Sensitisation waves in a bidomain fire-diffuse-fire model of intracellular Ca²⁺ dynamics

We present a bidomain threshold model of intracellular calcium (Ca²⁺) dynamics in which, as suggested by recent experiments, the cytosolic threshold for Ca²⁺ liberation is modulated by the Ca²⁺ concentration in the releasing compartment. We explicitly construct stationary fronts and determine their stability using an Evans function approach. Our results show that a biologically motivated choice of a dynamic threshold, as opposed to a constant threshold, can pin stationary fronts that would otherwise be unstable. This illustrates a novel mechanism to stabilise pinned interfaces in continuous excitable systems. Our framework also allows us to compute travelling pulse solutions in closed form and systematically probe the wave speed as a function of physiologically important parameters. We find that the existence of travelling wave solutions depends on the time scale of the threshold dynamics, and that facilitating release by lowering the cytosolic threshold increases the wave speed. The construction of the Evans function for a travelling pulse shows that of the co-existing fast and slow solutions the slow one is always unstable

Cardiac cell modelling: Observations from the heart of the cardiac physiome project

In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field

Phytochemical Diversity in Essential Oil of Vitex negundo L. Populations from India

Vitex negundo L., commonly known as the ‘Nirgundi’ has a long history of medicinal use in traditional and folk medicines for various diseases. To explore the diversity of the essential oil yield and composition of V. negundo, 23 populations were collected during spring season from the western Himalayan region. The essential oil yields varied from 0.06 to 0.10% in different populations of V. negundo. GC-FID, GC-MS, and statistical analysis of the leaf volatile oils showed significant phytochemical diversity. The volatiles of V. negundo were complex mixtures of 61 constituents, with sabinene (2.8-40.8%), viridiflorol (10.7%-23.8%), β-caryophyllene (5.3-21.4%), terpinen-4-ol (0.1-7.2%), epi-laurenene (2.2-5.9%), humulene epoxide II (0.5-4.6%), and abietadiene (0.1%-4.3%) as major constituents. Based on the distribution of major constituents, four groups were noticed by the multidimensional scaling and hierarchical average linkage cluster analyses. In conclusion, the yield and composition of the essential oils isolated from V. negundo varied considerably, depending on the origin

Arsenic hyperaccumulation efficiency depends on time and tissue in Pteris vittata

The metalloid arsenic is a toxic environmental pollutant. Arsenic pollution becomes serious due to mining, mineral, smelting and tannery industry. Leaching of naturally occurring arsenic into drinking water aquifers, has been reported in many countries including India and Bangladesh. Available engineering methods for remediation is costly and difficult. Many plant species reported to accumulate arsenic. Pteris vittata has been reported as arsenic hyperaccumulator. An Indian eco-type of P. vittata has been used to study the arsenic accumulation. The plants were grown in arsenic containing soil along with soil without arsenic (control). The ferns were separated into two portions, i.e., above ground (fronds), stage specific as well as tissues from different position of pinnae and below ground (roots and rhizomes). Futher, it was also harvested at different time interval. Dried fern samples (0.1 g) were digested with mixture of concentrated nitric acid and perchloric acid. Heavy metal measurement in foliar and root samples was performed with ICP-OES. Tissue specific arsenic accumulation indicates that juvenile leaf contains highest arsenic than mature leaf. Middle pinnae of mature leaf show high arsenic content compared to upper and lower pinnae. Among the underground parts of the plant, rhizome contains high arsenic than roots. Further, time dependent arsenic accumulation study indicates that active accumulation of arsenic starts from day 7 to day 30 in leaf tissue, while in roots, day 3 to 7 show sudden increase and no much drastic change in accumulation from day 7 onwards

Waiting time distributions for clusters of complex molecules

Waiting time distributions are in the core of theories for a large variety of subjects ranging from the analysis of patch clamp records to stochastic excitable systems. Here, we present a novel exact method for the calculation of waiting time distributions for state transitions of complex molecules with independent subunit dynamics. The absorbing state is a specific set of subunit states, i.e. is defined on the molecule level. Consequently, we formulate the problem as a random walk in the molecule state space. The subunits can possess an arbitrary number of states and any topology of transitions between them. The method circumvents problems arising from combinatorial explosion due to subunit coupling and requires solutions of the subunit master equation only

cDNA cloning and characterization of tryptophan synthase alpha subunit from Polygonum tinctorium

Polygonum tinctorium is a cultivated plant that produces indigo, a natural blue dye. Its leaves contain a large amount of indican (indoxyl-beta-D-glucoside), a colorless precursor of indigo. The enzyme beta-glucosidase, which degrades indican, is present in leaf cells. If the leaves ar e scratched because of some external factors, indican is enzymatically degraded into indoxyl and glucose. Because of the chemical instability of indoxyl, it is immediately oxidized to indigo by atmospheric oxygen. Beta-glucosidase is located in chloroplasts, whereas the substrate indican is stored in vacuoles. Therefore, indigo is only produced if leaf cells are physically broken. The insoluble indigo may have a negative effect on infectious fungi and bacteria as well as on invasive insects and other animals. We hypothesize that the physiological role of indican as a secondary metabolite is of a defense system against predators. In a previous study, we have shown that indican is synthesized from indoxyl and UDP-glucose by the catalysis of UDP-glucosyltransferase. The substrate indoxyl is probably produced by the hydroxylation of indole catalyzed by cytochrome P450. Indole is an intermediate product in tryptophan syn thesis, which is the final step of the shikimic acid pathway, a primary metabolic pathway. The tryptophan synthase consists of four subunits: two alpha subunits (TSA) and two beta subunits (TSB). Only TSA catalyzes the synthetic reaction of indole. Subsequently, indole is converted to tryptophan by the action of TSB. The purpose of this study is to uncover the complete indican synthetic pathway and to provide insight into the switching mechanism from primary to secondary metabolism. Here, we report on the cDNA cloning, expression, and characterization of TSA from P. tinctorium. Transcriptome analysis using mRNA from P. tinctorium leaf tissue resulted in a one-fragment sequence that has homology with sequences from other plant TSAs. Based on this sequence, the RACE method was used to get the complete length of the TSA cDNA. The obtained cDNA consisted of 1,469 bp encoding a polypeptide of 315 amino acids. The primary structure contained the consensus sequences of TSAs and the regions for interaction with beta subunits. P. tinctorium TSA, which we named as ptTSA1, showed high homology to some enzymes from plants; this was the case particularly with TSA from Isatis tinctoria, another indigo plant, which showed 95.7% homology to ptTSA1. To analyze the properties and functions of ptTSA1, the recombinant protein was expressed in Escherichia coli. In addition, the ptTSA1 cDNA was used to examine whether ptTSA1 could complement a TSA deletion in E. coli. ptTSA1 protein expression and mRNA levels in various tissues of P. tinctorium were examined by the Western blot analysis and semi-quantitative RT-PCR. These expression patterns were also compared with those of TSBs. Here, we will further discuss regarding the analysis of ptTSA1 and the interaction between TSA and TSB

Cell cultures and molecular investigation on Polygonum tinctorium and Indigofera tinctoria plants to understand indican biosynthesis

Indican biosynthesis in Indigofera tinctoria and Polygonum tinctorium plants is of topical interest due to its academic and industrial relevance for indigo dye production. Dye yield depends on indican content in the plant biomass. Cell culture and molecular biological investigations were carried out to assess indican biosynthesis in these plants. Tissue culture protocols were optimized for explant identification, decontamination, in vitro culture medium & suitable growth regulators and culture conditions for P. tinctorium at Okayama University of Science, and I. tinctoria at CSIR-NEERI. Four different growth hormones i.e. BA, Kin, NAA, 2,4-D, at 0.01 –2 mg L-1 culture medium, in random combination, and two different explants i.e. leaf and internode of both plants were experimented. In both plants, callus proliferation was better from leaf tissue with growth index (GI) up to 10 on MS agar gelled medium fortified with BA+NAA in comparison to BA+2,4-D. Suspension cell cultures of I. tinctorium were induced in MS liquid medium with only 2,4-D through 3 stages with GI up to 30. In vitro raised cell biomass of I. tinctorium presented higher indican synthesis (p> 0.5) in comparison to that of P. tinctorium. Both of these plants synthesize indican, but the differential response under in vitro is interesting. Total transcriptomes of both plants were worked out and annotated. Comparative analysis of transcriptome profile indicated >80% genes are similar for the indican biosynthetic pathways. Complete alignment of both transcriptomes and validation for biosynthesis pathways specific genes is needed in both the plants to ascertain their differential expression

Mobility promotes and jeopardizes biodiversity in rock-paper-scissors games

Biodiversity is essential to the viability of ecological systems. Species diversity in ecosystems is promoted by cyclic, non-hierarchical interactions among competing populations. Such non-transitive relations lead to an evolution with central features represented by the `rock-paper-scissors' game, where rock crushes scissors, scissors cut paper, and paper wraps rock. In combination with spatial dispersal of static populations, this type of competition results in the stable coexistence of all species and the long-term maintenance of biodiversity. However, population mobility is a central feature of real ecosystems: animals migrate, bacteria run and tumble. Here, we observe a critical influence of mobility on species diversity. When mobility exceeds a certain value, biodiversity is jeopardized and lost. In contrast, below this critical threshold all subpopulations coexist and an entanglement of travelling spiral waves forms in the course of temporal evolution. We establish that this phenomenon is robust, it does not depend on the details of cyclic competition or spatial environment. These findings have important implications for maintenance and evolution of ecological systems and are relevant for the formation and propagation of patterns in excitable media, such as chemical kinetics or epidemic outbreaks.Comment: Final submitted version; the printed version can be found at http://dx.doi.org/10.1038/nature06095 Supplementary movies are available at http://www.theorie.physik.uni-muenchen.de/lsfrey/images_content/movie1.AVI and http://www.theorie.physik.uni-muenchen.de/lsfrey/images_content/movie2.AV

A Bayesian approach to modelling heterogeneous calcium responses in cell populations

Calcium responses have been observed as spikes of the whole-cell calcium concentration in numerous cell types and are essential for translating extracellular stimuli into cellular responses. While there are several suggestions for how this encoding is achieved, we still lack a comprehensive theory. To achieve this goal it is necessary to reliably predict the temporal evolution of calcium spike sequences for a given stimulus. Here, we propose a modelling framework that allows us to quantitatively describe the timing of calcium spikes. Using a Bayesian approach, we show that Gaussian processes model calcium spike rates with high fidelity and perform better than standard tools such as peri-stimulus time histograms and kernel smoothing. We employ our modelling concept to analyse calcium spike sequences from dynamically-stimulated HEK293T cells. Under these conditions, different cells often experience diverse stimuli time courses, which is a situation likely to occur in vivo. This single cell variability and the concomitant small number of calcium spikes per cell pose a significant modelling challenge, but we demonstrate that Gaussian processes can successfully describe calcium spike rates in these circumstances. Our results therefore pave the way towards a statistical description of heterogeneous calcium oscillations in a dynamic environmen