Regenerative Ionic Currents and Bistability

What every neuroscientist should know about the mathematical modeling of excitable cells. Combining empirical physiology and nonlinear dynamics, this text provides an introduction to the simulation and modeling of dynamic phenomena in cell biology and neuroscience. It introduces mathematical modeling techniques alongside cellular electrophysiology. Topics include membrane transport and diffusion, the biophysics of excitable membranes, the gating of voltage and ligand-gated ion channels, intracellular calcium signalling, and electrical bursting in neurons and other excitable cell types. It introduces mathematical modeling techniques such as ordinary differential equations, phase plane, and bifurcation analysis of single-compartment neuron models. With analytical and computational problem sets, this book is suitable for life sciences majors, in biology to neuroscience, with one year of calculus, as well as graduate students looking for a primer on membrane excitability and calcium signalling.https://scholarworks.wm.edu/asbookchapters/1133/thumbnail.jp

Allostery in Oligomeric Receptor Models

We show how equilibrium binding curves of receptor homodimers can be expressed as rational polynomial functions of the equilibrium binding curves of the constituent monomers, without approximation and without assuming independence of receptor monomers. Using a distinguished spanning tree construction for reduced graph powers, the method properly accounts for thermodynamic constraints and allosteric interactions between receptor monomers (i.e. conformational coupling). The method is completely general; it begins with an arbitrary undirected graph representing the topology of a monomer state-transition diagram and ends with an algebraic expression for the equilibrium binding curve of a receptor oligomer composed of two or more identical and indistinguishable monomers. Several specific examples are analysed, including guanine nucleotide-binding protein-coupled receptor dimers and tetramers composed of multiple ‘ternary complex’ monomers

A Likelihood Ratio Test for Changes in Homeolog Expression Bias

Background Gene duplications are a major source of raw material for evolution and a likely contributor to the diversity of life on earth. Duplicate genes (i.e., homeologs, in the case of a whole genome duplication) may retain their ancestral function, sub- or neofunctionalize, or be lost entirely. A primary way that duplicate genes evolve new functions is by altering their expression patterns. Comparing the expression patterns of duplicate genes gives clues as to whether any of these evolutionary processes have occurred. Results We develop a likelihood ratio test for the analysis of the expression ratios of duplicate genes across two conditions (e.g., tissues). We demonstrate an application of this test by comparing homeolog expression patterns of 1448 homeologous gene pairs using RNA-seq data generated from leaves and petals of an allotetraploid monkeyflower (Mimulus luteus). We assess the sensitivity of this test to different levels of homeolog expression bias and compare the method to several alternatives. Conclusions The likelihood ratio test derived here is a direct, transparent, and easily implemented method for detecting changes in homeolog expression bias that outperforms alternative approaches. While our method was derived with homeolog analysis in mind, this method can be used to analyze changes in the ratio of expression levels between any two genes in any two conditions

Subgenome Dominance in an Interspecific Hybrid, Synthetic Allopolyploid, and a 140-Year-Old Naturally Established Neo-Allopolyploid Monkeyflower

Recent studies have shown that one of the parental subgenomes in ancient polyploids is generally more dominant, having retained more genes and being more highly expressed, a phenomenon termed subgenome dominance. The genomic features that determine how quickly and which subgenome dominates within a newly formed polyploid remain poorly understood. To investigate the rate of emergence of subgenome dominance, we examined gene expression, gene methylation, and transposable element (TE) methylation in a natural, \u3c140-year-old allopolyploid (Mimulus peregrinus), a resynthesized interspecies triploid hybrid (M. robertsii), a resynthesized allopolyploid (M. peregrinus), and progenitor species (M. guttatus and M. luteus). We show that subgenome expression dominance occurs instantly following the hybridization of divergent genomes and significantly increases over generations. Additionally, CHH methylation levels are reduced in regions near genes and within TEs in the first-generation hybrid, intermediate in the resynthesized allopolyploid, and are repatterned differently between the dominant and recessive subgenomes in the natural allopolyploid. Subgenome differences in levels of TE methylation mirror the increase in expression bias observed over the generations following hybridization. These findings provide important insights into genomic and epigenomic shock that occurs following hybridization and polyploid events and may also contribute to uncovering the mechanistic basis of heterosis and subgenome dominance

Role of Synaptic Inhibition in the Coupling of the Respiratory Rhythms that Underlie Eupnea and Sigh Behaviors

The preBötzinger complex (preBötC) gives rise to two types of breathing behavior under normal physiological conditions: eupnea and sighing. Here, we examine the neural mechanisms that couple their underlying rhythms. We measured breathing in awake intact adult mice and recorded inspiratory rhythms from the preBötC in neonatal mouse brainstem slice preparations. We show previously undocumented variability in the temporal relationship between sigh breaths or bursts and their preceding eupneic breaths or inspiratory bursts. Investigating the synaptic mechanisms for this variability in vitro, we further show that pharmacological blockade of chloride-mediated synaptic inhibition strengthens inspiratory-to-sigh temporal coupling. These findings contrast with previous literature, which suggested glycinergic inhibition linked sigh bursts to their preceding inspiratory bursts with minimal time intervals. Furthermore, we verify that pharmacological disinhibition did not alter the duration of the prolonged interval that follows a sigh burst before resumption of the inspiratory rhythm. These results demonstrate that synaptic inhibition does not enhance coupling between sighs and preceding inspiratory events or contribute to post-sigh apneas. Instead, we conclude that excitatory synaptic mechanisms coordinate inspiratory (eupnea) and sigh rhythms

The Regulatory Network for Petal Anthocyanin Pigmentation is Shaped by the MYB5a/NEGAN Transcription Factor in Mimulus

Much of the visual diversity of angiosperms is due to the frequent evolution of novel pigmentation patterns in flowers. The gene network responsible for anthocyanin pigmentation, in particular, has become a model for investigating how genetic changes give rise to phenotypic innovation. In the monkeyflower genus Mimulus, an evolutionarily recent gain of petal lobe anthocyanin pigmentation in M. luteus var. variegatus was previously mapped to genomic region pla2. Here, we use sequence and expression analysis, followed by transgenic manipulation of gene expression, to identify MYB5a—orthologous to the NEGAN transcriptional activator from M. lewisii—as the gene responsible for the transition to anthocyanin-pigmented petals in M. l. variegatus. In other monkeyflower taxa, MYB5a/NEGAN is part of a reaction-diffusion network that produces semi-repeating spotting patterns, such as the array of spots in the nectar guides of both M. lewisii and M. guttatus. Its co-option for the evolution of an apparently non-patterned trait—the solid petal lobe pigmentation of M. l. variegatus—illustrates how reaction-diffusion can contribute to evolutionary novelty in non-obvious ways. Transcriptome sequencing of a MYB5a RNAi line of M. l. variegatus reveals that this genetically simple change, which we hypothesize to be a regulatory mutation in cis to MYB5a, has cascading effects on gene expression, not only on the enzyme-encoding genes traditionally thought of as the targets of MYB5a but also on all of its known partners in the anthocyanin regulatory network

Transcriptomes of Electrophysiologically Recorded Dbx1-derived Respiratory Neurons of the preBötzinger Complex in Neonatal Mice

Breathing depends on interneurons in the preBötzinger complex (preBötC) derived from Dbx1-expressing precursors. Here we investigate whether rhythm- and pattern-generating functions reside in discrete classes of Dbx1 preBötC neurons. In a slice model of breathing with ~ 5 s cycle period, putatively rhythmogenic Type-1 Dbx1 preBötC neurons activate 100–300 ms prior to Type-2 neurons, putatively specialized for output pattern, and 300–500 ms prior to the inspiratory motor output. We sequenced Type-1 and Type-2 transcriptomes and identified differential expression of 123 genes including ionotropic receptors (Gria3, Gabra1) that may explain their preinspiratory activation profiles and Ca2+ signaling (Cracr2a, Sgk1) involved in inspiratory and sigh bursts. Surprisingly, neuropeptide receptors that influence breathing (e.g., µ-opioid and bombesin-like peptide receptors) were only sparsely expressed, which suggests that cognate peptides and opioid drugs exert their profound effects on a small fraction of the preBötC core. These data in the public domain help explain the neural origins of breathing

Forest biodiversity, ecosystem functioning and the provision of ecosystem services

Forests are critical habitats for biodiversity and they are also essential for the provision of a wide range of ecosystem services that are important to human well-being. There is increasing evidence that biodiversity contributes to forest ecosystem functioning and the provision of ecosystem services. Here we provide a review of forest ecosystem services including biomass production, habitat provisioning services, pollination, seed dispersal, resistance to wind storms, fire regulation and mitigation, pest regulation of native and invading insects, carbon sequestration, and cultural ecosystem services, in relation to forest type, structure and diversity. We also consider relationships between forest biodiversity and multifunctionality, and trade-offs among ecosystem services. We compare the concepts of ecosystem processes, functions and services to clarify their definitions. Our review of published studies indicates a lack of empirical studies that establish quantitative and causal relationships between forest biodiversity and many important ecosystem services. The literature is highly skewed; studies on provisioning of nutrition and energy, and on cultural services, delivered by mixed-species forests are under-represented. Planted forests offer ample opportunity for optimising their composition and diversity because replanting after harvesting is a recurring process. Planting mixed-species forests should be given more consideration as they are likely to provide a wider range of ecosystem services within the forest and for adjacent land uses. This review also serves as the introduction to this special issue of Biodiversity and Conservation on various aspects of forest biodiversity and ecosystem services

Population genetics of transposable element load: A mechanistic account of observed overdispersion.

In an empirical analysis of transposable element (TE) abundance within natural populations of Mimulus guttatus and Drosophila melanogaster, we found a surprisingly high variance of TE count (e.g., variance-to-mean ratio on the order of 10 to 300). To obtain insight regarding the evolutionary genetic mechanisms that underlie the overdispersed population distributions of TE abundance, we developed a mathematical model of TE population genetics that includes the dynamics of element proliferation and purifying selection on TE load. The modeling approach begins with a master equation for a birth-death process and extends the predictions of the classical theory of TE dynamics in several ways. In particular, moment-based analyses of population distributions of TE load reveal that overdispersion is likely to arise via copy-and-paste proliferation dynamics, especially when the elementary processes of proliferation and excision are approximately balanced. Parameter studies and analytic work confirm this result and further suggest that overdispersed population distributions of TE abundance are probably not a consequence of purifying selection on total element load

Endosperm-based incompatibilities in hybrid monkeyflowers

Endosperm is an angiosperm innovation central to their reproduction whose development, and thus seed viability, is controlled by genomic imprinting, where expression from certain genes is parent-specific. Unsuccessful imprinting has been linked to failed inter-specific and inter-ploidy hybridization. Despite their importance in plant speciation, the underlying mechanisms behind these endosperm-based barriers remain poorly understood. Here, we describe one such barrier between diploid Mimulus guttatus and tetraploid M. luteus. The two parents differ in endosperm DNA methylation, expression dynamics, and imprinted genes. Hybrid seeds suffer from underdeveloped endosperm, reducing viability, or arrested endosperm and seed abortion when M. guttatus or M. luteus is seed parent, respectively, and transgressive methylation and expression patterns emerge. The two inherited M. luteus subgenomes, genetically distinct but epigenetically similar, are expressionally dominant over the M. guttatus genome in hybrid embryos and especially their endosperm, where paternal imprints are perturbed. In aborted seeds, de novo methylation is inhibited, potentially owing to incompatible paternal instructions of imbalanced dosage from M. guttatus imprints. We suggest that diverged epigenetic/regulatory landscapes between parental genomes induce epigenetic repatterning and global shifts in expression, which, in endosperm, may uniquely facilitate incompatible interactions between divergent imprinting schemes, potentially driving rapid barriers