Interactions with John Gurdon – muscle as a mesodermal read-out and the community effect

John Gurdon has made major contributions to developmental biology in addition to his Nobel prize winning work on nuclear reprogramming. With the frog, Xenopus, as a vertebrate model, his work on mesoderm induction led him to identify a community effect required for tissue differentiation after progenitor cells have entered a specific mesodermal programme. It is in the context of this biologically important concept, with myogenesis as an example, that we have had most scientific exchanges. Here I trace my contacts with him, from an interest in histone regulation of gene expression and reprogramming, to myogenic determination factors as markers of early mesodermal induction, to the role of the community effect in the spatiotemporal control of skeletal muscle formation. I also recount some personal anecdotes from encounters in Oxford, Paris and Cambridge, to illustrate my appreciation of him as a scientist and a colleague.     

Speaking out about the social implications of science: the uneven legacy of H. J. Muller

H. J. Muller (1890-1967) was unusual as a scientist because he spoke out on numerous occasions about the uses and abuses of genetics in society. In this article, I follow Muller's efforts to do so and the consequences that they had on his career, his productivity as a research scientist, and his reputation. The shifting sites of Muller's work--which ranged from Columbia University to Texas, from Berlin to Moscow and Leningrad, from Madrid to Edinburgh, and from Amherst to Indiana University--made his activism unusual. Muller paid a price for his activism, and his reputation today is still marred by what most historians would consider risky judgments and reversals of position about genetics and society. My analysis is not a defense but rather an evaluation of the circumstances that led him to these positions and an analysis of the consequences of challenging society when scientists believe their science is being ignored or abused.     

The Plaintiff's Attorney and Obstetrics

This paper was presented before a meeting of plaintiffs'' attorneys, including those who specialize in malpractice actions against physicians—the National Association of Claimants'' Compensation Attorneys (NACCA).Doctor Eastman is known internationally for his contribution in the field of obstetrics. In recent years his interests have led him into the field of forensic obstetrics, a complex and difficult subject. Some of these problems are explored by Dr. Eastman in this paper and his comments will be of interest to physicians and attorneys.It is to be hoped that NACCA members benefited by this accurate and scientific presentation.     

Distribution of mechanical stress in the Escherichia coli cell envelope

The cell envelope in Gram-negative bacteria comprises two distinct membranes with a cell wall between them. There has been a growing interest in understanding the mechanical adaptation of this cell envelope to the osmotic pressure (or turgor pressure), which is generated by the difference in the concentration of solutes between the cytoplasm and the external environment. However, it remains unexplored how the cell wall, the inner membrane (IM), and the outer membrane (OM) effectively protect the cell from this pressure by bearing the resulting surface tension, thus preventing the formation of inner membrane bulges, abnormal cell morphology, spheroplasts and cell lysis. In this study, we have used molecular dynamics (MD) simulations combined with experiments to resolve how and to what extent models of the IM, OM, and cell wall respond to changes in surface tension. We calculated the area compressibility modulus of all three components in simulations from tension-area isotherms. Experiments on monolayers mimicking individual leaflets of the IM and OM were also used to characterize their compressibility. While the membranes become softer as they expand, the cell wall exhibits significant strain stiffening at moderate to high tensions. We integrate these results into a model of the cell envelope in which the OM and cell wall share the tension at low turgor pressure (0.3 atm) but the tension in the cell wall dominates at high values (>1 atm).     

The microenvironment matters

The physical and biochemical properties of the microenvironment regulate cell behavior and modulate tissue development and homeostasis. Likewise, the physical and interpersonal cues a trainee receives profoundly influence his or her scientific development, research perspective, and future success. My cell biology career has been greatly impacted by the flavor of the scientific environments I have trained within and the diverse research mentoring I have received. Interactions with physical and life scientists and trainees and exposure to a diverse assortment of interdisciplinary environments have and continue to shape my research vision, guide my experimental trajectory, and contribute to my scientific success and personal happiness.     

Q & A. [interview

George Oster is Professor of Biophysics, University of California, Berkeley. He received his B.S. at the U.S. Merchant Marine Academy and his Ph.D. at Columbia University. He began his career in biophysics as a postdoc at the Weizmann Institute under Aharon Katchalsky, where his research involved membrane biophysics and irreversible thermodynamics. His concern for environmental issues led him into population biology, which shaded into evolutionary biology and thence to developmental biology, cell biology and, most recently, protein motors and bacterial motility and pattern formation. His tools are mathematics, physics and computer simulation. He is currently a faculty member in the Departments of Molecular and Cellular Biology and the College of Natural Resources at Berkeley.     

Professor Ebashi's impact on the study of the regulation of striated muscle contraction

The field of striated muscle regulation has changed tremendously over the last forty years. Many of the problems solved by Dr. Ebashi and by those stimulated by him offer new challenges for future generations of scientists. Many questions remain to be solved, and it should give particular pleasure to Dr. Ebashi to see how the seeds sown by him and his colleagues have now grown into a beautiful tree that bears rich fruit at present and will continue to do so for a long time in the future.     

The Paradoxical Anthropology of Leslie White

The many contradictions in the anthropology of Leslie White derive mainly from the fact that he embraced two contradictory models of culture: the sui generis conception that he received from his Boasian education, and the materialist-utilitarian framework that developed out of his concern with cultural evolutionism. White never reconciled the two, but in any instance of conflict he gave preference to the sui generis, Boasian-derived conception. This led him eventually to repudiate significant aspects of his utilitarian-adaptive framework.     

Ksenia Guseva: Formation and Cooperative Behavior of Protein Complexes on the Cell Membrane

The thesis as a book on formation and cooperative behavior of protein complexes on the cell membrane highlights three major sections on protein oligomerization on cell surface, review approaches on membrane protein oligomerization and validation of oligomer formation process mainly using pure physical/theoretical models. These chapters cover an existing knowledge on membrane protein oligomer formation, experimental approaches with focus on mechanosensitive channels, interactions in oligomer assembly/stability, protein fragmentation, and pore formation in Tat complex system. In almost every chapter, physical/theoretical models have been integrated. A merger of protein oligomerization phenomena and theoretical physics is not quite intriguing for biologists/biochemists lacking adequate knowledge in physical modeling and its theoretical applications, and vice versa.     

Cytoskeletal dynamics: A view from the membrane

ConclusionsAs more mechanistic connections emerge between the membrane and the cytoskeleton, it is becoming clear that a new generation of tools is needed. In particular, being able to track the dynamics and localization of specific lipid species, as well as physical methods to measure membrane rigidity in living cells, is critical. Additionally, most studies have been performed in individual cells, but not in the context of developing tissues or varied extracellular environments. Thus, how mechanical strains on the membrane translate into cytoskeletal reorganization ultimately effecting cell physiology and development constitutes the next generation of questions in cytoskeletal dynamics.     

The structure of a photoreceptor organelle in the eye of Pterotrachea mutica

Summary The photoreceptor cell of Pterotrachea consists of an elongated cell some 100 m long with recogniseable inner and outer segments. The photoreceptor membranes point towards the light. There are about 300 discs per photoreceptor, a small number of discs arising from a single ciliary base. There are bout 75–100 such bases on each receptor cell. The receptor cells themselves (the inner segments) have four recognisable regions. The vacuolated region, the region of mitochondria, the nuclear region, and the axonal region.The photoreceptor cells are organised in five roughly parallel rows, and separated from one another by pale supporting cells.My thanks are due to Professor J. Z. Young, F. R. S. for his enthusiastic support and help during this work. Dr. R. Bellairs kindly provided electron microscope facilities. Mr. R. Moss, Mrs. J. Hamilton and Mr. A. Aldridge provided excellent technical and photographic assistance.     

The actin slingshot

Actin polymerization generates the force that deforms the cell membrane, pulls the cell forward and propels endosomes and bacteria within the cell. The mechanism of force generation has been probed using experimental biomimetic systems where force generation and movement occur by the same actin-polymerization processes observed in cells. The advantage of such systems over living cells is that their physical properties can be changed, such as the size of the load, its composition and its deformability, in order to respond to specific questions. Recent experimental developments and associated theoretical models have provided us with a better understanding of motility based on actin polymerization. This paves the way towards a better comprehension of cell motility.     

Model answers to lipid membrane questions

Ever since it was discovered that biological membranes have a core of a bimolecular sheet of lipid molecules, lipid bilayers have been a model laboratory for investigating physicochemical and functional properties of biological membranes. Experimental and theoretical models help the experimental scientist to plan experiments and interpret data. Theoretical models are the theoretical scientist's preferred toys to make contact between membrane theory and experiments. Most importantly, models serve to shape our intuition about which membrane questions are the more fundamental and relevant ones to pursue. Here we review some membrane models for lipid self-assembly, monolayers, bilayers, liposomes, and lipid-protein interactions and illustrate how such models can help answering questions in modern lipid cell biology.     

Cellular dynamics and molecular control of the development of organizer-derived cells in quail-chick chimeras

Malformations affecting the nervous system in humans are numerous and various in etiology. Many are due to genetic deficiencies or mechanical accidents occurring at early stages of development. It is thus of interest to reproduce such human malformations in animal models. The avian embryo is particularly suitable for researching the role of morphogenetic movements and genetic signaling during early neurogenesis. The last ten years of research with Nicole Le Douarin in the Nogent Institut have brought answers to questions formulated by Etienne Wolff at the beginning of his career, by showing that Hensen's node, the avian organizer, is at the source of all the midline cells of the embryo and ensures cell survival, growth and differentiation of neural and mesodermal tissues.     

The Singular Quest for a Universal Tree of Life

Carl Woese developed a unique research program, based on rRNA, for discerning bacterial relationships and constructing a universal tree of life. Woese''s interest in the evolution of the genetic code led to him to investigate the deep roots of evolution, develop the concept of the progenote, and conceive of the Archaea. In so doing, he and his colleagues at the University of Illinois in Urbana revolutionized microbiology and brought the classification of microbes into an evolutionary framework. Woese also provided definitive evidence for the role of symbiosis in the evolution of the eukaryotic cell while underscoring the importance of lateral gene transfer in microbial evolution. Woese and colleagues'' proposal of three fundamental domains of life was brought forward in direct conflict with the prokaryote-eukaryote dichotomy. Together with several colleagues and associates, he brought together diverse evidence to support the rRNA evidence for the fundamentally tripartite nature of life. This paper aims to provide insight into his accomplishments, how he achieved them, and his place in the history of biology.     

Blood as a near-"ideal" emulsion: a retrospective on the concept of the red cell as a fluid drop, its implications for the structure of the red cell membrane

Although the question whether the red cell is fluid or solid has been discussed since 17th century, it was the author's measurement of the relative viscosity of blood in 1960's that supplied the first direct evidence that the red cell interior is fluid. Furthermore, through his application of the equations of Taylor and, later, Oldroyd, to this problem, it became evident that, for the red cell to exhibit fluid-drop-like behavior, the membrane must also be fluid. This led to his concept of the red cell membrane as a complex two-phase structure (lipoprotein micelles and two-dimensional protein networks) which was similar to the one accepted nearly a decade later. The requirements of the theory of ideal emulsions that the shear stress be transmitted into the cell interior via low viscosity membrane, are met in the later work of other investigators using the concept of a tank-treading membrane having viscoelastic properties. This paper reviews the original work of the author which led to the development of an equation for the relative viscosity of blood as a function of volume concentration, C: nr = (1 - TkC)-2.5, valid at shear rates above 180 sec-1, in which T is the Taylor factor which gives a measure of fluidity of the red cell, and k is a plasma trapping factor. Both T and k increase with increasing rigidity of the red cell. Finally, the effect of the membrane viewed as a complex two-phase fluid, on the rheology of the red cell is discussed.     

The lateral cervical nucleus in the cat

Summary Profiles of 14 neurons all sectioned through the nucleolar plane and 87 isolated dendritic profiles have been analyzed with respect to the surface area covered by boutons and astroglial processes. This analysis has revealed two different types of neurons within the lateral cervical nucleus (LCN) of the cat. The cell types also differ in other ultrastructural respects. One type, which probably consists of projection neurons, is characterized by a rather large size, a relatively small nucleus, numerous mitochondria, well developed granular and agranular endoplasmic reticulum. The cell membrane of these cells shows somatic spines and the perikaryon is covered with boutons to a mean extent of 42%. The other cell type, which probably is internuncial, is smaller, has a proportionally larger nucleus, few mitochondria and a poorly developed granular and agranular endoplasmic reticulum. These cells show no somatic spines and the perikaryal membrane is covered with boutons to an extent of about 10%. Also the bouton populations contacting the two cell types differ from one another. The proportion of internuncial neurons within the LCN has been estimated to about 8%. The internuncial neurons seem to have no preferential localization.The primary dendrites of the projection neurons have a bouton covering of about 48%. No proportional differences in covering could be revealed between different sizes of dendrites.The results are discussed in relation to what is known about the anatomical and physiological organization of the LCN, and also compared with the results obtained in other similar investigations on other parts of the central nervous system.The author is grateful to fil.kand. Göran Engholm for his help with the statistical considerations.This work was supported by grants from Anders Otto Swärds Stiftelse, Stiftelsen Lars Hiertas minne, Åhlén och Holms stiftelse, Åke Wibergs stiftelse and the Swedish Medical Research Council (Project No B70-12X-2710).     

The interface of natural theology and science in the ethology of W. H. Thorpe

Conclusion It should be clear by now the extent to which many features of Thorpe's interpretation of animal behavior and of the animal mind rested, at bottom, not simply on conventional scientific proofs but on interpretive inferences, which in turn rested on a willingress to make extensions of human experience to animals. This, in turn, rested on his view of evolution and his view of reality. And these were governed by his natural theology, which was the fundamental stratum of his intellectual experience.Contrary to the scientific ethos, which restricts theory choice to scientific issues alone, Thorpe's career suggests that the actual reasons for theory choice among scientists often are not limited to science, but are multiple and may sometimes be difficult to discover. It is largely because Thorpe took a public part in the natural theology enterprise that we can know something about his religious beliefs and so can see their probable influence on his scientific decisions. Similar beliefs of other scientists are sometimes harder to get at. Most may be practically beyond discovery, for the ethos of science has discouraged public professions of personal belief in relation to scientific work.¹⁰¹ Yet does it seem plausible that, for example, the restriction of self-consciousness to humans by some scientists is a purely scientific decision?¹⁰² Surely not, any more than that the strong influence of natural theology on Thorpe's thought means that he was not a good scientist. His natural theology may have led him into incautious enthusiasms regarding the animal mind — such as the potential if unrealizable linguistic ability of chimpanzees — through a bias in favor of the continuity of emergents in a progressive evolutionary system, just as it led him to advocate animal consciousness long before the recent upsurge of interest, but the scientific integrity of his work overall is unimpeachable. And yet, that work is not comprehensible historically as science alone. Personal philosophy must not be discounted in writing the history of recent science. This somewhat obvious conclusion (obvious to historians of science) needs emphasis, for we are still prone to think that the sciences of our own time provide their own internal dynamic that is in itself sufficient to account for their content and development.