Towards a molecular understanding of cytokinesis

In this review, we focus on recent discoveries regarding the molecular basis of cleavage furrow positioning and contractile ring assembly and contraction during cytokinesis. However, some of these mechanisms might have different degrees of importance in different organisms. This synthesis attempts to uncover common themes and to reveal potential relationships that might contribute to the biochemical and mechanical aspects of cytokinesis. Because the information about cytokinesis is still fairly rudimentary, our goal is not to present a definitive model but to present testable hypotheses that might lead to a better mechanistic understanding of the process.     

Towards a more nuanced understanding of the relationship between sex-biased gene expression and rates of protein-coding sequence evolution

Genes that are differentially expressed between the sexes (sex-biased genes) are among the fastest evolving genes in animal genomes. The majority of sex-biased expression is attributable to genes that are primarily expressed in sex-limited reproductive tissues, and these reproductive genes are often rapidly evolving because of intra- and intersexual selection pressures. Additionally, studies of multiple taxa have revealed that genes with sex-biased expression are also expressed in a limited number of tissues. This is worth noting because narrowly expressed genes are known to evolve faster than broadly expressed genes. Therefore, it is not clear whether sex-biased genes are rapidly evolving because they have sexually dimorphic expression, because they are expressed in sex-limited reproductive tissues, or because they are narrowly expressed. To determine the extend to which other confounding variables can explain the rapid evolution of sex-biased genes, I analyzed the rates of evolution of sex-biased genes in Drosophila melanogaster and Mus musculus in light of tissue-specific measures of expression. I find that genes with sex-biased expression in somatic tissues shared by both sexes are often evolving faster than non-sex-biased genes, but this is best explained by the narrow expression profiles of sex-biased genes. Sex-biased genes in sex-limited tissues in D. melanogaster, however, evolve faster than other narrowly expressed genes. Therefore, the rapid evolution of sex-biased genes is limited only to those genes primarily expressed in sex-limited reproductive tissues.     

Towards a molecular understanding of Drosophila hearing

The Drosophila auditory system is presented as a powerful new genetic model system for understanding the molecular aspects of development and physiology of hearing organs. The fly's ear resides in the antenna, with Johnston's organ serving as the mechanoreceptor. New approaches using electrophysiology and laser vibrometry have provided useful tools to apply to the study of mutations that disrupt hearing. The fundamental developmental processes that generate the peripheral nervous system are fairly well understood, although specific variations of these processes for chordotonal organs (CHO) and especially for Johnston's organ require more scrutiny. In contrast, even the fundamental physiologic workings of mechanosensitive systems are still poorly understood, but rapid recent progress is beginning to shed light. The identification and analysis of mutations that affect auditory function are summarized here, and prospects for the role of the Drosophila auditory system in understanding both insect and vertebrate hearing are discussed.     

Towards a molecular understanding of titin.

Titin is at present the largest known protein (M(r) 3000 kDa) and its expression is restricted to vertebrate striated muscle. Single molecules span from M- to Z-lines and therefore over 1 micron. We have isolated cDNAs encoding five distant titin A-band epitopes, extended their sequences and determined 30 kb (1000 kDa) of the primary structure of titin. Sequences near the M-line encode a kinase domain and are closely related to the C-terminus of twitchin from Caenorhabditis elegans. This suggests that the function of this region in the titin/twitchin family is conserved throughout the animal kingdom. All other A-band sequences consist of 100 amino acid (aa) repeats predicting immunoglobulin-C2 and fibronectin type III globular domains. These domains are arranged into highly ordered 11 domain super-repeat patterns likely to match the myosin helix repeat in the thick filament. Expressed titin fragments bind to the LMM part of myosin and C-protein. Binding strength increases with the number of domains involved, indicating a cumulative effect of multiple binding sites for myosin along the titin molecule. We conclude that A-band titin is likely to be involved in the ordered assembly of the vertebrate thick filament.     

Towards understanding the immune system

It is proposed that using both self–non–self and danger theories give a better understanding of how the immune system works. It is proposed that comparing the immune system to the police force is useful in this case since the police respond both to danger or damage signals and foreign or suspicious behavior even if no danger signals existed. We also propose that due to low zone tolerance, immunotherapy needs to be combined with another treatment method for cancer, e.g., chemotherapy or/and radiotherapy, to get sufficient eradication of tumors. Finally, we propose that fractional order differential equations are more suitable than the familiar integer order differential equations. A fractional order example of two immune effectors attacking an antigen is given.     

Towards a more dynamic plant morphology

From the point of view of a dynamic morphology, form is not only the result of process(es) — it is process. This process may be analyzed in terms of two pairs of fundamental processes: growth and decay, differentiation and dedifferentiation. Each of these processes can be analyzed in terms of various modalities (parameters) and submodalities. This paper deals with those of growth (see Table 1). For the purpose of systematits and phylogenetic reconstruction the modalities and submodalities can be considered dynamic characters that have “states”. Each “state” of such a dynamic character is a more detailed process, hence not static. For example, determinate growth represents a “state” of the dynamic character (or modality) of growth duration. The processes of Table 1 can be applied to the whole plant kingdom (although in certain cases only some processes of the whole set may be applicable). Thus, the diversity of plant form is seen as a diversity of process combinations. From this point of view, change in form implies change in the process combination(s). Questions that arise are, for example, the following: Which process combinations actually occur? Which of these are the most frequent? How and why have process combinations changed during ontogeny and phylogeny? In comparative morphogenesis, process combinations are compared within an ontogeny or between ontogenies. The combinations may be repeated (i.e., conserved) or changed. Since repetition is limited, regularity that is the basis for structural categories is also limited or relative. With regard to change in process combinations, sequential change within an ontogeny and phylogenetic change between ontogenies can be distinguished. A large number of additional processes, such as heterochrony, that have been investigated by many zoologists and botanists, refer to these sequential and phylogenetic changes. General implications and consequences of the proposed approach are pointed out. As well, its limits, which are related to the language and concepts used, are discussed. The importance of a dynamic language is emphasized.     

Towards a functional understanding of protein N-terminal acetylation

Protein N-terminal acetylation is a major modification of eukaryotic proteins. Its functional implications include regulation of protein-protein interactions and targeting to membranes, as demonstrated by studies of a handful of proteins. Fifty years after its discovery, a potential general function of the N-terminal acetyl group carried by thousands of unique proteins remains enigmatic. However, recent functional data suggest roles for N-terminal acetylation as a degradation signal and as a determining factor for preventing protein targeting to the secretory pathway, thus highlighting N-terminal acetylation as a major determinant for the life and death of proteins. These contributions represent new and intriguing hypotheses that will guide the research in the years to come.     

Towards a more general species–area relationship: diversity on all islands, great and small

Aim

To demonstrate a new and more general model of the species–area relationship that builds on traditional models, but includes the provision that richness may vary independently of island area on relatively small islands (the small island effect).

Location

We analysed species–area patterns for a broad diversity of insular biotas from aquatic and terrestrial archipelagoes.

Methods

We used breakpoint or piecewise regression methods by adding an additional term (the breakpoint transformation) to traditional species–area models. The resultant, more general, species–area model has three readily interpretable, biologically relevant parameters: (1) the upper limit of the small island effect (SIE), (2) an estimate of richness for relatively small islands and (3) the slope of the species–area relationship (in semi‐log or log–log space) for relatively large islands.

Results

The SIE, albeit of varying magnitude depending on the biotas in question, appeared to be a relatively common feature of the data sets we studied. The upper limit of the SIE tended to be highest for species groups with relatively high resource requirements and low dispersal abilities, and for biotas of more isolated archipelagoes.

Main conclusions

The breakpoint species–area model can be used to test for the significance, and to explore patterns of variation in small island effects, and to estimate slopes of the species–area (semi‐log or log–log) relationship after adjusting for SIE. Moreover, the breakpoint species–area model can be expanded to investigate three fundamentally different realms of the species–area relationship: (1) small islands where species richness varies independent of area, but with idiosyncratic differences among islands and with catastrophic events such as hurricanes, (2) islands beyond the upper limit of SIE where richness varies in a more deterministic and predictable manner with island area and associated, ecological factors and (3) islands large enough to provide the internal geographical isolation (large rivers, mountains and other barriers within islands) necessary for in situ speciation.

     

Cancer: Towards a general theory of the target

General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality‐inhibition, and ‘acausal’ recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy (reduction in cancer burden) and selectivity (sparing of normal cells); if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions (cytoreduction, modulation, cytoprotection), potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable.     

Towards understanding the phosphorylation code of tau

We describe our efforts to combine in vitro enzymatic reactions with recombinant kinases to phosphorylate the neuronal tau protein, and NMR spectroscopy to unravel the resulting phosphorylation pattern in both qualitative and quantitative manners. This approach, followed by functional assays with the same samples, gives access to the complex phosphorylation code of tau. As a result, we propose a novel hypothesis for the link between tau (hyper)phosphorylation and aggregation.