Isolated primary osteocytes express functional gap junctions in vitro

The differentiation of the neuromuscular junction is a multistep process requiring coordinated interactions between nerve terminals and muscle. Although innervation is not needed for muscle production, the formation of nerve-muscle contacts, intramuscular nerve branching, and neuronal survival require reciprocal signals from nerve and muscle to regulate the formation of synapses. Following the production of muscle fibers, clusters of acetylcholine receptors (AChRs) are concentrated in the central regions of the myofibers via a process termed “prepatterning”. The postsynaptic protein MuSK is essential for this process activating possibly its own expression, in addition to the expression of AChR. AChR complexes (aggregated and stabilized by rapsyn) are thus prepatterned independently of neuronal signals in developing myofibers. ACh released by branching motor nerves causes AChR-induced postsynaptic potentials and positively regulates the localization and stabilization of developing synaptic contacts. These “active” contact sites may prevent AChRs clustering in non-contacted regions and counteract the establishment of additional contacts. ACh-induced signals also cause the dispersion of non-synaptic AChR clusters and possibly the removal of excess AChR. A further neuronal factor, agrin, stabilizes the accumulation of AChR at synaptic sites. Agrin released from the branching motor nerve may form a structural link specifically to the ACh-activated endplates, thereby enhancing MuSK kinase activity and AChR accumulation and preventing dispersion of postsynaptic specializations. The successful stabilization of prepatterned AChR clusters by agrin and the generation of singly innervated myofibers appear to require AChR-mediated postsynaptic potentials indicating that the differentiation of the nerve terminal proceeds only after postsynaptic specializations have formed.     

Proteasome system of protein degradation and processing

In eukaryotic cells, degradation of most intracellular proteins is realized by proteasomes. The substrates for proteolysis are selected by the fact that the gate to the proteolytic chamber of the proteasome is usually closed, and only proteins carrying a special “label” can get into it. A polyubiquitin chain plays the role of the “label”: degradation affects proteins conjugated with a ubiquitin (Ub) chain that consists at minimum of four molecules. Upon entering the proteasome channel, the polypeptide chain of the protein unfolds and stretches along it, being hydrolyzed to short peptides. Ubiquitin per se does not get into the proteasome, but, after destruction of the “labeled” molecule, it is released and labels another molecule. This process has been named “Ub-dependent protein degradation”. In this review we systematize current data on the Ub-proteasome system, describe in detail proteasome structure, the ubiquitination system, and the classical ATP/Ub-dependent mechanism of protein degradation, as well as try to focus readers’ attention on the existence of alternative mechanisms of proteasomal degradation and processing of proteins. Data on damages of the proteasome system that lead to the development of different diseases are given separately.     

Source-sink landscape theory and its ecological significance

Exploring the relationships between landscape pattern and ecological processes is the key topic of landscape ecology, for which, a large number of indices as well as landscape pattern analysis model were developed. However, one problem faced by landscape ecologists is that it is hard to link the landscape indices with a specific ecological process. Linking landscape pattern and ecological processes has become a challenge for landscape ecologists. “Source” and “sink” are common concepts used in air pollution research, by which the movement direction and pattern of different pollutants in air can be clearly identified. In fact, for any ecological process, the research can be considered as a balance between the source and the sink in space. Thus, the concepts of “source” and “sink” could be implemented to the research of landscape pattern and ecological processes. In this paper, a theory of sourcesink landscape was proposed, which include: (1) In the research of landscape pattern and ecological process, all landscape types can be divided into two groups, “source” landscape and “sink” landscape. “Source” landscape contributes positively to the ecological process, while “sink” landscape is unhelpful to the ecological process. (2) Both landscapes are recognized with regard to the specific ecological process. “Source” landscape in a target ecological process may change into a “sink” landscape as in another ecological process. Therefore, the ecological process should be determined before “source” or “sink” landscape were defined. (3) The key point to distinguish “source” landscape from “sink” landscape is to quantify the effect of landscape on ecological process. The positive effect is made by “source” landscape, and the negative effect by “sink” landscape. (4) For the same ecological process, the contribution of “source” landscapes may vary, and it is the same to the “sink” landscapes. It is required to determine the weight of each landscape type on ecological processes. (5) The sourcesink principle can be applied to non-point source pollution control, biologic diversity protection, urban heat island effect mitigation, etc. However, the landscape evaluation models need to be calibrated respectively, because different ecological processes correspond with different source-sink landscapes and evaluation models for the different study areas. This theory is helpful to further study landscape pattern and ecological process, and offers a basis for new landscape index design. __________ Translated from Acta Ecologica Sinica, 2006, 26(5): 1444–1449 [译自: 生态学报]     

The Morphostatic Limit for a Model of Skeletal Pattern Formation in the Vertebrate Limb

A recently proposed mathematical model of a “core” set of cellular and molecular interactions present in the developing vertebrate limb was shown to exhibit pattern-forming instabilities and limb skeleton-like patterns under certain restrictive conditions, suggesting that it may authentically represent the underlying embryonic process (Hentschel et al., Proc. R. Soc. B 271, 1713–1722, 2004). The model, an eight-equation system of partial differential equations, incorporates the behavior of mesenchymal cells as “reactors,” both participating in the generation of morphogen patterns and changing their state and position in response to them. The full system, which has smooth solutions that exist globally in time, is nonetheless highly complex and difficult to handle analytically or numerically. According to a recent classification of developmental mechanisms (Salazar-Ciudad et al., Development 130, 2027–2037, 2003), the limb model of Hentschel et al. is “morphodynamic,” since differentiation of new cell types occurs simultaneously with cell rearrangement. This contrasts with “morphostatic” mechanisms, in which cell identity becomes established independently of cell rearrangement. Under the hypothesis that development of some vertebrate limbs employs the core mechanism in a morphostatic fashion, we derive in an analytically rigorous fashion a pair of equations representing the spatiotemporal evolution of the morphogen fields under the assumption that cell differentiation relaxes faster than the evolution of the overall cell density (i.e., the morphostatic limit of the full system). This simple reaction–diffusion system is unique in having been derived analytically from a substantially more complex system involving multiple morphogens, extracellular matrix deposition, haptotaxis, and cell translocation. We identify regions in the parameter space of the reduced system where Turing-type pattern formation is possible, which we refer to as its “Turing space.” Obtained values of the parameters are used in numerical simulations of the reduced system, using a new Galerkin finite element method, in tissue domains with nonstandard geometry. The reduced system exhibits patterns of spots and stripes like those seen in developing limbs, indicating its potential utility in hybrid continuum-discrete stochastic modeling of limb development. Lastly, we discuss the possible role in limb evolution of selection for increasingly morphostatic developmental mechanisms.     

History of the use of “cedar glades” and other descriptive terms for vegetation on rocky limestone soils in the Central Basin of Tennessee

Use of “cedar glades” and other terms by geologists, botanists, soil scientists, and zoologists to describe vegetation on rocky limestone soils in the Central (Nashville) Basin of Tennessee from 1851 to 2003 is reviewed. Historically, in the Central Basin “cedar glades” has been applied to the rocky openings / redcedar / redcedar-hardwood / hardwood forest complex primarily on the (thin-bedded) Lebanon limestone but also on other (thick-bedded) Ordovician limestones. However, “cedar glades,” “limestone glades,” and “limestone cedar glades” increasingly are being used by botanists and plant ecologists for the rocky openings only, which have C4 native annual grass-C3 annual/perennial forb-cryptogam-dominated vegetation. Some erroneous statements in the literature that have resulted from misinterpretation or misunderstanding of “cedar glades” and other terms are discussed. Finally, a graphical model of the (apparent) pathways of development of cedar glade vegetation from bare rock to forest in the Central Basin is presented.     

Multisequence comparisons in protein coding genes

A very powerful method for detecting functional constraints operative in biological macromolecules is presented. This method entails performing a base permanence analysis of protein coding genes at each codon position simultaneously in different species. It calculates the degree of permanence of subregions of the gene by dividing it into segments,c codons long, counting how many sites remain unchanged in each segment among all species compared. By comparing the base permanence among several sequences with the expectations based on a stochastic evolutionary process, gene regions showing different degrees of conservation can be selected. This means that wherever the permanence deviates significantly from the expected value generated by the simulation, the corresponding regions are considered “constrained” or “hypervariable”. The constrained regions are of two types: α and β. The α regions result from constraints at the amino acid level, whereas the β regions are those probably involved in “control” processing. The method has been applied to mitochondrial genes coding for subunit 6 of the ATPase and subunit 1 of the cytochrome oxidase in four mammalian species: human, rat, mouse, and cow. In the two mitochondrial genes a few regions that are highly conserved in all codon positions have been identified. Among these regions a sequence, common to both genes, that is complementary to a strongly conserved region of 12S rRNA has been found. This method can also be of great help in studying molecular evolution mechanisms.     

Ecological explanations for successful invasion of exotic plants

The intentional introduction of exotic species can increase the level of local biodiversity, enrich people’s material lives, and bring significant social and economic benefits that are also the symbols of human progress. However, along with the frequent intercourse among countries and regions, the frequency of uncontrolled crossregional migration of species is increased and there is a lack of scientific management strategy for the intentional introduction of exotic species. Exotic species invasion, which is behind habitat fragmentation, has become the second largest threatening factor to the maintenance of the global-scale level of biological diversity. Exotic species invasion can destroy the structure of an ecosystem, disturb the economic life of a society, and do harm to human health. In this paper, the authors review some of the ecological explanations for issues such as “what causes or mechanisms have led to the successful invasion of exotic species”, including the “ideal weeds characteristics”, “biodiversity resistance hypothesis”, “enemies release hypothesis”, “evolution of increased competitive ability hypothesis”, “niche opportunity hypothesis”, and “novel weapon hypothesis”. The authors also analyze and evaluate the background and theoretical basis of the hypotheses, providing explanations for some phenomena, as well as the deficiencies of these explanations.     

On the adsorption of ions at charged sites in an electric field: II

A study is made of the adsorption of one kind of monovalent positive ion at a long chain of alternating monovalent negative fixed charged (“lattice”) and uncharged (“interstitial”) sites both of one type in an electric field. Considering only nearest neighbor interactions an expression is obtained for the grand partition function. The fractions of sites of both types which are occupied and unoccupied are determined. It is shown that an equilibrium constant can be defined for the adsorption of ions at oppositely charged sites.     

A Contact-Network-Based Formulation of a Preferential Mixing Model

Heterogeneity in the number of potentially infectious contacts and connectivity correlations (“like attaches to like” i.e., assortatively mixed or “opposites attract” i.e., disassortatively mixed) have important implications for the value of the basic reproduction ratio R ₀ and final epidemic size. In this paper, we present a contact-network-based derivation of a simple differential equation model that accounts for preferential mixing based on the number of contacts. We show that results based on this model are in good qualitative agreement with results obtained from preferential mixing models used in the context of sexually transmitted diseases (STDs). This simple model can accommodate any mixing pattern ranging from completely disassortative to completely assortative and allows the derivation of a series of analytical results.     

The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation

Amyloid fibrils and prions are proteinaceous aggregates that are based on a unique form of polypeptide configuration, termed cross-beta structure. Using a group of chemically distinct polyamino acids, we show here that the existence of such a structure does not require the presence of specific side chain interactions or sequence patterns. These observations firmly establish that amyloid formation and protein folding represent two fundamentally different ways of organizing polypeptides into ordered conformations. Protein folding depends critically on the presence of distinctive side chain sequences and produces a unique globular fold. By contrast, the properties of different polyamino acids suggest that amyloid formation arises primarily from main chain interactions that are, in some environments, overruled by specific side chain contacts. This side chain effect can be thought of as the inverse of the one that characterizes protein folding. Conditions including Alzheimer's and Creutzfeldt-Jakob diseases represent, on this basis, pathological cases in which a natural polypeptide chain has aberrantly adopted the conformation that is primarily defined by main chain interactions and not the structure that is determined by specific side chain contacts that depend on the polypeptide sequence.     

Formation of plant cell wall supramolecular structure

Plant cell wall is an example of a widespread natural supramolecular structure: its components are considered to be the most abundant organic compounds renewable by living organisms. Plant cell wall includes numerous components, mainly polysaccharidic; its formation is largely based on carbohydrate-carbohydrate interactions. In contrast to the extracellular matrix of most other organisms, the plant cell compartment located outside the plasma membrane is so structured that has been named “wall”. The present review summarizes data on the mechanisms of formation of this supramolecular structure and considers major difficulties and results of research. Existing approaches to the study of interactions between polysaccharides during plant cell wall formation have been analyzed, including: (i) characterization of the structure of natural polysaccharide complexes obtained during cell wall fractionation; (ii) analysis of the interactions between polysaccharides “at mixing in a tube”; (iii) study of the interactions between isolated individual plant cell wall matrix polysaccharides and microfibrils formed by cellulose-synthesizing microorganisms; and (iv) investigation of cell wall formation and modification directly in plant objects. The key stages in formation of plant cell wall supramolecular structure are defined and characterized as follows: (i) formation of cellulose microfibrils; (ii) interactions between matrix polysaccharides within Golgi apparatus substructures; (iii) interaction between matrix polysaccharides, newly secreted outside the plasma membrane, and cellulose microfibrils during formation of the latter; (iv) packaging of the formed complexes and individual polysaccharides in cell wall layers; and (v) modification of deposited cell wall layers.     

Connectivity and information transfer in flow networks: Two magic numbers in ecology?

An ecosystem can be visualized as a graph of certain preassigned trophic compartments; these nodes are then mutually connected through the internal exchanges of material and energy. The mathematical theory of information can be applied to such a graph in order to define two relevant indices: a measure of connectivity (the entropy H of the connections) and a measure of the degree of the “energetic” specialization (the internal transfer of informationI). The computation of these indices in stationary real cases suggests that the observed complexity of ecosystems is conditioned by two competing effects. The first can be interpreted as a “thermodynamical” principle related to the unavoidable irreversibility taking place inside the system, whereas the second can be taken as a “biological” principle concerned with the selection of some particular interactions: those which maximize the information circulating between the compartments.     

Hidden treatments in ecological experiments: re-evaluating the ecosystem function of biodiversity

Interactions between biotic and abiotic processes complicate the design and interpretation of ecological experiments. Separating causality from simple correlation requires distinguishing among experimental treatments, experimental responses, and the many processes and properties that are correlated with either the treatments or the responses, or both. When an experimental manipulation has multiple components, but only one of them is identified as the experimental treatment, erroneous conclusions about cause and effect relationships are likely because the actual cause of any observed response may be ignored in the interpretation of the experimental results. This unrecognized cause of an observed response can be considered a “hidden treatment.” Three types of hidden treatments are potential problems in biodiversity experiments: (1) abiotic conditions, such as resource levels, or biotic conditions, such as predation, which are intentionally or unintentionally altered in order to create differences in species numbers for “diversity” treatments; (2) non-random selection of species with particular attributes that produce treatment differences that exceed those due to “diversity” alone; and (3) the increased statistical probability of including a species with a dominant negative or positive effect (e.g., dense shade, or nitrogen fixation) in randomly selected groups of species of increasing number or “diversity.” In each of these cases, treatment responses that are actually the result of the “hidden treatment” may be inadvertently attributed to variation in species diversity. Case studies re-evaluating three different types of biodiversity experiments demonstrate that the increases found in such ecosystem properties as productivity, nutrient use efficiency, and stability (all of which were attributed to higher levels of species diversity) were actually caused by “hidden treatments” that altered plant biomass and productivity. Received: 16 December 1996 / Accepted: 2 March 1997     

Formation and participation of nano-amyloids in pathogenesis of Alzheimer’s disease and other amyloidogenic diseases

Studies of neurodegenerative disorders attract much attention of the world scientific community due to increasing dissemination of Alzheimer’s disease. The reason for such pathologies consists in transition of a “healthy” molecule or peptide from its native conformation into a very stable “pathological” form. During this process, molecules existing in the “pathological” conformation aggregate and form amyloid fibrils that can undergo an uncontrolled increase. Novel knowledge is required on sporadic forms of Alzheimer’s disease, on the nature of triggering mechanisms of the conformational transitions of beta-amyloid fragments from normally functioning proteins into new structure, nano-beta-amyloids, that escape of neuronal and whole-body control resulted in the loss of neurons. This review summarized results of studies on the formation of amyloid fibrils and their role in pathogenesis of amyloid diseases.     

A “micromere model” of cell-cell interactions in sea urchin early embryos

It has been shown that isolation of sea urchin blastomeres before the post-division adhesion leads mainly to the formation of equal blastomeres at the stage of 4th cleavage division, whereas isolation after adhesion results in the formation of micromeres simultaneous with that in intact embryos. Similar results were obtained in five sea urchin species. It has been concluded that there exists a critical point in the cleavage process, when blastomeres exchange information that determines the further cleavage pattern. It has been shown with this “micromere model” that serotonin and its analogs influence the cleavage pattern of half-embryos. These data have served as a basis for the hypothesis of “protosynapse,” a bilaterally symmetric structure in which the blastomeres are not only source and target of the signal but also a passive obstacle to leakage of the signal substance from the interblastomere cleft to the milieu. Such a structure may also specify the primary asymmetry of the blastomeres. The micromere model may be useful in specific pharmacological screening.     

Degeneracy-Driven Self-Structuring Dynamics in Selective Repertoires

Numerous biological interactions, such as interactions between T cell receptors or antibodies with antigens, interactions between enzymes and substrates, or interactions between predators and prey are often not strictly specific. In such less specific, or “sloppy,” systems, referred to here as degenerate systems, a given unit of a diverse resource (antigens, enzymatic substrates, prey) is at risk of being recognized and consumed by multiple consumers (lymphocytes, enzymes, predators). In this study, we model generalized degenerate consumer-resource systems of Lotka–Volterra and Verhulst types. In the degenerate systems of Lotka–Volterra, there is a continuum of types of consumer and resource based on variation of a single trait (characteristic, or preference). The consumers experience competition for a continuum of resource types. This non-local interaction system is modeled with partial differential-integral equations and shows spontaneous self-structuring of the consumer population that depends on the degree of interaction degeneracy between resource and consumer, but does not mirror the distribution of resource. We also show that the classical Verhulst (i.e. logistic) single population model can be generalized to a degenerate model, which shows qualitative behavior similar to that in the degenerate Lotka–Volterra model. These results provide better insight into the dynamics of selective systems in biology, suggesting that adaptation of degenerate repertoires is not a simple “mirroring” of the environment by the “fittest” elements of population.     

Using sensory weighting to model the influence of canal,otolith and visual cues on spatial orientation and eye movements

 The sensory weighting model is a general model of sensory integration that consists of three processing layers. First, each sensor provides the central nervous system (CNS) with information regarding a specific physical variable. Due to sensor dynamics, this measure is only reliable for the frequency range over which the sensor is accurate. Therefore, we hypothesize that the CNS improves on the reliability of the individual sensor outside this frequency range by using information from other sensors, a process referred to as “frequency completion.” Frequency completion uses internal models of sensory dynamics. This “improved” sensory signal is designated as the “sensory estimate” of the physical variable. Second, before being combined, information with different physical meanings is first transformed into a common representation; sensory estimates are converted to intermediate estimates. This conversion uses internal models of body dynamics and physical relationships. Third, several sensory systems may provide information about the same physical variable (e.g., semicircular canals and vision both measure self-rotation). Therefore, we hypothesize that the “central estimate” of a physical variable is computed as a weighted sum of all available intermediate estimates of this physical variable, a process referred to as “multicue weighted averaging.” The resulting central estimate is fed back to the first two layers. The sensory weighting model is applied to three-dimensional (3D) visual–vestibular interactions and their associated eye movements and perceptual responses. The model inputs are 3D angular and translational stimuli. The sensory inputs are the 3D sensory signals coming from the semicircular canals, otolith organs, and the visual system. The angular and translational components of visual movement are assumed to be available as separate stimuli measured by the visual system using retinal slip and image deformation. In addition, both tonic (“regular”) and phasic (“irregular”) otolithic afferents are implemented. Whereas neither tonic nor phasic otolithic afferents distinguish gravity from linear acceleration, the model uses tonic afferents to estimate gravity and phasic afferents to estimate linear acceleration. The model outputs are the internal estimates of physical motion variables and 3D slow-phase eye movements. The model also includes a smooth pursuit module. The model matches eye responses and perceptual effects measured during various motion paradigms in darkness (e.g., centered and eccentric yaw rotation about an earth-vertical axis, yaw rotation about an earth-horizontal axis) and with visual cues (e.g., stabilized visual stimulation or optokinetic stimulation). Received: 20 September 2000 / Accepted in revised form: 28 September 2001