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Why Specialized Metabolism Recurrently Emerges in Plants: Chemical and Genomic Biases in Metabolic Diversification.

Specialized metabolism plays a central role in mediating ecological interactions and adaptive responses in plants, while leaving enduring signatures in genome structure and evolution. Here, we synthesize advances in genomics, biochemistry, and evolutionary biology into a metabolite-driven genetic diversification (MGD) framework, in which metabolite chemistry biases the generation, retention, and reuse of genetic variation. When metabolic flux produces reactive, inhibitory, or otherwise costly intermediates, pathways handling these liabilities recurrently recruit gene dosage changes, duplication, and divergence at catalytic and regulatory choke points. These biases do not impose deterministic outcomes; instead, they shape which genomic variants are preferentially sampled and retained under selection, giving rise to predictable patterns of genomic change. Genome multiplication-through whole-genome duplication, allopolyploidy, and cell type-specific endoreduplication-amplifies these effects by altering dosage balance, regulatory context, and retention trajectories. Integrating MGD with genome-scale dosage dynamics explains why specialized metabolism repeatedly converges on similar solutions across plant lineages, even amid extensive genomic turnover and chemical diversity.

Journal Article↗

Transitional cell carcinoma of the uterine cervix. A report of six cases with clinical, histologic and cytologic findings.

BACKGROUND: Transitional cell carcinoma of the cervix (TCCC) is a rare neoplasm of recent description. The cytologic characteristics of the tumor have not been published to date. Six cases of TCCC are described, including their clinical, histologic, cytologic and immunohistochemical features. CASES: All cases presented at an advanced clinical stage; two recurred, and one metastasized. Five cases showed a papillary exophytic pattern, and one case showed an "inverted" endophytic pattern similar to that of transitional cell carcinoma of the urothelium (TCCU). The cytokeratin profile was similar to that of squamous cell carcinoma of the cervix (SCCC), positive for CK 7 and negative for CK 20. The cervical smears showed a background that was necrotic or hemorrhagic. The cells with transitional features formed cohesive groups in a multilayered fashion and had an oval or spindle shape with tapered ends. The nuclei were hyperchromatic, with coarse and medium-sized granules that frequently displayed a wrinkled membrane, nuclear grooves and rare pseudoinclusions. The nucleoli were small or absent. Others cells with cytologic characteristics of SCCC were seen in all cases. CONCLUSION: TCCC is a rare neoplasm that probably represents a subgroup of SCCC. The most frequent histologic pattern is papillary-exophytic, but it can be inverted-endophytic. In cervical smears there are cells with characteristics of regular SCCC and others resembling those of TCCU. A larger number of cases is needed to define the evolution and clinical outcome.

Adult↗

Prenatal development of reelin-immunoreactive neurons in the human neocortex.

Reelin, the protein defective in reeler mutant mice, is a secreted glycoprotein involved in the architectonic development of the central nervous system, more particularly in the development of neocortical lamination. In mice, reelin mRNA and protein expression are most robust in horizontal neurons of the embryonic marginal zone (MZ). By using monoclonal anti-reelin antibodies (de Bergeyck et al. [1998] J. Neurosci. Methods), the morphology and evolution of reelin-expressing neurons were studied in the MZ of the prenatal human neocortex. At 11 gestational weeks (GW), the MZ contained a single layer of reelin-positive mono- or bipolar horizontal Cajal-Retzius (CR) cells. From 14 GW onward, the subpial granular layer (SGL) invaded the MZ, forming a transient layer of undifferentiated, initially reelin-negative granule cells. In parallel to the emergence of the SGL and the morphological differentiation of the CR cells, a second population of reelin-positive cells appeared within the SGL. These cells, termed CR-like cells, were intermediate in size and shape between the CR cells and SGL granule cells. Between 16 GW and 24 GW, the packing density of the reelin-producing cells remained remarkably stable, despite the continuous growth of the cortical surface. During this period, CR cells settled progressively deeper within the MZ, although they remained in contact with the pial surface through radially ascending processes. Most CR cells disappeared at around 27 GW, in parallel with the dissolution of the SGL. During the last weeks of gestation, reelin was expressed by a few medium-sized, often horizontal neurons. These observations show that different neuronal populations in the human MZ express reelin and suggest that a possible function of the SGL is to supply reelin-producing cells through a gradual transformation of reelin-negative precursor cells into reelin-immunoreactive CR-like cells, thus coping with the protracted neurogenesis and dramatic surface expansion of the human neocortex.

Calbindin 2↗

Primary body axes of vertebrates: generation of a near-Cartesian coordinate system and the role of Spemann-type organizer.

A rationale for the complex-appearing generation of the primary body axes in vertebrates can be obtained if this process is divided into two parts. First, an ancestral system is responsible for the anteroposterior (AP) patterning of the brain and the positioning of the heart. The blastopore (marginal zone) acts as a source region that generates primary AP-positional information for the brain, a process that is largely independent of the organizer. This evolutionary old system was once organizing the single axis of radial-symmetric ancestors. Second, the trunk is assumed to be an evolutionary later addition. The AP organization of the trunk depends on a time-controlled posterior transformation in which an oscillation plays a crucial role. This oscillation also leads to the repetitive nature of the trunk pattern as seen in somites or segments. The function of the Spemann-type organizer is not to specify the dorsoventral (DV) positional information directly but to initiate the formation of a stripe-shaped midline organizer, realized with different structures in the brain and in the trunk (prechordal plate vs. notochord). The distance of the cells to this midline (rather than to the organizer) is crucial for the DV specification. The basically different modes of axes formation in vertebrates and insects is proposed to have their origin in the initial positioning of the mesoderm. Only in vertebrates the mesoderm is initiated in a ring at a posterior position. Thus, only in vertebrates complex tissue movements are required to transform the ring-shaped posterior mesoderm into the rod-shaped axial structures.

Animals↗

Genetic evidence for a role of centrin-associated proteins in the organization and dynamics of the infraciliary lattice in Paramecium.

Within the superfamily of "EF-hand Ca2+-modulated proteins," centrins constitute a family of cytoskeletal proteins that are highly conserved from lower eukaryotes to man. Their cytoskeletal specialization is manifest in their capacity to form filamentous contractile arrays of various shapes and functions and by their association with microtubule organizing centres (MTOCs). While the latter property has been conserved throughout the evolution of eukaryotes, centrin-based contractile structures are only found in protists where they form arrays of widely diverse organization and function. In the ciliate Paramecium tetraurelia, three centrin genes have been characterized, which may be part of a larger centrin gene family [Madeddu et al., 1996: Eur J. Biochem. 238:121-128]. The products of these genes were originally identified as components of the infraciliary lattice, a contractile cytoskeletal network [Garreau de Loubresse et al., 1991: Biol. Cell 71:217-225]. We show here that centrins are localized not only in this lattice but also in basal bodies and in the cord, a filamentous structure associated with the oral apparatus. We demonstrate that in the infraciliary lattice, but not in basal bodies, centrins are associated with high-molecular-weight proteins (ca. 350 kD). Their role in the biogenesis of the infraciliary lattice is documented by cytological and biochemical properties of the mutant "démaillé" (dem1) characterized by altered centrin-associated proteins and abnormal organization and dynamics of the infraciliary lattice.

Animals↗

Human development IV: the living cell has information-directed self-organisation.

In this paper, restricted to describe the ontogenesis of the cell, we discuss the processing of DNA through RNA to proteins and argue that this process is not able to transfer the information necessary to organize the proteins in the cell, but only to transfer the information necessary to form the shape of the proteins. We shortly describe the structure of the information carrying field recruited by the cells that we think is responsible for building the organelles and other cellular structures. We use the cells superior control of its cytoskeleton as an example of how the cell is using an informational field giving the positional information guiding all the local chemical processes behind the cell movement. We describe the information-directed self-organization in cells and argue that this can explain the ontogenesis of the cell. We also suggest the existence of an undiscovered phenomenon behind the information transmitting cell interactions. We conclude that during evolution the cell has developed into an information-guided self-organizing structure. The mystery we want to solve is: what is the mechanical cause and nature of biological information?

Animals↗

Vindhyan akinites: an indicator of mesoproterozoic biospheric evolution.

A wide size range of rod-shaped, ellipsoidal akinites assignable to Archaeoellipsoides are reported from the Newari locality of the Mesoproterozoic Kheinjua Formation of the Semri Group, Vindhyan Supergroup. These akinites of heterocystous cyanobacteria (Archaeoellipsoides) represent the smallest of the forms reported from any other assemblage to date and are well comparable to the akinites of modern bloom forming Anabaena species. Like any other Mesoproterozoic microfossil assemblage, The Newari microfossil assemblage is also dominated by cyanobacterial population, but the presence of Archaeoellipsoides (akinites) or heterocyst forming Nostocales and Stigonematales are rather rarely reported. These fossils set a minimum date for the evolution of derived cyanobacteria, capable of marked cell differentiation, and they corroborate geochemical evidence indicating that atmospheric oxygen level was above 1% of present day level during Mesoproterozoic time. In the presence of oxygen a protected environment for nitrogenase (an oxygen sensitive nitrogen fixing enzyme) is produced by these akinites, which were abundant in coastal communities of Mesoproterozoic shallow marine carbonates. It is therefore interpreted that the presence of Vindhyan's akinites indicate Mesoproterozoic biospheric evolution.

Biological Evolution↗

Comparative ultrastructure of the root system in rhizocephalan barnacles (Crustacea: Cirripedia: Rhizocephala).

Rhizocephalan barnacles are parasites of Crustacea. They lack even the rudiments of an alimentary canal, but infiltrate their hosts with a nutrient-absorbing system of rootlets. We review the ultrastructure of the rootlets using light microscopy, SEM, and TEM in nine species from five families, representing both suborders of the Rhizocephala: from the Kentrogonida Peltogaster paguri, P. curvatus, Peltogasterella sulcata, Cyphosaccus norvegicus (Peltogastridae); Lernaeodiscus porcellanae (Lernaeodiscidae); and Sacculina carcini (Sacculinidae); and from the Akentrogonida Clistosaccus paguri (Clistosaccidae); Chthamalophilus delagei, and Boschmaella japonica (Chthamalophilidae). With the exception of Chthamalophilus delagei, the root system of the investigated species shares numerous apomorphies at the ultrastructural level and displays at all levels specializations that maximize the surface area. The rootlets consist of a cuticle, an epidermis and a subjacent layer of axial cells that often, but not always surround, a central lumen. The rootlets are at all times enclosed in a less than 0.5 microm thick cuticle, which is never molted. The cuticle consists of an inner homogeneous layer with a slightly fibrous structure and an outer, less than 15-nm thick electron-dense layer, from which numerous microcuticular projections extend into the hemolymphatic space of the host. The microcuticular projections consist of the outer electron-dense layer and sometimes a core of the more translucent homogeneous layer. They vary among the species from being simple in Sacculina carcini to exhibiting complex branching patterns in Peltogasterella sulcata and Cyphosaccus norvegicus. Beneath the cuticle the epidermal plasma membrane is thrown into irregularly shaped projections. The epidermal cells are joined by long septate junctions and exhibit the characteristics of a transporting epithelium. Experiments with acid phosphatase revealed activity both in the epidermis and among the microcuticular projections. The projections may therefore form a domain that is important in absorption and extracellular digestion of nutrients from the host. The axial cells contain abundant endoplasmic reticulum and seem to convert absorbed carbohydrates into lipid, which is stored in large droplets. Subepidermal muscle cells cause sinuous movements of the rootlets, but it remains unknown how nutrients are transported along the rootlets towards the external reproductive body. In C. delagei the single, bladder-shaped rootlet lacks both the apical projections in the epidermis, the electron-dense cuticle layer, and the microcuticular projections. We review previous studies on the rhizocephalan root system and discuss functional and phylogenetic aspects of the morphology.

Acid Phosphatase↗

The ocular morphology of the southern hemisphere lamprey geotria australis gray, with special reference to optical specialisations and the characterisation and phylogeny of photoreceptor types.

This paper describes the ocular morphology of young adults of the southern hemisphere lamprey Geotria australis, the sole representative of the Geotriidae, and makes comparisons with those of holarctic lampreys (Petromyzontidae). As previously reported for the holarctic lamprey Ichthyomyzon unicuspis [Collin and Fritzsch, 1993], the lens of G. australis is non-spherical and possesses a cone-shaped posterior that may be capable of mediating variable focus. The avascular retina of G. australis is well differentiated, containing three retinal ganglion cell populations, three layers of horizontal cells and three photoreceptor types. In contrast to petromyzontids that contain only two photoreceptor types (short and long), G. australis possesses one rod-like (R1) and two cone-like (C1 and C2) photoreceptors. Although the rod-like receptor in G. australis may be homologous with the short receptors of holarctic lampreys, the two cone-like receptors have morphological characteristics that differ markedly from those of the long receptors of their holarctic counterparts. The features which distinguish the two cone-like receptors from those of the long receptor type in holarctic lampreys are the characteristics of the mitochondria and the presence of large amounts of two different types of stored secretory material in the endoplasmic reticulum of the myoid (refractile bodies). The endoplasmic reticulum of each receptor type has a different shape and staining profile and is polymorphic, each showing a continuum of distension. It is proposed that the presence of two cone-like photoreceptors with different characteristics would increase the spectral range of G. australis and thus be of value during the parasitic phase, when this lamprey lives in the surface marine waters. The irideal flap, present in G. australis but not petromyzontids, would assist in reducing intraocular flare during life in surface waters. The results of this study, which are discussed in the context of the proposed evolution of lampreys, emphasise that it is important to take into account the characteristics of the eyes of southern hemisphere lampreys when making generalizations about the eyes of lampreys as a whole.

Animals↗

Structural/functional homology between the bacterial and eukaryotic cytoskeletons.

Structural proteins are now known to be as necessary for controlling cell division and cell shape in prokaryotes as they are in eukaryotes. Bacterial ParM and MreB not only have atomic structures that resemble eukaryotic actin and form similar filaments, but they are also equivalent in function: the assembly of ParM drives intracellular motility and MreB maintains the shape of the cell. FtsZ resembles tubulin in structure and in its dynamic assembly, and is similarly controlled by accessory proteins. Bacterial MinD and eukaryotic dynamin appear to have similar functions in membrane control. In dividing eukaryotic organelles of bacterial origin, bacterial and eukaryotic proteins work together.

Actins↗

Forebrain development in control and hypothyroid larvae of Triturus cristatus carnifex.

Some cytological and developmental aspects of the forebrain gray matter were studied in the control and the hypothyroid larvae of Triturus cristatus carnifex. The mitotic cell percentages in the periventricular germinal layer, the fusiform shape of the recently divided neuronal cells and the transitory gray matter cleavage, are characteristic of the immature status of the central nervous system (CNS) in this species. The hypothyroidism obtained during two months of thiourea treatment slows down the development in all the forebrain areas of the experimental larvae. Nevertheless, the nucleus olfactorius anterior and the corpus striatum, which have a longer mitotic activity with respect to the other neuronal structures, are more deeply affected by thyroid atrophy. Thyroid activity and forebrain maturation are discussed on the basis of the literature and our data with regard to their influence on behavior and evolution.

Aging↗

Ampullary sense organs, peripheral, central and behavioral electroreception in chimeras (Hydrolagus, Holocephali, Chondrichthyes).

Ampullary sense organs are distributed in groups over the head of Hydrolagus colliei with their pores in clusters and innervated by the buccal, hyomandibular and superficial ophthalmic branches of the anterior lateral line nerve. The ampullae contain ciliated sense cells in an alveolate-shaped epithelium, which communicates to the surface through a jelly-filled tube. The sense cells synapse at their bases with the afferent nerve fibers that terminate in the dorsal nucleus of the anterior lateral line lobe of the medulla. The anatomy and ultrastructure support the homology with the ampullae of Lorenzini of elasmobranchs. Single units recorded from the buccal branch of the anterior lateral line nerve are either lateral line or ampullary in character, the former being sensitive only to mechanical stimuli, the latter to both mechanical and to weak electric stimuli. They are also distinguished by the positions of their receptive fields. The electroreceptive units are spontaneously active and are excited by a cathode placed near the opening of their pore and inhibited by an anode. Compound evoked potentials are recorded from beneath the lateral aspect of the tectum in response to weak electric fields in the bath. Each recording locus has a best position and orientation of the electric field. The electric fields are effective if their duration is longer than ca. 2 ms; longer than 10 ms makes no difference until an OFF effect becomes distinct at ca. 50 ms. The reception is tuned to low frequencies but is not sensitive to maintained current (DC). Evoked potentials summating moderate numbers of responses are clear at < 1 microV/cm. Ratfish were conditioned in a ring-shaped tank to reverse the direction of swimming when an electric field was switched ON. The stimulus was a 5 Hz square wave or the onset of a DC of 1-10 microA between a pair of electrodes on the floor of the tank. The fish responded to fields as weak as 0.2 microV/cm. A specialized sense modality for electroreception, similar to that in elasmobranchs and most other groups of nonteleost fishes, except for Myxini and Neopterygii (holosteans), is present in the subclass Holocephali. The notion is supported that this modality and its central as well as peripheral apparatus arose early in the evolution of vertebrates. Only two losses of the whole system need be hypothesized, on this idea, once in the ancestors of the hagfishes and once in the ancestors of the neopterygians, which include the teleosts. Some orders of teleosts then evolved a new system of electroreception independently. The ciliary receptor cells are probably primitive; microvillar sense cells evolved independently.

Animals↗

The eyes of mesopelagic crustaceans. III. Thysanopoda tricuspidata (Euphausiacea).

The compound eyes of the mesopelagic eupausiid Thysanopoda tricuspidata were investigated by light-, scanning-, and transmission electron microscopy. The eyes are spherical and have a diameter that corresponds to 1/6 of the carapace length. The hexagonal facets have strongly curved outer surfaces. Although there are four crystalline cone cells, only two participate in the formation of the cone, which is 90-120 micrometer long and appears to have a radial gradient of refractive index. The clear zone, separating dioptric structures and retinula, is only 90-120 micrometer wide. In it lie the very large oval nuclei of the seven retinula cells. Directly in front of the 70 micrometer long and 15 micrometer thick rhabdom a lens-like structure of 12 micrometer diameter is developed. This structure, known in only a very few arthropods, seems to be present in all species of Euphausiacea studied to date. It is believed that the rhabdom lens improves near-field vision and absolute light sensitivity. Rod-shaped pigment grains and mitochondria of the tubular type are found in the plasma of retinula cells. The position of the proximal screening pigment as well as the microvillar organization in the rhabdom are indicative of light-adapted material. The orthogonal alignment of rhabdovilli suggests polarization sensitivity. Behind each rabdom there is a cup-shaped homogenous structure of unknown, but possibly optical function. Finally, the structure and the function of the euphysiid eye are reviewed and the functional implications of individual components are discussed.

Biological Evolution↗

Cells showing immunoreactivity for calcitonin or calcitonin gene-related peptide (CGRP) in the central nervous system of some invertebrates.

In the central nervous system of some species of several invertebrate phyla, including land planarians (Platyhelminthes), ribbon worms (Nemertina), slugs (Mollusca), polychaetes, earthworms and leeches (Annelida), pill bugs (Arthropoda), and beard worms (Pogonophora), salmon calcitonin-immunoreactive cells and rat calcitonin gene-related peptide (CGRP)-immunoreactive cells were found by immunohistochemistry. These immunoreactive cells were located in the region surrounding the neuropile, although the sizes of the cells varied according to species. Some of them were round or polygonal and regarded as apolar nerve cells because of their lack of cytoplasmic processes, whereas others were spindle-shaped or elongated, being comparable with unipolar nerve cells because of extension of their cytoplasmic processes in the direction of the neuropile. In some cases, it was noted that the cytoplasmic processes had complicated branches or formed loop-like structures at their ends. These observations suggest that a calcitonin-like or CGRP-like substance is extensively present in invertebrates as well as vertebrates.

Animals↗

Neuropeptide function: the invertebrate contribution.

The following is a list of generalizations that arise from considering the present state of knowledge concerning the functions of invertebrate peptides. Some of these clearly also apply to vertebrates. Invertebrate peptides can be classified into structurally related groups. Structural similarity of peptides may represent true evolutionary homology by selection acting on an original gene. Alternatively, independent evolution of similar genes may have occurred because certain amino acid sequences represent optimal solutions to complex functional problems. Invertebrate neuropeptides have multiple functions. Thus, proctolin is a cardioactive peptide, a skeletal neuromuscular transmitter, a hindgut neuropeptide, a peptide of CNS interneurons (Keshishian & O'Shea 1984) and may have humoral roles. Invertebrate peptides act through a variety of molecular mechanisms. Generalizations about the mechanism cannot yet be made. Thus, proctolin's action on crustacean skeletal muscle is not associated with stimulation of cyclic-AMP or protein phosphorylation, but the action of SCPB on molluscan skeletal muscle involves elevation of cAMP. Invertebrate peptide inactivation can be caused by proteolysis that can also function to enhance peptide bioactivity. Proctolin is made virtually biologically inactive by any proteolysis, but alpha-BCP bioactivity is enhanced by two steps of carboxy peptidase digestion before being functionally inactivated. Protease action on released peptides is not necessarily a "simple" form of transmitter inactivation. Protease action also involves functional processing whereby the temporal and spatial parameters of a peptide's action may be shaped. Invertebrate neuropeptides are frequently co-localized with other neuroeffectors. Peptides may be co-localized and released with other active peptides as in the bag-cell example, or may be coactive with more conventional transmitters, as in the Ds motoneuron example. In such circumstances there is no reason to view either transmitter as primary or secondary. Invertebrate neuropeptides are widely involved in the control of muscle contraction. These effects may be locally and directly mediated as in the Ds motoneuron example or may be humoral. The peptide may act directly on the muscle contractile system or function to modulate the muscles' response to other motor input. Muscle contraction may be induced by a neuropeptide without depolarization of the muscle cells, for example see proctolin. Invertebrate neuropeptides are frequently involved in the control of oscillatory functions. In several examples peptides activate rhythmic myogenic contractions of cardiac and skeletal muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Quantitative method to study the network formation of endothelial cells in response to tumor angiogenic factors.

To study the network formation of endothelial cells (ECs) in an extracellular matrix (ECM) environment, we have devised an EC aggregation-type model based on a diffusion limited cluster aggregation model (DLCA), where clusters of particles diffuse and stick together upon contact. We use this model to quantify EC differentiation into cord-like structures by comparing experimental and simulation data. Approximations made with the DLCA model, when combined with experimental kinetics and cell concentration results, not only allow us to quantify cell differentiation by a pseudo diffusion coefficient, but also measure the effects of tumor angiogenic factors (TAFs) on the formation of cord-like structures by ECs. We have tested our model by using an in vitro assay, where we record EC aggregation by analysing time-lapse images that provide us with the evolution of the fractal dimension measure through time. We performed these experiments for various cell concentrations and TAFs (e.g. EVG, FGF-b, and VEGF). During the first six hours of an experiment, ECs aggregate quickly. The value of the measured fractal dimension decreases with time until reaching an asymptotic value that depends solely on the EC concentration. In contrast, the kinetics depend on the nature of TAFs. The experimental and simulation results correlate with each other in regards to the fractal dimension and kinetics, allowing us to quantify the influence of each TAF by a pseudo diffusion coefficient. We have shown that the shape, kinetic aggregation, and fractal dimension of the EC aggregates fit into an in vitro model capable of reproducing the first stage of angiogenesis. We conclude that the DLCA model, combined with experimental results, is a highly effective assay for the quantification of the kinetics and network characteristics of ECs embedded in ECM proteins. Finally, we present a new method that can be used for studying the effect of angiogenic drugs in in vitro assays.

Angiogenesis Inducing Agents↗

Feature activated molecular dynamics: an efficient approach for atomistic simulation of solid-state aggregation phenomena.

An efficient approach is presented for performing efficient molecular dynamics simulations of solute aggregation in crystalline solids. The method dynamically divides the total simulation space into "active" regions centered about each minority species, in which regular molecular dynamics is performed. The number, size, and shape of these regions is updated periodically based on the distribution of solute atoms within the overall simulation cell. The remainder of the system is essentially static except for periodic rescaling of the entire simulation cell in order to balance the pressure between the isolated molecular dynamics regions. The method is shown to be accurate and robust for the Environment-Dependant Interatomic Potential (EDIP) for silicon and an Embedded Atom Method potential (EAM) for copper. Several tests are performed beginning with the diffusion of a single vacancy all the way to large-scale simulations of vacancy clustering. In both material systems, the predicted evolutions agree closely with the results of standard molecular dynamics simulations. Computationally, the method is demonstrated to scale almost linearly with the concentration of solute atoms, but is essentially independent of the total system size. This scaling behavior allows for the full dynamical simulation of aggregation under conditions that are more experimentally realizable than would be possible with standard molecular dynamics.

Chemistry, Physical↗

A three-dimensional dynamic simulation model of epithelial tissue renewal.

OBJECTIVE: Based on the study of existing simulation and mathematical models, a dynamic simulation and three-dimensional (3-D) visualization model of the normal and pathologic architecture of the nasal epithelium is proposed. STUDY DESIGN: Positions, sizes, shapes and orientations of the nuclei, basal lamina and lumen were used for 3-D representation of the epithelium. Static modeling was applied to simulate the normal, metaplastic and dysplastic stages of the nasal epithelium. Then, dynamic modeling, starting from a static representation of a normal or a pathologic stage, used the starting values of cell proliferation parameters to simulate a tissue growth process. The basic hypothesis is that consecutive transformations through stages are mainly due to increased cell growth. RESULTS: Normal tissue renewal and progressive transitions between normality and hyperplasia after exposure to formaldehyde were obtained. CONCLUSION: A model that allows study of the evolution of the 3-D tissue architecture during the preneoplastic process in external epithelium is now available. Improvement of the model, consisting of adding information concerning cell communication, extracellular matrix and cell cycle modeling, should help to formulate and sharpen hypotheses concerning structural and kinetic dynamics of this tissue during the preneoplastic process.

Epithelial Cells↗