General theory of competitive coexistence in spatially-varying environments

A general model of competitive and apparent competitive interactions in a spatially-variable environment is developed and analyzed to extend findings on coexistence in a temporally-variable environment to the spatial case and to elucidate new principles. In particular, coexistence mechanisms are divided into variation-dependent and variation-independent mechanisms with variation-dependent mechanisms including spatial generalizations of relative nonlinearity and the storage effect. Although directly analogous to the corresponding temporal mechanisms, these spatial mechanisms involve different life history traits which suggest that the spatial storage effect should arise more commonly than the temporal storage effect and spatial relative nonlinearity should arise less commonly than temporal relative nonlinearity. Additional mechanisms occur in the spatial case due to spatial covariance between the finite rate of increase of a local population and its local abundance, which has no clear temporal analogue. A limited analysis of these additional mechanisms shows that they have similar properties to the storage effect and relative nonlinearity and potentially may be considered as enlargements of the earlier mechanisms. The rate of increase of a species perturbed to low density is used to quantify coexistence. A general quadratic approximation, which is exact in some important cases, divides this rate of increase into contributions from the various mechanisms above and admits no other mechanisms, suggesting that opportunities for coexistence in a spatially-variable environment are fully characterized by these mechanisms within this general model. Three spatially-implicit models are analyzed as illustrations of the general findings and of techniques using small variance approximations. The contributions to coexistence of the various mechanisms are expressed in terms of simple interpretable formulae. These spatially-implicit models include a model of an annual plant community, a spatial multispecies version of the lottery model, and a multispecies model of an insect community competing for spatially-patchy and ephemeral food.     

A three-dimensional computer model of four hypothetical mechanisms protecting biofilms from antimicrobials

Four hypothetical mechanisms for protection of biofilms against antimicrobials were incorporated into a three-dimensional model of biofilm growth and development. The model integrated processes of substrate utilization, diffusion, growth, cell migration, death, and detachment in a cellular automaton framework. Compared to simulations of unprotected biofilms, each of the protective mechanisms provided some tolerance to antimicrobial action. When the mechanisms were compared to each other, the behaviors of the four protective mechanisms produced distinct shapes of killing curves, nonuniform spatial patterns of survival and cell type distribution, and anticipated susceptibility patterns for dispersed biofilm cells. The differences between the protective mechanisms predicted in these simulations could guide the design of experiments to discriminate antimicrobial tolerance mechanisms in biofilms. Each of the mechanisms could be a plausible avenue of biofilm protection.     

Integrated tolerance mechanisms: constitutive and adaptive plant responses to elevated metal concentrations in the environment

Isolation and study of metal tolerant and hypersensitive strains of higher plant (and yeast) species has greatly increased our knowledge of the individual pathways that are involved in tolerance. Plants have both constitutive (present in most phenotypes) and adaptive (present only in tolerant phenotypes) mechanisms for coping with elevated metal concentrations. Where studies on the mechanisms of tolerance fall down is in their failure to integrate tolerance mechanisms within cell or whole-plant function by not relating adaptive mechanisms to constitutive mechanisms. This failure often distorts the relative importance of a proposed tolerance mechanism, and indeed has confused the search for adaptive mechanisms. The fundamental goal of both constitutive and adaptive mechanisms is to limit the perturbation of cell homeostasis after exposure to metals so that normal or near-normal physiological function may take place. Consideration of the response to metals at a cellular rather than a biochemical level will lead to a greater understanding of mechanisms to withstand elevated levels of metals in both contaminated and uncontaminated environments. Recent advances in the study of Al, As, Cd, and Cu tolerance and hypersensitivity are reported with respect to the cellular response to toxic metals. The role of genetics in unravelling tolerance mechanisms is also considered.     

Spatial sensing of stimulus gradients can be superior to temporal sensing for free-swimming bacteria.

Predictions of the minimal size an organism must have to swim along stimulus gradients were used to compare the relative advantages of sensory systems employing spatial (simultaneous) and temporal (sequential) gradient detection mechanisms for small free-swimming bacteria, leading to the following conclusions: 1) there are environmental conditions where spatial detection mechanisms can function for smaller organisms than can temporal mechanisms, 2) temporal mechanisms are superior (have a smaller size limit) for the difficult conditions of low concentration and shallow gradients, but 3) observed bacterial chemotaxis occurs mostly under conditions where spatial mechanisms have a smaller size limit, and 4) relevant conditions in the natural environment favor temporal mechanisms in some cases and spatial mechanisms in others. Thus, sensory ecology considerations do not preclude free-swimming bacteria from employing spatial detection mechanisms, as has been thought, and microbiologists should be on the lookout for them. If spatial mechanisms do not occur, the explanation should be sought elsewhere.     

A Three-Dimensional Computer Model of Four Hypothetical Mechanisms Protecting Biofilms from Antimicrobials

Four hypothetical mechanisms for protection of biofilms against antimicrobials were incorporated into a three-dimensional model of biofilm growth and development. The model integrated processes of substrate utilization, diffusion, growth, cell migration, death, and detachment in a cellular automaton framework. Compared to simulations of unprotected biofilms, each of the protective mechanisms provided some tolerance to antimicrobial action. When the mechanisms were compared to each other, the behaviors of the four protective mechanisms produced distinct shapes of killing curves, nonuniform spatial patterns of survival and cell type distribution, and anticipated susceptibility patterns for dispersed biofilm cells. The differences between the protective mechanisms predicted in these simulations could guide the design of experiments to discriminate antimicrobial tolerance mechanisms in biofilms. Each of the mechanisms could be a plausible avenue of biofilm protection.     

Mechanisms of pattern formation in development and evolution

We present a classification of developmental mechanisms that have been shown experimentally to generate pattern and form in metazoan organisms. We propose that all such mechanisms can be organized into three basic categories and that two of these may act as composite mechanisms in two different ways. The simple categories are cell autonomous mechanisms in which cells enter into specific arrangements ('patterns') without interacting, inductive mechanisms in which cell communication leads to changes in pattern by reciprocal or hierarchical alteration of cell phenotypes ('states') and morphogenetic mechanisms in which pattern changes by means of cell interactions that do not change cell states. The latter two types of mechanism can be combined either morphostatically, in which case inductive mechanisms act first, followed by the morphogenetic mechanism, or morphodynamically, in which case both types of mechanisms interact continuously to modify each other's dynamics. We propose that this previously unexplored distinction in the operation of composite developmental mechanisms provides insight into the dynamics of many developmental processes. In particular, morphostatic and morphodynamic mechanisms respond to small changes in their genetic and microenvironmental components in dramatically different ways. We suggest that these differences in 'variational properties' lead to morphostatic and morphodynamic mechanisms being represented to different extents in early and late stages of development and to their contributing in distinct ways to morphological transitions in evolution.     

Oscillations in a Simple Neuromechanical System: Underlying Mechanisms

A half-center neural oscillator was coupled to a simple mechanical system to study the closed-loop interactions between a central pattern generator and its effector muscles. After a review of the open-loop mechanisms that were previously introduced by Skinner et al. (1994), we extend their geometric approach and introduce four additional closed-loop mechanisms by the inclusion of an antagonistic muscle pair acting on a mass and connected to the half-center neural oscillator ipsilaterally. Two of the closed-loop mechanisms, mechanical release mechanisms, have close resemblance to open-loop release mechanisms whereas the latter two, afferent mechanisms, have a strong dependence on the mechanical properties of the system. The results also show that stable oscillations can emerge in the presence of sensory feedback even if the neural system is not oscillatory. Finally, the feasibility of the closed-loop mechanisms was shown by weakening the idealized assumptions of the synaptic and the feedback connections as well as the rapidity of the oscillations.     

Mechanisms of statin-induced new-onset diabetes

Statins, with their lipid-lowering properties, are a first-line therapy for the prevention of cardiovascular diseases. Recent evidence, however, suggests that statins can increase the risk of new-onset diabetes (NOD). The molecular mechanisms of statin-induced NOD are not precisely known, although some pathophysiologic mechanisms have been suggested. Specific to the beta cell, these mechanisms include alterations in insulin secretion, changes in ion channels, modulation of signaling pathways, and inflammation/oxidative stress. Outwith the beta cell, other suggested mechanisms involve adipocytes, including alterations in adipocyte differentiation and modulation of leptin and adiponectin, and genetic and epigenetic mechanisms, including alterations in microRNA. The evidence supporting these and other mechanisms will be discussed. Greater understanding of the underlying mechanisms linking the onset of diabetes to statin therapy is essential and clinically relevant, as it may enable novel preventative or therapeutic approaches to be instituted and guide the production of a new generation of statins lacking this side effect.     

A balance of lipid-sensing mechanisms in the brain and liver

Recent work has cast a spotlight on the brain as a nutrient-sensing organ that regulates the body's metabolic processes. Here we discuss the physiological and molecular mechanisms of brain lipid sensing and compare these mechanisms to liver lipid sensing. A direct comparison between the lipid-sensing mechanisms in the brain and liver reveals similar biochemical/molecular but opposing physiological mechanisms in operation. We propose that an imbalance between the lipid-sensing mechanisms in the brain and liver may contribute to obesity-associated type 2 diabetes.     

Autophagy,anoikis, ferroptosis,necroptosis, and endoplasmic reticulum stress: Potential applications in melanoma therapy

Melanoma as the most major skin malignancy has attracted much attention, so far. Although a successful therapeutic strategy requires an accurate understanding of the precise mechanisms for the initiation and progression of the melanoma. Several types of cell death mechanisms have recently been identified along with conventional cell death mechanisms such as apoptosis and necrosis. Among those mechanisms, necroptosis, anoikis, ferroptosis, and autophagy may be considered to have remarkable modulatory impacts on melanoma. In the present review, we explain the mechanisms of cell death signaling pathways related to autophagy, ferroptosis, anoikis, necroptosis, and reticulum endoplasmic stress in cells and describe how those mechanisms transduce signals in melanoma cells. Meanwhile, we describe how we can modulate those mechanisms to eliminate melanoma.     

Perception and transduction of abscisic acid signals: keys to the function of the versatile plant hormone ABA

During the past decade, much progress has been made toward understanding the mechanisms underlying plant hormone activity, from perception to nuclear events. However, the signaling mechanisms for abscisic acid (ABA) have remained largely obscure. Recent breakthroughs identifying FCA, which is an RNA-binding protein, the Mg-chelatase H subunit, and a G protein-coupled receptor as receptors for ABA provide a major leap forward in understanding the initial steps of ABA signaling mechanisms. Recent studies have also revealed the molecular mechanisms of second messenger production, protein modifications such as phosphorylation, and regulatory mechanisms of gene expression in the ABA response. Therefore, the connections between these events are also beginning to be determined. Here, we review recent progress and discuss the overall scheme of the ABA response mechanisms.     

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis

Despite substantial evidence for sex differences in addiction epidemiology, addiction‐relevant behaviors and associated neurobiological phenomena, the mechanisms and implications of these differences remain unknown. Genetic analysis in model organism is a potentially powerful and effective means of discovering the mechanisms that underlie sex differences in addiction. Human genetic studies are beginning to show precise risk variants that influence the mechanisms of addiction but typically lack sufficient power or neurobiological mechanistic access, particularly for the discovery of the mechanisms that underlie sex differences. Our thesis in this review is that genetic variation in model organisms are a promising approach that can complement these investigations to show the biological mechanisms that underlie sex differences in addiction.     

In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges.

This review focuses on the neural and local mechanisms that have been demonstrated to effect cutaneous vasodilation and vasoconstriction in response to heat and cold stress in vivo in humans. First, our present understanding of the mechanisms by which sympathetic cholinergic nerves mediate cutaneous active vasodilation during reflex responses to whole body heating is discussed. These mechanisms include roles for cotransmission as well as nitric oxide (NO). Next, the mechanisms by which sympathetic noradrenergic nerves mediate cutaneous active vasoconstriction during whole body cooling are reviewed, including cotransmission by neuropeptide Y (NPY) acting through NPY Y1 receptors. Subsequently, current concepts for the mechanisms that effect local cutaneous vascular responses to direct skin warming are examined. These mechanisms include the roles of temperature-sensitive afferent neurons as well as NO in causing vasodilation during local heating of skin. This section is followed by a review of the mechanisms that cause local cutaneous vasoconstriction in response to direct cooling of the skin, including the dependence of these responses on intact sensory and sympathetic, noradrenergic innervation as well as roles for nonneural mechanisms. Finally, unresolved issues that warrant further research on mechanisms that control cutaneous vascular responses to heating and cooling are discussed.     

The derivation of theoretical resistance mechanisms to antibacterial agents

The elucidation of molecular mechanisms whereby bacterial cells become resistant to the inhibitory effects of antibacterial agents is of importance in the design and development of new agents. Using a reaction path model to describe the interaction between a hypothetical drug and a susceptible cell-system, an extensive range of theoretical mechanisms of resistance are derived. It is presumed that such resistances are genome-mediated and the intention is to define the subcellular mechanisms resulting from genotype alterations. The derivation of such an extensive range of potential mechanisms provides the investigator of unknown mechanisms with a detailed analysis of the range of options available. It is suggested that the principles involved are applicable to drug-resistance studies in any chemotherapeutic context, irrespective of the type of organism involved.     

Evolution of time-keeping mechanisms: early emergence and adaptation to photoperiod

Virtually all species have developed cellular oscillations and mechanisms that synchronize these cellular oscillations to environmental cycles. Such environmental cycles in biotic (e.g. food availability and predation risk) or abiotic (e.g. temperature and light) factors may occur on a daily, annual or tidal time scale. Internal timing mechanisms may facilitate behavioural or physiological adaptation to such changes in environmental conditions. These timing mechanisms commonly involve an internal molecular oscillator (a 'clock') that is synchronized ('entrained') to the environmental cycle by receptor mechanisms responding to relevant environmental signals ('Zeitgeber', i.e. German for time-giver). To understand the evolution of such timing mechanisms, we have to understand the mechanisms leading to selective advantage. Although major advances have been made in our understanding of the physiological and molecular mechanisms driving internal cycles (proximate questions), studies identifying mechanisms of natural selection on clock systems (ultimate questions) are rather limited. Here, we discuss the selective advantage of a circadian system and how its adaptation to day length variation may have a functional role in optimizing seasonal timing. We discuss various cases where selective advantages of circadian timing mechanisms have been shown and cases where temporarily loss of circadian timing may cause selective advantage. We suggest an explanation for why a circadian timing system has emerged in primitive life forms like cyanobacteria and we evaluate a possible molecular mechanism that enabled these bacteria to adapt to seasonal variation in day length. We further discuss how the role of the circadian system in photoperiodic time measurement may explain differential selection pressures on circadian period when species are exposed to changing climatic conditions (e.g. global warming) or when they expand their geographical range to different latitudes or altitudes.     

Seed dispersal systems in the New Zealand flora

Knowledge of the dispersal mechanisms used by plants is important in phylogenetic, ecological, biogeographical, and conservation studies. Here we attempt to assign dispersal mechanisms to the entire flora-2595 plant species of the New Zealand Botanical Region. Anemochory is the most frequent dispersal mechanism, utilised by 79% of species. The next most frequent mechanisms are endozoochory (33%), hydrochory (28%), epizoochory (26%), and ballistic (8%). Polychory is common, particularly in monocotyledonous and dicotyledonous families and hydrochorous, epizoochorous, and ballistically dispersed species. Epizoochory is more common in New Zealand than in other regions, and species using this dispersal mechanism are over-represented among threatened species. Frugivory is less common than previously reported, and is under-represented among threatened species. Some mechanisms are poorly known, and entanglement and capsulivory are dispersal mechanisms apparently unique to New Zealand. Dispersal mechanisms reflective of New Zealand's distinctive assemblages of large flightless birds and reptiles are not apparent. A pattern of reduction in dispersal-related structures is evident in some genera. The mechanisms utilised by some species are ambiguous. Thus there remains a need for further investigation of the dispersal mechanisms utilised by plants in New Zealand.     

Theoretical investigation of the neuronal Na+ channel SCN1A: abnormal gating and epilepsy

Epilepsy is a paroxysmal neurological disorder resulting from abnormal cellular excitability and is a common cause of disability. Recently, some forms of idiopathic epilepsy have been causally related to genetic mutations in neuronal ion channels. To understand disease mechanisms, it is crucial to understand how a gene defect can disrupt channel gating, which in turn can affect complex cellular dynamic processes. We develop a theoretical Markovian model of the neuronal Na+ channel NaV1.1 to explore and explain gating mechanisms underlying cellular excitability and physiological and pathophysiological mechanisms of abnormal neuronal excitability in the context of epilepsy. Genetic epilepsy has been shown to result from both mutations that give rise to a gain of channel function and from those that reduce the Na+ current. These data may suggest that abnormal excitation can result from both hyperexcitability and hypoexcitability, the mechanisms of which are presumably distinct, and as yet elusive. Revelation of the molecular origins will allow for translation into targeted pharmacological interventions that must be developed to treat syndromes resulting from divergent mechanisms. This work represents a first step in developing a comprehensive theoretical model to investigate the molecular mechanisms underlying runaway excitation that cause epilepsy.     

Pattern formation on the combs of honeybees: increasing fitness by coupling self-organization with templates

Biological patterns are often constructed via a combination of mechanisms including self-organization, templates and recipes. Our understanding of self-organization is becoming increasingly clear, yet how multiple mechanisms work together and what selective advantage they confer over simpler mechanisms is poorly understood. Honeybee (Apis mellifera) combs exhibit a pattern of brood at the bottom, pollen in a band next to it and honey at the top. This study constructs an agent-based model, derived from experimental studies, to determine both how self-organization interacts with two templates and to elucidate a selective basis for the use of multiple mechanisms. The vertical pattern of honey and brood is shown to be dependent on a gravity-based template, while the pollen band is shown to form via the interaction of a queen-based template and self-organization. The study suggests that the selective basis for this complex mechanism may be that colonies have higher growth rates when multiple mechanisms are used as opposed to self-organization alone. As self-organization is used in many contexts in which the addition of supplemental mechanisms could be advantageous, this result may be of general significance to many biological systems.     

Correcting the short-term effect of food deprivation in a damselfly: mechanisms and costs

1. Mass at emergence is a life-history trait strongly linked to adult fitness. Therefore, when faced with transient food shortage in the larval stage, mass-correcting mechanisms are common. 2. These correcting mechanisms may carry costs with them. On one hand, these costs may be overestimated because they can be confounded with the direct effects of the transient food shortage itself. On the other hand, costs may be underestimated by ignoring physiological costs. Another largely neglected topic is that correcting mechanisms and costs may critically depend upon other stressors that often co-occur. 3. Here, we identify the mass-correcting mechanisms and their associated costs at emergence in the damselfly Coenagrion puella, after being stressed by a transient period of starvation and a subsequent exposure to pesticide stress during the larval stage. We introduce path analysis to disentangle direct costs of starvation and the mass-correcting mechanisms in terms of immune response. 4. As predicted, we found no differences in mass at emergence. Starvation directly resulted in a costly delayed emergence and a decreased immune response at emergence. Mass-correcting mechanisms included a prolonged post-starvation period, reduced mass loss at emergence and compensatory growth, although the latter only in females under pesticide stress. 5. The mass-correcting mechanisms were associated with beneficial effects on investment in immune response, but only in the absence of pesticide stress. Under pesticide stress, these beneficial effects were mostly undone or overruled, resulting in negative effects of the mass-correcting mechanisms in terms of immune response. 6. Our results stress the importance of and introduce a statistical way of disentangling direct costs of starvation and the mass-correcting mechanisms themselves, and the importance of including physiological endpoints in this kind of studies.     

Transplantation tolerance: from phenomenon to mechanism

The term "transplantation tolerance" is used for a state when a histoincompatible graft, i.e. one from a genetically different donor, survives in a recipient in which it would have been rejected under normal circumstances. Transplantation tolerance was first experimentally induced in 1953 and since that time the mechanisms underlying this phenomenon have been analysed. Originally, attention was paid to passive mechanisms of transplantation tolerance more recently, active mechanisms of tolerance, have been discovered. The recognition of these regulatory mechanisms and the development of ability to manipulate them has already had and will continue to have increasing impact on aimed the immunoregulation in therapeutic transplantation.