Ectogenesis and the case against the right to the death of the foetus

Ectogenesis, or the use of an artificial womb to allow a foetus to develop, will likely become a reality within a few decades, and could significantly affect the abortion debate. We first examine the implications for Judith Jarvis Thomson’s violinist analogy, which argues for a woman’s right to withdraw life support from the foetus and so terminate her pregnancy, even if the foetus is granted full moral status. We show that on Thomson’s reasoning, there is no right to the death of the foetus, and abortion is not permissible if ectogenesis is available, provided it is safe and inexpensive. This raises the question of whether there are persuasive reasons for the right to the death of the foetus that could be exercised in the context of ectogenesis. Eric Mathison and Jeremy Davis have examined several arguments for this right, doubting that it exists, while Joona Räsänen has recently criticized their reasoning. We respond to Räsänen’s analysis, concluding that his arguments are unsuccessful, and that there is no right to the death of the foetus in these circumstances.     

Senescence: the good the bad and the dysfunctional

Nearly 50 years have elapsed since Hayflick challenged the dogma that individual human cells were immortal by demonstrating that after a predictable number of cellular divisions, normal human fibroblasts eventually entered a state of permanent growth arrest [Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965, 37:614-636.; Hayflick L, Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res 1961, 25:585-621]. This growth arrest, referred to as senescence, was hypothesized to function as a tumor suppressive mechanism, capable of limiting the replicative capacity of an incipient tumor cell. While originally met with skepticism, the existence of senescence and its importance as a tumor suppressive mechanism is now accepted. Here, we highlight this work and introduce studies that indicate that while senescent cells themselves cannot produce a neoplasia, they possess the ability to promote the growth of nearby preneoplastic cells and in this way may contribute to age-related increases in tumor incidences. This added level of complexity suggests that senescence functions as a biological 'double edged sword.'     

Frequency of the stages in the cycle of the seminiferous epithelium in the rat

This study determined the optimum number of tubules to be counted per testis cross section, and the number of animals per treatment group, when changes in stage frequencies in the cycle of the seminiferous epithelium are criteria for assessing effects of treatment on spermatogenesis. A data base of 9,672 observed and staged tubules was collected from testicular cross sections of 15 Sprague-Dawley rats. A significant variation between animals was found for the frequencies of Stages I, II, IV, VI, VIII, and XIII. Computer simulation was used to randomly select different combinations of animal and tubule numbers from the observed data. Stage frequency means from each simulation experiment were compared statistically to observed mean frequencies. A model that used data from all 14 stages was analyzed. The following conclusions were made: a) a minimum of 200 tubule cross sections/testis is recommended for estimating stage frequencies; b) for a fixed number of tubules scored, the number of animals sampled is more important than the number of tubules per animal in reducing variance; c) to detect a difference of 2 standard deviations from the mean with a 2% error rate and examining 200 tubules/testis, at least 12 animals must be used per group when assessing all 14 stages; d) when individual stages are examined using 10 animals per group, only Stage VII has 80% or greater power of test (alpha = 0.05) to detect a frequency difference; e) pooling stages into 3-4 groups is recommended to improve the power of detecting a treatment difference.     

Understanding the role of the cytoskeleton in the complex regulation of the endothelial repair

Actin microfilaments and microtubules are important cytoskeletal proteins that regulate endothelial repair through alterations in cell shape and through regulation of cell migration following wounding of the endothelium. Upstream pathways have been identified in the regulation of actin and microtubule organization, especially small GTPases. Recently, there have been numerous proteins suggested to be capable of regulating interaction between microtubules and microfilaments to mediate microtubule regulation of endothelial repair, an important process in limiting injury to the artery wall and in reducing the extent of arterial disease. If disrupted, a rapid repair mechanism is important in reestablishing the integrity of the endothelium in order to reestablish its function as a macromolecular barrier, a thromboresistant surface, and a biologically active tissue. Strategies to improve repair should alter the pathobiology of the atherosclerotic plaque and thus improve the prognosis of patients with atherosclerosis.     

Characterization of the guanidinobenzoatase in the epididymal fluids of the mouse

Guanidinobenzoatase (GB), a proteolytic enzyme found in the epididymal fluids of mice, was purified to apparent homogeneity by molecular sieving and affinity chromatography. It has a molecular mass of 71 kDa and its enzymatic activity is heat labile and sensitive to EGTA. Its kinetic parameters (Km of 6.66 μM and a Vmax of 4.38 nmol/min/mg) were determined using 4-methylumbelliferyl-p-guanidinobenzoate (MUGB) as the substrate. GB activity is concentrated in the cauda epididymal region of the genital tract. Heat-solubilized whole zonae, biologically active ZP3, and several serine proteinase inhibitors, including a proteinase inhibitor endogenous to the male genital tract, effectively block the ability of GB to hydrolyze MUGB. Pretreating cumulus-free, zonae intact oocytes with purified GB reduces, in a concentration-dependent manner, the number of sperm able to bind to the zonae. The function of the soluble enzyme is not known. Its ability to bind both trypsin inhibitors and ZP3 suggests a possible role in gamete recognition. Mol. Reprod. Dev. 47:204–209, 1997. © 1997 Wiley-Liss, Inc.     

On the existence and the role of chaotic processes in the nervous system

Chaos theory is a rapidly growing field. As a technical term, “chaos” refers to deterministic but unpredictable processes being sensitively dependent upon initial conditions. Neurobiological models and experimental results are very complicated and some research groups have tried to pursue the “neuronal chaos”. Babloyantz's group has studied the fractal dimension (d) of electroencephalograms (EEG) in various physiological and pathological states. From deep sleep (d=4) to full awakening (d>8), a hierarchy of “strange” attractors paralles the hierarchy of states of consciousness. In epilepsy (petit mal), despite the turbulent aspect of a seizure, the attractor dimension was near to 2. In Creutzfeld-Jacob disease, the regular EEG activity corresponded to an attractor dimension less than the one measured in deep sleep. Is it healthy to be chaotic? An “active desynchronisation” could be favourable to a physiological system. Rapp's group reported variations of fractal dimension according to particular tasks. During a mental arithmetic task, this dimension increased. In another task, a P300 fractal index decreased when a target was identified. It is clear that the EEG is not representing noise. Its underlying dynamics depends on only a few degrees of freedom despite yet it is difficult to compute accurately the relevant parameters. What is the cognitive role of such a chaotic dynamics? Freeman has studied the olfactory bulb in rabbits and rats for 15 years. Multi-electrode recordings of a few mm² showed a chaotic hierarchy from deep anaesthesia to alert state. When an animal identified a previously learned odour, the fractal dimension of the dynamics dropped off (near limit cycles). The chaotic activity corresponding to an alert-and-waiting state seems to be a field of all possibilities and a focused activity corresponds to a reduction of the attractor in state space. For a couple of years, Freeman has developed a model of the olfactory bulb-cortex system. The behaviour of the simple model “without learning” was quite similar to the real behaviour and a model “with learning” is developed. Recently, more and more authors insisted on the importance of the dynamic aspect of nervous functioning in cognitive modelling. Most of the models in the neural-network field are designed to converge to a stable state (fixed point) because such behaviour is easy to understand and to control. However, some theoretical studies in physics try to understand how a chaotic behaviour can emerge from neural networks. Sompolinsky's group showed that a sharp transition from a stable state to a chaotic state occurred in totally interconnected networks depending on the value of one control parameter. Learning in such systems is an open field. In conclusion, chaos does exist in neurophysiological processes. It is neither a kind of noise nor a pathological sign. Its main role could be to provide diversity and flexibility to physiological processes. Could “strange” attractors in nervous system embody mental forms? This is a difficult but fascinating question.     

Forms of the Word and the Mystery of the Objectified Nature of the Word

The time has come to proceed from forms of givenness of the word to forms of the word as such. They can, if you like, be called external and inner structures. Humboldt, however, preferred to speak of the external and inner forms of the language. Shpet adopted precisely this distinction. Why did this problem interest Shpet? Already in [Appearance and sense], he had set the task of returning to the source of pretheoretical, living science. Shpet wrote that the outer cover of words and logical expressions obscure the objectified meaning and that it was necessary to remove another cover from the objectified sign so as to grasp a certain genuine intimacy, and in it the fullness of being (Shpet, 1914. Pp. 5-6). We shall keep in mind this major undertaking posed by this scientist. The existence of the inner form of words should not come as a surprise. That same year (1914) Ortega y Gasset wrote that material objects have a third dimension. However, we cannot see or touch it: "For just as depth needs a surface beneath which to be concealed, the surface, or outer cover, in order to be so, needs something over which to spread, covering it" (Ortega y Gasset, 2000. Pp. 62-63).     

Rock-scissors-paper and the survival of the weakest.

In the children's game of rock-scissors-paper, players each choose one of three strategies. A rock beats a pair of scissors, scissors beat a sheet of paper and paper beats a rock, so the strategies form a competitive cycle. Although cycles in competitive ability appear to be reasonably rare among terrestrial plants, they are common among marine sessile organisms and have been reported in other contexts. Here we consider a system with three species in a competitive loop and show that this simple ecology exhibits two counter-intuitive phenomena. First, the species that is least competitive is expected to have the largest population and, where there are oscillations in a finite population, to be the least likely to die out. As a consequence an apparent weakening of a species leads to an increase in its population. Second, evolution favours the most competitive individuals within a species, which leads to a decline in its population. This is analogous to the tragedy of the commons, but here, rather than leading to a collapse, the 'tragedy' acts to maintain diversity.     

Interrelationship of the mediator receptors in the terminals of the afferent nerves of the cornea of the eye]

In local application of substances with a mediator action (adrenaline, acetylcholine, histamine) and blockers of specific receptors (dihydroergotoxin, inderal, atropine and of subcutaneous dimedrol) together with dicaine it was possible to reveal a distinct presence in the cornea of the eye of the mediator receptors capable of influencing one another. Pharmacological analysis permitted a supposition to be made that there were two receptor systems in the sensory nerve endings of the cornea; these systems were in reciprocal inhibitory relations; due to this their regular influence on the processes of excitation and inhibition is effected in the sensory nerve ending.     

Sometimes the result is not the answer: the truths and the lies that come from using the complementation test

It is standard genetic practice to determine whether or not two independently obtained mutants define the same or different genes by performing the complementation test. While the complementation test is highly effective and accurate in most cases, there are a number of instances in which the complementation test provides misleading answers, either as a result of the failure of two mutations that are located in different genes to complement each other or by exhibiting complementation between two mutations that lie within the same gene. We are primarily concerned here with those cases in which two mutations lie in different genes, but nonetheless fail to complement each other. This phenomenon is often referred to as second-site noncomplementation (SSNC). The discovery of SSNC led to a large number of screens designed to search for genes that encode interacting proteins. However, screens for dominant enhancer mutations of semidominant alleles of a given gene have proved far more effective at identifying interacting genes whose products interact physically or functionally with the initial gene of interest than have SSNC-based screens.     

On the shape of the erythrocyte

A model is postulated which attributes the distinctive biconcave shape of the human erythrocyte to a balance of forces acting on the membrane. The forces considered are electrostatic forces due to a charge distribution on the membrane, a hydrostatic pressure difference acting across the membrane, and forces arising from a constant tension in the membrane. A numerical study indicates that the postulated model will produce an equilibrium shape which is very similar to the observed shape of the human erythrocyte.     

Effects of turn residues in directing the formation of the beta-sheet and in the stability of the beta-sheet

The designed peptide (denoted 20-mer, sequence VFITS(D)PGKTYTEV(D)PGOKILQ) has been shown to form a three-strand antiparallel beta-sheet. It is generally believed that the (D)Pro-Gly segment has the propensity to adopt a type II' beta-turn, thereby promoting the formation of this beta-sheet. Here, we replaced (D)Pro-Gly with Asp-Gly, which should favor a type I' turn, to examine the influence of different type of turns on the stability of the beta-sheet. Contrary to our expectation, the mutant peptide, denoted P6D, forms a five-residue type I turn plus a beta-bulge between the first two strands due to a one amino-acid frameshift in the hydrogen bonding network and side-chain inversion of the first beta-strand. In contrast, the same kind of substitution at (D)Pro-14 in the double mutant, denoted P6DP14D, does not yield the same effect. These observations suggest that the SDGK sequence disfavors the type I' conformation while the VDGO sequence favors a type I' turn, and that the frameshift in the first strand provides a way for the peptide to accommodate a disfavored turn sequence by protruding a bulge in the formation of the beta-hairpin. Thus, different types of turns can affect the stability of a beta-structure.     

On the origin of the genetic code and the stability of the translation apparatus

An “error theory” is developed which can be applied to determine the stability of a macromolecular translation machinery which reproduces itself. It is shown that the overall effects of a multitude of possible error versions of macromolecules can be treated statistically, and that such a statistical approach is of considerable usefulness in the theoretical treatment of complex macromolecular systems. The theory is developed within the context of a detailed treatment of the “frozen accident” hypothesis for the origin of the genetic code. A model is described which permits some thermodynamic characterization of the components involved in the code nucleation. The model also proves useful in resolving a stability “paradox” described by Orgel, which relates to the translation stability in present-day organisms and mechanisms of ageing. It indicates that any experimentally found decrease in translation accuracy with age is probably not due to an inherent instability in the translation apparatus. Relevant experiments are suggested.     

Changes since the turn of the century in the fish fauna and the fisheries of the Oslofjord

Summary 1. The material for this study is drawn from two sources, (a) investigations of the fish fauna in the inner Oslofjord between 1897 and 1967, (b) fish landing statistics available since 1872 at the Oslo fish market.2. The investigations of the fish fauna reveal that 4 species of fish — 2 sharks and 2 arctic bullheads — have disappeared from the deep waters of the Oslofjord where they were known to exist in 1897. We assume that unfavourable conditions, great changes in temperature or lack of oxygen in the stagnant deep water to which these species belonged have been injurious to their propagation and survival.3. The annual fluctuations in the landed quantities of fish are great, but nevertheless there exists a marked decreasing trend since about 1930; total landings in recent years are less than 1/10 of what they were 30 or 40 years ago.4. The fluctuations in the landings of cod, herring and mackerel are studied in some detail. Three periods (of 20 to 22 years' duration) from 1872 to 1932 show increasing average landings of cod: 44, 57, and 74 tons respectively; in the period 1933 to 1955 landings decreased to an average of 16 tons per year. The effect of fluctuating year classes is discussed.5. The landings of herring and mackerel were very good between 1911 and 1919 or 1920 with a maximum of 1500 tons of herring and 800 tons of mackerel. In the following years there was a trend of decrease with a few years of moderately good landings. Mature mackerels are immigrating into the fjord for feeding and spawning, while mature herrings, to a major extent, are supposed to belong to a local stock. The highest landings of both species are due to extremely great catches of young fish, and the success of the fishery in any one year, therefore, dependent of a successful spawning and hatching one ort two years before.6. In conclusion, the attention is drawn to the fact that there are reasons to believe that the profuse growth of bacteria in the polluted waters seems to be injurious to the hatching of fish eggs and to the survival of fish larvae (Dannevig 1945,Oppenheimer 1955).

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Veränderungen der Fischfauna und der Fischerei des Oslofjords seit der Jahrhundertwende

Kurzfassung Das Material zu dieser Untersuchung stammt aus zwei Quellen: (a) vier Untersuchungen über die Fischfauna des Oslofjords im Zeitraum zwischen 1897 und 1967, und (b) Statistiken für den Zeitraum von 1872 bis 1964 über die Fischmengen, die im inneren Oslofjord gefangen und an die Fischhalle in Oslo geliefert worden sind. Ein Vergleich der Resultate mit den vier Untersuchungen über die Fischfauna zeigt, daß vier Arten von Tiefwasserfischen aus dem inneren Oslofjord völlig verschwunden sind, nämlichEtmopterus spinax, Somniosus microcephalus, Artediellus uncinatus undIcelus bicornis, die beiden zuletzt genannten wahrscheinlich schon vor 1930. Eine Anzahl anderer Arten, die früher häufig waren, sind jetzt selten. Statistische Erhebungen über die im Oslofjord gefangenen Fische lassen erkennen, daß die Erträge seit den zwanziger und dreißiger Jahren stark zurückgegangen sind. Gleichzeitig hat die Zahl der Fischer abgenommen. Es wird die Schlußfolgerung gezogen, daß die Veränderungen des Oslofjords sich besonders in den letzten 30 Jahren für mehrere Fischarten als schädigend erwiesen haben. Diese Auffassung wird unterstützt durch die Untersuchungen vonDannevig (1945) undOppenheimer (1955), die gezeigt haben, daß die reiche Bakterienflora des Oslofjords für die Entwicklung der pelagischen Fischeier schädlich ist.

     

On the structure and dynamics of the complex of the nucleosome and the linker histone

Several different models of the linker histone (LH)–nucleosome complex have been proposed, but none of them has unambiguously revealed the position and binding sites of the LH on the nucleosome. Using Brownian dynamics-based docking together with normal mode analysis of the nucleosome to account for the flexibility of two flanking 10 bp long linker DNAs (L-DNA), we identified binding modes of the H5-LH globular domain (GH5) to the nucleosome. For a wide range of nucleosomal conformations with the L-DNA ends less than 65 Å apart, one dominant binding mode was identified for GH5 and found to be consistent with fluorescence recovery after photobleaching (FRAP) experiments. GH5 binds asymmetrically with respect to the nucleosomal dyad axis, fitting between the nucleosomal DNA and one of the L-DNAs. For greater distances between L-DNA ends, docking of GH5 to the L-DNA that is more restrained and less open becomes favored. These results suggest a selection mechanism by which GH5 preferentially binds one of the L-DNAs and thereby affects DNA dynamics and accessibility and contributes to formation of a particular chromatin fiber structure. The two binding modes identified would, respectively, favor a tight zigzag chromatin structure or a loose solenoid chromatin fiber.     

From the trap to the basket: getting to the bottom of the nuclear pore complex

Nuclear pore complexes (NPCs) are large supramolecular assemblies that perforate the double-membraned nuclear envelope and serve as the sole gateways of molecular exchange between the cytoplasm and the nucleus in interphase cells. Combining novel specimen preparation regimes with innovative use of high-resolution scanning electron microscopy, Hans Ris produced in the late eighties stereo images of the NPC with unparalleled clarity and structural detail, thereby setting new standards in the field. Since that time, efforts undertaken to resolve the molecular structure and architecture, and the numerous interactions that occur between NPC proteins (nucleoporins), soluble transport receptors, and the small GTPase Ran, have led to a deeper understanding of the functional role of NPCs in nucleocytoplasmic transport. In spite of these breakthroughs, getting to the bottom of the actual cargo translocation mechanism through the NPC remains elusive and controversial. Here, we review recent insights into NPC function by correlating structural findings with biochemical data. By introducing new experimental and computational results, we reexamine how NPCs can discriminate between receptor-mediated and passive cargo to promote vectorial translocation in a highly regulated manner. Moreover, we comment on the importance and potential benefits of identifying and experimenting with individual key components implicated in the translocation mechanism. We conclude by dwelling on questions that we feel are pertinent to a more rational understanding of the physical aspects governing NPC mechanics. Last but not least, we substantiate these uncertainties by boldly suggesting a new direction in NPC research as a means to verify such novel concepts, for example, a de novo designed ‘minimalist’ NPC. This article is dedicated to the memory of Hans Ris.     

Importance of the signals provided by the buck for the success of the male effect in goats

Under temperate and subtropical latitudes, ewes and goats display a reproductive seasonal pattern and their sexual activity during the anestrous period can be stimulated and synchronized by the introduction of males in the group, which is called the "male effect". The response of females to the male effect in the middle of the anestrous season is weak or absent. This failure may be due to the inability of the female to respond to males, as a result of a refractoriness of the female to the male stimulus. But, it may also be due to a low quality stimulus provided by the male which is, as the females, in seasonal rest. We tested this latter hypothesis in seasonally inactive goats kept under subtropical conditions by comparing the use of males with their sexual behavior stimulated or not by photoperiodic treatments. Treated males were able to induce estrous activity of females during the whole anestrus season. We have also determined that previous separation of the males and continuous contact during teasing are not absolute requisites when active bucks are used. While odor from the male and its sexual behavior play a primary role in inducing ovulation, vocalizations appear to facilitate the display of the does' estrous. It remains to be determined to which extent these conclusions apply under temperate latitudes and with more seasonal breeds.     

Studies on the excitability of the central program generator in the spinal cord of the terrapin Pseudemys scripta elegans

We present observations on the multicyclic scratch reflex in spinal terrapins as produced by electrical stimuli applied to the shell at the specific regions at which a mechanical stimulus produces the reflex. EMGs and hip and knee movements are recorded. The responses to the electrical stimuli are similar to the responses to mechanical stimuli. There is a three phase EMG pattern (Stein and Grossman, 1980), to which the movement pattern is related (Bakker and Crowe, 1982). A response may consist of a series of up to 25 movement cycles with a total time course of up to about 30 sec. The initial cycles of a response are relatively fast (less than 1 sec), but the cycles at the expiration of the response may have a duration of 2-3 sec. A single electrical stimulus pulse is often insufficient to trigger a series response. Instead, a weak EMG burst of a few tenths of a second duration, together with a slight movement, is often seen. However, a second pulse can set the cycle series in motion even after an interval of 40 sec between the pulses. A further booster stimulus pulse given while a reflex response is taking place can increase the speed of the movement. If the booster pulse is given just after cessation of reflex activity it can restart the activity, but this second cycle series is often shorter than the first one. The results indicate that the excitability of the central program generator is not constant. Long duration changes in the excitability are produced within the spinal cord.     

A new stem craniate from the Ordovician of Morocco and the search for the sister group of the craniata

The investigation of the development of the trigeminal jaw adductor musculature in the turtle Chelydra serpentina documents the early aggregation of muscle rudiments around the innervating nerve branches, probably a consequence of inductive interaction. This may explain the early continuity of the intramandibularis with the intermandibularis muscle. Several aspects of muscle development differ in the turtle as compared to lizards. These differences highlight the fact that conjectures of homology, based on a static topographical correspondence of adult structures, cannot capture the dynamics of the developmental process. The intramandibularis muscle of turtles, comparable to that of crocodiles, represents a plesiomorphous structure which is not homologous to the intramandibularis muscle of lacertoid lizards, a derived feature of the Lacertoidea. A derived feature of the chelonian jaw adductor musculature is the posterodorsal expansion of the external adductor along a supraoccipital crest, developing according to a pattern of Haeckelian recapitulation. Muscle development serves to corroborate the concept of a monophyletic Eureptilia, including diapsids and synapsids, as opposed to the (paraphyletic) Anapsida. The impact of the differentiation of the external adductor into a pulley system on cranial kinesis is analysed in biomechanical terms.