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PubMed1996

Evolutionary relationships of eukaryotic kingdoms.

The evolutionary relationships of four eukaryotic kingdoms--Animalia, Plantae, Fungi, and Protista--remain unclear. In particular, statistical support for the closeness of animals to fungi rather than to plants is lacking, and a preferred branching order of these and other eukaryotic lineages is still controversial even though molecular sequences from diverse eukaryotic taxa have been analyzed. We report a statistical analysis of 214 sequences of nuclear small-subunit ribosomal RNA (srRNA) gene undertaken to clarify these evolutionary relationships. We have considered the variability of substitution rates and the nonindependence of nucleotide substitution across sites in the srRNA gene in testing alternative hypotheses regarding the branching patterns of eukaryote phylogeny. We find that the rates of evolution among sites in the srRNA sequences vary substantially and are approximately gamma distributed with size and shape parameter equal to 0.76. Our results suggest that (1) the animals and true fungi are indeed closer to each other than to any other "crown" group in the eukaryote tree, (2) red algae are the closest relatives of animals, true fungi, and green plants, and (3) the heterokonts and alveolates probably evolved prior to the divergence of red algae and animal-fungus-green-plant lineages. Furthermore, our analyses indicate that the branching order of the eukaryotic lineages that diverged prior to the evolution of alveolates may be generally difficult to resolve with the srRNA sequence data.

Animals↗
PubMed2006

An evolutionary perspective on the photoreceptor damage response.

PURPOSE: To review recent advances related to the response to photoreceptor damage and to place this knowledge in an evolutionary context. DESIGN: Synthesis of published laboratory, clinical, and epidemiologic data. METHODS: The authors have synthesized the principal published findings related to the mechanism and function of the photoreceptor damage response with the goal of trying to understand the selective pressures that shaped its evolution. RESULTS: The past several years have seen considerable advances in understanding the molecular and cellular basis of the retina's response to photoreceptor damage. From their analysis of laboratory, clinical, and epidemiologic data, the authors suggest that the photoreceptor damage response may have evolved to counter the effects of retinal tears and detachment, infectious retinitis, and/or light damage. CONCLUSIONS: If the natural response to photoreceptor damage can be fully defined, it may be possible to augment desirable aspects of the damage response and/or suppress undesirable ones in the context of a wide variety of photoreceptor diseases.

Animals↗
PubMed2005

Evidence of selection for low cognate amino acid bias in amino acid biosynthetic enzymes.

If the enzymes responsible for biosynthesis of a given amino acid are repressed and the cognate amino acid pool suddenly depleted, then derepression of these enzymes and replenishment of the pool would be problematic, if the enzymes were largely composed of the cognate amino acid. In the proverbial "Catch 22", cells would lack the necessary enzymes to make the amino acid, and they would lack the necessary amino acid to make the needed enzymes. Based on this scenario, we hypothesize that evolution would lead to the selection of amino acid biosynthetic enzymes that have a relatively low content of their cognate amino acid. We call this the "cognate bias hypothesis". Here we test several implications of this hypothesis directly using data from the proteome of Escherichia coli. Several lines of evidence show that low cognate bias is evident in 15 of the 20 amino acid biosynthetic pathways. Comparison with closely related Salmonella typhimurium shows similar results. Comparison with more distantly related Bacillus subtilis shows general similarities as well as significant differences in the detailed profiles of cognate bias. Thus, selection for low cognate bias plays a significant role in shaping the amino acid composition for a large class of cellular proteins.

Amino Acids↗
PubMed1989

Simplicity and complexity in MIRROR universes.

The scientific simplicity principle (OCCAM's razor) has always been strongly enforced by the available modelling tools. Moreover, the concept of simplicity itself is shaped by these (classical) tools. Computer models are less subject to simplicity constraints than other models are. It may be argued that complexity is the preeminent property for biological systems to study. In this paper we discuss our MIRROR modelling methodology in which (a concept of) simplicity is reconciled with biological complexity. Simplicity resides in the simple "TODO" ("do what there is to do") of the "individuals" (molecules, cells, organisms) which inhabit the model universe. The complexity appears in the multiple (levels of) individuals and the multiple levels of observable behavior of the universe. Examples are given of the development of complex, self-regulating social structures by simple interactions of individuals, and the adaptability of TODO based entities is compared to that of evolving entities. On the basis of these examples we sketch a slightly unconventional image of the evolution of complexity in biotic systems and discuss observations on the molecular record of biotic evolution which seem to fit this image.

Artificial Intelligence↗
PubMed2003

Hepatitis C virus in the human liver transplantation model.

Hepatitis C virus-related liver failure is the single leading indication for liver transplantation, and the study of HCV in the transplant setting has enhanced the understanding of the natural history of disease and putative mechanisms by which HCV causes liver injury. In a subset of patients, allograft cirrhosis develops within a few years after transplantation, and recent findings suggest these individuals are immunologically impaired compared with individuals with mild HCV recurrence at long-term follow-up. Fig. 9 shows a conceptual paradigm of mechanisms potentially involved in shaping HCV outcome after transplantation. It is possible that relative antiviral control by innate and adaptive immune responses (to maintain HCV replication below a certain threshold) prevents direct cytopathic injury and induction of oxidative stress and apoptosis of cells. Additional phenomena that may contribute to induction of apoptosis (eg, genetic polymorphisms within the donor organ. CMV coinfection, and ischemic-preservation injury) may augment the initial cascade of liver injury. Recruitment to the allograft of nonspecific cells may decrease viral replication by way of noncytolytic mechanisms or augment viral replication (eg, Th2 phenotype) and direct cytopathic injury. The immune response is likely insufficiently vigorous to keep viral replication under control, but may maintain chronic liver injury. The liver transplant model is unique in that distinct phenotypic outcomes can be observed over a short period of time. A consideration of the temporal evolution of different mechanisms is also important, because mechanisms that initially predominate may become less important over time, and conversely, as suggested with the inverse correlation between viral load at 5 years and allograft fibrosis, new immune responses may emerge that modify the host-virus interaction. Prospective characterization of the immunoregulatory and virologic mechanisms involved in the liver transplantation model hopefully will help unravel the causal basis of reported associations, lead to the development of highly specific therapeutic strategies, and ultimately diminish the rate of graft loss from recurrent disease.

Animals↗
PubMed1993

CD68 positive epidermal dendritic cells.

In a pilot study designed to investigate immunopathologic events in the evolution of cutaneous lesions in pemphigus foliaceus, we found that in this condition the epidermis is replete with CD68+ dendritic cells. The present study was designed to investigate the nature of this novel intraepidermal CD68+ cell population. For that purpose lesional skin of five patients with PF and, for comparison, of patients with another acantholytic autoimmune disease, pemphigus vulgaris, were examined using a panel of monoclonal antibodies in a three-step immunoperoxidase technique, in an immunofluorescence double-labeling technique, and by immunoelectron microscopy. We found epidermal CD1a+ Langerhans cells significantly decreased in pemphigus foliaceus compared to pemphigus vulgaris, but pemphigus foliaceus and not pemphigus vulgaris epidermis harbored large amounts of bone marrow-derived (CD45+) cells that expressed CD68, HLA-DR, and beta 2-integrin antigens, the most pronounced expression being observed for CD11c and CD18. These epidermal CD68+ cells were of dendritic shape, were CD1a-, and lacked Birbeck granules (BG); however, a small portion of CD68+ cells was also CD1a+ and exhibited BG as revealed by immunoelectron microscopy. These findings demonstrate that in certain conditions, i.e., in pemphigus foliaceus but not in pemphigus vulgaris, there is a shift from CD1a+/CD68- epidermal Langerhans cells towards CD1a-/CD68+ dendritic epidermal cells. The detection of a small number of CD1a+/CD68+/BG+ dendritic epidermal cells may identify these cells as a link between the CD1a+/CD68+/BG+ Langerhans cells and the CD1a-/CD68+/BG- cell population and suggests that these cells represent a transitional form of myelomonocytic cells during their phenotypic and morphologic transformation into resident epidermal Langerhans cells.

Adolescent↗
PubMed2004

Blue integumentary structural colours in dragonflies (Odonata) are not produced by incoherent Tyndall scattering.

For nearly 80 years, the non-iridescent, blue, integumentary structural colours of dragonflies and damselflies (Odonata) have been attributed to incoherent Tyndall or Rayleigh scattering. We investigated the production of the integumentary structural colours of a damselfly--the familiar bluet, Enallagma civile (Coenagrionidae)--and a dragonfly--the common green darner, Anax junius (Aeshnidae)--using fibre optic spectrophotometry and transmission electron microscopy (TEM). The reflectance spectra of both species showed discrete reflectance peaks of approximately 30% reflectance at 475 and 460 nm, respectively. These structural colours are produced by light scattering from closely packed arrays of spheres in the endoplasmic reticulum of box-shaped epidermal pigment cells underlying the cuticle. The observed reflectance spectra do not conform to the inverse fourth power relationship predicted for Tyndall/Rayleigh scattering. Two-dimensional (2-D) Fourier analysis of the TEM images of the colour-producing arrays reveals ring-shaped distributions of Fourier power at intermediate spatial frequencies, documenting a quasiordered nanostructure. The nanostructured Fourier power spectra falsify the assumption of spatial independence of scatterers that is required for incoherent scattering. Radial averages of the Fourier power spectrum indicate that the spheres are substantially nanostructured at the appropriate spatial scale to produce visible colours by coherent scattering. However, the spatial periodicity of the arrays is apparently too large to produce the observed colour by coherent scattering. The nanospheres could have expanded substantially (approximately 50%) during preparation for TEM. Alternatively, coherent light scattering could be occurring both from the surfaces and from structures at the centre of the spheres. These arrays of colour-producing spheres within pigment cells have convergently evolved at least 11-14 times independently within the Odonata. Structural colouration from arrays in living cells has also fostered the convergent evolution of temperature-dependent colour change in numerous odonate lineages.

Animals↗
PubMed2005

Viscosity contrast effects on fingering formation in rotating Hele-Shaw flows.

The different finger morphologies that arise at the interface separating two immiscible fluids in a rotating Hele-Shaw cell are studied numerically. The whole range of viscosity contrast is analyzed and a variety of fingering patterns systematically introduced, including the case in which the inner fluid is less viscous than the outer one. Our numerical results demonstrate that both the magnitude and the sign of the viscosity contrast strongly affect the shape of the emerging fingers, and also their length distribution. We have also found that the occurrence and location of pinch-off singularities are remarkably modified when the inner fluid is less viscous: instead of generating an isolated detaching drop, a full finger is disconnected from the interface. Finally, we have verified that the finger competition phenomena revealed by our simulations are correctly predicted by a weakly nonlinear analysis of the pattern development, showing that such important finger competition dynamics is already set at relatively early stages of interfacial evolution.

Journal Article↗
PubMed2003

The developing mouse dentition: a new tool for apoptosis study.

Developing limb or differentiating neural and blood cells are traditional models used to study programmed cell death in mammals. The developing mouse dentition can also be an attractive model for studying apoptosis regulation. Apoptosis is most extant during early odontogenesis in mice. The embryonic tooth pattern is comprised not only of anlagen of functional teeth (incisor, molars), but also of vestiges of ancestral tooth primordia that must be suppressed. Apoptosis is involved in (a) the elimination of vestigial tooth primordia in the prospective toothless gap (diastema) between the incisor and molars and (b) the shaping of germs in functional teeth. This type of apoptosis occurs in the dental epithelium according to a characteristic temporo-spatial pattern. Where apoptosis concentrates, specific signaling is also found. We proposed a hypothesis to explain the stimulation of apoptosis in the dental epithelium by integrating two concepts: (1) The regulation of epithelial budding by positional information generated from interactions between growth-activating and growth-inhibiting signals, and (2) apoptosis stimulation by the failure of death-suppressing signals. During the budding of the dental epithelium, local excess in growth inhibitors (e.g., Bmps) might lead to the epithelial cells' failure to receive adequate growth-activating (apoptosis-suppressing) signals (e.g., Fgfs). The resulting signal imbalance leads to cell "suicide" by apoptosis. Understanding of apoptosis regulation in the vestigial tooth primordia can help to elucidate the mechanism of their suppression during evolution and to identify factors essential for tooth survival. The latter knowledge will be important for developing a technology of tooth engineering.

Animals↗
PubMed1978

Development of hepatic angiosarcoma in man induced by vinyl chloride, thorotrast, and arsenic. Comparison with cases of unknown etiology.

Examples of human angiosarcoma following exposure to vinyl chloride, Thorotrast, or arsenic (medicinal and industrial) and cases, including children, of unknown etiology were studied to establish diagnostic criteria and to study their evolution. The uniform evolution suggests an environmental factor also in the cases of unknown etiology, which may be established by epidemiologic studies. A precursor stage is charaterized by areas of combined hyperlasia of hepatocytes and a variety of sinusoidal and perisinusoidal cells associated with excess of reticulin and with sinusoidal dialation. The diagnostically useful picture in silver impregnations indicated reticulum formation by the perisinusoidal cells, presumably the libocytes. The hepatocytic proliferation suggests a hepatocarcinogenic but usually not fully expressed potential. The mixed hyperplasia of the various sinusoidal cells proceeds to an overgrowth of angiosarcoma cells, presumably derived from endothelial cells. In early stages they are usually in contact with hepatocytes (intralobular growth). A trabecular arrangement results from loosening of the lobular plate arrangement by dilatation of sinusoids, leading to primary peliosis. With disappearance of the hepatocytes, various growth patterns develop, terminating in nodular, solid angiosarcoma composed of either spindle-shaped or polyhedral cells which undergo necrosis or hemorrhage (secondary peliosis). The interaction between hepatocytes and sinusoidal cells requires elucidation.

Adolescent↗
PubMedDate not supplied

Long L1 insertions in human gene introns specifically reduce the content of corresponding primary transcripts.

LINE-1 (L1) retrotransposons comprise about 17% of the human genome and include a recently transposed set of Ta-L1 elements that are polymorphic in humans. Although it is widely believed that L1s play an essential role in shaping and functioning of mammalian genomes, the understanding of the impact of L1 insertions on gene expression is far from being comprehensive. Here we compared hnRNA contents for allele pairs of genes heterozygous for Ta-L1 insertions in their introns in human cell lines of various origin. We demonstrated that some Ta-L1 insertions correlated with decreased content of the corresponding hnRNAs. This effect was characteristic of only nearly full-sized L1s and seemed to be tissue specific.

Alleles↗
PubMed2006

Mechanical adaptability of a sponge extracellular matrix: Evidence for cellular control of mesohyl stiffness in Chondrosia reniformis Nardo.

The marine sponge Chondrosia reniformis Nardo consists largely of a collagenous tissue, the mesohyl, which confers a cartilaginous consistency on the whole animal. This investigation was prompted by the incidental observation that, despite a paucity of potentially contractile elements in the mesohyl, intact C. reniformis stiffen noticeably when touched. By measuring the deflection under gravity of beam-shaped tissue samples, it was demonstrated that the flexural stiffness of the mesohyl is altered by treatments that influence cellular activities, including [Ca2+] manipulation, inorganic and organic calcium channel-blockers and cell membrane disrupters, and that it is also sensitive to extracts of C. reniformis tissue that have been repeatedly frozen then thawed. Since the membrane disrupters and tissue extracts cause marked stiffening of mesohyl samples, it is hypothesised that cells in the mesohyl store a stiffening factor and that the physiologically controlled release of this factor is responsible for the touch-induced stiffening of intact animals.

Animals↗
PubMed1992

The natural history of intraepithelial neoplasia: relevance to the search for intermediate endpoint biomarkers.

The development of carcinomas, defined as invasive epithelial neoplasms, is preceded by a preinvasive stage termed intraepithelial neoplasia that typically lasts for years. Intraepithelial neoplasia is the target tissue for the action of chemopreventive agents and the site where biomarkers frequently develop. The term "dysplasia" refers to the morphological alterations that characterize intraepithelial neoplasia and, according to many authors, consists of seven basic changes that are the same for the majority of epithelia. These are increased nuclear size, abnormal nuclear shape, increased nuclear stain uptake, nuclear pleomorphism (increased variation in size, shape, and stain uptake), increased mitoses, abnormal mitoses, and disordered or absent differentiation. Clonal evolution appears to begin early in the neoplastic process during intraepithelial neoplasia. The use of intraepithelial neoplasia as an intermediate endpoint biomarker requires that effective chemopreventive agents cause it to regress. Two examples are the regression of dysplastic oral leukoplakia produced by beta-carotene and the regression of colonic polyps in familial polyposis patients following treatment with the nonsteroidal antiinflammatory drug sulindac. There is a critical need to identify and develop biomarkers that correlate with the appearance and regression of intraepithelial neoplasia.

Biomarkers↗
PubMed2006

Dissociated cortical networks show spontaneously correlated activity patterns during in vitro development.

In vitro cultured neuronal networks coupled to microelectrode arrays (MEAs) constitute a valuable experimental model for studying changes in the neuronal dynamics at different stages of development. After a few days in culture, neurons start to connect each other with functionally active synapses, forming a random network and displaying spontaneous electrophysiological activity. The patterns of collective rhythmic activity change in time spontaneously during in vitro development. Such activity-dependent modifications play a key role in the maturation of the network and reflect changes in the synaptic efficacy, fact widely recognized as a cellular basis of learning, memory and developmental plasticity. Getting advantage from the possibilities offered by the MEAs, the aim of our study is to analyze and characterize the natural changes in dynamics of the electrophysiological activity at different ages of the culture, identifying peculiar steps of the spontaneous evolution of the network. The main finding is that between the second and the third week of culture, the network completely changes its electrophysiological patterns, both in terms of spiking and bursting activity and in terms of cross-correlation between pairs of active channels. Then the maturation process can be characterized by two main phases: modulation and shaping in the synaptic functional connectivity of the network (within the first and second week) and general moderate correlated activity, spread over the entire network, with connections properly formed and stabilized (within the fourth and fifth week).

Action Potentials↗
PubMedDate not supplied

Histopathological features of acral melanocytic nevi in children: study of 21 cases.

Benign melanocytic lesions in children may give cause for some concern histologically. This is because they represent a specific entity, or they reflect the state of evolution of the lesion or the anatomical location. This latter phenomenon has been poorly documented in children. In this study, we address the problem of atypical features frequently seen in benign nevi from acral sites in a group of patients aged 18 years or less. Twenty-one cases (12 female, 9 male) were identified from the Department of Pathology files during the years 1975-1988. All were Caucasian. Histological examination revealed that 6 cases were congenital and 15 were acquired; of these, 19 cases (90%) had a junctional component and all of these exhibited architecture atypia in the form of either lentiginous proliferation (84%) or confluence of junctional nests (84%). Forty-two percent (8/19) showed a mixture of both. Thirty-seven percent (7/19) exhibited transepidermal elimination of melanocytic nests, with 13/19 (68%) showing single cell infiltration of the epidermis. Atypical size, shape, and location of the junctional nests were present in 10/19 cases (53%). Within this group there appears to be no relationship between the age of the patient and the degree of architectural atypia. Mild cytological atypia was common. This report stresses the importance of anatomic subsite in the assessment of melanocytic lesions in children as well as in adults.

Adolescent↗
PubMed1995

The immune self: a selectionist theory of recognition, learning, and remembering within the immune system.

In this paper, I have briefly explored metaphors shared by the immune and nervous systems and shown that this exercise can lead to the elucidation of common principles of organization, as well as to predictions concerning how the immune system functions. Metaphor itself undoubtedly reflects the way in which we categorize and retrieve information 44], so it is not surprising that the deep processes of language tend to sample information from related data categories. Although the nervous and immune systems are obviously not the same and metaphors are indeed just that, my primary goal has been to suggest that by virtue of their having evolved in parallel over millions of years, the nervous and immune systems currently use the same archetypal principles and strategies to address related challenges in information processing and retrieval. Ultimately, nature is conservative. One need only look at a tree, a river, the airways, or the vascular bed in order to see how a fractal pattern of repetitive dichotomous branching has been used by each, in order to optimize the transport of fluids over large distances [45]. While each system has had to adopt different materials in order to solve the problem, the shape of their solutions is remarkably alike. In the immune and nervous systems, the elements used to produce optimal functional responses are also quite different, but again the solutions have been achieved by comparable strategies. I am certain that these two great systems of information processing, each responding with vastly different kinetics, will prove to be far more integrally interdependent than has been previously recognized. For example, should a swift response by the immune system be required in an overwhelming invasion by microbial pathogens, the immune system may be able to cooperate with the rapidly reacting nervous system to rid the host of the invaders. In this regard, we have shown that the beta-adrenergic hormone epinephrine rapidly increases the traffic of memory T-cells to mucosal sites, presumably representing an immune component of the fight-or-flight response [46]. Neural evolution appears to have as its goal the development of more efficient information processing systems that lead to higher levels of consciousness. However, in modern times, technologic advances in information processing have rapidly outstripped the slower adaptations that can be made by evolution. In order to satisfy his compulsive quest for information, man has recently developed and recruited the aid of computers.(ABSTRACT TRUNCATED AT 400 WORDS)

Association Learning↗
PubMed2000

Secretory structures on the leaf rachis of Caesalpinieae and Mimosoideae (Leguminosae): implications for the evolution of nectary glands.

Cup- or sometimes slit-shaped nectary glands on the rachis are a widespread trait in the legume subfamily Mimosoideae, especially in derived tribes. Their spotty occurrence in genera that appear to be basal has led to uncertainty about when in the mimosoid radiation this character evolved. Until now, specialized rachis glands were unknown in caesalpinioids thought to be related to ancestral mimosoids. We report here the occurrence of rachis glands in seven of the ten species of the Paleotropical genus Erythrophleum, a member of the Dimorphandra group of caesalpinioids thought to include the sister group(s) of mimosoids. The histological structure and location of Erythrophleum glands suggest homology with those of mimosoids; these glands are simpler structurally than rachis glands of any known mimosoid. The Erythrophleum glands differ from those of most mimosoids in the following respects: (1) they are smaller than glands of mimosoids; (2) the secretory surface is sunken in a pit capped by a small round pore rather than exposed on a broad concave or flat surface; (3) a smaller number of cells are involved in production and secretion of nectar; (4) vascular supply to the nectary is less extensive; and (5) mechanical support tissue (sclerenchyma) is less extensive and less organized. Rachis glands appear to be absent in the nine other genera included in the Dimorphandra group. We also report the occurrence of other secretory structures (patches of glandular trichomes) on the rachis of some Caesalpinieae and Mimoseae that lack specialized nectary glands and suggest that these patches of trichomes are primitive homologues of more organized glands. We discuss the significance of these glands and of the patches of trichomes for understanding relationships among primitive mimosoids and related caesalpinioids, and for understanding the origin of ant-guard defenses typical of many mimosoids.

Journal Article↗
PubMedDate not supplied

Ion channels and receptors: molecular targets for behavioral evolution.

Ion channels and receptors play critical roles in shaping neuronal activity, and thus are appropriate targets for evolutionary change to generate new behaviors. In this review, the evolution and differentiation of the many voltage-gated ion channels and transmitter-activated receptors is summarized; these channels and receptors evolved very early, and with some exceptions all species with nervous systems use similar sets of channels and receptors. Several examples are given of mechanisms for species-specific behavioral evolution that arise from mutations involving the structure, alternative splicing, level of expression, targeting and modulation of these important neural proteins.

Animals↗