Is the philosophy of mechanism philosophy enough?

Recognition of the widespread use of the word 'mechanism' in bio-molecular research has resulted in the concept of 'mechanism' becoming a focal point for a highly visible group of philosophers of biology. Rather, however, than grasping and elucidating the situated aims and practices of biologists themselves, the philosophical investigation of the contemporary meaning of mechanism in biology has been commandeered by the needs of 'hard naturalists' to replace the old deductive-nomological model of the 'received view' with a new normative-explanatory gold-standard. It is argued that rather than an orientation toward an increasingly precise characterization of mechanisms as being an ultimate end in biological research, in actual biological practice 'mechanism' means different things in different contexts, pragmatically draws on our embodied know-how in the use of machines and is not, nor should be, an ultimate end of biological research. Further, it is argued, that classic work on low-level mechanisms became taken up qualitatively as parts of the scaffolding for investigating higher level regulatory processes and that in so doing, and in light of new findings such as that of the regulatory significance of 'pleiomorphic ensembles' and 'intrinsically unstructured proteins' the explanatory limits of the mechanism image have already come into view.     

The challenge of sustainability: Is integrating environment and economy enough?

Conclusions Beyond Interdependence, along with each of the other books, appeared after publication of Our Common Future but before the Earth Summit in Rio. It was a time to be optimistic, and each book is optimistic, if cautiously so. Certainly the impact of the Brundtland Report has been enormous, perhaps not beyond the dreams of the members of the Commission, but certainly beyond their expectations. The impact of the Earth Summit has been much smaller, certainly well short of the dreams of those involved though perhaps within their expectations.If the Brundtland Report and the books reviewed in this essay show the potential, the Earth Summit shows the limits. What have been called the inner limits of interests, institutions, and politics turn out to be far more important than the outer limits of ecology and even economics. The next steps are going to be difficult, and books such as Beyond Interdependence are needed to indicate when, where and how to take such steps. There may eventually be a Mark II framework convention for climate change, forestry and biodiversity (p. 115–116), but along the way there will be many more national actions, bi- or tri-national agreements, and Montreal Protocols. In the words of MacNeill, Winsemius and Yakushiji (p. 117), A Grand Global Bargain could be the sum of 1,000 small bargains. Even if, in my view and the views of Goodland et al. and Meadows et al., Beyond Interdependence is inadequate to get us onto a fully sustainable path, there is little if anything in its recommendations that would be inappropriate in our search for that path.How can we go beyond integration of environment and economy? A number of authors have begun to make suggestions (e.g., Ekins, 1987; Brooks, 1991; Durning, 1992; Harrison, 1992). Certainly, one can agree with MacNeill, Winsemius and Yakushiji that we need not spend any more time defining sustainable development. (By 1990, there were already some 40 definitions in the literature.) The definition provided by the Brundtland Report is good enough for working purposes. What is needed now is not more discussion about sustainable development but more experimentation with it. We must try different development strategies, and keep trying until the best fit is found for particular times, particular places and particular peoples. Some policies will get us closer; others will turn out to be inefficient, destructive, or inequitable. But the experiments must continue until each community finds a set that works economically, ecologically and politically. In the words of Rabbi Tarphon, who lived nearly two millennia ago and contributed to the Talmud, It is not up to us to complete the task, but neither are we free to refrain from getting started on it.     

Is MHC enough for understanding wildlife immunogenetics?

Along with reproductive success and predation, infectious disease is a major demographic and evolutionary driver of natural populations. To understand the evolutionary impacts of disease, research has focussed on the major histocompatibility complex (MHC), a genetic region involved in antigen presentation. There is a pressing need for the broader research currently conducted on traditional vertebrate models to be transferred to wildlife. Incorporating such knowledge will enable a broader understanding of the levels at which natural selection can act on immunity. We propose two new approaches to wildlife immunogenetics and discuss the challenges of conducting such studies. At a time when novel pathogens are increasingly emerging in natural populations, these new approaches are integral to understanding disease dynamics and assessing epidemic risks.     

Is stress really all that important?

There is growing concern in many parts of the world that fertility of dairy cattle is reducing as milk yields increase. Stress could be one important cause. As an example, fertility is lower after caesarian operations. Delayed uterine involution after dystocia is associated with abnormal ovarian cyclicity and prolonged intervals to the next pregnancy. There is a greater reduction in fertility as the clinical conditions of lameness, milk fever or mastitis worsen. Changes in social groupings greatly increase the number of inseminations required per pregnancy. Transport reduces the number of CL after superovulation, and can interfere with pregnancy rates after estrous synchronization. Embryos collected from heat-stressed donors are less viable and have delayed trophoblast function. Human-animal interactions influence stress-responses in cattle--the behavior of stockman and embryo transfer personnel could affect success. Putting aside financial aspects, exposure of an animal to avoidable stress compromises welfare, whether application of biotechnology is involved or not. The fact that stressors can be deleterious to such an important function as reproduction, emphasizes that stress is very important and should be minimized whenever possible.     

Is outer arm dynein intermediate chain 1 multifunctional?

The outer arm dynein of sea urchin sperm axoneme contains three intermediate chains (IC1, IC2, and IC3; M(r) 128,000, 98,000, and 74,000, respectively). IC2 and IC3 are members of the WD family; the WD motif is responsible for a protein-protein interaction. We describe here the molecular cloning of IC1. IC1 has a unique primary structure, the N-terminal part is homologous to the sequence of thioredoxin, the middle part consists of three repetitive sequences homologous to the sequence of nucleoside diphosphate kinase, and the C-terminal part contains a high proportion of negatively charged glutamic acid residues. Thus, IC1 is a novel dynein intermediate chain distinct from IC2 and IC3 and may be a multifunctional protein. The thioredoxin-related part of IC1 is more closely related to those of two redox-active Chlamydomonas light chains than thioredoxin. Antibodies were prepared against the N-terminal and middle domains of IC1 expressed as His-tagged proteins in bacteria. These antibodies cross-reacted with some dynein polypeptides (potential homologues of IC1) from distantly related species. We propose here that the three intermediate chains are the basic core units of sperm outer arm dynein because of their ubiquitous existence. The recombinant thioredoxin-related part of IC1 and outer arm dyneins from sea urchin and distantly related species were specifically bound to and eluted from a phenylarsine oxide affinity column with 2-mercaptoethanol, indicating that they contain vicinal dithiols competent to undergo reversible oxidation/reduction.     

Motor grading of elbow flexion – is Medical Research Council grading good enough?

We present a new surgical technique for a pedicled teres major muscle transfer to improve shoulder abduction and flexion in children with sequelae of obstetric brachial plexus palsy. In addition, we provide the clinical outcome in the first 17 operated children.     

Is supercomplex organization of the respiratory chain required for optimal electron transfer activity?

The supra-molecular assembly of the main respiratory chain enzymatic complexes in the form of "super-complexes" has been proved by structural and functional experimental evidence. This evidence strongly contrasts the previously accepted Random Diffusion Model stating that the complexes are functionally connected by lateral diffusion of small redox molecules (i.e. Coenzyme Q and cytochrome c). This review critically examines the available evidence and provides an analysis of the functional consequences of the intermolecular association of the respiratory complexes pointing out the role of Coenzyme Q and of cytochrome c as channeled or as freely diffusing intermediates in the electron transfer activity of their partner enzymes.     

Is the sperm type of the Nemertodermatida close to that of the ancestral Platyhelminthes?

Results from a transmission electron microscope study of the spermiogenesis and spermatozoon of Meara stichopi (Nemertodermatida, Platyhelminthes) indicate that the sperm type of the Nemertodermatida has evolved from the primitive metazoan sperm type rather than from an aberrant biflagellar sperm type as found in many other flatworms. The spirally coiled mitochondrial derivative in the mature spermatozoon develops from two large oval mitochondria in the early spermatid stages. A single flagellum grows out from a peripheral basal body adjacent to a perpendicularly placed accessory centriole. The basal body moves to a distal depression of the nucleus, and becomes equipped with an anchoring fibre apparatus. Most of the flagellum becomes axially incorporated into the developing spermatid. No trace of a second flagellum was found in any stage of the spermiogenesis. Rounded vesicles appear around the proximal, tapering end of the elongating nucleus. Most probably these vesicles form a thin acrosomal structure in the mature spermatozoon. No dense bodies, characteristic of many other ‘turbellarian’ flatworm sperm types, were found. This revised version was published online in July 2006 with corrections to the Cover Date.     

Is EGF a physiological inhibitor of mouse mammary casein synthesis? Unphysiological responses to pharmacological levels of hormones

It has been observed that EGF inhibits the induction of casein synthesis by mouse mammary tissue in vitro in addition to acting as a promoter of mammary epithelial proliferation. However, since the circulating level of EGF increases during lactation, and since functional EGF receptors are retained by the lactating cells, it seemed unlikely that EGF is an inhibitor of mammary differentiation in vivo. The current studies demonstrate, in fact, that EGF inhibits the induction of casein synthesis in vitro only when insulin is present in the culture medium at unphysiologically high concentrations. Other artifactual responses to high levels of hormones are described.     

Is innate enough? The innate immune response in Drosophila

In recent years, the innate immune system has emerged from the shadow of adaptive immune responses as a major area of research in its own right. One of the most significant model systems that has been used to investigate this phenomenon has been the fruit fly, Drosophila melanogaster. Exploration of the differential immune response presented by Drosophila led to the discovery of important signalling events and transduction pathways, which were thereafter shown to be specific for the type of infecting pathogen. These factors and pathways were subsequently found to have homologues in many other organisms, including those with adaptive immune responses. In light of the present status of studies in innate immunity, this review describes the current state of understanding of the Drosophila immune response.     

The Carboxy-Terminal Domain of Erb1 Is a Seven-Bladed ?-Propeller that Binds RNA

Erb1 (Eukaryotic Ribosome Biogenesis 1) protein is essential for the maturation of the ribosomal 60S subunit. Functional studies in yeast and mammalian cells showed that altogether with Nop7 and Ytm1 it forms a stable subcomplex called PeBoW that is crucial for a correct rRNA processing. The exact function of the protein within the process remains unknown. The N-terminal region of the protein includes a well conserved region shown to be involved in PeBoW complex formation whereas the carboxy-terminal half was predicted to contain seven WD40 repeats. This first structural report on Erb1 from yeast describes the architecture of a seven-bladed β-propeller domain that revealed a characteristic extra motif formed by two α-helices and a β-strand that insert within the second WD repeat. We performed analysis of molecular surface and crystal packing, together with multiple sequence alignment and comparison of the structure with other β-propellers, in order to identify areas that are more likely to mediate protein-protein interactions. The abundance of many positively charged residues on the surface of the domain led us to investigate whether the propeller of Erb1 might be involved in RNA binding. Three independent assays confirmed that the protein interacted in vitro with polyuridilic acid (polyU), thus suggesting a possible role of the domain in rRNA rearrangement during ribosome biogenesis.