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PubMed2001

Microscopic observation of aerobic granulation in sequential aerobic sludge blanket reactor.

AIMS: This paper attempts to provide visual evidence of how aerobic granulation evolves in sequential aerobic sludge blanket reactors. METHODS AND RESULTS: A series of experiments were conducted in two column-type sequential aerobic sludge reactors fed with glucose and acetate as sole carbon source, respectively. The evolution of aerobic granulation was monitored using image analysis and optical and scanning electron microscopy. The results indicated that the formation of aerobic granules was a gradual process from seed sludge to compact aggregates, further to granular sludge and finally to mature granules with the sequential operation proceeding. Glucose- and acetate-fed granules have comparable characteristics in terms of settling velocity, size, shape, biomass density and microbial activity. However, the microbial diversity of the granules was associated with the carbon source supplied. In this work, an important aerobic starvation phase was identified during sequential operation cycles. It was found that periodical aerobic starvation was an effective trigger for microbial aggregation in the reactor and further strengthened cell-cell interaction to form dense aggregates, which was an essential step of granulation. The periodical starvation-induced aggregates would finally be shaped to granules by hydrodynamic shear and flow. CONCLUSION: Aerobic granules can be formed within 3 weeks in the systems. The periodical starvation and hydrodynamic conditions would play a crucial role in the granulation process. SIGNIFICANCE AND IMPACT OF THE STUDY: Aerobic granules have excellent physical characteristics as compared with conventional activated sludge flocs. This research could be helpful for the development of an aerobic granule-based novel type of reactor for handling high strength organic wastewater.

Aerobiosis↗
PubMed2004

Characterization of evolutionary rates and constraints in three Mammalian genomes.

We present an analysis of rates and patterns of microevolutionary phenomena that have shaped the human, mouse, and rat genomes since their last common ancestor. We find evidence for a shift in the mutational spectrum between the mouse and rat lineages, with the net effect being a relative increase in GC content in the rat genome. Our estimate for the neutral point substitution rate separating the two rodents is 0.196 substitutions per site, and 0.65 substitutions per site for the tree relating all three mammals. Small insertions and deletions of 1-10 bp in length ("microindels") occur at approximately 5% of the point substitution rate. Inferred regional correlations in evolutionary rates between lineages and between types of sites support the idea that rates of evolution are influenced by local genomic or cell biological context. No substantial correlations between rates of point substitutions and rates of microindels are found, however, implying that the influences that affect these processes are distinct. Finally, we have identified those regions in the human genome that are evolving slowly, which are likely to include functional elements important to human biology. At least 5% of the human genome is under substantial constraint, most of which is noncoding.

Animals↗
PubMed1998

T cell receptor repertoire in rheumatoid arthritis.

CD4+ T cells are a major component of the inflammatory infiltrate in rheumatoid synovitis. Within synovial lesions, clonal CD4+ T cell populations are detectable, supporting the notion of an antigen specific recognition even in the joint. In general, the clonal size of individual T cell clones is small and does not lead to a marked distortion of the synovial T cell receptor (TCR) repertoire. Comparison of TCR sequences derived from different patients has not provided evidence for common sequences. Either multiple antigens are recognized or the TCR repertoire is sufficiently plastic with a multitude of different TCR structures responding to the same antigen(s). However, within one individual, the repertoire of clonal T cell populations is restricted. Identical T cell clones can be identified in different joints and at different timepoints of the disease, emphasizing that the spectrum of antigens recognized is conserved over time and that the T cell response pattern is not subject to evolution. Characterization of antigens involved in the latter stages of the disease may thus provide critical information on disease-initiating events. Recent data have led to the new concept that the role of T cells in rheumatoid arthritis (RA) is not limited to synovial inflammation. Evidence has been provided that the premorbid TCR repertoires of RA patients and normal controls can be distinguished. The T cell repertoire in RA patients is prone to recognize certain microbial products and autoantigens. The selection of this response pattern can only partially be attributed to the disease associated HLA-DRB1 alleles. Additional factors common in RA patients but not in HLA-DR matched control individuals seem to be important in shaping the TCR repertoire. Furthermore, the repertoire of mature T cells in RA patients is characterized by oligoclonality which involves T cells in the peripheral blood compartment. Possibly, these clonal T cell populations react to widespread autoantigens, raising the possibility that RA patients have a defect in controlling peripheral tolerance and an anomaly of lymphoproliferation. In contrast to joint residing CD4+ T cells, expanded clonotypes isolated from the blood of different patients have been described to share TCR beta chain structures. How these characteristic features of the global TCR repertoire in RA patients translate into mechanisms of disease remains to be elucidated.

Arthritis, Rheumatoid↗
PubMed1978

Surface changes during development and involution of the cement gland of Xenopus laevis.

The cement gland was studied from stage 17, when the anlage is established, to stage 49, shortly before its disappearance. At early stages, the apical membrane is covered by small microvilli that are more abundant than in the surrounding epiblast cells. Vesicular protrusions along the cell boundaries are also more numerous in the gland cells. When the gland reaches maturity, the apical membranes of gland cells differentiate into two regions. In the cranial, kidney-shaped region, the membranes are very narrow and protrude above the level of cell boundaries. Long and slender villi raise from the surface adjacent to cell boundaries. Apical surfaces in the caudal portion are larger and flattened. Cell boundaries are lined with shorter and thicker surface projections. At these stages, the bordering cells are covered with secretion vesicles. During involution the number of cells is progressively reduced. The area of the caudal portion increases relative to the area of the cranial portion. Apical surfaces become more flattened. Surface projections become much shorter and invade the whole of the apical surface. Bordering cells lose their secretion vesicles and their apical surface becomes ruffled with numerous short wrinkles. The significance of the apical structures and their evolution is discussed.

Animals↗
PubMed1989

Chromobindin A, a Ca2+- and ATP-dependent chromaffin granule-binding protein, is found in a variety of tissues and in yeast.

Chromobindin A is a ring shaped, multisubunit protein which exhibits Ca2+ and ATP-dependent binding to chromaffin granule membranes. Here we report biochemical and immunochemical evidence for the presence of chromobindin A in a surprisingly broad range of tissues: The protein is abundant in bovine skeletal muscle, pancreas, adrenal cortex and in brain gray and white matter; it is present in low quantities in the parotid, intestine and spleen and is undetectable in lung. Interestingly, chromobindin A was also detected in extracts of yeast. Electron micrographs of the yeast protein reveal a morphology virtually identical to the mammalian protein. These results suggest that chromobindin A is an important protein in a wide variety of cell types and that it has been highly conserved through evolution.

Animals↗
PubMed2006

Topology of resultant networks shaped by evolutionary pressure.

Understanding the topology of complex systems abstracted to networks is important for unraveling their functional capabilities. Many such networks follow the small-world and scale-free regimes. Several models of artificially growing networks lead to this observed network topology. Most previously proposed models for growing networks, such as rich-get-richer and duplication-divergence, produce realistic network topologies but do not consider the effects of exogenous forces such as optimization for adaptation in shaping network topology. It is likely that such forces have shaped complex systems throughout their evolution. To develop further insights into possible mechanisms that shape networks, a model that uses several previously proposed network growth algorithms was developed to grow networks that adapt under exogenous stress. A decision tree problem was used to generate a complex Boolean function. Growing networks were required to adapt to correctly decode this function using an evolutionary selection process. Under this growth regimen all growing network models are similarly adaptable. The newly added nodes tend to cluster into pathways emanating from few inputs, regardless of the growth algorithm. Distribution of redundant pathways from inputs to the output follow a power-law function with a scaling exponent (approximately 1.3). Similar distribution of redundant pathways was observed from inputs in a cell signaling network and an air traffic control network. A flat distribution of redundant pathways from inputs was observed in growing networks that do not attempt to adapt. This analysis provides initial insights into distribution of pathways in naturally evolving complex systems that have defined input-output relationships.

Algorithms↗
PubMed2002

Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level.

Antigen-specific T cell immunity is HLA-restricted. Human immunodeficiency virus-type 1 (HIV-1) mutations that allow escape from host immune responses may therefore be HLA allele-specific. We analyzed HIV-1 reverse transcriptase sequences from a large HLA-diverse population of HIV-1-infected individuals. Polymorphisms in HIV-1 were most evident at sites of least functional or structural constraint and frequently were associated with particular host HLA class I alleles. Absence of polymorphism was also HLA allele-specific. At a population level, the degree of HLA-associated selection in viral sequence was predictive of viral load. These results support a fundamental role for HLA-restricted immune responses in driving and shaping HIV-1 evolution in vivo.

Adaptation, Physiological↗
PubMed2004

Molecular interference of Cd(2+) with Photosystem II.

Many heavy metals inhibit electron transfer reactions in Photosystem II (PSII). Cd(2+) is known to exchange, with high affinity in a slow reaction, for the Ca(2+) cofactor in the Ca/Mn cluster that constitutes the oxygen-evolving center. This results in inhibition of photosynthetic oxygen evolution. There are also indications that Cd(2+) binds to other sites in PSII, potentially to proton channels in analogy to heavy metal binding in photosynthetic reaction centers from purple bacteria. In search for the effects of Cd(2+)-binding to those sites, we have studied how Cd(2+) affects electron transfer reactions in PSII after short incubation times and in sites, which interact with Cd(2+) with low affinity. Overall electron transfer and partial electron transfer were studied by a combination of EPR spectroscopy of individual redox components, flash-induced variable fluorescence and steady state oxygen evolution measurements. Several effects of Cd(2+) were observed: (i) the amplitude of the flash-induced variable fluorescence was lost indicating that electron transfer from Y(Z) to P(680)(+) was inhibited; (ii) Q(A)(-) to Q(B) electron transfer was slowed down; (iii) the S(2) state multiline EPR signal was not observable; (iv) steady state oxygen evolution was inhibited in both a high-affinity and a low-affinity site; (v) the spectral shape of the EPR signal from Q(A)(-)Fe(2+) was modified but its amplitude was not sensitive to the presence of Cd(2+). In addition, the presence of both Ca(2+) and DCMU abolished Cd(2+)-induced effects partially and in different sites. The number of sites for Cd(2+) binding and the possible nature of these sites are discussed.

Cadmium↗
PubMed1994

Benign "metastatic" cellular blue nevus.

This report illustrates the case of a patient with a pigmented lesion on the dorsal skin of his left foot associated with a bulky homolateral inguinal mass. A metastatic melanoma was clinically suspected; therefore, the pigmented foot lesion was excised and grafted, and the groin mass was dissected. The histological examination of the foot lesion revealed a well-preserved epidermal layer, beneath which spindle cells endowed with regular nuclei yet without any atypia or mitotic figures, were present. Melanin-rich histiocytes surrounded the nerve fibers and the vessels that intermingled with such spindle cells. Under light microscopy, the sections of the inguinal lymph nodes revealed clusters of pigmented cells that looked very much like those found in the foot skin lesion. These spindle-shaped cells infiltrated the nodes' capsule and peripheral sinuses and left the inner parenchyma unaltered. The inguinal mass revealed a thick, fibrous capsule surrounding a heavily pigmented tissue rich with blue nevus cells with islands of melanophages. In the case presented here, the differential diagnosis between cellular blue nevus and nodular melanoma was mandatory. In this case report, we provide the differential diagnosis and review the criteria used for it. Further support for the diagnosis was obtained from immunohistochemical findings that were positive for S-100 protein and not for HMB-45. Wide but conservative surgery appears to be the treatment of choice for cellular blue nevus. In fact, the patient described here is still alive 5 years postoperatively. Hence, the clinical evolution of the patient's lesions can be considered benign.

Diagnosis, Differential↗
PubMed2004

[The role of leukocytes in microcirculation dynamics in the norm and pathology].

The physiological functions grow to be more perfect and complicated in the process of evolution. However, a developing function could display some evidence of regress and, in certain cases, it can trigger serious diseases including autoimmune ones. Conventionally, we refer to the above cases as to "errors" of evolution. The present case study deals with a negative factor of leukocytes in the cerebral microcirculation. Leukocytes were shown, experimentally, to inhibit the capillary blood flow owing to their big volume (2-2.5-fold more versus that of erythrocytes). An increasing trend to adhesion due to hypoxia is responsible for shaping of leukocytes' conglomerates, which cause the occlusion of venules and of the smallest cerebral veins. It entails the effect known as "no re-flow" resulting in death.

Animals↗
PubMed1975

Flash kinetics and light intensity dependence of oxygen evolution in the blue-green alga Anacystis nidulans.

Patterns of oxygen evolution in flashing light for the glue-green alga Anacystis nidulans are compared with those for broken spinach chloroplasts and whole cells of the green alga Chlorella pyrenoidosa. The oscillations of oxygen yield with flash number that occur in both Anacystis and Chlorella, display a greater degree of damping than do those of isolated spinach chloroplasts. The increase in damping results from a two- to threefold increase in the fraction (alpha) of reaction centers "missed" by a flash. The increase in alpha cannot be explained by non-saturing flash intensities or by the dark reduction of the oxidized intermediates formed by the flash. Anaerobic conditions markedly increase alpha in Anacystis and Chlorella but have no effect on alpha in broken spinach chloroplasts. The results signify that the mechanism of charge separation and water oxidation involved in all three orgainsms is the same, but that the pool of secondary electron acceptors between Photosystem II and Photosystem I is more reduced in the dark, in the algal cells, than in the isolated spinach chloroplasts. Oxygen evolution in flashing light for Anacystis and Chlorella show light saturation curves for the oxygen yield of the third flash (Y3) that differ markedly from those of the steady-state flashes(YS). In experiments in which all flashes are uniformly attenuated, Y3 requires nearly twice as much light as YS to reach half-saturation. Under these conditions Y3 has a sigmoidal dependence on intensity, while that of YS is hyperbolic. These differences depend on the number of flashes attenuated. When any one of the first three flashes is attenuated, the variation of Y3 with intensity resembles that of YS. When two of the first three flashes are attenuated, Y3 is intermediate in shape between the two extremes. A quantitative interpretation of these results based on the model of Kok et al. (Kik, B., Forbush, B.and McGloin, M. (1970) Photochem. Photobiol. 14, 307-321) fits the experimental data.

Chlorella↗
PubMed1995

Microscopical evaluation of the crystalline lens of the squid (Loligo opalescens) during embryonic development.

The similarity between the cephalopod lens and the teleost (vertebrate) lens can be considered an optical example of convergent evolution. However, the embryology and ultrastructure of the cephalopod lens appear to be different from that of vertebrates, and perhaps unique to the animal kingdom. Using light and scanning electron microscopy, the morphogenesis of the squid (Loligo opalescens) lens is characterized. Results indicate that the posterior lens primordium appears first during development and is derived from cellular processes which extend from a middle group, group 2, of lentigenic (ectodermal) cells. The processes extend from the basal aspect of the lentigenic cells, project down into the optic vesicle during early stages of development, and fuse to form the posterior lens primordium. During later stages, the processes extend from surrounding lentigenic cells and are applied to the stalk of the lens, where they form bud-shaped protrusions. Once applied to the lens, the processes form lens elements that later fuse into plate-like elements evident in later-staged embryo and adult lenses. The anterior lens primordium is derived from an anterior group, group 1, of lentigenic cells, during later stages of development. Lentigenic processes extend from these lentigenic cells and are laid down in a circumferential fashion to form the anterior lens cap. As in the posterior lens, evidence indicates that the anterior lens elements fuse to form plate-like elements. The ultrastructure and morphogenesis of the cephalopod lens is discussed and contrasted with other strategies of lens development.

Animals↗
PubMed1998

Microsporidian Encephalitozoon cuniculi, a unicellular eukaryote with an unusual chromosomal dispersion of ribosomal genes and a LSU rRNA reduced to the universal core.

Microsporidia are eukaryotic parasites lacking mitochondria, the ribosomes of which present prokaryote-like features. In order to better understand the structural evolution of rRNA molecules in microsporidia, the 5S and rDNA genes were investigated in Encephalitozoon cuniculi . The genes are not in close proximity. Non-tandemly arranged rDNA units are on every one of the 11 chromosomes. Such a dispersion is also shown in two other Encephalitozoon species. Sequencing of the 5S rRNA coding region reveals a 120 nt long RNA which folds according to the eukaryotic consensus structural shape. In contrast, the LSU rRNA molecule is greatly reduced in length (2487 nt). This dramatic shortening is essentially due to truncation of divergent domains, most of them being removed. Most variable stems of the conserved core are also deleted, reducing the LSU rRNA to only those structural features preserved in all living cells. This suggests that the E.cuniculi LSU rRNA performs only the basic mechanisms of translation. LSU rRNA phylogenetic analysis with the BASEML program favours a relatively recent origin of the fast evolving microsporidian lineage. Therefore, the prokaryote-like ribosomal features, such as the absence of ITS2, may be derived rather than primitive characters.

Animals↗
PubMed2007

The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.

Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.

Adolescent↗
PubMedDate not supplied

Evolution of dorsal-ventral axis formation in arthropod appendages: H15 and optomotor-blind/bifid-type T-box genes in the millipede Glomeris marginata (Myriapoda: Diplopoda).

In Drosophila, the T-box genes optomotor-blind (omb) and H15 have been implicated in specifying the development of the dorso-ventral (DV) axis of the appendages. Results from the spider Cupiennius salei have suggested that this DV patterning system may be at least partially conserved. Here we extend the study of the DV patterning genes omb and H15 to a representative of the Myriapoda in order to add to the existing comparative data set and to gain further insight into the evolution of the DV patterning system in arthropod appendages. The omb gene of the millipede Glomeris marginata is expressed on the dorsal side of all appendages including trunk legs, maxillae, mandibles, and antennae. This is similar to what is known from Drosophila and Cupiennius and suggests that the role of omb in instructing dorsal fates is conserved in arthropods. Interestingly, the lobe-shaped portions of the mouthparts do not express omb, indicating that these are ventral components and thus may be homologous to the endites present in the corresponding appendages in insects. Concerning the H15 gene we were able to identify two paralogous genes in Glomeris. Both genes are expressed in the sensory organs of the maxilla and antenna, but only Gm-H15-1 is expressed along the ventral side of the trunk legs. The expression is more extensive than in Cupiennius, but less so than in Drosophila. In addition, no ventral expression domain is present in the maxilla, mandible, and antenna. Because of this, the role of H15 in the determination of ventral fate remains unclear.

Animals↗
PubMed2000

Shapes in the shadow: evolutionary dynamics of morphogenesis.

This article investigates the evolutionary dynamics of morphogenesis. In this study, morphogenesis arises as a side-effect of maximization of number of cell types. Thus, it investigates the evolutionary dynamics of side-effects. Morphogenesis is governed by the interplay between differential cell adhesion, gene-regulation, and intercellular signaling. Thus, it investigates the potential to generate complex behavior by entanglement of relatively "boring" processes, and the (automatic) coordination between these processes. The evolutionary dynamics shows all the hallmarks of evolutionary dynamics governed by nonlinear genotype phenotype mapping: for example, punctuated equilibria and diffusion on neutral paths. More striking is the result that interesting, complex morphogenesis occurs mainly in the "shadow" of neutral paths which preserve cell differentiation, that is, the interesting morphologies arise as mutants of the fittest individuals. Characteristics of the evolution of such side-effects in the shadow appear to be the following: (1) The specific complex morphologies are unique (or at least very rare) among the set of de novo initiated evolutionary histories. (2) Similar morphologies are reinvented at large temporal distances during one evolutionary history and also when evolution is restarted after the main cell differentiation pattern has been established. (3) A mosaic-like evolution at the morphological level, where different morphological features occur in many combinations, while at the genotypic level recombination is not implemented and genotypes diverge linearly and at a constant rate.

Animals↗
PubMed2004

Origins and evolution of cell phenotypes in breast tumors.

This study presents a stochastic model that correlates genomic instability with tumor formation. The model describes the time- and space-variant volumetric concentrations of cancer cells of various phenotypes in a breast tumor. The cells of epithelial origin in the cancerous breast tissue are classified into four different phenotypes, normal epithelial cells and the grade 1, grade 2 and grade 3 cancer cell types with increasing potential for growth and invasion. Equations governing the time course of volumetric concentrations of cell phenotypes are derived by using the principle of conservation of mass. Cell migration into and from the stroma is taken into account. The transformations between cell phenotypes are due to genetic inheritance and chromosome aberrations. These transformations are assumed to be stochastic functions of the local cell concentration. The simulations of the model for planar geometry replicate the shapes of human breast tumors and capture the time history of tumor growth in animal models. Simulations point to transformation of tumor cell population from heterogeneous compositions to a single phenotype at advanced stages of invasive tumors. Systematic variations of model parameters in the computations indicate the important roles the migration capacity, proliferation rate, and phenotype transition probability play in tumor growth. The model developed provides realistic simulations for standard breast cancer therapies and can be used in the optimization studies of chemotherapy, radiotherapy, hormone therapy and emerging individualized therapies for cancer.

Animals↗
PubMed2000

Drosophila dumpy is a gigantic extracellular protein required to maintain tension at epidermal-cuticle attachment sites.

BACKGROUND: Growth and morphogenesis during development depend both on patterning genes, which assign positional information, and on genes that regulate mechanical forces. The dumpy gene of the fruit fly Drosophila melanogaster is an example of the latter class, with mutant phenotypes affecting size and shape of the limbs, thoracic cuticle, trachea and mouthparts. RESULTS: The genetically complex dumpy locus was found to span over 100 kb and encode a gigantic 2.5 MDa extracellular matrix protein. Dumpy represents an extreme form of modular protein evolution, containing 308 epidermal growth factor (EGF) modules, interspersed with a new module class, DPY, and terminating in a crosslinking zona pellucida domain and membrane anchor sequence. We determined the three-dimensional structure of the DPY module by nuclear magnetic resonance (NMR) spectroscopy and found that it forms a disulphide-stabilised beta sheet motif, capable of linking end-to-end with EGF modules to form a fibre. Consistent with its cuticle phenotypes, dumpy is expressed at several sites of cuticle-epidermal cell attachment, including the trachea and the muscle tendon cells, which mediate anchorage of the muscles to the cuticle. CONCLUSIONS: The dumpy gene encodes a gigantic extracellular molecule that we predict to be a membrane-anchored fibre of almost a micrometer in length. Insertion and crosslinking of this fibre within the cuticle may provide a strong anchor for the underlying tissue, allowing it to maintain mechanical tension at sites under stress. This would explain its contribution to tissue morphogenesis through its regulation of mechanical properties.

Amino Acid Sequence↗