Modeling chemotaxis reveals the role of reversed phosphotransfer and a bi-functional kinase-phosphatase

Understanding how multiple signals are integrated in living cells to produce a balanced response is a major challenge in biology. Two-component signal transduction pathways, such as bacterial chemotaxis, comprise histidine protein kinases (HPKs) and response regulators (RRs). These are used to sense and respond to changes in the environment. Rhodobacter sphaeroides has a complex chemosensory network with two signaling clusters, each containing a HPK, CheA. Here we demonstrate, using a mathematical model, how the outputs of the two signaling clusters may be integrated. We use our mathematical model supported by experimental data to predict that: (1) the main RR controlling flagellar rotation, CheY6, aided by its specific phosphatase, the bifunctional kinase CheA3, acts as a phosphate sink for the other RRs; and (2) a phosphorelay pathway involving CheB2 connects the cytoplasmic cluster kinase CheA3 with the polar localised kinase CheA2, and allows CheA3-P to phosphorylate non-cognate chemotaxis RRs. These two mechanisms enable the bifunctional kinase/phosphatase activity of CheA3 to integrate and tune the sensory output of each signaling cluster to produce a balanced response. The signal integration mechanisms identified here may be widely used by other bacteria, since like R. sphaeroides, over 50% of chemotactic bacteria have multiple cheA homologues and need to integrate signals from different sources.

Modification of hemicellulose content by antisense down-regulation of UDP-glucuronate decarboxylase in tobacco and its consequences for cellulose extractability

Extractability and recovery of cellulose from cell walls influences many industrial processes and also the utilisation of biomass for energy purposes. The utility of genetic manipulation of lignin has proven potential for optimising such processes and is also advantageous for the environment. Hemicelluloses, particularly secondary wall xylans, also influence the extractability of cellulose. UDP-glucuronate decarboxylase produces UDP-xylose, the precursor for xylans and the effect of its down-regulation on cell wall structure and cellulose extractability in transgenic tobacco has been investigated. Since there are a number of potential UDP-glucuronate decarboxylase genes, a 490 bp sequence of high similarity between members of the family, was chosen for general alteration of the expression of the gene family. Sense and antisense transgenic lines were analysed for enzyme activity using a modified and optimised electrophoretic assay, for enzyme levels by western blotting and for secondary cell wall composition. Some of the down-regulated antisense plants showed high glucose to xylose ratios in xylem walls due to less xylose-containing polymers, while arabinose and uronic acid contents, which could also have been affected by any change in UDP-xylose provision, were unchanged. The overall morphology and stem lignin content of the modified lines remained little changed compared with wild-type. However, there were some changes in vascular organisation and reduction of xylans in the secondary walls was confirmed by immunocytochemistry. Pulping analysis showed a decreased pulp yield and a higher Kappa number in some lines compared with controls, indicating that they were less delignified, although the level of residual alkali was reduced. Such traits probably indicate that lignin was less available for removal in a reduced background of xylans. However, the viscosity was higher in most antisense lines, meaning that the cellulose was less broken-down during the pulping process. This is one of the first studies of a directed manipulation of hemicellulose content on cellulose extractability and shows both positive and negative outcomes.

Modification of hemicellulose content by antisense down-regulation of UDP-glucuronate decarboxylase in tobacco and its conscequence for cellulose extractability

Extractability and recovery of cellulose from cell walls influences many industrial processes and also the utilisation of biomass for energy purposes. The utility of genetic manipulation of lignin has proven potential for optimising such processes and is also advantageous for the environment. Hemicelluloses, particularly secondary wall xylans, also influence the extractability of cellulose. UDP-glucuronate decarboxylase produces UDP-xylose, the precursor for xylans and the effect of its down-regulation on cell wall structure and cellulose extractability in transgenic tobacco has been investigated. Since there are a number of potential UDP-glucuronate decarboxylase genes, a 490 bp sequence of high similarity between members of the family, was chosen for general alteration of the expression of the gene family. Sense and antisense transgenic lines were analysed for enzyme activity using a modified and optimised electrophoretic assay, for enzyme levels by western blotting and for secondary cell wall composition. Some of the down-regulated antisense plants showed high glucose to xylose ratios in xylem walls due to less xylose-containing polymers, while arabinose and uronic acid contents, which could also have been affected by any change in UDP-xylose provision, were unchanged. The overall morphology and stem lignin content of the modified lines remained little changed compared with wild-type. However, there were some changes in vascular organisation and reduction of xylans in the secondary walls was confirmed by immunocytochemistry. Pulping analysis showed a decreased pulp yield and a higher Kappa number in some lines compared with controls, indicating that they were less delignified, although the level of residual alkali was reduced. Such traits probably indicate that lignin was less available for removal in a reduced background of xylans. However, the viscosity was higher in most antisense lines, meaning that the cellulose was less broken-down during the pulping process. This is one of the first studies of a directed manipulation of hemicellulose content on cellulose extractability and shows both positive and negative outcomes.

Rossby waves and two-dimensional turbulence in a large-scale zonal jet

The theory of homogeneous barotropic beta-plane turbulence is here extended to include effects arising from spatial inhomogeneity in the form of a zonal shear flow. Attention is restricted to the geophysically important case of zonal flows that are barotropically stable and are of larger scale than the resulting transient eddy field. Because of the presumed scale separation, the disturbance enstrophy is approximately conserved in a fully nonlinear sense, and the (nonlinear) wave-mean-flow interaction may be characterized as a shear-induced spectral transfer of disturbance enstrophy along lines of constant zonal wavenumber k. In this transfer the disturbance energy is generally not conserved. The nonlinear interactions between different disturbance components are turbulent for scales smaller than the inverse of Rhines's cascade-arrest scale κβ[identical with] (β0/2urms)½ and in this regime their leading-order effect may be characterized as a tendency to spread the enstrophy (and energy) along contours of constant total wavenumber κ [identical with] (k2 + l2)½. Insofar as this process of turbulent isotropization involves spectral transfer of disturbance enstrophy across lines of constant zonal wavenumber k, it can be readily distinguished from the shear-induced transfer which proceeds along them. However, an analysis in terms of total wavenumber K alone, which would be justified if the flow were homogeneous, would tend to mask the differences. The foregoing theoretical ideas are tested by performing direct numerical simulation experiments. It is found that the picture of classical beta-plane turbulence is altered, through the effect of the large-scale zonal flow, in the following ways: (i) while the turbulence is still confined to K Kβ, the disturbance field penetrates to the largest scales of motion; (ii) the larger disturbance scales K < Kβ exhibit a tendency to meridional rather than zonal anisotropy, namely towards v2 > u2 rather than vice versa; (iii) the initial spectral transfer rate away from an isotropic intermediate-scale source is significantly enhanced by the shear-induced transfer associated with straining by the zonal flow. This last effect occurs even when the large-scale shear appears weak to the energy-containing eddies, in the sense that dU/dy [double less-than sign] κ for typical eddy length and velocity scales.

The impracticality of a universal drought definition

This paper demonstrates the impracticality of a comprehensive mathematical definition of the term `drought' which formalises the general qualitative definition that drought is `a deficit of water relative to normal conditions'. Starting from the local water balance, it is shown that a universal description of drought requires reference to water supply, demand and management. The influence of human intervention through water management is shown to be intrinsic to the definition of drought in the universal sense and can only be eliminated in the case of purely meteorological drought. The state of `drought' is shown to be predicated on the existence of climatological norms for a multitude of process specific terms. In general these norms are either difficult to obtain or even non-existent in the non-stationary context of climate change. Such climatological considerations, in conjunction with the difficulty of quantifying human influence, lead to the conclusion that we cannot reasonably expect the existence of any workable generalised objective definition of drought.

Phylloxera and the grapevine: a sense of common purpose?

The purpose of life is its continuation: survival is the reason things live. Here we explore this 'basic' of biology, by reference to the extraordinary life-cycle of the aphid-like pest phylloxera, and the complexity of its relationship with its host the grapevine. The effort and ingenuity that phylloxera employs to continue itself leads to a doubt that survival alone is sufficient reason. It has frequently been suggested that the reduction of life to a catalogue of facts (by science) creates this doubt, because it robs existence of its essence (which is something other than its mechanics). The part that science is said to steal is what Robert Pirsig calls Quality-the harmonious balance of things. Pirsig seems to imply that this is something inherent in things-and independent from us. A more mundane explanation is that the difference between facts and the complete reality is us-the tendency of mind to connect freely between different kinds of information. This possibility is briefly illustrated here by a myth based on the facts of phylloxera.

Making sense of supply chain management: acomparative study of aerospace and construction

Current recipes for learning across business sectors too often fail to recognize the embedded and contextual nature of management practice. The existing literature gives little emphasis to the symbiotic relationship between supply chain management and the broader dynamics of context. The aerospace and construction sectors are selected for comparison on the basis that they are so different. The UK aerospace sector has undergone extensive consolidation as a result of the imperatives of global competitive pressures. In contrast, the construction industry has experienced decades of fragmentation and remains highly localized. An increasing proportion of output in the aerospace sector occurs within a small number of large, globally orientated firms. In contrast, construction output is dominated by a plethora of small firms with high levels of subcontracting and a widespread reliance on self-employment. These differences have fundamental implications for the way that supply chain management is understood and implemented in the two sectors. Semi-structured interviews with practitioners from both sectors support the contention that supply chain management is more established in aerospace than construction. The introduction of prime contracting and the increasing use of framework agreements within the construction sector potentially provide a much more supportive climate for supply chain management than has traditionally prevailed. However, progress depends upon an improved continuity of workload under such arrangements.

Place attachment and sense of belonging in the offices

Examines the concept of “place attachment” as defined in various disciplines and develops an effective conceptual approach that can be applied to facilities management. Describes the development of a model-matchmaking process adapted from Passini's model of cognitive mapping. Findings that the emergence of the new economy is undermining our ability to form attachments with people, places and companies. However, one of the unintended effects of this is that it has strengthened the value of place and aroused a longing for community. Moreover, loyalty to an organisation is increasingly determined by social and place attachment. Proposes that further research needs to be undertaken to “engineer out” the negative impacts of flexibility associated with loss of place. States that place attachment presents a challenging view of the world that is contrary to all the received wisdom in facilities management, where flexibility has always assumed an unchallenged position in relation to buildings and people. Concludes that this research area presents many pragmatic design and operational questions for facilities managers.

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants.

Conjecture, proof, and sense in Wittgenstein's philosophy of mathematics

One of the key tenets in Wittgenstein’s philosophy of mathematics is that a mathematical proposition gets its meaning from its proof. This seems to have the paradoxical consequence that a mathematical conjecture has no meaning, or at least not the same meaning that it will have once a proof has been found. Hence, it would appear that a conjecture can never be proven true: for what is proven true must ipso facto be a different proposition from what was only conjectured. Moreover, it would appear impossible that the same mathematical proposition be proven in different ways. — I will consider some of Wittgenstein’s remarks on these issues, and attempt to reconstruct his position in a way that makes it appear less paradoxical.