase involves a rapid physicochemical adsorption of Cd onto cell wall binding sites, which are probably proteins and (or) polysaccharides. This is followed by a lag period and then a slow, steady intracellular uptake. This latter phase is energy dependent and may involve transport systems used to accumulate other divalent cations, such as Mn2+ and Ca2+. Some data indicate that Cd resistance, and possibly uptake, in algae and cyanobacteria is controlled by a plasmid-encoded gene(s). Although considerable information is available on Cd toxicity to, and uptake in fungi, further work is clearly needed in several areas. There is little information about Cd uptake by filamentous fungi, and even in yeasts, information on the specificity, kinetics, and mechanisms of Cd uptake is limited.(ABSTRACT TRUNCATED AT 400 WORDS)     

Earth, sky, wind, and weather

This paper seeks to understand what it means to live 'in the open'. It begins with an account of experiments that test whether children have acquired a scientifically correct understanding of the shape of the earth, according to which people live all around on the outside of a solid sphere. This understanding cannot accommodate the phenomenon of the sky, in relation to which the earth can appear only as the ground of human habitation. James Gibson's ecological approach to perception offers a possible alternative, depicting earth and sky as complementary hemispheres. Yet for Gibson, this earth-sky can be inhabited only insofar as it is furnished with objects. To that extent, it ceases to be open. Drawing on elements of Merleau-Ponty's phenomenology, it is argued that in the open world persons and things relate not as closed forms but by virtue of their common immersion in the generative fluxes of the medium – in wind and weather. Fundamental to life is the process of respiration, by which organisms continually disrupt any boundary between earth and sky, binding substance and medium together in forging their own growth and movement. Thus to inhabit the open is not to be stranded on the outer surface of the earth but to be caught up in the transformations of the weather-world.     

Photons, clocks, and consciousness

Light profoundly impacts human consciousness through the stimulation of the visual system and powerfully regulates the human circadian system, which, in turn, has a broad regulatory impact on virtually all tissues in the body. For more than 25 years, the techniques of action spectroscopy have yielded insights into the wavelength sensitivity of circadian input in humans and other mammalian species. The seminal discovery of melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, has provided a significant turning point for understanding human circadian phototransduction. Action spectra in humans show that the peak wavelength sensitivity for this newly discovered sensory system is within the blue portion of the spectrum. This is fundamentally different from the three-cone photopic visual system, as well as the individual rod and cone photoreceptor peaks. Studies on rodents, nonhuman primates, and humans indicate that despite having a different wavelength fingerprint, these classic visual photoreceptors still provide an element of input to the circadian system. These findings open the door to innovations in light therapy for circadian and affective disorders, as well as possible architectural light applications.     

Membranes,viruses, detergents,and endosomes

The fluid mosaic model for biological membranes was formulated 40 years ago. Ten years later endosomes were discovered as important prelysosomal organelles. At the outset of my research career, I was fortunate to witness both these turning points in biochemistry and cell biology from close up, and to participate in some of the studies. In this short essay, I will describe how this came about, and also try to provide some background as to the general starting situation in those not so distant pioneering years of membrane biology.     

Modules, kinds, and homology

Developmental modules are best conceptualized as homeostatic property cluster natural kinds. As is true in other fields of biology, an individual may instantiate properties of various natural kinds. Through their dissociability, developmental modules can be recruited to function as evolutionary modules. The proper analogy to developmental modules, atoms, or biological species depends on the scope over which specific developmental modules allow generalizations. The nature of the relationship between developmental modules, evolutionary modules, and taxic (phylogenetic) homology are explored. Similarity of gene expression patterns and developmental pathways as captured by biological homology may support hypotheses of taxic homology, but not the other way around.     

Incorporating Science,Technology, Fairness,and Accountability in Environmental,Health, and Safety Decisions

The Precautionary Principle is in sharp political focus today because (1) the nature of scientific uncertainty is changing and (2) there is increasing pressure to base governmental action on more “rational” schemes, such as cost-benefit analysis and quantitative risk assessment, the former being an embodiment of ‘rational choice theory’ promoted by the Chicago school of law and economics. The Precautionary Principle has been criticized as being both too vague and too arbitrary to form a basis for rational decision making. The assumption underlying this criticism is that any scheme not based on cost-benefit analysis and risk assessment is both irrational and without secure foundation in either science or economics. This paper contests that view and makes explicit the rational tenets of the Precautionary Principle within an analytical framework as rigorous as uncertainties permit, and one that mirrors democratic values embodied in regulatory, compensatory, and common law. Unlike other formulations that reject risk assessment, this paper argues that risk assessment can be used within the formalism of tradeoff analysis—a more appropriate alternative to traditional cost-benefit analysis and one that satisfies the need for well-grounded public policy decision making. This paper will argue that the precautionary approach is the most appropriate basis for policy, even when large uncertainties do not exist, especially where the fairness of the distributions of costs and benefits of hazardous activities and products are a concern. Furthermore, it will offer an approach to making decisions within an analytic framework, based on equity and justice, to replace the economic paradigm of utilitarian cost-benefit analysis.     

Present knowledge and controversies,deficiencies, and misconceptions on nitric oxide synthesis,sensing, and signaling in plants

After 30 years of intensive work, nitric oxide (NO) has just started to be characterized as a relevant regulatory molecule on plant development and responses to stress. Its reactivity as a free radical determines its mode of action as an inducer of posttranslational modifications of key target proteins through cysteine S-nitrosylation and tyrosine nitration. Many of the NO-triggered regulatory actions are exerted in tight coordination with phytohormone signaling. This review not only summarizes and updates the information accumulated on how NO is synthesized, sensed, and transduced in plants but also makes emphasis on controversies, deficiencies, and misconceptions that are hampering our present knowledge on the biology of NO in plants. The development of noninvasive accurate tools for the endogenous NO quantitation as well as the implementation of genetic approaches that overcome misleading pharmacological experiments will be critical for getting significant advances in better knowledge of NO homeostasis and regulatory actions in plants.     

Resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics

Macrolides have enjoyed a resurgence as new derivatives and related compounds have come to market. These newer compounds have become important in the treatment of community-acquired pneumoniae and nontuberculosis-Mycobacterium diseases. In this review, the bacterial mechanisms of resistance to the macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics, the distribution of the various acquired genes that confer resistance, as well as mutations that have been identified in clinical and laboratory strains are examined.     

Cellulase, Clostridia, and Ethanol

Biomass conversion to ethanol as a liquid fuel by the thermophilic and anaerobic clostridia offers a potential partial solution to the problem of the world's dependence on petroleum for energy. Coculture of a cellulolytic strain and a saccharolytic strain of Clostridium on agricultural resources, as well as on urban and industrial cellulosic wastes, is a promising approach to an alternate energy source from an economic viewpoint. This review discusses the need for such a process, the cellulases of clostridia, their presence in extracellular complexes or organelles (the cellulosomes), the binding of the cellulosomes to cellulose and to the cell surface, cellulase genetics, regulation of their synthesis, cocultures, ethanol tolerance, and metabolic pathway engineering for maximizing ethanol yield.     

Sympathy and suspicion: torture,asylum, and humanity

This article examines the assessment of claims about torture in the British asylum process. It is compassion in the face of suffering that underlies much of the ethical objection to torture. Yet, at the same time, torture survivors, as with asylum seekers more broadly, are subjected to widespread suspicions about the genuineness of their claims. This article argues that the very process of imagined identification found in compassion can lie behind suspicion. Anthropology has largely treated otherness as a cause of fear and suspicion. However, the denial of another's suffering is not always about a failure to recognize mutual humanity. It can also be a product of a sense of fundamental similarity, based on assumptions about the mutual capacity to dissimulate. Ultimately, though, scepticism is on just as shaky ground as belief, as it is filtered through the lens of imagined identification. Denial is just as vicarious as acknowledgement.     

Science, senators, and uncertainty.

Members of Congress consider value judgments and the likelihood of successful enactment as well as scientific facts in formulating policy. If scientists would provide a range of scientifically acceptable options at the same time as they recommend the scientifically optimal solutions, politicans could choose the best scientific option that is also politically acceptable. In the context of research funding Congress needs to be presented with more realistic expectations about the time it takes for different levels of research to result in practical applications, so as to provide better continuity in research funding.     

Signs, communication, and language

Noting the vagueness and confusion in the literature on animal behavior with regard to the phenomenon of communication, an attempt is made to define “sign” and “communication” from the point of view of cybernetics, drawing also on Susanne Langer's philosophy of symbols. The author argues that neither communication nor language can be successfully investigated as long as the dogmatic behaviorist's taboo against goal-directed or purposive activities is maintained. In accord with recent developments in feedback theory, he shows that the cyberneticist's concept of purpose can be used quite legitimately in the scientific analysis of behavior and that it makes possible a viable classification of signs as well as the discrimination of communication from other types of interaction. In conclusion some of Hockett's “design features” of language are discussed and an attempt is made to formulate criteria for the form of communcation that should be called linguistic.     

Convergence, adaptation, and constraint

Convergent evolution of similar phenotypic features in similar environmental contexts has long been taken as evidence of adaptation. Nonetheless, recent conceptual and empirical developments in many fields have led to a proliferation of ideas about the relationship between convergence and adaptation. Despite criticism from some systematically minded biologists, I reaffirm that convergence in taxa occupying similar selective environments often is the result of natural selection. However, convergent evolution of a trait in a particular environment can occur for reasons other than selection on that trait in that environment, and species can respond to similar selective pressures by evolving nonconvergent adaptations. For these reasons, studies of convergence should be coupled with other methods-such as direct measurements of selection or investigations of the functional correlates of trait evolution-to test hypotheses of adaptation. The independent acquisition of similar phenotypes by the same genetic or developmental pathway has been suggested as evidence of constraints on adaptation, a view widely repeated as genomic studies have documented phenotypic convergence resulting from change in the same genes, sometimes even by the same mutation. Contrary to some claims, convergence by changes in the same genes is not necessarily evidence of constraint, but rather suggests hypotheses that can test the relative roles of constraint and selection in directing phenotypic evolution.     

Red, Yellow, and Super-White Sclera

The sclera, the eye’s tough outer layer, is, among primates, white only in humans, providing the ground necessary for the display of colors that vary in health and disease. The current study evaluates scleral color as a cue of socially significant information about health, attractiveness, and age by contrasting the perception of eyes with normal whites with copies of those eyes whose whites were reddened, yellowed, or further whitened by digital editing. Individuals with red and yellow sclera were rated to be less healthy, less attractive, and older than individuals with untinted control sclera. Individuals with whitened, “super-white” sclera were rated as younger, although not more healthy or attractive, than controls. In humans, clear, white sclera may join such traits as smooth skin and long, lustrous hair as signs of health, beauty, and reproductive fitness. The evolution of a white sclera may have contributed to the emergence of humans as a social species.     

Sugars, signalling, and plant development

Like all organisms, plants require energy for growth. They achieve this by absorbing light and fixing it into a usable, chemical form via photosynthesis. The resulting carbohydrate (sugar) energy is then utilized as substrates for growth, or stored as reserves. It is therefore not surprising that modulation of carbohydrate metabolism can have profound effects on plant growth, particularly cell division and expansion. However, recent studies on mutants such as stimpy or ramosa3 have also suggested that sugars can act as signalling molecules that control distinct aspects of plant development. This review will focus on these more specific roles of sugars in development, and will concentrate on two major areas: (i) cross-talk between sugar and hormonal signalling; and (ii) potential direct developmental effects of sugars. In the latter, developmental mutant phenotypes that are modulated by sugars as well as a putative role for trehalose-6-phosphate in inflorescence development are discussed. Because plant growth and development are plastic, and are greatly affected by environmental and nutritional conditions, the distinction between purely metabolic and specific developmental effects is somewhat blurred, but the focus will be on clear examples where sugar-related processes or molecules have been linked to known developmental mechanisms.     

Conjugates of abscisic acid, brassinosteroids, ethylene, gibberellins, and jasmonates

Phytohormones, including auxins, abscisic acid, brassinosteroids, cytokinins, ethylene, gibberellins, and jasmonates, are involved in all aspects of plant growth, and developmental processes as well as environmental responses. However, our understanding of hormonal homeostasis is far from complete. Phytohormone conjugation is considered as a part of the mechanism to control cellular levels of these compounds. Active phytohormones are changed into multiple forms by acylation, esterification or glycosylation, for example. It seems that conjugated compounds could serve as pool of inactive phytohormones that can be converted to active forms by de-conjugation reactions. Some conjugates are thought to be temporary storage forms, from which free active hormones can be released after hydrolysis. It is also believed that conjugation serves functions, such as irreversible inactivation, transport, compartmentalization, and protection against degradation. The nature of abscisic acid, brassinosteroid, ethylene, gibberellin, and jasmonate conjugates is discussed.     

CO metabolism, sensing, and signaling

CO is a colorless and odorless gas produced by the incomplete combustion of hydrocarbons, both of natural and anthropogenic origin. Several microorganisms, including aerobic and anaerobic bacteria and anaerobic archaea, use exogenous CO as a source of carbon and energy for growth. On the other hand, eukaryotic organisms use endogenous CO, produced during heme degradation, as a neurotransmitter and as a signal molecule. CO sensors act as signal transducers by coupling a "regulatory" heme-binding domain to a "functional" signal transmitter. Although high CO concentrations inhibit generally heme-protein actions, low CO levels can influence several signaling pathways, including those regulated by soluble guanylate cyclase and/or mitogen-activated protein kinases. This review summarizes recent insights into CO metabolism, sensing, and signaling.     

Mitochondrial Metabolism,Sirtuins, and Aging

The sirtuins are a family of proteins that act predominantly as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases. In mammals seven sirtuin family members exist, including three members, Sirt3, Sirt4, and Sirt5, that localize exclusively within the mitochondria. Although originally linked to life-span regulation in simple organisms, this family of proteins appears to have various and diverse functions in higher organisms. One particular property that is reviewed here is the regulation of mitochondrial number, turnover, and activity by various mitochondrial and nonmitochondrial sirtuins. An emerging consensus from these recent studies is that sirtuins may act as metabolic sensors, using intracellular metabolites such as NAD and short-chain carbon fragments such as acetyl coenzyme A to modulate mitochondrial function to match nutrient supply.