A tribute to Achim Trebst,a friend

I honor here a friend, Achim Trebst, on his 80th birthday on June 9, 2009. I have known his outstanding research, on the biochemistry of photosynthesis, for years. My brief tribute, which includes personal, scientific and a cultural component, is followed by excellent tributes by Volker ter Meulen and Rudolf K. Thauer, by Heinrich Strotmann, and by Walter Oettmeier (this issue).     

Neuroglia at the crossroads of homoeostasis,metabolism and signalling: evolution of the concept

Ever since Rudolf Virchow in 1858 publicly announced his apprehension of neuroglia being a true connective substance, this concept has been evolving to encompass a heterogeneous population of cells with various forms and functions. We briefly compare the 19th–20th century perspectives on neuroglia with the up-to-date view of these cells as an integral, and possibly integrating, component of brain metabolism and signalling in heath and disease. We conclude that the unifying property of otherwise diverse functions of various neuroglial cell sub-types is to maintain brain homoeostasis at different levels, from whole organ to molecular.     

Virus, development and pluripotent stem cells - an interview with Rudolf Jaenisch

Rudolf Jaenisch explains how the quest for an answer to the simple question of viral tropism in the mouse lead him to a life-long career in regulation of gene expression in the early embryo and pluripotent stem cells. He shares his experience about what it takes to develop into a successful scientist; expresses his concern about the challenges facing young scientists entering the field - not all of them funding related - and candidly offers some solid tips on opportunities to take advantage of and mistakes to avoid. Being mindful of when to let go of a project, and staying focused on what is important, are probably obvious tips, but they need to be re-stated, since they also appear to be the most difficult to accomplish. Dr. Jaenisch continues to work tirelessly on the problem of epigenetic control in the early embryo and its connection with stem cells.     

ENHANCING EVOLUTION AND ENHANCING EVOLUTION

It has been claimed in several places that the new genetic technologies allow humanity to achieve in a generation or two what might take natural selection hundreds of millennia in respect of the elimination of certain diseases and an increase in traits such as intelligence. More radically, it has been suggested that those same technologies could be used to instil characteristics that we might reasonably expect never to appear due to natural selection alone. John Harris, a proponent of this genomic optimism, claims in his book Enhancing Evolution that we not only have it in our power to enhance evolution, but that we also have a duty to do so. In this paper, I claim that Harris' hand is strong but that he overplays it nevertheless. He is correct to dismiss the arguments of the anti‐enhancement lobby and correct to say that enhancement is permissible; but ‘good’ is different from ‘permissible’ and his argument for the goodness of enhancement is less convincing. Moreover, he is simply wrong to claim that it generates a duty to enhance.     

Epistemology, necessity, and evolution: a critical review of Michael Ruse��s Philosophy After Darwin

Michael Ruse??s new anthology Philosophy After Darwin provides great history and background in the major impacts Darwinism has had on philosophy, especially in ethics and epistemology. This review focuses on epistemology understood through the lens of evolution by natural selection. I focus on one of Ruse??s own articles in the collection, which responds to two classic articles by Konrad Lorenz and David Hull on the two major forms of evolutionary epistemology. I side with Ruse against Lorenz??s account of the necessity we think our principles of reasoning have, though I disagree with Ruse??s particular example. I also argue that Ruse??s alternative explanation is lacking. Against Hull, I side with Ruse in his doubts that a sociobiological approach to science will prove fruitful, though I point out that it has certain advantages other approaches do not have. Although I side with Ruse on the issue, I conclude that the two views do not really come into direct conflict and so one needs not reject either. Finally, I discuss Ruse??s positive view and raise questions for his conception of evolutionary epistemology. I conclude that his arguments are insufficient to overcome opposing views and his view has at least as many unintuitive conclusions as the alternatives.     

From irreversible thermodynamics to network thermodynamics

Whenever the subject of the thermodynamics of irreversible processes TIP is brought up among biologists, there seems to be a very polarized reaction: some have found it a useful tool, others reject it utterly, and for some reason which I do not understand, even fervently. For the present school, Professor Aharon Katchalsky had suggested that we try together to point out some ways in which TIP has been useful, to discuss limitations and shortcomings, and, finally, to show the direction and first results of present efforts, mainly in network thermodynamics¹. It would have been my task to show you the darker side of the coin, but now Aharon is not with us to show you the shining side in his unique way, to carry you along with his enthusiasm. I believe it is in Aharon's spirit that I do not attempt to evaluate or commemorate his contributions and achievements, but just talk science and try to convey a little of what was at the center of his interest during the last years.     

INTRODUCTION

.In view of the growing importance of fish for native consumption, the resources of the African lakes are sure to be exploited in the near future, but it is essential to have a sound understanding of the fish and other fauna and flora in each lake before exploitation is started. This paper places on record the available data for Lake Rudolf and Lake Baringo, on which no previous ecological work had been attempted.
Lake Rudolf is characterized by a high temperature and very alkaline water, and contains a variety of environments inhabited by different fish-associations. The fauna has pronounced nilotic affinities, except that there is only one member of the family Mormyridae. Several species, however, have come to differ from their nilotic ancestors, and the comparison of the fauna with that of other waters can be used as evidence for past changes in the drainage systems of East Africa.
The fish fauna of Lake Rudolf is roughly divisible into three main associations of species–one in the inshore waters, one in the open water, and one near the bottom. Prom data supplied by large numbers of stomach examinations, the food-chains for each of these habitats can be reconstructed.
Lake Baringo is less warm, the water has a relatively low alkalinity, and is uniformly shallow and muddy. The fish fauna consists of few species, and shows affinities with that of the East African rivers which flow to the Indian Ocean.
Owing to the shallowness of Lake Baringo, there is no differentiation into species-associations, and the food-chains are complicated by the presence of food from the bottom in all the species of fish.
The bulk of this paper contains analyses of field-observations on the size, feeding and breeding habits of each of the species found in the lakes,     

Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells

Recent cloning of a cold/menthol-sensitive TRPM8 channel (transient receptor potential melastatine family member 8) from rodent sensory neurons has provided the molecular basis for the cold sensation. Surprisingly, the human orthologue of rodent TRPM8 also appears to be strongly expressed in the prostate and in the prostate cancer-derived epithelial cell line, LNCaP. In this study, we show that despite such expression, LNCaP cells respond to cold/menthol stimulus by membrane current (I(cold/menthol)) that shows inward rectification and high Ca(2+) selectivity, which are dramatically different properties from "classical" TRPM8-mediated I(cold/menthol). Yet, silencing of endogenous TRPM8 mRNA by either antisense or siRNA strategies suppresses both I(cold/menthol) and TRPM8 protein in LNCaP cells. We demonstrate that these puzzling results arise from TRPM8 localization not in the plasma, but in the endoplasmic reticulum (ER) membrane of LNCaP cells, where it supports cold/menthol/icilin-induced Ca(2+) release from the ER with concomitant activation of plasma membrane (PM) store-operated channels (SOC). In contrast, GFP-tagged TRPM8 heterologously expressed in HEK-293 cells target the PM. We also demonstrate that TRPM8 expression and the magnitude of SOC current associated with it are androgen-dependent. Our results suggest that the TRPM8 may be an important new ER Ca(2+) release channel, potentially involved in a number of Ca(2+)- and store-dependent processes in prostate cancer epithelial cells, including those that are important for prostate carcinogenesis, such as proliferation and apoptosis.     

The Pore-Domain of TRPA1 Mediates the Inhibitory Effect of the Antagonist 6-Methyl-5-(2-(trifluoromethyl)phenyl)-1H-indazole

The transient receptor potential ion channel TRPA1 confers the ability to detect tissue damaging chemicals to sensory neurons and as a result mediates chemical nociception in vivo. Mouse TRPA1 is activated by electrophilic compounds such as mustard-oil and several physical stimuli such as cold temperature. Due to its sensory function inhibition of TRPA1 activity might provide an effective treatment against chronic and inflammatory pain. Therefore, TRPA1 has become a target for the development of analgesic drugs. 6-Methyl-5-(2-(trifluoromethyl)phenyl)-1H-indazole (Compound 31) has been identified by a chemical screen and lead optimization as an inhibitor of chemical activation of TRPA1. However, the structures or domains of TRPA1 that mediate the inhibitory effect of Compound 31 are unknown. Here, we screened 12,000 random mutant clones of mouse TRPA1 for their sensitivity to mustard-oil and the ability of Compound 31 to inhibit chemical activation by mustard-oil. In addition, we separately screened this mutant library while stimulating it with cold temperatures. We found that the single-point mutation I624N in the N-terminus of TRPA1 specifically affects the sensitivity to mustard-oil, but not to cold temperatures. This is evidence that sensitivity of TRPA1 to chemicals and cold temperatures is conveyed by separable mechanisms. We also identified five mutations located within the pore domain that cause loss of inhibition by Compound 31. This result demonstrates that the pore-domain is a regulator of chemical activation and suggests that Compound 31 might be acting directly on the pore-domain.     

“Hand down,Man down.” Analysis of Defensive Adjustments in Response to the Hot Hand in Basketball Using Novel Defense Metrics

The hot-hand phenomenon, according to which a player’s performance is significantly elevated during certain phases relative to the expected performance based on the player’s base rate, has left many researchers and fans in basketball puzzled: The vast majority of players, coaches and fans believe in its existence but statistical evidence supporting this belief has been scarce. It has frequently been argued that the hot hand in basketball is unobservable because of strategic adjustments and defensive interference of the opposing team. We use a dataset with novel metrics, such as the number of defenders and the defensive intensity for each shot attempt, which enable us to directly measure defensive pressure. First, we examine how the shooting percentage of NBA players changes relative to the attributes of each metric. We find that it is of lesser importance by how many defenders a player is guarded but that defensive intensity, e.g., whether a defender raises his hand when his opponent shoots, has a larger impact on shot difficulty. Second, we explore how the underlying metrics and shooting accuracy change as a function of streak length. Our results indicate that defensive pressure and shot difficulty increase (decrease) during hot (cold) streaks, so that defenders seem to behave according to the hot-hand belief and try to force hot players into more difficult shots. However, we find that shooting percentages of presumably hot players do not increase and that shooting performance is not related to streakiness, so that the defenders’ hot-hand behavior cannot be considered ecologically rational. Therefore, we are unable to find evidence in favor of the hot-hand effect even when accounting for defensive pressure.     

Standardization of anthropometric technics

The problem of the unification of anthropometrical examination methods was solved for decades by Rudolf Martin in his standard work. The demands now placed on anthropometric examination techniques by industrial anthropology and legislators can no longer be met by Martin's system, and a demand for clearer and more exact measurement definitions and procedures has arisen. In year-long cooperation with industrial anthropologists the German Institute of Industrial Standards has established standards for body-measurements, measurement methods, and definitions in DIN 33 402. A reciprocal international standard (ISO) can be expected. The present paper presents the anthropometric part of the new standard which contains 56 body measurements.     

Cranial and dental remains of Deinotherium bozasi (Mammalia: Proboscidea) from East Rudolf, Kenya

A skull, three immature mandibles and a number of isolated teeth belonging to Deinotherium bozasi have been collected from Plio-Pleistocene sediments to the east of Lake Rudolf, Kenya. D. bozasi is the youngest representative of the family Deinotheriidae and the skull is the most complete yet found of this taxon. The East Rudolf specimens are contrasted with comparable specimens of Prodeinotherium hobleyi from East and North Africa and of Deinotherium giganteum from Europe. The size and morphology of the cranial vault of the East Rudolf skull confirms allocation to the genus Deinotherium but other dental and cranial evidence confirms taxonomic differentiation from D. giganteum and direct descent from P. hobleyi. Although the postcranial elements of D. bozasi are poorly known it is considered unlikely that this species developed the cursorial adaptations of D. giganteum. The extinction of D. bozasi is attributable to major changes in ecologic conditions towards the end of the early Pleistocene.     

Type I restriction enzymes and their relatives

Type I restriction enzymes (REases) are large pentameric proteins with separate restriction (R), methylation (M) and DNA sequence-recognition (S) subunits. They were the first REases to be discovered and purified, but unlike the enormously useful Type II REases, they have yet to find a place in the enzymatic toolbox of molecular biologists. Type I enzymes have been difficult to characterize, but this is changing as genome analysis reveals their genes, and methylome analysis reveals their recognition sequences. Several Type I REases have been studied in detail and what has been learned about them invites greater attention. In this article, we discuss aspects of the biochemistry, biology and regulation of Type I REases, and of the mechanisms that bacteriophages and plasmids have evolved to evade them. Type I REases have a remarkable ability to change sequence specificity by domain shuffling and rearrangements. We summarize the classic experiments and observations that led to this discovery, and we discuss how this ability depends on the modular organizations of the enzymes and of their S subunits. Finally, we describe examples of Type II restriction–modification systems that have features in common with Type I enzymes, with emphasis on the varied Type IIG enzymes.     

Vegetative anatomy and systematics of subtribe Dendrobiinae (Orchidaceae)

Anatomy of leaf, stem, and root of more than 100 species in subtribe Dendrobiinae (Orchidaceae) was studied with the light microscope to provide a comparative anatomical treatment of these organs, to serve as an independent source of evidence that might be taxonomically important, and to recommend such reinterpretations of existing classifications as are suggested by a phylogenetic assessment of data. We based our classification on that of Rudolf Schlechter as the most complete and widely accepted today. We found that the anatomy of plants in subtribe Dendrobiinae reflects a high degree of morphological diversity, and many of the anatomical characters appear to be homoplasous. When these anatomical data are used to interpret the systematic relationships among the genera, they indicate that Dendrobium is not monophyletic and that Cadetia and Pseuderia are apparently nested within the structure of Dendrobium when section Grastidium is chosen as a functional outgroup. Lack of resolution in the strict consensus tree illustrates the difficulty of determining the phylogenetic relationships of many of Schlechter's sections using anatomical characters. Nevertheless, we recommend that his sectional classification, with appropriate modifications based on available data, be retained for the present, pending a more detailed understanding of the phylogeny of Dendrobiinae based on morphology, micromorphology, anatomy, and DNA studies.     

The Unabomber’s ethics

In this paper, I present and criticize Ted Kaczynski’s (“The Unabomber”) theory that industrialization has been terrible for humanity, and that we should use any means necessary, including violent means, to induce a return to pre‐industrial ways of living. Although Kaczynski’s manifesto, Industrial society and its future, has become widely known, his ideas have never before been subject to careful philosophical criticism. In this paper I show how Kaczynski’s arguments rely on a number of highly implausible philosophical premises. I further make the case that, although his theory as a whole should be rejected, Kaczynski raises a number of worries about technological development that ought to receive serious attention. Some of these worries have recently come to be shared by prominent defenders of human enhancement, including Nick Bostrom and Julian Savulescu. In the last section I indicate why I believe it is important that academic philosophers scrutinize ideas that motivate acts of violence.     

Perspectives and prospects

The study of the nonhuman primates offers great opportunities for the development of an experimental anthropology. Whether one is concerned with variations in sutures, in locomotor patterns or the distribution of genetic polymorphisms, study of the nonhuman primates may offer clues. Whether one is interested in adaptation to desert, to tropic heat, or to cold, the nonhuman primate offers a far greater range of variations than man. For many problems they are the laboratory animals of choice, and their exploitation is necessary if we are ever to have an experimental physical anthropology. Interest in the nonhuman primates brings us into touch with many other sciences, as has been shown at this symposium. But I would particularly stress how it strengthens the relations of the parts of anthropology. The social system, communication, learning, these problems are important to all of anthropology, and the study of evolution, and particularly of our nearest relatives, has much to offer to the understanding of man and his behaviors.     

The paradigm of Huntington disease.

I recall it as vividly as though it had occurred but yesterday. It made a most enduring impression upon my boyish mind which was my very first impulse to choosing chorea as my virgin contribution to medical lore. Driving with my father through a wooded road leading from East Hampton to Amagansett we suddenly came upon two women, mother and daughter, both tall and thin, almost cadaverous, both bowing, twisting, grimacing. I stared in wonderment, almost in fear. What could it mean? My father paused to speak with them and we passed on. Then my Gamaliel-like instruction began; my medical education had its inception. From this point on, my interest in the disease has never wholly ceased. [George Huntington, at 59, recalling how at the age of 8 years he first saw Huntington disease while traveling with his physician father on his professional rounds in 1858].     

An undignified bioethics: there is no method in this madness

In a recent article, Alasdair Cochrane argues for the need to have an undignified bioethics. His is not, of course, a call to transform bioethics into an inelegant, pathetic discipline, or one failing to meet appropriate disciplinary standards. His is a call to simply eliminate the concept of human dignity from bioethical discourse. Here I argue that he fails to make his case. I first show that several of the flaws that Cochrane identifies are not flaws of the conceptions of dignity he discusses but rather flaws of his, often problematic, understanding of such conceptions. Second, I argue that Cochrane's case against the concept of human dignity goes too far. I thus show that were one to agree that these are indeed flaws that require that we discard our ethical concepts, then following Cochrane's recommendations would commit us not only to an undignified bioethics, i.e. a bioethics without dignity, but to a bioethics without much ethics at all.     

Two kinds of physician‐assisted death

I argue that the concept ‘physician‐assisted suicide’ covers two procedures that should be distinguished: giving someone access to humane means to end his own life, and taking co‐responsibility for the safe and effective execution of that plan. In the first section I explain the distinction, in the following sections I show why it is important. To begin with I argue that we should expect the laws that permit these two kinds of ‘assistance’ to be different in their justificatory structure. Laws that permit giving access only presuppose that the right to self‐determination implies a right to suicide, but laws that permit doctors to take co‐responsibility may have to appeal to a principle of mercy or beneficence. Actually this difference in justificatory structure can to some extent be found in existing regulatory systems, though far from consistently. Finally I argue that if one recognizes a right to suicide, as Oregon and other American states implicitly do, and as the European Court of Human Rights has recently done explicitly, one is committed to permit the first kind of ‘assistance’ under some conditions.