Site of graviperception in roots: a re-examination

Two lines of evidence have been cited to support the assertion that the root cap is the sole site of graviperception in the root. The first evidence is based on surgical removal of the cap, which abolishes the response to gravity. This is sufficient to conclude that the cap is involved in gravitropism, but not to conclude that the cap is the site of graviperception. The second is based on the results of centrifugation experiments, in which different parts of the plant are subjected to different centrifugal forces. The data from such experiments have been cited to support the conclusion that the perception of gravity is limited to the rootcap. However, these data actually support the conclusion that gravity is perceived throughout the root tip, and not only in the root cap. We believe that the data support the conclusion that the root cap is involved in root gravitropism, but that there is inadequate evidence to conclude that the cap is the sole site of graviperception.     

A Structure-Activity Relationship for the Hydrolysis of Acetylamino Acids by Porcine Aminoacylase

A structure-activity relationship is presented that satisfactorily predicts the rates of hydrolysis of a series of acetylglycine derivatives by porcine aminoacylase. It is apparent that the substrate specificity of aminoacylase is mainly kinetic in origin, the observed correlation with Taft's E(s) parameter supporting the notion that enzymolysis proceeds through a mechanism that is analogous to chemical hydrolysis. It is suggested that the alpha-CH(2)CH group of those substrates that possess this moiety is conformationally immobile upon binding. This lock facilitates rapid hydrolysis and results from steric interactions between the enzyme and substrate. The incorporation of alpha-methyl amino acid derivatives in the structure-activity relationship is consistent with a flexible active site model and it is concluded that the alpha-methyl effect in this system is a binding phenomenon. It is evident that the active center of porcine aminoacylase can comfortably accommodate amino acid derivatives with side chains containing less than six carbon atoms, contrary to previous assertions. It is suggested that the binding of bulkier derivatives necessitates the distortion of the active site. Derivatives possessing beta-hydroxyl groups are found to deviate from expected behavior and a nonproductive binding model is presented. Copyright 2000 Academic Press.     

<Emphasis Type="Italic">kuzbanian</Emphasis> is required cell autonomously during Notch signalling in the <Emphasis Type="Italic">Drosophila </Emphasis>wing

The kuzbanian gene encodes a metalloprotease of the ADAM family that is involved in Notch signalling. However, its precise role is a matter of controversy. While original reports concluded that kuz is required on the receiving side of the Notch signalling pathway, a more recent report suggests that Kuz is required on the signal-emitting side for the generation of an active secreted form of the ligand Delta. In this scenario, kuz should act cell non-autonomously. A third possibility is that Kuz is required on the signal-emitting as well as the receiving side. Here I present the clonal analysis of kuz in Drosophila wing. The results show that Kuz acts on the receiving side of the pathway and is not required for Delta signalling. This further confirms the hypothesis that Kuz is required for the release of the intracellular domain of Notch that transduces the signal to the nucleus. The presented results complement recent data that indicate that Kuz can perform the S2 proteolytic cleavage of the Notch receptor that is required for its activation.     

FtsZ ring: the eubacterial division apparatus conserved in archaebacteria

FtsZ is a tubulin-like protein that is essential for cell division in eubacteria. It functions by forming a ring at the division site that directs septation. The archaebacteria constitute a kingdom of life separate from eubacteria and eukaryotes. Like eubacteria, archaebacteria are prokaryotes, although they are phylogenetically closer to eukaryotes. Here it is shown that archaebacteria also possess FtsZ and that it is biochemically similar to eubacterial FtsZs. Significantly, FtsZ from the archaebacterium Haloferax volcanii is a GTPase that is localized to a ring that coincides with the division constriction. These results indicate that the FtsZ ring was part of the division apparatus of a common prokaryotic ancestor that was retained by both eubacteria and archaebacteria.     

Autogenous control of Escherichia coli threonyl-tRNA synthetase expression in vivo

The regulation of the expression of thrS, the structural gene for threonyl-tRNA synthetase, was studied using several thrS-lac fusions cloned in lambda and integrated as single copies at att lambda. It is first shown that the level of beta-galactosidase synthesized from a thrS-lac protein fusion is increased when the chromosomal copy of thrS is mutated. It is also shown that the level of beta-galactosidase synthesized from the same protein fusion is decreased if wild-type threonyl-tRNA synthetase is overproduced from a thrS-carrying plasmid. These results strongly indicate that threonyl-tRNA synthetase controls the expression of its own gene. Consistent with this hypothesis it is shown that some thrS mutants overproduce a modified form of threonyl-tRNA synthetase. When the thrS-lac protein fusion is replaced by several types of thrS-lac operon fusions no effect of the chromosomal thrS allele on beta-galactosidase synthesis is observed. It is also shown that beta-galactosidase synthesis from a promoter-proximal thrS-lac operon fusion is not repressed by threonyl-tRNA synthetase overproduction. The fact that regulation is seen with a thrS-lac protein fusion and not with operon fusions indicates that thrS expression is autoregulated at the translational level. This is confirmed by hybridization experiments which show that under conditions where beta-galactosidase synthesis from a thrS-lac protein fusion is derepressed three- to fivefold, lac messenger RNA is only slightly increased.     

Models for testing

Summary This is a comment on a note by Solow (1990). It is shown that Solow's simulation results indicate that Bulmer's test for density dependence is non-robust to a particular kind of second-order Markovity that might well be overlooked by an ecologist. It is suggested that Solow's claim that Bulmer's test is insensitive is not wholly justified. Some scepticism concerning the applicability of statistical testing theory to animal population data is expressed.Communication no. 410 of the Biological Station, Wijster     

Consideration of the Possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues.

A model is proposed to account for the observation that the denaturation of small proteins apparently occurs in two kinetic phases. It is suggested that only one of these phases--the fast one--is actually an unfolding process. The slow phase is assumed to arise from the cis-trans isomerism of proline residues in the denaturated protein. From model compound data, it is shown that the expected rate for isomerism is in satisfactory agreement with the rates actually observed for protein folding. It is also shown that a simple model of protein unfolding based on the isomerism concept is very successful in accounting for many known experimental characteristics of the kinetics and thermodynamic of protein denaturation. Thus, the model is able to predict that two kinetic phases will be seen in the transition region while none are seen in the base-line regions, that both the fast and slow refolding phases lead to the native protein as the product, that the fast phase becomes the only observable phase for jumps ending far in the denatured base-line region, that most or all small proteins show a limiting low-temperature activation energy of ca. 20,000 cal, and that the relaxtion time for the slow phase seen in cytochrome c denaturation is much shorter than for all other small proteins. By utilizing "double-jump" experiments, it is shown directly that the slow phase is not part of the unfolding process but that it corresponds to a transition among two or more denatured forms which have identical spectroscopic (286.5 nm) properties. Thus, the slow relaxation is "invisible" except in the transition region where it couples to the fast unfolding equilibrium. Finally, since the present model assumes that only one of the major kinetic phases seen in denaturation reactions is concerned with the denaturation process per se, it is in agreement with numerous thermodynamic studies which show consistency with the two-state model for unfolding.     

The role of variant surface antigens on malaria-infected red blood cells.

It has been proposed that the primary role of variant antigens appearing on the surface of red blood cells infected with malaria parasites is to mediate cytoadherence, and that the antigenic variation they display is an adaptation to avoid immune attack. Here, Allan Saul proposes that their role is the opposite: that their primary purpose is to generate an immune response, which regulates their growth and thereby establishes a chronic infection, and that the role of cytoadherence is to ensure that parasites failing to express this flag to the immune system are destroyed by the spleen.     

GTPase-dependent signaling in bacteria: characterization of a membrane-binding site for era in Escherichia coli.

Era is an Escherichia coli GTPase that is essential for cell viability and is peripherally associated with the cytoplasmic membrane. Both immunoelectron microscopy and subcellular-fractionation experiments have shown that Era is present in cytoplasmic as well as membrane-associated pools. These data led to speculation that the mechanism of action of Era may require cycling between membrane and cytoplasmic sites. In order to investigate this possibility, an in vitro binding assay was developed to characterize the binding of Era to membrane fractions. Competition and saturation binding experiments suggest that a site that is specific for Era and capable of binding up to 5 ng of Era per microgram of membrane protein is present in membrane preparations. The binding curve is complex, indicating that multiple equilibria describe the interaction. The binding of Era to this putative receptor is dependent on guanine nucleotides; binding cannot be measured in the absence of nucleotide, and neither ATP nor UTP can substitute. Subfractionation of cell walls showed that the guanine nucleotide-dependent binding site was present in fractions enriched in cytoplasmic membrane. These data provide evidence that Era may be involved in a GTPase-receptor-coupled membrane-signaling pathway that is essential for growth in E. coli.     

THE ROLE OF GLUCOCORTICOID HORMONES IN THE CONTROL OF EPIDERMAL MITOSIS

It has previously been established that the epidermal chalone inhibits epidermal mitotic activity more powerfully in the presence of adrenalin, although adrenalin itself is not a mitotic inhibitor. It is now shown that in low concentrations hydrocortisone has little if any antimitotic activity, that when it is present together with chalone and adrenalin it does not markedly increase their antimitotic activity, but that it does act to prolong the mitotic depression which they induce. It is known that, without hydrocortisone, adrenalin rapidly escapes from epidermal cells so that the chalone action is weakened. It appears that the role of hydrocortisone may be to reduce the rate of adrenalin loss and thus to prolong the chalone-adrenalin activity. It is also shown that the rate of loss of adrenalin from epidermal cells is inhibited, though to a much lesser extent, in the presence of excess chalone.     

The PCM–basal body/primary cilium coalition

The centrosome is an organelle that acts as a microtubule-organizing center (MTOC) throughout the cell cycle. Within the centrosome are often two components that each have an ability to organize microtubule structures: the centriole that has the potential to function as a basal body and nucleate a cilium or a flagellum and a mass of protein material that in the presence of a centriole is commonly referred to as the pericentriolar material (PCM) that organizes cytoplasmic and spindle microtubule arrays. One characteristic of a large variety of cells is the ability to express a non-motile primary cilium. It is now appreciated that the function of the primary cilium is integral to a variety of essential cell functions and defects affecting this structure underlie a variety of human disease. While the function of the primary cilium and manner in which a basal body organizes a primary cilium has received extensive attention there is now a need to explore the inter-relationship between the PCM and the basal body/primary cilium. It is this latter topic that is the focus of this review where we show that the PCM is integrated with the centriole to form a coalition that is essential for both the expression and function of the primary cilium as well as the organization and function of the cellular environment that surrounds it.     

Polarity and form regulation in development and reconstitution

In the literature, it is often assumed, for example with respect to Hydra, that several Turing systems coexist and it is also assumed that maintaining the polar profile, even when the system increases in size, is important for the polarity of the final phenotype. It is shown here that in reality there is only one Turing system, Child's system. To obtain a complete polar individual or organ, whether in reconstitution or development, it is essential that the complete succession of metabolic patterns occurs. Child's concepts of physiological dominance, subordination and isolation are interpreted in the light of Turing theory and in particular the Turing wavelength. It is emphasised, particularly by pointing to Child's metabolic patterns in coelenterates, both in development and in reconstitution, that it is the elongation that drives the succession polar metabolic pattern-->bipolar metabolic pattern, and this corresponds to the prediction of Turing theory supporting the thesis that Child's metabolic pattern is a Turing pattern. It is shown that if we assume that ATP is the Turing inhibitor then the many results of Child about the reduction of the scale of organisation with the decrease in the intensity of the energy metabolism correspond to the reduction of the Turing wavelength. The interplay between the Turing wavelength and the length of the form explains the conditions of reconstitution under which partial forms, wholes and form regulation are obtained. It is suggested that higher metabolism is responsible for both larger size and larger Turing wavelength thus securing form regulation. The results could be of importance in modern 'regenerative biology'. Heteromorphosis, i.e. animals with two heads (or two tails), one at each end, is explained by a bipolar Turing-Child metabolic pattern replacing a polar metabolic pattern. This can be brought about by chemical or by genetic means and indeed the prediction for Drosophila that the transition, wild type-->Bicaudal D, occurs because a polar Turing pattern is replaced by bipolar Turing pattern is confirmed, again if we accept that Child's metabolic pattern is the underlying Turing pattern. Child's experiments on Drosophila, including the requirement of critical length for metabolic polarity, are explained by Turing theory. Phenocopies and phenotypes are explained by the Turing-Child theory. It is shown that both Child's results about metabolic patterns and modern results for Hydra about gap junctions, 'endogeneous inhibitor' and gene expression, are correlated and explained by (cAMP, ATP) Turing theory. It is argued that the double-gradient hypothesis is incorrect in its original formulation and that it is Child's conception of succeeding metabolic patterns that is the correct one and that it corresponds to the prediction of the Turing theory.     

Adaptation of prey and predators between patches

Mathematical models are proposed to simulate migrations of prey and predators between patches. In the absence of predators, it is shown that the adaptation of prey leads to an ideal spatial distribution in the sense that the maximal capacity of each patch is achieved. With the introduction of co-adaptation of predators, it is proved that both prey and predators achieve ideal spatial distributions when the adaptations are weak. Further, it is shown that the adaptation of prey and predators increases the survival probability of predators from the extinction in both patches to the persistence in one patch. It is also demonstrated that there exists a pattern that prey and predators cooperate well through adaptations such that predators are permanent in every patch in the case that predators become extinct in each patch in the absence of adaptations. For strong adaptations, it is proved that the model admits periodic cycles and multiple stability transitions.     

What is this stuff called fitness?

This paper considers a variety of attempts to define fitness in such a way as to defend the theory of evolution by natural selection from the criticism that it is a circular argument. Each of the definitions is shown to be inconsistent with the others. The paper argues that the environment in which an animal evolves can be defined only with respect to the properties of the phenotype of the animal and that it is therefore not illuminating to try to explain the phenotypic properties of the animal in terms of adaptation to an environment that is defined by those very properties. Furthermore, since there is no way that the environment can be defined independently of the presence of the animal there is no way that the quality of an animal can be assessed; and there can be no objective criteria by whichany form of selection can be carried out, therefore there can be no criteria by whichnatural selection can be carried out. It is proposed that fitness is nothing more than the production of offspring, that this is a phenotypic property like all the others, and if it is heritable then the offspring of the parents that produce the most offspring will themselves produce the most offspring, and that in principle it is impossible to account for this in terms of the other phenotypic properties of the fittest animals except by circular argument. Differential rates of reproduction are the causes of evolution and the phenotypic causes are strictly inexplicable.     

A Highlights from MBoC Selection: A Phosphatidylinositol 3-Kinase/Protein Kinase B-independent Activation of Mammalian Target of Rapamycin Signaling Is Sufficient to Induce Skeletal Muscle Hypertrophy

It has been widely proposed that signaling by mammalian target of rapamycin (mTOR) is both necessary and sufficient for the induction of skeletal muscle hypertrophy. Evidence for this hypothesis is largely based on studies that used stimuli that activate mTOR via a phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)-dependent mechanism. However, the stimulation of signaling by PI3K/PKB also can activate several mTOR-independent growth-promoting events; thus, it is not clear whether signaling by mTOR is permissive, or sufficient, for the induction of hypertrophy. Furthermore, the presumed role of mTOR in hypertrophy is derived from studies that used rapamycin to inhibit mTOR; yet, there is very little direct evidence that mTOR is the rapamycin-sensitive element that confers the hypertrophic response. In this study, we determined that, in skeletal muscle, overexpression of Rheb stimulates a PI3K/PKB-independent activation of mTOR signaling, and this is sufficient for the induction of a rapamycin-sensitive hypertrophic response. Transgenic mice with muscle specific expression of various mTOR mutants also were used to demonstrate that mTOR is the rapamycin-sensitive element that conferred the hypertrophic response and that the kinase activity of mTOR is necessary for this event. Combined, these results provide direct genetic evidence that a PI3K/PKB-independent activation of mTOR signaling is sufficient to induce hypertrophy. In summary, overexpression of Rheb activates mTOR signaling via a PI3K/PKB-independent mechanism and is sufficient to induce skeletal muscle hypertrophy. The hypertrophic effects of Rheb are driven through a rapamycin-sensitive (RS) mechanism, mTOR is the RS element that confers the hypertrophy, and the kinase activity of mTOR is necessary for this event.     

Rationality, biology and optimality*

A historical theory of rational norms claims that, if we are supposed to think rationally, this is because it is biologically normal for us to do so. The historical theorist is committed to the view that we are supposed to think rationally only if, in the past, adult humans sometimes thought rationally. I consider whether there is any plausible model of rational norms that can be adopted by the historical theorist that is compatible with the claim that adult human beings are subject to rational norms, given certain plausible empirical assumptions about our history and capabilities. I suggest that there is one such model: this model centres on the idea that a procedure is rational if it has been endorsed (or at least not rejected) by mechanisms that have the function to ensure that the subject learns to reason in a way that approaches a certain kind of optimality. This revised version was published online in July 2006 with corrections to the Cover Date.     

Homology and function in the wings of Heteroptera

Abstract. The homology of veins and other wing characters in Heteroptera is reviewed in the light of palaeontology and new functional studies. A cladogram is given for the higher taxa of Hemiptera. It is probable that the vannus is an autapomorphy of Auchenorrhyncha+Heteropteroidea; that the leading edge vein of heteropteran fore- and hindwings is C+Sc; that Rs cannot be distinguished from R; that the hamus is part of M; that the glochis is a secondary structure. The difficulty of defining a vein is stressed. The functional significance of the hemielytron, cuneal fracture and longitudinal flexion lines is discussed. A preliminary ground-plan for Heteroptera wings is presented.     

Cofilin-mediated F-actin severing is regulated by the Rap GTPase and controls the cytoskeletal dynamics that drive lymphocyte spreading and BCR microcluster formation

When lymphocytes encounter APCs bearing cognate Ag, they spread across the surface of the APC to scan for additional Ags. This is followed by membrane contraction and the formation of Ag receptor microclusters that initiate the signaling reactions that lead to lymphocyte activation. Breakdown of the submembrane cytoskeleton is likely to be required for the cytoskeleton reorganization that drives cell spreading and for removing physical barriers that limit Ag receptor mobility. In this report, we show that Ag receptor signaling via the Rap GTPases promotes the dephosphorylation and activation of the actin-severing protein cofilin and that this results in increased severing of cellular actin filaments. Moreover, we show that this cofilin-mediated actin severing is critical for the changes in actin dynamics that drive B and T cell spreading, for the formation of BCR microclusters, and for the increased mobility of BCR microclusters within the plasma membrane after BCR engagement. Finally, using a model APC, we show that activation of this Rap-cofilin signaling module controls the amount of Ag that is gathered into BCR microclusters and that this is directly related to the magnitude of the resulting BCR signaling that is initiated during B cell-APC interactions. Thus, Rap-dependent activation of cofilin is critical for the early cytoskeletal changes and BCR reorganization that are involved in APC-dependent lymphocyte activation.     

Cancer Development and Progression: A Non-Adaptive Process Driven by Genetic Drift

The current mainstream in cancer research favours the idea that malignant tumour initiation is the result of a genetic mutation. Tumour development and progression is then explained as a sort of micro-evolutionary process, whereby an initial genetic alteration leads to abnormal proliferation of a single cell that leads to a population of clonally derived cells. It is widely claimed that tumour progression is driven by natural selection, based on the assumption that the initial tumour cells acquire some properties that endow such cells with a selective advantage over the normal cells from which the tumour cells are derived. The standard view assumes that the transformed bodily cell somehow acquires "responsiveness" to natural selection independently of the whole organism to which the cell belongs. Yet, it is never explained where such an acquired capacity to respond to natural selection by the individual bodily cell comes from. This situation poses many difficult questions that so far have been left unanswered. For example, there is no explanation why some cells belonging to an organised whole and as such having no independent capacity for survival, apparently become 'independent' entities, able to respond to selective pressures in an autonomous fashion and then to be evaluated by natural selection. Hereunder it is argued that such a qualitative change cannot be the consequence of specific genetic mutations. Moreover, it is shown that natural selection is unlikely to be acting within the organism during tumour development and progression and that tumour evolution is a random, non-adaptive process, driven by no fundamental biological principle. Thus, mutations in the so-called oncogenes and tumour suppressor genes observed in epithelial cancers (that constitute more than 90% of all cancers) are not the result of selection for better cellular growth or survival under restrictive conditions. Instead, here it is suggested that they are the consequence of genetic drift acting upon gene functions that become non-relevant, either for the individual or the species fitness, once the organism is past its reproductive prime and as such, they also become superfluous for cell survival in the short term. It is proposed that the origin of cancer is epigenetic and it is a consequence of the need for a continued turnover of the individuals that constitute a species.