A functional�Cstructural modelling approach to autoregulation of nodulation

Background and Aims

Autoregulation of nodulation is a long-distance shoot–root signalling regulatory system that regulates nodule meristem proliferation in legume plants. However, due to the intricacy and subtleness of the signalling nature in plants, molecular and biochemical details underlying mechanisms of autoregulation of nodulation remain largely unknown. The purpose of this study is to use functional–structural plant modelling to investigate the complexity of this signalling system. There are two major challenges to be met: modelling the 3D architecture of legume roots with nodulation and co-ordinating signalling-developmental processes with various rates.

Methods

Soybean (Glycine max) was chosen as the target legume. Its root system was observed to capture lateral root branching and nodule distribution patterns. L-studio, a software tool supporting context-sensitive L-system modelling, was used for the construction of the architectural model and integration with the internal signalling.

Key Results

A branching pattern with regular radial angles was found between soybean lateral roots, from which a root mapping method was developed to characterize the laterals. Nodules were mapped based on ‘nodulation section’ to reveal nodule distribution. A root elongation algorithm was then developed for simulation of root development. Based on the use of standard sub-modules, a synchronization algorithm was developed to co-ordinate multi-rate signalling and developmental processes.

Conclusions

The modelling methods developed here not only allow recreation of legume root architecture with lateral branching and nodulation details, but also enable parameterization of internal signalling to produce different regulation results. This provides the basis for using virtual experiments to help in investigating the signalling mechanisms at work.     

Simulating seasonal and inter-annual variations in energy and carbon exchanges and forest dynamics using a process-based atmosphere�Cvegetation dynamics model

The present paper shows simulated results of seasonal and inter-annual variations in energy and carbon exchanges and forest dynamics in a sub-boreal deciduous forest using a fully coupled atmosphere?Cvegetation interaction model [multilayered integrated numerical model of surface physics-growing plants interaction (MINoSGI)]. With careful adjustment of site-specific eco-physiological parameters, MINoSGI reproduced successfully stand biomass?Ctree density relationship based on the forest inventory data for 7 years (1999?C2005) and seasonal and inter-annual variations in energy and CO₂ fluxes measured by means of eddy covariance technique for 3 years (2003?C2005) in the sub-boreal forest, northern Japan. In addition, MINoSGI estimated annual evapotranspiration (E _vt) at 328.6 ± 25.8 mm year^?1, net primary production (NPP) at 372.1 ± 31.5 gC m^?2 year^?1 and net ecosystem exchange (NEE) at ?224.2 ± 32.2 gC m^?2 year^?1. We found the estimate of annual NEE in our site lies among the estimates at other forest stands with the almost same climatic conditions in northern Japan, although the tree species and stand age of these forests are different from those of our site. Overall, MINoSGI was found useful to present simultaneous simulations of forest dynamics, surface energy, and carbon exchanges of a forest stand in the future from micro-meteorological and ecophysiological points of view.     

In vivo effects of γ-irradiation on the functional architecture of the lampbrush chromosomes in Pleurodeles (Amphibia,Urodela)

In vivo irradiation of ovaries of Pleurodeles poireti by -rays leads to structural rearrangement of lampbrush chromosomes in late vitellogenic oocytes (stages V and VI). The loops collapse into the chromomeres and the axes condense. Doses between 200 and 2,000 rads have been tested. We observed that such changes were dependent on the irradiation dose though the chronological order of the events was irrespective of the dose. The maximum effect was attained about 10 h after irradiation. The alterations are totally reversible. Over a period of 3 days, chromosomes gradually relax, regenerate loops and recover their normal appearance. In mid vitellogenic oocytes (stages III and IV) lampbrush chromosomes do not undergo radiation induced alterations. It seems that only full-grown oocytes are competent to respond to the ionizing-flow.     

Molecular dynamics simulation integrating the inhibition kinetics of hydroxysafflor yellow A on α-glucosidase

Inhibition of α-glucosidase has attracted the attention of researchers due to its connection to type-2 diabetes. Hydroxysafflor yellow A (HSYA) extracted from Carthamus tinctorius L. is a natural antioxidant used in traditional Chinese medicine. In this study, the effect of HSYA on α-glucosidase was evaluated using inhibitory kinetics based on the antioxidant properties of HSYA and by performing computational simulation integration methods. HSYA reversibly inhibited α-glucosidase in a competitive inhibition manner and the evaluated kinetic parameters were IC₅₀ = 1.1 ± 0.22 mM and K_i = 1.04 ± 0.23 mM, respectively. The results of spectrofluorimetry showed that the inner hydrophobic regions of α-glucosidase, which are mostly in the active site, were exposed to the surface with increasing HSYA concentrations, indicating that the inactivation of α-glucosidase by HSYA was accompanied by regional unfolding. The molecular dynamics simulations indicated that the four rings of HSYA interact with four residues such as G217, A278, H279, and G280 at the entrance of the active site. Our study provides insight into the inhibition of α-glucosidase and the accompanying structural changes by HSYA. Based on its α-glucosidase-inhibiting effect and its potential as a natural antioxidant, HSYA is a potential agent for treating α-glucosidase-associated type-2 diabetes.     

Imperfect Batesian mimicry—the effects of the frequency and the distastefulness of the model

Batesian mimicry is the resemblance between unpalatable models and palatable mimics. The widely accepted idea is that the frequency and the unprofitability of the model are crucial for the introduction of a Batesian mimic into the prey population. However, experimental evidence is limited and furthermore, previous studies have considered mainly perfect mimicry (automimicry). We investigated imperfect Batesian mimicry by varying the frequency of an aposematic model at two levels of distastefulness. The predator encountered prey in a random order, one prey item at a time. The prey were thus presented realistically in a sequential way. Great tits (Parus major) were used as predators. This experiment, with a novel signal, supports the idea that Batesian mimics gain most when the models outnumber them. The mortalities of the mimics as well as the models were significantly dependent on the frequency of the model. Both prey types survived better the fewer mimics there were confusing the predator. There were also indications that the degree of distastefulness of the model had an effect on the survival of the Batesian mimic: the models survived significantly better the more distasteful they were. The experiment supports the most classical predictions in the theories of the origin and maintenance of Batesian mimicry.     

A fast computational model for circulatory dynamics: effects of left ventricle–aorta coupling

The course of diseases such as hypertension, systolic heart failure and heart failure with a preserved ejection fraction is affected by interactions between the left ventricle (LV) and the vasculature. To study these interactions, a computationally efficient, biophysically based mathematical model for the circulatory system is presented. In a four-chamber model of the heart, the LV is represented by a previously described low-order, wall volume-preserving model that includes torsion and base-to-apex and circumferential wall shortening and lengthening, and the other chambers are represented using spherical geometries. Active and passive myocardial mechanics of all four chambers are included. The cardiac model is coupled with a wave propagation model for the aorta and a closed lumped-parameter circulation model. Parameters for the normal heart and aorta are determined by fitting to experimental data. Changes in the timing and magnitude of pulse wave reflections by the aorta are demonstrated with changes in compliance and taper of the aorta as seen in aging (decreased compliance, increased diameter and length), and resulting effects on LV pressure–volume loops and LV fiber stress and sarcomere shortening are predicted. Effects of aging of the aorta combined with reduced LV contractile force (failing heart) are examined. In the failing heart, changes in aortic properties with aging affect stroke volume and sarcomere shortening without appreciable augmentation of aortic pressure, and the reflected pressure wave contributes an increased proportion of aortic pressure.

     

The challenge of sustainability: Is integrating environment and economy enough?

Conclusions Beyond Interdependence, along with each of the other books, appeared after publication of Our Common Future but before the Earth Summit in Rio. It was a time to be optimistic, and each book is optimistic, if cautiously so. Certainly the impact of the Brundtland Report has been enormous, perhaps not beyond the dreams of the members of the Commission, but certainly beyond their expectations. The impact of the Earth Summit has been much smaller, certainly well short of the dreams of those involved though perhaps within their expectations.If the Brundtland Report and the books reviewed in this essay show the potential, the Earth Summit shows the limits. What have been called the inner limits of interests, institutions, and politics turn out to be far more important than the outer limits of ecology and even economics. The next steps are going to be difficult, and books such as Beyond Interdependence are needed to indicate when, where and how to take such steps. There may eventually be a Mark II framework convention for climate change, forestry and biodiversity (p. 115–116), but along the way there will be many more national actions, bi- or tri-national agreements, and Montreal Protocols. In the words of MacNeill, Winsemius and Yakushiji (p. 117), A Grand Global Bargain could be the sum of 1,000 small bargains. Even if, in my view and the views of Goodland et al. and Meadows et al., Beyond Interdependence is inadequate to get us onto a fully sustainable path, there is little if anything in its recommendations that would be inappropriate in our search for that path.How can we go beyond integration of environment and economy? A number of authors have begun to make suggestions (e.g., Ekins, 1987; Brooks, 1991; Durning, 1992; Harrison, 1992). Certainly, one can agree with MacNeill, Winsemius and Yakushiji that we need not spend any more time defining sustainable development. (By 1990, there were already some 40 definitions in the literature.) The definition provided by the Brundtland Report is good enough for working purposes. What is needed now is not more discussion about sustainable development but more experimentation with it. We must try different development strategies, and keep trying until the best fit is found for particular times, particular places and particular peoples. Some policies will get us closer; others will turn out to be inefficient, destructive, or inequitable. But the experiments must continue until each community finds a set that works economically, ecologically and politically. In the words of Rabbi Tarphon, who lived nearly two millennia ago and contributed to the Talmud, It is not up to us to complete the task, but neither are we free to refrain from getting started on it.     

Media effects on the dynamics of a stochastic SIRI epidemic model with relapse and Lévy noise perturbation

In this paper, we study the dynamic properties of an SIRI epidemic model incorporating media coverage, and stochastically perturbed by a Lévy noise. We establish the existence of a unique global positive solution. We investigate the dynamic properties of the solution around both disease-free and endemic equilibria points of the deterministic model depending on the basic reproduction number under some noise excitation. Furthermore, we present some numerical simulations to support the theoretical results.     

Physical and functional interaction between the α- and γ-secretases: A new model of regulated intramembrane proteolysis

Many single-transmembrane proteins are sequentially cleaved by ectodomain-shedding α-secretases and the γ-secretase complex, a process called regulated intramembrane proteolysis (RIP). These cleavages are thought to be spatially and temporally separate. In contrast, we provide evidence for a hitherto unrecognized multiprotease complex containing both α- and γ-secretase. ADAM10 (A10), the principal neuronal α-secretase, interacted and cofractionated with γ-secretase endogenously in cells and mouse brain. A10 immunoprecipitation yielded γ-secretase proteolytic activity and vice versa. In agreement, superresolution microscopy showed that portions of A10 and γ-secretase colocalize. Moreover, multiple γ-secretase inhibitors significantly increased α-secretase processing (r = −0.86) and decreased β-secretase processing of β-amyloid precursor protein. Select members of the tetraspanin web were important both in the association between A10 and γ-secretase and the γ→α feedback mechanism. Portions of endogenous BACE1 coimmunoprecipitated with γ-secretase but not A10, suggesting that β- and α-secretases can form distinct complexes with γ-secretase. Thus, cells possess large multiprotease complexes capable of sequentially and efficiently processing transmembrane substrates through a spatially coordinated RIP mechanism.     

A data-driven framework to model the organism–environment system

Organisms modify their development and function in response to the environment. At the same time, the environment is modified by the activities of the organism. Despite the ubiquity of such dynamical interactions in nature, it remains challenging to develop models that accurately represent them, and that can be fitted using data. These features are desirable when modeling phenomena such as phenotypic plasticity, to generate quantitative predictions of how the system will respond to environmental signals of different magnitude or at different times, for example, during ontogeny. Here, we explain a modeling framework that represents the organism and environment as a single coupled dynamical system in terms of inputs and outputs. Inputs are external signals, and outputs are measurements of the system in time. The framework uses time-series data of inputs and outputs to fit a nonlinear black-box model that allows to predict how the system will respond to novel input signals. The framework has three key properties: it captures the dynamical nature of the organism–environment system, it can be fitted with data, and it can be applied without detailed knowledge of the system. We study phenotypic plasticity using in silico experiments and demonstrate that the framework predicts the response to novel environmental signals. The framework allows us to model plasticity as a dynamical property that changes in time during ontogeny, reflecting the well-known fact that organisms are more or less plastic at different developmental stages.     

The actin binding domain of βI-spectrin regulates the morphological and functional dynamics of dendritic spines

Actin microfilaments regulate the size, shape and mobility of dendritic spines and are in turn regulated by actin binding proteins and small GTPases. The βI isoform of spectrin, a protein that links the actin cytoskeleton to membrane proteins, is present in spines. To understand its function, we expressed its actin-binding domain (ABD) in CA1 pyramidal neurons in hippocampal slice cultures. The ABD of βI-spectrin bundled actin in principal dendrites and was concentrated in dendritic spines, where it significantly increased the size of the spine head. These effects were not observed after expression of homologous ABDs of utrophin, dystrophin, and α-actinin. Treatment of slice cultures with latrunculin-B significantly decreased spine head size and decreased actin-GFP fluorescence in cells expressing the ABD of α-actinin, but not the ABD of βI-spectrin, suggesting that its presence inhibits actin depolymerization. We also observed an increase in the area of GFP-tagged PSD-95 in the spine head and an increase in the amplitude of mEPSCs at spines expressing the ABD of βI-spectrin. The effects of the βI-spectrin ABD on spine size and mEPSC amplitude were mimicked by expressing wild-type Rac3, a small GTPase that co-immunoprecipitates specifically with βI-spectrin in extracts of cultured cortical neurons. Spine size was normal in cells co-expressing a dominant negative Rac3 construct with the βI-spectrin ABD. We suggest that βI-spectrin is a synaptic protein that can modulate both the morphological and functional dynamics of dendritic spines, perhaps via interaction with actin and Rac3.     

A multiscale, mechanism-driven, dynamic model for the effects of 5α-reductase inhibition on prostate maintenance

A systems-level mathematical model is presented that describes the effects of inhibiting the enzyme 5α-reductase (5aR) on the ventral prostate of the adult male rat under chronic administration of the 5aR inhibitor, finasteride. 5aR is essential for androgen regulation in males, both in normal conditions and disease states. The hormone kinetics and downstream effects on reproductive organs associated with perturbing androgen regulation are complex and not necessarily intuitive. Inhibition of 5aR decreases the metabolism of testosterone (T) to the potent androgen 5α-dihydrotestosterone (DHT). This results in decreased cell proliferation, fluid production and 5aR expression as well as increased apoptosis in the ventral prostate. These regulatory changes collectively result in decreased prostate size and function, which can be beneficial to men suffering from benign prostatic hyperplasia (BPH) and could play a role in prostate cancer. There are two distinct isoforms of 5aR in male humans and rats, and thus developing a 5aR inhibitor is a challenging pursuit. Several inhibitors are on the market for treatment of BPH, including finasteride and dutasteride. In this effort, comparisons of simulated vs. experimental T and DHT levels and prostate size are depicted, demonstrating the model accurately described an approximate 77% decrease in prostate size and nearly complete depletion of prostatic DHT following 21 days of daily finasteride dosing in rats. This implies T alone is not capable of maintaining a normal prostate size. Further model analysis suggests the possibility of alternative dosing strategies resulting in similar or greater effects on prostate size, due to complex kinetics between T, DHT and gene occupancy. With appropriate scaling and parameterization for humans, this model provides a multiscale modeling platform for drug discovery teams to test and generate hypotheses about drugging strategies for indications like BPH and prostate cancer, such as compound binding properties, dosing regimens, and target validation.     

Land use effects on erosion and carbon storage of the Río Chimbo watershed, Ecuador

Background and aims

Soil carbon storage is an important component of global carbon cycling. Andean Andisols have high carbon content and are vulnerable to erosion because of agricultural intensification and deforestation. This study examines the effects of land use on erosion and soil carbon storage in the Río Chimbo watershed of Ecuador.

Methods

Soil carbon content, age, and erosion estimated from ¹³⁷Cs inventories was measured along an elevational transect under annual cropping, natural forest, páramo, pasture, and tree plantations.

Results

Land use, particularly annual cropping, affected ¹³⁷Cs levels in the upper soil layers, but did not have an impact on total carbon storage to a depth of 1 m. Relative erosion rates estimated from ¹³⁷Cs inventories at sites under annual cropping averaged 27 t ha^?1?y^?1 over the erosion rate of non-cultivated sites. A linear relationship was observed between soil carbon age (determined by ¹⁴C levels) and ¹³⁷Cs levels, where pasture sites had lower ¹³⁷Cs and older carbon compared to natural forest sites.

Conclusions

The effects of land use on soil loss in the Río Chimbo watershed suggest a loss and/or removal of soil carbon, particularly under annual cropping.     

Anesthetic effects on the structure and dynamics of the second transmembrane domains of nAChR α4β2

Channel functions of the neuronal α4β2 nicotinic acetylcholine receptor (nAChR), one of the most widely expressed subtypes in the brain, can be inhibited by volatile anesthetics. Our Na⁺ flux experiments confirmed that the second transmembrane domains (TM2) of α4 and β2 in 2:3 stoichiometry, (α4)₂(β2)₃, could form pentameric channels, whereas the α4 TM2 alone could not. The structure, topology, and dynamics of the α4 TM2 and (α4)₂(β2)₃ TM2 in magnetically aligned phospholipid bicelles were investigated using solid-state NMR spectroscopy in the absence and presence of halothane and isoflurane, two clinically used volatile anesthetics. ²H NMR demonstrated that anesthetics increased lipid conformational heterogeneity. Such anesthetic effects on lipids became more profound in the presence of transmembrane proteins. PISEMA experiments on the selectively ¹⁵N-labeled α4 TM2 showed that the TM2 formed transmembrane helices with tilt angles of 12° ± 1° and 16° ± 1° relative to the bicelle normal for the α4 and (α4)₂(β2)₃ samples, respectively. Anesthetics changed the tilt angle of the α4 TM2 from 12° ± 1° to 14° ± 1°, but had only a subtle effect on the tilt angle of the (α4)₂(β2)₃ TM2. A small degree of wobbling motion of the helix axis occurred in the (α4)₂(β2)₃ TM2. In addition, a subset of the (α4)₂(β2)₃ TM2 exhibited counterclockwise rotational motion around the helix axis on a time scale slower than 10^- 4 s in the presence of anesthetics. Both helical tilting and rotational motions have been identified computationally as critical elements for ion channel functions. This study suggested that anesthetics could alter these motions to modulate channel functions.     

urce, biological community and soil functional stability dynamics at the soil–litter interface

The interface between decaying plant residues and soil is a focus for soil ecological processes because of resources from the residues diffusing into the soil, and microfauna that proliferate in the adjacent soil. Given that the recovery of soil function following disturbance depends on immigration, colonization and establishment of exotic organisms from adjacent un-disturbed habitats, and the availability of bio-available resources, we hypothesized that the soil–litter interface could contribute to soil functional stability. In laboratory pot trials, soil was separated into two parts by a mesh bag with the inner section amended, or not amended, with rice straw; an outer layer of unamended soil, adjacent to the litter (1.5 cm thick, either heated or not), provided a soil–litter interface. This enabled us to examine the dynamics of dissolved organic carbon (DOC), mineral nitrogen, microbial biomass carbon (MBC), nematode assemblages and functional stability during 35 days incubation. Either 1 mm or 5 μm meshes were used, which allowed nematodes to migrate (SR1) or not (SR5) through the mesh to the soil–litter interface; thus also enabling us to evaluate the role of nematodes in soil functional stability. Higher DOC and MBC but lower mineral nitrogen concentrations were found at the soil–litter interface. Heating increased the availability of soil resources such as mineral nitrogen and DOC, but decreased the MBC and total nematode abundance in the soil. The soil–litter interface was characterized by a higher abundance of nematodes, particularly microbivores, regardless of mesh aperture or disturbance. The difference in nematode abundance between SR1 and SR5 indicated that nematode propagation, due to resource diffusion and nematode migration through the mesh, contributed to the changing numbers of microbivorous nematodes depending on incubation time. The soil functional stability was calculated as a relative change in the functioning of short-term barley decomposition. Soil functional resistance, defined as the instantaneous effect of disturbance on decomposition measured on the first day, was highest in the SR5 treatment. However, soil functional resilience, defined as the recovery of soil function over the whole incubation period (35d), was highest in the SR1 treatment, which is most probably attributed to the functioning of microbivorous nematodes. Our results suggest that small-scale spatial heterogeneity, due to organic residue decomposition, can help maintain soil functions following disturbance.     

Invasion waves and pinning in the Kirkpatrick–Barton model of evolutionary range dynamics

Journal of Mathematical Biology - The Kirkpatrick–Barton model, well known to invasion biologists, is a pair of reaction–diffusion equations for the joint evolution of population...     

Resource, biological community and soil functional stability dynamics at the soil–litter interface

The interface between decaying plant residues and soil is a focus for soil ecological processes because of resources from the residues diffusing into the soil, and microfauna that proliferate in the adjacent soil. Given that the recovery of soil function following disturbance depends on immigration, colonization and establishment of exotic organisms from adjacent un-disturbed habitats, and the availability of bio-available resources, we hypothesized that the soil–litter interface could contribute to soil functional stability. In laboratory pot trials, soil was separated into two parts by a mesh bag with the inner section amended, or not amended, with rice straw; an outer layer of unamended soil, adjacent to the litter (1.5 cm thick, either heated or not), provided a soil–litter interface. This enabled us to examine the dynamics of dissolved organic carbon (DOC), mineral nitrogen, microbial biomass carbon (MBC), nematode assemblages and functional stability during 35 days incubation. Either 1 mm or 5 μm meshes were used, which allowed nematodes to migrate (SR1) or not (SR5) through the mesh to the soil–litter interface; thus also enabling us to evaluate the role of nematodes in soil functional stability. Higher DOC and MBC but lower mineral nitrogen concentrations were found at the soil–litter interface. Heating increased the availability of soil resources such as mineral nitrogen and DOC, but decreased the MBC and total nematode abundance in the soil. The soil–litter interface was characterized by a higher abundance of nematodes, particularly microbivores, regardless of mesh aperture or disturbance. The difference in nematode abundance between SR1 and SR5 indicated that nematode propagation, due to resource diffusion and nematode migration through the mesh, contributed to the changing numbers of microbivorous nematodes depending on incubation time. The soil functional stability was calculated as a relative change in the functioning of short-term barley decomposition. Soil functional resistance, defined as the instantaneous effect of disturbance on decomposition measured on the first day, was highest in the SR5 treatment. However, soil functional resilience, defined as the recovery of soil function over the whole incubation period (35d), was highest in the SR1 treatment, which is most probably attributed to the functioning of microbivorous nematodes. Our results suggest that small-scale spatial heterogeneity, due to organic residue decomposition, can help maintain soil functions following disturbance.     

Alterations of β3-adrenoceptors expression and their myocardial functional effects in physiological model of chronic exercise-induced cardiac hypertrophy

Physical training induces cardiovascular autonomic nervous system regulation adaptations, which could result from β adrenergic receptor (AR) modifications. Among them, β₃ AR alterations have been recently reported but their functional effect remained to discuss. To explain the β₃ AR gene expression in relation to function, we simultaneously studied the left ventricle (LV) β₃ AR mRNA and protein levels and the myocardial functional effects of a β₃ AR agonist following physical training. Forty rats were assigned to either a control (C; N = 20) or a trained (T; N = 20) group. The treadmill running protocol was performed for 8 weeks. Histological measurements on LV slices were quantified. The β₃ AR mRNA abundance was studied with RT-PCR and β₃ AR protein density with Western-Blot analysis. Myocardial functional effects of a β₃ AR agonist, BRL37344 (10⁻⁸ M), were studied in Langendorff-perfused hearts. Histological data confirmed the adapted patterns of the physiological cardiac hypertrophy observed in T (P < 0.01), with a significant increase in arteries density (P < 0.01) and an unchanged collagen concentration. The β₃ AR protein density was increased in T (154 ± 38% in T vs. 100 ± 24% in C; P < 0.05), but no change was noted concerning the β₃ AR mRNA level. After BRL37344 perfusion LVDP, +dP/dT and −dP/dT, in C (P < 0.01), and only +dP/dT in T (P < 0.05) were decreased. Moreover, all LV hemodynamic parameters were more altered after BRL37344 in C than in T (P < 0.01). Thus, in this physiological model of cardiac hypertrophy, an increase of β₃ AR density without β₃ AR mRNA alteration was observed. Classical negative myocardial lusitropic and inotropic effects induced by a specific agonist of β₃ AR were diminished in trained rats.     

A structural and functional perspective on the evolution of the heme–copper oxidases

The heme–copper oxidases (HCOs) catalyze the reduction of O₂ to water, and couple the free energy to proton pumping across the membrane. HCOs are divided into three sub-classes, A, B and C, whose order of emergence in evolution has been controversial. Here we have analyzed recent structural and functional data on HCOs and their homologues, the nitric oxide reductases (NORs). We suggest that the C-type oxidases are ancient enzymes that emerged from the NORs. In contrast, the A-type oxidases are the most advanced from both structural and functional viewpoints, which we interpret as evidence for having evolved later.