Trophic Units Research Articles

Increased expression of Cathepsin C in airway epithelia exacerbates airway remodeling in asthma.

Airway remodeling is a critical factor determining the pathogenesis and treatment sensitivity of severe asthma (SA) or uncontrolled asthma (UA). The activation of epithelial-mesenchymal trophic units (EMTUs) regulated by airway epithelial cells (AECs) has been proven to induce airway remodeling directly. However, the triggers for EMTU activation and the underlying mechanism of airway remodeling are not fully elucidated. Here, we screened the differentially expressed gene Cathepsin C (CTSC)/dipeptidyl peptidase 1 (DPP-1) in epithelia of SA and UA patients using RNA sequencing data and further verified the increased expression of CTSC in induced sputum of asthma patients which was positively correlated with the severity and airway remodeling. Moreover, direct instillation of exogenous CTSC induced airway remodeling. Genetic inhibition of CTSC suppressed EMTU activation and airway remodeling in two asthma models with airway remodeling. Mechanistically, increased secretion of CTSC from AECs induced EMTU activation through p38-mediated pathway, further inducing airway remodeling. Meanwhile, inhibition of CTSC also reduced the infiltration of inflammatory cells and the production of inflammatory factors in the lungs of asthmatic mice. Consequently, targeting CTSC with compound AZD7986 protected against airway inflammation, EMTU activation and remodeling in asthma model. Based on the dual effects of CTSC on airway inflammation and remodeling, CTSC is a potential biomarker and therapeutic target for SA or UA.

Airway epithelial overexpressed cathepsin K induces airway remodelling through epithelial-mesenchymal trophic unit activation in asthma.

Airway epithelial cells (AECs) regulate the activation of epithelial-mesenchymal trophic units (EMTUs) during airway remodelling through secretion of signalling mediators. However, the major trigger and the intrinsic pathogenesis of airway remodelling is still obscure. The differing expressed genes in airway epithelia related to airway remodelling were screened and verified by RNA-sequencing and signalling pathway analysis. Then, the effects of increased cathepsin K (CTSK) in airway epithelia on airway remodelling and EMTU activation were identified both in vitro and in vivo, and the molecular mechanism was elucidated in the EMTU model. The potential of CTSK as an an effective biomarker of airway remodelling was analysed in an asthma cohort of differing severity. Finally, an inhibitor of CTSK was administered for potential therapeutic intervention for airway remodelling in asthma. The expression of CTSK in airway epithelia increased significantly along with the development of airway remodelling in a house dust mite (HDM)-stressed asthma model. Increased secretion of CTSK from airway epithelia induced the activation of EMTUs by activation of the PAR2-mediated pathway. Blockade of CTSK inhibited EMTU activation and alleviated airway remodelling as an effective intervention target of airway remodelling. Increased expression of CTSK in airway epithelia is involved in the development of airway remodelling in asthma through EMTU activation, mediated partly through the PAR2-mediated signalling pathway. CTSK is a potential biomarker for airway remodelling, and may also be a useful intervention target for airway remodelling in asthma patients.

Individual diet variability shapes the architecture of Antarctic benthic food webs

Antarctic biodiversity is affected by seasonal sea-ice dynamics driving basal resource availability. To (1) determine the role of intraspecific dietary variability in structuring benthic food webs sustaining Antarctic biodiversity, and (2) understand how food webs and the position of topologically central species vary with sea-ice cover, single benthic individuals’ diets were studied by isotopic analysis before sea-ice breakup and afterwards. Isotopic trophospecies (or Isotopic Trophic Units) were investigated and food webs reconstructed using Bayesian Mixing Models. As nodes, these webs used either ITUs regardless of their taxonomic membership (ITU-webs) or ITUs assigned to species (population-webs). Both were compared to taxonomic-webs based on taxa and their mean isotopic values. Higher resource availability after sea-ice breakup led to simpler community structure, with lower connectance and linkage density. Intra-population diet variability and compartmentalisation were crucial in determining community structure, showing population-webs to be more complex, stable and robust to biodiversity loss than taxonomic-webs. The core web, representing the minimal community ‘skeleton’ that expands opportunistically while maintaining web stability with changing resource availability, was also identified. Central nodes included the sea-urchin Sterechinus neumayeri and the bivalve Adamussium colbecki, whose diet is described in unprecedented detail. The core web, compartmentalisation and topologically central nodes represent crucial factors underlying Antarctica’s rich benthic food web persistence.

Projecting community trophic structures for the last 120 000 years

Studying past community dynamics can provide valuable insights for anticipating future changes in the world's biota. However, the existing fossil record is too sparse to enable continuous temporal reconstructions of wholesale community dynamics. In this study, we utilise machine learning to reconstruct Late Quaternary community structure, leveraging the climate–trophic structure relationship. We followed a four‐stage approach: 1) identify and map trophic structure units (TSUs) at the global scale based on the guild richness and composition of terrestrial mammal species weighing over 3 kg; 2) train a random forest classifier to predict the observed distribution of TSUs based on contemporary climatic conditions; 3) hindcast the global distribution of TSUs using climatic conditions as reconstructed over the past 120 000 years; and 4) compare TSU hindcasts against elements of community structure as estimated with the fossil record. Models project significant shifts in the geographical distribution of community trophic structures, with more pronounced changes occurring during the Pleistocene–Holocene transition. These shifts exhibit regional variations, particularly in Eurasia and North America, where the models project reductions in the distribution of less‐complex trophic structures over the last 24 000 years. Hindcasts partially identified the alterations in community structure seen in the fossil record, demonstrating a match between the observed and predicted times of change in mammal community structure (between 24 and 8 ka BP). However, projections of trophic guilds diverged from fossil records during the Holocene. While the fossil record indicated a decrease in the number of grazers and carnivores, our models projected an increase in these numbers. Characterising community‐wide responses to climatic changes is essential to address key questions about past and future impacts of such changes. Although further research is needed to refine the models, our approach offers a perspective for addressing the complex interactions among climate and trophic structures and model their distributions over time.

Influence of the azo-dye amaranth on the trophic structure of activated sludge in a model experiment.

The textile industry generates significant amounts of wastewater containing high concentrations of azo dyes. An important point in the process of purification of azo dyes is their influence on the activated sludge (AS) in wastewater treatment plants. Azo dyes, such as amaranth, play the role of xenobiotics. This article seeks to answer the question of how organisms manage to respond to xenobiotics remains very important and open, i.e., how they will react to toxic conditions. The aim of this research was to study how these changes are expressed in terms of the different trophic levels of AS. In our experiment, it was found that the dominant trophic units are significantly changed due to the xenobiotic entering the system. The data reveal the significant development of the bacterial segment (genusPseudomonasand azo-degrading bacteria) at times of large amaranth removal. In the most active phase of amaranth biodetoxification (48h), the culturable bacteria of the genus Pseudomonas change by about 40%, while the azo-degrading bacteria change by about 2%. Fauna organisms have a sharp change in the dominant groups-from attached and crawling ciliates and testate amoebas to the mass development of small and large flagellates. This is of great importance because micro- and metafauna play an important role in the detoxification process by ingesting some of the xenobiotics. This role is expressed in the fact that after dying, macro-organisms release this xenobiotic in small portions so that it can then be effectively degraded by adapting to the amaranth biodegradation bacteria. In this study, it is clear that all these events lead to a decline in the quality of AS. But on the other hand, these allow AS to survive as a microbial community, and the fauna segment does not disappear completely.

Airway epithelial ITGB4 deficiency induces airway remodeling in a mouse model

Airway epithelial cells (AECs) with impaired barrier function contribute to airway remodeling through the activation of epithelial-mesenchymal trophic units (EMTUs). Although the decreased expression of ITGB4 in AECs is implicated in the pathogenesis of asthma, how ITGB4 deficiency impacts airway remodeling remains obscure. This study aims to determine the effect of epithelial ITGB4 deficiency on the barrier function of AECs, asthma susceptibility, airway remodeling, and EMTU activation. AEC-specific ITGB4 conditional knockout mice (ITGB4-/-) were generated and an asthma model was employed by the sensitization and challenge of house dust mite (HDM). EMTU activation-related growth factors were examined in ITGB4-silenced primary human bronchial epithelial cells of healthy subjects after HDM stimulation. Dexamethasone, the inhibitors of JNK phosphorylation or FGF2 were administered for the identification of the molecular mechanisms of airway remodeling in HDM-exposed ITGB4-/- mice. ITGB4 deficiency in AECs enhanced asthma susceptibility and airway remodeling by disrupting airway epithelial barrier function. Aggravated airway remodeling in HDM-exposed ITGB4-/- mice was induced through the enhanced activation of EMTU mediated by Src homology domain 2-containing protein tyrosine phosphatase 2/c-Jun N-terminal kinase/Jun N-terminal kinase-dependent transcription factor/FGF2 (SHP2/JNK/c-Jun/FGF2) signaling pathway, which was partially independent of airway inflammation. Both JNK and FGF2 inhibitors significantly inhibited the aggravated airway remodeling and EMTU activation in HDM-exposed ITGB4-/- mice. Airway epithelial ITGB4 deficiency induces airway remodeling in a mouse model of asthma through enhanced EMTU activation that is regulated by the SHP2/JNK/c-Jun/FGF2 pathway.

Содержание ртути и свинца в кормовой базе ценных видов рыб Каспийского моря

Mercury and lead are not essential elements and have a high degree of toxicity to all groups of living organisms, including hydrobionts. In turn, the accumulation of dangerous chemical elements in the primary trophic units of marine ecosystems is also reflected in the high level of accumulation and toxication of fish-valuable objects of fishing. As part of the study of the ecological state of the biota of the Volga-Caspian basin, there is a need to study the concentrations of heavy metals such as mercury and lead. The aim of the work is to study the content of mercury and lead in some invertebrate species of the Caspian Sea. The main source of mercury and lead in the body of the studied species is the water of the north-western part of the Caspian Sea. Among the studied taxonomic groups of organisms, mercury accumulators were all species of mollusks, as well as Balanus improvises and Rhithropanopeus harrisii. The lead concentrating organisms were Cerastoderma lamarcki and Mytilaster lineatus, Rhithropanopeus harrisii, and Balanus improvises.

Changing Isotopic Food Webs of Two Economically Important Fish in Mediterranean Coastal Lakes with Different Trophic Status

Transitional waters are highly productive ecosystems, providing essential goods and services to the biosphere and human population. Human influence in coastal areas exposes these ecosystems to continuous internal and external disturbance. Nitrogen-loads can affect the composition of the resident community and the trophic relationships between and within species, including fish. Based on carbon (δ13C) and nitrogen (δ15N) stable isotope analyses of individuals, we explored the feeding behaviour of two ecologically and economically important omnivorous fish, the eel Anguilla anguilla and the seabream Diplodus annularis, in three neighbouring lakes characterised by different trophic conditions. We found that A. anguilla showed greater generalism in the eutrophic lake due to the increased contribution of basal resources and invertebrates to its diet. By contrast, the diet of D. annularis, which was mainly based on invertebrate species, became more specialised, focusing especially on polychaetes. Our results suggest that changes in macroinvertebrate and fish community composition, coupled with anthropogenic pressure, affect the trophic strategies of high trophic level consumers such as A. anguilla and D. annularis. Detailed food web descriptions based on the feeding choices of isotopic trophospecies (here Isotopic Trophic Units, ITUs) enable identification of the prey taxa crucial for the persistence of omnivorous fish stocks, thus providing useful information for their management and habitat conservation.

The Problem of Biological Obstacles in the Operation of Nuclear Power Plants (Illustrated by the Operation of Zaporizhzhya NPP Techno-Ecosystem)

The article shows the research results on biological obstacles of the Zaporizhzhya NPP cooling pond, which may be harmful for the technological cycles of the plant or even cause emergency in the NPP.
 This problem is particular importance for cooling water reservoir of energy objects, since the increased temperature regime in such reservoirs creates favorable conditions for the mass development of certain types of hydrobionts, which hinder the operation of hydraulic structures.
 It was established that for the studied cooling water reservoir of Zaporizhzhya NPP all types of biological barriers that are found in technical reservoirs of nuclear power plants of Ukraine are characteristic.
 It has been established that all types of biological obstacles found in technical reservoirs of nuclear power plants of Ukraine are common for the researched reservoir.
 The most common are biological obstacles of bacterial, plant and animal origin. Plant biological obstacles are represented by the excessive growth of blue-green algae, which in the summer cause the "water blooming" of the cooling pond, and the filamentous algae that form thickets on the surfaces of concrete slabs and hydraulic structures. Animal biomarkers include the rapid spread of the mollusks of the Thiaridae family, which were accidentally inhabited into the water reservoir and caused massive fouling of the water development facilities of the NPP.
 One of the areas of biological control of biological barriers in a Zaporizhzhya NPP cooling water reservoir is ichthyomelioration – biomeliorative release the fish into the reservoir As fish occupy higher trophic levels in aquatic ecosystems, they accumulate organic matter from other trophic units and can inhibit the massive development of hydrobionts.
 The presented scientific results formed the basis of "Technological substantiation of the biological method of reducing the amount of phytoplankton and mollusks in the hydraulic engineering system of the ZNPP and conducting biomeliorative works using biomeliorative fish for the period2018-2022", the observance of which allows partial resolution of the problems of biological barriers caused by the mass development of certain species.

The Impact of Environmental Factors on the Amount of Nitrates and Nitrites in Different Types of Soils and Ways of Their Utilization

Abstract Despite the last decade considerable advances in the study of nitrate and nitrite pollution of soil, there are still some gaps in research related to neglecting or ignoring the role of soil in the food chain and its effects on upper trophic units. The article presents the results of a study on the impact of air and soil humidity and temperature, as well as soil type and utilization on the amount of nitrates and nitrites in the soil solution at the end of vegetation period. It was proved that statistically significant impact on the amounts of residual nitrate and nitrite ions was caused by the temperature and moisture of soil, its type, and the specific properties of the crops grown.

Биологическая продуктивность великих озер России: сравнение результатов моделирования и натурных наблюдений

Results of analysis of the mass-balance model simulating biotic energy flows in the great lakes of Russia –Ladoga, Onego and Baikal- ecosystems have been presented. Season-average biomass and annual production of prime producers, reducers and consumers including fish have been forecasted. Permissible fish catch has been assessed. The model data were compared with the field observations results. Importance of the great lakes of Russia researches with the use of the mass-balance model is stipulated by their size and value as the biggest and Europe, besides, Lake Baikal is the greatest water body of the world in terms of the fresh water stock. Determination of these lakes’ trophic status is of primary importance for water quality assessment and for prediction their total biological productivity, fish productivity and permissible fish catch. This is possible only provided application of the balance-energy approach based on the knowledge of regularities of the organic matter and energy transfer through the ecosystem trophic units. A forecast of the lakes biological productivity was composed on the basis of quantitative links between key biotic and abiotic components of an aquatic ecosystem summed up in the form of the massbalance model. Results of the model test by the empiric data have shown that it possesses sufficient prediction reliability and is applicable for development of the lacustrine ecosystems’ biotic balances. The model can serve as a good tool for reconstruction of the lacking data and expert assessment of the ecosystems’ trophic status provided the specific local conditions are taken into account. Moreover, it can be used for cross-checking of empiric and the model predicted data reliability.

Volume Transmission in Central Dopamine and Noradrenaline Neurons and Its Astroglial Targets

Already in the 1960s the architecture and pharmacology of the brainstem dopamine (DA) and noradrenaline (NA) neurons with formation of vast numbers of DA and NA terminal plexa of the central nervous system (CNS) indicated that they may not only communicate via synaptic transmission. In the 1980s the theory of volume transmission (VT) was introduced as a major communication together with synaptic transmission in the CNS. VT is an extracellular and cerebrospinal fluid transmission of chemical signals like transmitters, modulators etc. moving along energy gradients making diffusion and flow of VT signals possible. VT interacts with synaptic transmission mainly through direct receptor-receptor interactions in synaptic and extrasynaptic heteroreceptor complexes and their signaling cascades. The DA and NA neurons are specialized for extrasynaptic VT at the soma-dendrtitic and terminal level. The catecholamines released target multiple DA and adrenergic subtypes on nerve cells, astroglia and microglia which are the major cell components of the trophic units building up the neural-glial networks of the CNS. DA and NA VT can modulate not only the strength of synaptic transmission but also the VT signaling of the astroglia and microglia of high relevance for neuron-glia interactions. The catecholamine VT targeting astroglia can modulate the fundamental functions of astroglia observed in neuroenergetics, in the Glymphatic system, in the central renin-angiotensin system and in the production of long-distance calcium waves. Also the astrocytic and microglial DA and adrenergic receptor subtypes mediating DA and NA VT can be significant drug targets in neurological and psychiatric disease.

Alimentacion de la anchoveta (Engraulis ringens) en el norte de Chile (1825, 2540S) en diciembre de 2010

Engraulis ringens diet, in order to determine possible differences in their feeding behavior by size and latitudinal gradient is analyzed. The samples were obtained between 18o25’S and 24o40’S, during the hydroacoustic recruitment assessment cruise conducted between 1 and 20 December 2010. The analysis included the determination of the diet composition in a total of 294 stomachs from 18 sampling stations and distributed in three size classes (pre-recruits, recruits and adults) the were determinate. The diet was described by numerical method, frequency of occurrence and relative importance index, plus dietary similarity in size and latitude and specialization. E. ringens showed a wide spectrum, both phytoplankton and zooplankton prey with a high prevalence of phytoplankton on zooplankton, over 2.5 orders of magnitude in size and latitude range. The components of relative importance in the diet were diatoms of the genus Rhizosolenia and Chaetoceros and Copepoda in the zooplankton. The analysis of intraspecific similarity showed a high overlap between size groups, forming a “trophic unit”. While the latitudinal analysis revealed a high overlap with a tendency to form two trophic units, but without a definite pattern. The results confirm the nature of a generalist and E. ringens in opportunistic predator of E. ringens in northern Chile during the period analyzed.

Trophic ecology of terapontid fishes (Pisces: Terapontidae): the role of morphology and ontogeny

With the covariation between fish form and function of long-standing interest to fish biologists, ecomorphological research provides a framework for assessing the interaction between the morphology of an organism and their ecology. Whereas ecomorphological studies of Australian fishes are rare, the terapontid grunters are an ideal candidate for study because of their diversity of dietary habits. We examined the morphological correlates of the diet of 21 species of northern Australia’s terapontids and their constituent ontogenetic trophic units. Preliminary analyses focusing on morphology identified the role of allometric growth – in characters such as intestinal length, maxilla length and mouth width – as driving considerable ontogenetic divergence in interspecific morphological trajectories. A significant relationship was identified between diet and morphology across species, although morphology explained only half of the observed dietary variation. Body size, and its relationship to allometric development of several morphological parameters, appears to constrain the trophic habits expressed by many terapontids at different life-history stages. Many of the diet–morphology relationships evident within the Terapontidae parallel those seen in other studies, providing substantial corroboration for the ecomorphological approach. This demonstrates that selective pressures have driven morphology in terapontids to converge morphologically with other ecologically comparable fishes across the globe.

Contrasting Global Game Fish and Non‐Game Fish Species

ABSTRACT:We compared biological and ecological traits between global game fish and non‐game fish species using an analysis with randomly chosen fish species from each group and an analysis where species were matched by body length. We used data from the International Game Fish Association (IGFA), FishBase, and the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. Game fish species were defined as being present in the IGFA world record list. The random comparison revealed that on average game fish were significantly larger (155.0 ± 121.5 versus 34.1± 59.5 cm), occupied shallower minimum depths (19.4 ± 58.8 versus 130.0± 359.0 m), had a broader latitudinal range (51°.2 ± 29.4° versus 31.1°± 25.9°), and significantly higher trophic levels (4.1 ±0.1 versus 3.4± 0.1 trophic units) than non‐game fish species. The length‐matched analysis simüarly identified that game fish species occupied higher trophic levels than non‐game fish (3.9 ± 0.4 versus 3.6± 0.6 trophic units), but latitudinal range and depth associations did not differ between groups. Both the random and length‐matched analyses revealed that game fish were more commonly found in freshwater than non‐game fish. Both analyses found that game fish species were more migratory and that both groups differed in their geographical distributions. The random comparison revealed that game fish were significantly more targeted by commercial fisheries, less resilient, and more threatened relative to non‐game fish. Caution must be exercised when synthesizing data from broad data sources, yet this study identifies important differences between game fish and non‐game fish species, which are relevant to management and conservation initiatives.

Long-term feeding ecology of Great Black-backed Gulls (Larus marinus) in the northwest Atlantic: 110 years of feather isotope data

Recent changes to the ecology of the northwest Atlantic are affecting feeding relationships at many trophic levels. With declining fish stocks and fewer fisheries discards, generalist birds such as Great Black-backed Gulls ( Larus marinus L., 1758) may shift their diets. To test whether such a change has occurred, we measured stable nitrogen and carbon isotope ratios of flight feathers collected from modern and museum-preserved birds (1896–2006). We then compared trends in isotope ratios with trends in regional fisheries productivity to determine if gull diets and fisheries changes were associated. We found a significant decline in stable nitrogen isotope ratios of feathers over time, indicating that the gulls’ trophic feeding level has decreased by approximately 2.26‰, or 0.82 trophic units. In contrast, we found no significant change in carbon isotope ratios, giving no clear evidence for a shift to more offshore or terrestrial foraging. The declining stable nitrogen ratio was significantly and positively correlated with both regional groundfish captures and regional fisheries trophic level, and was negatively correlated with each of (i) crab captures and (ii) herring, sardine, and anchovy captures. Our study gives evidence for a shift in diets of Great Black-backed Gulls over time and further suggests that these changes may be related to ongoing changes in fisheries.

The influence of ontogeny and environment on the diet of lookdown dory, Cyttus traversi

Research on trophic relationships is an important component in the move towards an ecosystem approach to fisheries management. The diet of lookdown dory, Cyttus traversi, was determined from examination of stomach contents of 239 specimens of 13.9–50.7 cm total length (TL), sampled at depths of 220–744m on Chatham Rise, New Zealand. The diet was characterised by the macrourid fish, Coelorinchus oliverianus, the natant decapods, Lipkius holthuisi, Campylonotus rathbunae, Sergestes spp., Notopandalus magnoculus, and Pasiphaea spp., and the galatheid, Munida gracilis. Multivariate analyses using distance-based linear models, non-parametric multi-dimensional scaling and similarity percentages indicated the best predictors of diet variability were depth and fish length. Diet changes associated with depth were most apparent in the crustacean prey. Changes in the diet with ontogeny suggested four ontogenetic trophic units: pelagic (<13.9 cm TL), juveniles (13.9–25.8 cm TL; benthopelagic invertebrate feeders), maturing females and males (26–39.5 cm; benthopelagic omnivores) and mature females (>40 cm TL; benthopelagic piscivores/omnivores).

Trophic level of fishes caught by trawls in Thracian Sea

Discarding practices of bottom trawlers were studied seasonally in the Thracian Sea from autumn 1996 to May 1998. Sampling was conducted following normal, commercial fishing practices. Overall, 114 hauls were performed at depths ranging from 19 to 356 m. In total, 141 fish species, belonging to 53 families, were caught. Of those, 17 were exclusively marketable, 58 discarded, and 66 species had individuals in both the marketable and discarded fractions. The mean trophic level increased with depth, both for the discarded and marketable catches. In addition, the mean weighted trophic level of the discarded fishes was significantly lower (P<0.05) than that of the marketable ones by approximately 0.5–0.6 trophic level units. This might indicate that trawling in the north Aegean removes species of higher trophic level from the ecosystem, thus contributing to fishing down.

Aβ peptides as one of the crucial volume transmission signals in the trophic units and their interactions with homocysteine. Physiological implications and relevance for Alzheimer’s disease

Amyloid peptides (Abeta) can operate as volume transmission (VT) signals since they are continuously released from cells of the central nervous system and diffuse in the extra-cellular space of the brain. They have both regulatory and trophic functions on cellular networks. In agreement with Abeta regulatory actions on glial-neuronal networks, the present paper reports new findings demonstrating that intrastriatal injections of Abeta peptides reduce striatal tyrosine hydroxylase, increase striatal GFAP immunoreactivities and lower pain threshold in experimental rats. Furthermore, it has been demonstrated that exogenous homocysteine (Hcy) binds Abeta(1-40) favouring its beta-sheet conformation both in vitro and in vivo and hence the formation of beta-fibrils and development of neurotoxicity. Thus, the hypothesis is discussed that Abeta peptides represent crucial VT-signals in the brain and their action is altered by dysmetabolic signals such as high Hcy extra-cellular levels, known to be an important risk factor for Alzheimer's disease.

Observations of synaptic structures: origins of the neuron doctrine and its current status

The neuron doctrine represents nerve cells as polarized structures that contact each other at specialized (synaptic) junctions and form the developmental, functional, structural and trophic units of nervous systems. The doctrine provided a powerful analytical tool in the past, but is now seldom used in educating neuroscientists. Early observations of, and speculations about, sites of neuronal communication, which were made in the early 1860s, almost 30 years before the neuron doctrine was developed, are presented in relation to later accounts, particularly those made in support of, or opposition to, the neuron doctrine. These markedly differing accounts are considered in relation to limitations imposed by preparative and microscopical methods, and are discussed briefly as representing a post-Darwinian, reductionist view, on the one hand, opposed to a holistic view of mankind as a special part of creation, on the other. The widely misunderstood relationship of the neuron doctrine to the cell theory is discussed, as is the degree to which the neuron doctrine is still strictly applicable to an analysis of nervous systems. Current research represents a 'post-neuronist' era. The neuron doctrine provided a strong analytical approach in the past, but can no longer be seen as central to contemporary advances in neuroscience.