On the origins of morphological variation, canalization, robustness, and evolvability

Canalization is a concept, introduced by Waddington that describesthe reduced sensitivity of a phenotype to genetic and environmentalperturbations. Some research in canalization assumes that lackof variation in a trait in one genotype with respect to anothergenotype in a population, is due to the existence of bufferingmechanisms against environmental and/or genetic variation. Thisarticle criticizes this assumption and out points out otherpossible problems with the concepts of canalization, robustness,and evolvability. These involve: the neglect of alternativeexplanations for the lack of variation in a trait, the incompatibilitywith current understanding of development, the way the mutivariatenature of morphological variation is considered. In addition,this article tries to explain that these concepts implicitlyassume, although not generally acknowledged, that without bufferingany genetic or environmental variation should give rise to adistinct phenotypic outcome. This can be avoided by restrictingthe use of canalization to cases in which, as in hsp90, thereis direct evidence of buffering. For the other cases it wouldbe clearer to talk about variational properties or simply typeof variation. The concept of evolvability is also biased towardsunivariate comparisons and is dependent on selective pressures.It is suggested that this can be replaced by "type of phenotypicvariation" from a genotype or variational properties. Overall,this article proposes that the concepts of canalization andevolvability involve some assumptions that, in most situations,unnecessarily complicate the study of evolution and development.     

Noise and robustness in phyllotaxis

A striking feature of vascular plants is the regular arrangement of lateral organs on the stem, known as phyllotaxis. The most common phyllotactic patterns can be described using spirals, numbers from the Fibonacci sequence and the golden angle. This rich mathematical structure, along with the experimental reproduction of phyllotactic spirals in physical systems, has led to a view of phyllotaxis focusing on regularity. However all organisms are affected by natural stochastic variability, raising questions about the effect of this variability on phyllotaxis and the achievement of such regular patterns. Here we address these questions theoretically using a dynamical system of interacting sources of inhibitory field. Previous work has shown that phyllotaxis can emerge deterministically from the self-organization of such sources and that inhibition is primarily mediated by the depletion of the plant hormone auxin through polarized transport. We incorporated stochasticity in the model and found three main classes of defects in spiral phyllotaxis--the reversal of the handedness of spirals, the concomitant initiation of organs and the occurrence of distichous angles--and we investigated whether a secondary inhibitory field filters out defects. Our results are consistent with available experimental data and yield a prediction of the main source of stochasticity during organogenesis. Our model can be related to cellular parameters and thus provides a framework for the analysis of phyllotactic mutants at both cellular and tissular levels. We propose that secondary fields associated with organogenesis, such as other biochemical signals or mechanical forces, are important for the robustness of phyllotaxis. More generally, our work sheds light on how a target pattern can be achieved within a noisy background.     

Oomycetes, effectors, and all that jazz

Plant pathogenic oomycetes secrete a diverse repertoire of effector proteins that modulate host innate immunity and enable parasitic infection. Understanding how effectors evolve, translocate and traffic inside host cells, and perturb host processes are major themes in the study of oomycete-plant interactions. The last year has seen important progress in the study of oomycete effectors with, notably, the elucidation of the 3D structures of five RXLR effectors, and novel insights into how cytoplasmic effectors subvert host cells. In this review, we discuss these and other recent advances and highlight the most important open questions in oomycete effector biology.     

Stratigraphical classification and all that

Quantitative treatment of the geological sciences must remain limited; there continues to be need for a language of words. This is keenly felt in stratigraphy, where the practising geologist is dismayed by the effusions of the stratigraphical philosophers. The situation, in so far as it appears to remain in some ways obscure or troublesome, is briefly reviewed in terms of lithostratigraphy. biostratigraphy. and chronostratigraphy. A revised version of a controversial diagram is presented, in which the role of the boundary stratotype as anchor point is believed to be clarified. Finally a synthesis is attempted of relationships between the various stratigraphical procedures and the provision of dates in years through the parallel discipline of geochronometry.     

Oncogenic ILK,tumor suppression and all that JNK

In neoplastic cells, proteins exert either pro or anti-tumorigenic functions. However, some proteins exhibit both properties, commonly dependent on specific aberrations occurring in a tumor-specific context. Recently, we demonstrated that the integrin-linked kinase (ILK), generally characterized as an oncogenic protein kinase, functions as a tumor suppressor protein in vitro and in vivo in the aggressive pediatric tumor, rhabdomyosarcoma (RMS). Other studies have similarly demonstrated both growth and tumor suppressive functions for ILK in normal and transformed tissues. The mechanism of ILK tumor suppression in RMS relies on expression levels of another kinase, the c-jun amino terminal kinase-1 (JNK1). These findings support a model in which ILK tumor suppression is mediated in part by elevated JNK1 expression, and indicate both a rationale for stratification of patients to receive anti-ILK therapies, and a need to better understand the context in which ILK displays its seemingly contradictory functions. This review discusses the complex roles of ILK in tumorigenesis, and offers arguments to harness ILK and JNK signaling as novel targets for anti-cancer therapy.     

On the estimation of robustness and filtering ability of dynamic biochemical networks under process delays, internal parametric perturbations and external disturbances

Inherently, biochemical regulatory networks suffer from process delays, internal parametrical perturbations as well as external disturbances. Robustness is the property to maintain the functions of intracellular biochemical regulatory networks despite these perturbations. In this study, system and signal processing theories are employed for measurement of robust stability and filtering ability of linear and nonlinear time-delay biochemical regulatory networks. First, based on Lyapunov stability theory, the robust stability of biochemical network is measured for the tolerance of additional process delays and additive internal parameter fluctuations. Then the filtering ability of attenuating additive external disturbances is estimated for time-delay biochemical regulatory networks. In order to overcome the difficulty of solving the Hamilton Jacobi inequality (HJI), the global linearization technique is employed to simplify the measurement procedure by a simple linear matrix inequality (LMI) method. Finally, an example is given in silico to illustrate how to measure the robust stability and filtering ability of a nonlinear time-delay perturbative biochemical network. This robust stability and filtering ability measurement for biochemical network has potential application to synthetic biology, gene therapy and drug design.     

Oculomotor control: Listing's law and all that

Previously, eye positions were characterized by the direction of sight, which has two degrees of freedom for conjugate movements and three degrees of freedom for vergent movements. Several groups have recently presented reliable data and unconventional models on binocular coordination, where all three degrees of freedom for one or both eyes have been taken into account. The results illustrate Bernstein's principle that in order to simplify control, the brain establishes unique relations between the target and motor space, in which non-Euclidean geometry of rotations is observed.     

Exploration of the postponing mechanism that delays carcinoma onset

The average age at onset of malignancies arising from epithelial tissues is between 40 and 70 years old even in familial cancers. Although it is believed that the accumulation of multiple genetic alterations is needed for cancer onset, we hypothesize--based on the diversity of ages at onset for most types of epithelial cancer--that there is a postponing mechanism inside the human body that significantly delays the process of carcinogenesis. The key molecules controlling the cancer onset, here called "postponers", are hypothesized to be functioning in the individuals carrying susceptibility genes. As a consequence, cancers occur in middle age or even old age, with several decades of cancer-free lifetime for the patient. Genome-wide association studies and genomic expression profiling are suggested to identify candidate postponers. Hypothetic gene expression patterns for identifying candidate postponers are illustrated. Animal models will be helpful to test whether the absence or presence of the postponer molecules can alter the onset age of spontaneous tumors. If this hypothesis is true, by amplification of the postponing mechanism we might be able to significantly delay the onset of tumors, so that individuals carrying cancer susceptibility traits could gain an additional significant period of cancer-free life. Moreover, destructive prophylactic surgeries, e.g., for women who have BRCA1/2 gene mutations, might be avoided.