Do innate killing mechanisms activated by inflammasomes have a role in treating melanoma?

Melanoma, as for many other cancers, undergoes a selection process during progression that limits many innate and adaptive tumor control mechanisms. Immunotherapy with immune checkpoint blockade overcomes one of the escape mechanisms but if the tumor is not eliminated other escape mechanisms evolve that require new approaches for tumor control. Some of the innate mechanisms that have evolved against infections with microorganisms and viruses are proving to be active against cancer cells but require better understanding of how they are activated and what inhibitory mechanisms may need to be targeted. This is particularly so for inflammasomes which have evolved against many different organisms and which recruit a number of cytotoxic mechanisms that remain poorly understood. Equally important is understanding of where these mechanisms will fit into existing treatment strategies and whether existing strategies already involve the innate killing mechanisms.     

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.     

The role of hormones of hypothalamic-pituitary-adrenocortical system in regulation of pain sensitivity

The review focuses on the role of hypothalamic-pituitary-adrenocortical system (HPAS) in regulation of pain sensitivity and discusses the mechanisms involved in this process. Analgesic effects of exogenous hormones of HPAS (corticotropin-releasing hormone (CRH), ACTH, glucocorticoids) have been shown in rats. It is mediated by both opioid and non-opioid mechanisms. Endogenous glucocorticoids produce development of analgesia mediated by non-opioid mechanisms. Analgesic effect of ACTH is mediated by both non-glucocorticoids mechanisms associated with endogenous glucocorticoids and opioid mechanisms. In contrast to ACTH, analgesic effect of CRH is mediated only by non-opioid mechanisms associated or dissociated with endogenous glucocorticoids. The neurons of midbrain periaqueductal gray matter may be involved in the analgesia induced by glucocorticoids.     

The mechanism of leaf morphogenesis

Whether cell division is a driving force in plant morphogenesis has long been debated. In this review, the evidence for the existence of cell division-dependent and cell division-independent mechanisms of plant morphogenesis is discussed. The potential mechanisms themselves are then analysed, as is our understanding of the regulation of these mechanisms and how they are integrated into development, with particular emphasis on data arising from the investigation of leaf morphogenesis. The analysis indicates the existence of both cell division-dependent and cell division-independent mechanisms in leaf morphogenesis and highlights the importance of future investigations to unravel the co-ordination of these mechanisms.     

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.     

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.     

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.     

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.     

Some mechanisms of Helicobacter pylori persistence

The mechanisms of the pathogenesis of Helicobacter pylori infection, ensuring the prolonged survival of these bacteria in the aggressive medium (gastric mucosa), are considered. A new approach to the systematization of the mechanisms of H. pylori persistence is proposed: the mechanisms ensuring the stability of H. pylori in the presence of aggressive physical and chemical factors, the mechanisms ensuring antagonistic effects in biocenosis and the mechanisms ensuring resistance to the protective factors of the host. Data on the persistence potential of H. pylori in accordance with the proposed classification are presented.     

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.     

A kinetic analysis of enzyme systems involving four substrates

A treatment of kinetic data for enzyme mechanisms involving four substrates is described. The initial-rate equations and product-inhibition patterns for such mechanisms are presented. The treatment is extended to include analysis of enzyme mechanisms involving three substrates in which two molecules of one substrate are used.     

Quorum sensing and signal interference: diverse implications

Quorum sensing (QS) is a community genetic regulation mechanism that controls microbiological functions of medical, agricultural and industrial importance. Discovery of microbial QS signals and the signalling mechanisms led to identification of numerous enzymatic and non-enzymatic signal interference mechanisms that quench microbial QS signalling. Evidence is accumulating that such signal interference mechanisms can be developed as promising approaches to control microbial infection and biofilm formation. In addition, these mechanisms exist not only in microorganisms but also in the host organisms of bacterial pathogens, highlighting their potential implications in microbial ecology and in host-pathogen interactions. Investigation of QS and signal interference mechanisms might significantly broaden the scope of research in microbiology.     

Molecular mechanisms of vertebrate photoreceptor light adaptation.

An important recent advance in the understanding of vertebrate photoreceptor light adaptation has come from the discovery that as many as eight distinct molecular mechanisms may be involved, and the realization that one of the principal mechanisms is not dependent on calcium. Quantitative analysis of these mechanisms is providing new insights into the nature of rod photoreceptor light adaptation.     

Drosophila follicle cells: morphogenesis in an eggshell

Epithelial morphogenesis is important for organogenesis and pivotal for carcinogenesis, but mechanisms that control it are poorly understood. The Drosophila follicular epithelium is a genetically tractable model to understand these mechanisms in vivo. This epithelium of follicle cells encases germline cells to create an egg. In this review, we summarize progress toward understanding mechanisms that maintain the epithelium or permit migrations essential for oogenesis. Cell-cell communication is important, but the same signals are used repeatedly to control distinct events. Understanding intrinsic mechanisms that alter responses to developmental signals will be important to understand regulation of cell shape and organization.     

Spatial organization of the eukaryotic genome and the action of epigenetic mechanisms

Genome activity in eukaryotic cells is regulated at different levels. Long-term activation and repression of gene expression is controlled by epigenetic mechanisms. The main feature of epigenetic mechanisms is that regulatory events, provided by these mechanisms, are preserved in a series of cellular generations upon mitotic division, i.e., in a certain sense are inherited. Most of the epigenetic mechanisms, known so far, act at the level of nucleosomes and the dynamics of nucleosomal fibre. The important signal elements of epigenetic system are DNA methylation, histone modifications, and the inclusion of noncanonical forms of the histones in nucleosomes. In the present study, we substantiate the statement that the large-scale spatial organization of the DNA in eukaryotic cell also plays an important role in the action of epigenetic mechanisms.     

A call to arms: coevolution of animal viruses and host innate immune responses

Virus infection is generally disadvantageous to the host and strongly selects for host antiviral mechanisms. Therefore, viruses must develop counter-mechanisms to guarantee their survival. This arms race between pathogen and host leads to positive selection for both cellular antiviral mechanisms and viral inhibitors of such mechanisms. Here, we characterize this arms race in the context of the RNA interference (RNAi) pathway, which is used as an innate immune response against viral infection by animals. We review how RNAi is used as an antiviral strategy and the mechanisms that viruses have evolved to suppress the RNAi response.     

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.     

Spatial organization of the eukaryotic genome and the action of epigenetic mechanisms

Genome activity in eukaryotic cells is regulated at different levels. Long-term activation and repression of gene expression is controlled by epigenetic mechanisms. The main feature of epigenetic mechanisms is that regulatory events, provided by these mechanisms, are preserved in a series of cellular generations upon mitotic division, i.e., in a certain sense are inherited. Most of the epigenetic mechanisms, known so far, act at the level of nucleosomes and the dynamics of nucleosomal fibre. The important signal elements of epigenetic system are DNA methylation, histone modifications, and the inclusion of noncanonical forms of the histones in nucleosomes. In the present study, we substantiate the statement that the large-scale spatial organization of the DNA in eukaryotic cell also plays an important role in the action of epigenetic mechanisms.