Plant cortical microtubules are putative sensors under abiotic stresses

In this article, we review current knowledge on the dynamic changes and roles of microtubule (MT) arrays under abiotic stresses. The results emphasize the existence of highly dynamic changes, complex regulatory networks, and the vitally important role of MTs in the response to abiotic stresses. In particular, some findings indicate that cortical microtubules (CMTs) underlying the plasma membrane play an important role in abiotic stress-induced signaling pathways. Therefore, we also discuss the relationship between CMTs and abiotic stress signaling. The data show that at least three early response mechanisms, namely, Ca²⁺ signaling, abscisic acid biosynthesis, and the formation of plant cell walls, follow CMT reorganization and are mediated by dynamic changes in the CMTs. Consequently, we propose that the CMTs are not only part of the plant response to abiotic stresses but might also serve as a type of cell wall membrane-bound sensor that perceives the stress stimuli to generate adaptive signals and responses of cells.     

Bioimprinting strategies: From soft lithography to biomimetic sensors and beyond

Imprinting is a straightforward, yet a reliable technique to develop dynamic artificial recognition materials—so called as synthetic antibodies. Surface imprinting strategies such as soft lithography allow biological stereotyping of polymers and sol–gel phases to prepare extremely selective receptor layers, which can be combined with suitable transducer systems to develop high performance biomimetic sensors. This article presents an overview of the remarkable technical advancements in the field of surface bioimprinting with particular emphasis on surface imprinted bioanalyte detection systems and their applications in rapid bioanalysis and biotechnology. Herein, we discuss a variety of surface imprinting strategies including soft lithography, template immobilization, grafting, emulsion polymerization, and others along with their biomimetic sensor applications, merits and demerits. The pioneering research works on surface patterned biosensors are described with selected examples of detecting biological agents ranging from small biomolecules and proteins to living cells and microorganisms.     

From systems biology to systems biomedicine

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine.     

From genomes to systems

A report on the 2nd Conference of the Consortium for Post-Genome Science (CPGS) 'Genomes to Systems', Manchester, UK, 1-3 September 2004.     

From conventional sensors to fibre optic sensors for strain and force measurements in biomechanics applications: A review

In vivo measurement, not only in animals but also in humans, is a demanding task and is the ultimate goal in experimental biomechanics. For that purpose, measurements in vivo must be performed, under physiological conditions, to obtain a database and contribute for the development of analytical models, used to describe human biomechanics. The knowledge and control of the mechanisms involved in biomechanics will allow the optimization of the performance in different topics like in clinical procedures and rehabilitation, medical devices and sports, among others.     

From membranes to systems: self-configuration and self-replication in membrane systems

Membrane systems are purely abstract computational models afar inspired by biological cells, their membranes, and their biochemistry. The inherently parallel nature of membrane systems makes them obviously highly inefficient to execute on a sequential von Neumann computer architecture and in addition, programming a membrane system is often a painstakingly difficult undertaking. The main goal of this paper is to provide some key elements for bringing membrane systems from the abstract model closer to a genuine, novel, and unconventional in silico computer architecture. In particular, we will address the mechanisms of self-configuration and self-replication on a macroscopic level and will discuss some general issues related to genuine hardware realizations on the microscopic level.     

From sensors to spikes: evolving receptive fields to enhance sensorimotor information in a robot-arm

In biological systems, instead of actual encoders at different joints, proprioception signals are acquired through distributed receptive fields. In robotics, a single and accurate sensor output per link (encoder) is commonly used to track the position and the velocity. Interfacing bio-inspired control systems with spiking neural networks emulating the cerebellum with conventional robots is not a straight forward task. Therefore, it is necessary to adapt this one-dimensional measure (encoder output) into a multidimensional space (inputs for a spiking neural network) to connect, for instance, the spiking cerebellar architecture; i.e. a translation from an analog space into a distributed population coding in terms of spikes. This paper analyzes how evolved receptive fields (optimized towards information transmission) can efficiently generate a sensorimotor representation that facilitates its discrimination from other "sensorimotor states". This can be seen as an abstraction of the Cuneate Nucleus (CN) functionality in a robot-arm scenario. We model the CN as a spiking neuron population coding in time according to the response of mechanoreceptors during a multi-joint movement in a robot joint space. An encoding scheme that takes into account the relative spiking time of the signals propagating from peripheral nerve fibers to second-order somatosensory neurons is proposed. Due to the enormous number of possible encodings, we have applied an evolutionary algorithm to evolve the sensory receptive field representation from random to optimized encoding. Following the nature-inspired analogy, evolved configurations have shown to outperform simple hand-tuned configurations and other homogenized configurations based on the solution provided by the optimization engine (evolutionary algorithm). We have used artificial evolutionary engines as the optimization tool to circumvent nonlinearity responses in receptive fields.     

Membrane protein synthesis in cell-free systems: From bio-mimetic systems to bio-membranes

When taking up the gauntlet of studying membrane protein functionality, scientists are provided with a plethora of advantages, which can be exploited for the synthesis of these difficult-to-express proteins by utilizing cell-free protein synthesis systems. Due to their hydrophobicity, membrane proteins have exceptional demands regarding their environment to ensure correct functionality. Thus, the challenge is to find the appropriate hydrophobic support that facilitates proper membrane protein folding. So far, various modes of membrane protein synthesis have been presented. Here, we summarize current state-of-the-art methodologies of membrane protein synthesis in biomimetic-supported systems. The correct folding and functionality of membrane proteins depend in many cases on their integration into a lipid bilayer and subsequent posttranslational modification. We highlight cell-free systems utilizing the advantages of biological membranes.     

A VIP hybrid antagonist: From developmental neurobiology to clinical applications

Summary 1. The 28 amino acid vasoactive intestinal peptide, VIP, was originally isolated from the intestine, following a bioassay measuring vasodilating properties. Immunocytochemistry, receptor binding assays and in situ hybridizations have demonstrated VIP abundance in the nervous system, suggesting multiple bioactivities.2. A pharmacological approach was chosen to dissect VIP activities and a prototype VIP antagonist (Met-Hybrid) consisting of a carboxyl fragment of VIP_7–28 and a six amino acid fragment of neurotensin, neurotensin_6–11-VIP_7–28 was synthesized.3. This hybrid peptide was designed to maintain the binding capacity of one parent molecule (VIP), while loosing the agonistic properties, representing a classical competitive receptor antagonist. Furthermore, the new molecule exhibited increased specificity to central nervous system VIP receptors.4. The Met-Hybrid was originally discovered as a potent inhibitor of VIP functionin vivo. In the adult rodent, acute administration of the antagonist resulted in blockade of VIP-mediated potentiation of sexual behavior and chronic intracerebroventricular application impaired VIP-associated learning abilities. During ontogeny, chronic injections of the molecule resulted in neuronal damage, disruption of the diurnal rhythmicity of motor behavior, and retardation in the acquisition of neonatal reflexes in the rat.5. During gestation, severe microcephaly was induced by acute administration of the Met-Hybrid to pregnant mice. The hybrid antagonist inhibited VIP-stimulated mitosis in whole embryo cultures and in a variety of cancer cell linesin vitro andin vivo, suggesting therapeutical potential.     

Insect-symbiont systems: From complex relationships to biotechnological applications

Microbial symbiosis is a ubiquitous aspect of life and was a major element in the ability of insects to explore several adverse environments. To date, the study of symbiosis in insects has been impaired by the unculturability of most symbionts. However, some molecular methods represent powerful tools to help understand insect-microorganism associations and to disclose new symbiont-host systems. Beyond playing an essential role in nutrition and development of the insects, symbionts can produce bioactive compounds that protect the host against adverse environmental conditions, predators and/or direct competitors. Since the search for natural bioactive products and new enzymes is a developing area, understanding the diversity and nature of symbiont-host relationships paves the way for the exploitation of new resources in biotechnology. Furthermore, genetic transformation of the symbionts with genes that code for compounds that are toxic for pathogenic and phytopathogenic agents is also a promising area of application of the insect-symbiont relationships. The search for new bioactive compounds, the use of symbionts for pest and disease control and the molecular strategies applied for these purposes are issues of particular interest for innovative biotechnological applications and are addressed in the present review.     

Plasma membranes as heat stress sensors: From lipid-controlled molecular switches to therapeutic applications

The classic heat shock (stress) response (HSR) was originally attributed to protein denaturation. However, heat shock protein (Hsp) induction occurs in many circumstances where no protein denaturation is observed. Recently considerable evidence has been accumulated to the favor of the “Membrane Sensor Hypothesis” which predicts that the level of Hsps can be changed as a result of alterations to the plasma membrane. This is especially pertinent to mild heat shock, such as occurs in fever. In this condition the sensitivity of many transient receptor potential (TRP) channels is particularly notable. Small temperature stresses can modulate TRP gating significantly and this is influenced by lipids. In addition, stress hormones often modify plasma membrane structure and function and thus initiate a cascade of events, which may affect HSR. The major transactivator heat shock factor-1 integrates the signals originating from the plasma membrane and orchestrates the expression of individual heat shock genes. We describe how these observations can be tested at the molecular level, for example, with the use of membrane perturbers and through computational calculations. An important fact which now starts to be addressed is that membranes are not homogeneous nor do all cells react identically. Lipidomics and cell profiling are beginning to address the above two points. Finally, we observe that a deregulated HSR is found in a large number of important diseases where more detailed knowledge of the molecular mechanisms involved may offer timely opportunities for clinical interventions and new, innovative drug treatments. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.     

From patterns to processes and back: analysing density-dependent responses to an abiotic stressor by statistical and mechanistic modelling

Our knowledge about population-level effects of abiotic stressors is limited, largely due to lack of appropriate time-series data. To analyse interactions between an abiotic stressor and density-dependent processes, we used experimental time-series data for stage-structured populations (the blowfly Lucilia sericata) exposed to the toxicant cadmium through 20 generations. Resource limitation results in competition both in the larval and the adult stages. The toxicant has only negative effects at the organism level, but nevertheless, there were positive population-level effects. These are necessarily indirect, and indicate overcompensatory density-dependent responses. A non-parametric model (generalized additive model) was used to investigate the density-dependent structures of the demographic rates, without making assumptions about the functional forms. The estimated structures were used to develop a parametric model, with which we analysed effects of the toxicant on density-dependent and density-independent components of the stage-specific demographic rates. The parameter estimates identified both synergistic and antagonistic density-toxicant interactions. It is noteworthy that the synergistic interaction occurred together with a net positive effect of the toxicant. Hence, the effects of such interactions should be considered together with the capacity for compensatory responses. The combination of the two modelling approaches provided new insight into mechanisms for compensatory responses to abiotic stressors.     

Heme-based sensors in biological systems

The past several years have been witness to a staggering rate of advancement in the understanding of how organisms respond to changes in the availability of diatomic molecules that are toxic and/or crucial to survival. Heme-based sensors presently constitute the majority of the proteins known to sense NO, O2 and CO and to initiate the chemistry required to adapt to changes in their availabilities. Knowledge of the three characterized members of this class, soluble guanylate cyclase, FixL and CooA, has grown substantially during the past year. The major advances have resulted from a broad range of approaches to elucidation of both function and mechanism. They include growth in the understanding of the interplay between the heme and protein in soluble guanylate cyclase, as well as alternate means for its stimulation. Insight into the O2-induced structural changes in FixL has been supplied by the single crystal structure of the heme domain of Bradyrhizobium japonicum. Finally, the ligation environment and ligand interchange that facilitates CO sensing by CooA has been established by spectroscopic and mutagenesis techniques.     

From the ground up: biotic and abiotic features that set the course from genes to ecosystems

Spatial variation in cone serotiny in Rocky Mountain lodgepole pine (Pinus contorta ssp. latifolia) across Yellowstone National Park influences initial pine recruitment after stand‐replacing fire with tremendous population, community, and ecosystem consequences. A previous study showed that much of the spatial variation in serotiny results from the balance of selection arising from high frequencies of fire favoring serotiny countered by opposing selection exerted by American red squirrels (Tamiasciurus hudsonicus) as seed predators. This earlier study, however, assumed stable local red squirrel densities over multiple generations of pines. Here, we examine environmental properties that might contribute to long‐term stability in the densities of red squirrels among sites. We found that the amount of clay in the soil, an indicator of plant and fungal growth—the latter an important food resource for red squirrels—and the coefficient of variation (CV) in diameter at breast height (DBH) of forest trees together account for a substantial amount of variation in red squirrel density. Soil development occurs over very long time scales, and thus, intersite variation in the amount of clay is unlikely to shift across pine generations. However, CV of DBH and squirrel density increase with stand age, which acts to amplify selection against serotiny with increasing interfire interval. Regardless, much of the variation in the CV of DBH is accounted for by soil bulk density, mean annual temperature, and surface curvature, which are unlikely to vary in their relative differences among sites over time. Consequently, these soil and abiotic attributes could contribute to consistent spatial patterns of red squirrel densities from one pine generation to the next, resulting in consistent local and spatial variation in selection exerted by red squirrels against serotiny.     

From selection to complementarity: the shift along the abiotic stress gradient in a controlled biodiversity experiment

The effects of principal mechanisms (selection and complementarity) of biodiversity on ecosystem functionality have been well studied. However, it remains unknown how environmental conditions affect the relative strength of these two mechanisms. To answer this question, a controlled pot experiment was conducted in which species diversity was manipulated in low (natural soil) and high stress (mine tailing) plots, respectively. Our results demonstrate that the principal mechanism underlying the increasing biomass shifts from the selection to complementarity with increasing abiotic stress. The shift occurs because species interactions varied with increasing abiotic stress. Competition prevails in low stress plots, while facilitation dominates in high stress plots. In low stress plots, the monoculture biomass of a specific species is a good indicator of the competitive ability of that species in the mixture, and the dominant species significantly affects the plot biomass. In high stress plots, the tolerance indexes of all individual species increase with the manipulated species richness, providing clear evidence for the increasing role of facilitation.