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PubMed1989

Developmental expression of the glial fibrillary acidic protein mRNA in the central nervous system and in cultured astrocytes.

The expression of glial fibrillary acidic protein (GFAP)-mRNA during mouse brain development and in astroglial primary cultures has been investigated by using two approaches: Northern-blot evaluation using a specific cDNA probe, and cell-free translation associated with immunoprecipitation. During brain maturation (4-56 days postnatal), the GFAP-mRNA underwent a biphasic evolution. An increase was observed between birth and day 15 (i.e., during the period of astroglial proliferation), which was followed by a decrease until day 56 (i.e., during astroglial cell differentiation). At older stages (300 days), an increase was observed, which might reflect gliosis. During astroglial in vitro development (7-32 days in culture), the GFAP-mRNA showed similar variations. An increase, observed during the period of astroglial proliferation (7-18 days), was followed by a decrease which occurred in parallel to marked changes in cell shape, cell process outgrowth, and the organization and accumulation of gliofilaments. During the same culture period (7-32 days), alpha-tubulin mRNA, which was used as an internal standard, did not vary significantly. These results show that the increase of the GFAP protein and of gliofilaments observed both in vivo and in vitro during astroglial differentiation cannot be ascribed to an accumulation of the GFAP-mRNA. It might be that more than one mechanism regulates the levels of free and polymerized GFAP and of its encoding mRNA.

Animals↗
PubMedDate not supplied

Interleukin-1-beta activation of cultured glomerular epithelial cells.

In crescentic glomerulonephritis, crescent formation involves the active participation of glomerular epithelial cells (GEC) and macrophages recruited to the glomerulus during the evolution of the disease. Cytokines derived from macrophages may affect many functions of GEC. In this study, we found that interleukin-1 beta (IL-1 beta) inhibited GEC growth (DNA synthesis and cell number) in vitro in a dose- and time-dependent manner. This effect was not mediated by tumor growth factor beta (TGF beta) which is a potent inhibitor of GEC growth in vitro. Treatment of GEC with various concentrations of IL-1 beta induced morphologic changes consisting in the loss of their cobblestone shape and acquisition of a fibroblast-like appearance. Moreover, IL-1 beta was shown to stimulate the expression of interleukin-6 (IL-6) by GEC. The increase in IL-6 secretion by GEC treated with IL-1 beta was observed at both the protein and mRNA levels. IL-1 beta also affected the metabolism of laminin in cultured GEC, inducing a dose-dependent increase in laminin production in culture supernatants harvested from GEC. Finally, we investigated the expression of MHC class II antigens and intercellular adhesion molecule-1 (ICAM-1) in GEC, and found that unstimulated GEC are negative for MHC class II antigens, as detected by flow cytometry. In contrast to the induction of effector functions, expression of MHC class II antigens stringently required interferon-gamma. IL-1 beta did not induce MHC class I antigen expression. The regulation of ICAM-1 expression in that unstimulated GEC expressed ICAM-1, and this expression was upregulated by IL-1 beta. We conclude that IL-1 beta alters many functions of GEC, and these changes may be involved in the initiation and amplification of glomerular injury.

Cell Count↗
PubMed2005

Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain.

Staphylococcus aureus is an opportunistic pathogen and the major causative agent of numerous hospital- and community-acquired infections. Staphylococcus epidermidis has emerged as a causative agent of infections often associated with implanted medical devices. We have sequenced the approximately 2.8-Mb genome of S. aureus COL, an early methicillin-resistant isolate, and the approximately 2.6-Mb genome of S. epidermidis RP62a, a methicillin-resistant biofilm isolate. Comparative analysis of these and other staphylococcal genomes was used to explore the evolution of virulence and resistance between these two species. The S. aureus and S. epidermidis genomes are syntenic throughout their lengths and share a core set of 1,681 open reading frames. Genome islands in nonsyntenic regions are the primary source of variations in pathogenicity and resistance. Gene transfer between staphylococci and low-GC-content gram-positive bacteria appears to have shaped their virulence and resistance profiles. Integrated plasmids in S. epidermidis carry genes encoding resistance to cadmium and species-specific LPXTG surface proteins. A novel genome island encodes multiple phenol-soluble modulins, a potential S. epidermidis virulence factor. S. epidermidis contains the cap operon, encoding the polyglutamate capsule, a major virulence factor in Bacillus anthracis. Additional phenotypic differences are likely the result of single nucleotide polymorphisms, which are most numerous in cell envelope proteins. Overall differences in pathogenicity can be attributed to genome islands in S. aureus which encode enterotoxins, exotoxins, leukocidins, and leukotoxins not found in S. epidermidis.

Biofilms↗
PubMed2006

Dynamic determination of the concentration of volatile alcohols in a fixed bed of zeolite 13X by FT-IR.

A series of dynamic adsorptions of volatile methanol, ethanol, and iso-propanol (IPA) onto zeolite 13X were studied. Instead of traditional gas chromatography (GC), a gas-phase Fourier Transformation-IR (FT-IR) spectrometer was used to measure the evolution of concentrations of these volatile alcohols due to its quick response to the instantaneous changes of the gas concentration. Even though it has rarely been used in dynamic adsorption experiments in the literature, an FT-IR equipped with a constant-temperature gas cell was shown to be adequate to obtain breakthrough curves. In this study, the experiments were carried out at different gas flow rates and feed concentrations for each type of alcohol. Significant influences of the operating conditions on the breakthrough time, the shape of the breakthrough curve, and the uptake of each alcohol were found. A simple mathematical model proposed by Yoon and Nelson was applied to fit the experimental data. Good consistency between the experimental data and the regressed breakthrough curves was observed.

Adsorption↗
PubMed2003

Polymorphisms past and present.

Polymorphisms, particularly genetic variants of the red blood cell, have served as a major focus for the research of Frank B. Livingstone over the course of a long and productive career. Recent investigations confirm the value of key insights that he contributed to this area more than four decades ago. As Livingstone recognized, the same underlying evolutionary model that guides genetic studies in present populations also provides a productive framework for interpreting patterns of variation in the skeleton and dentition throughout past human evolution. Examples explored in detail here include polymorphisms in hominoid nasal bone shapes and fourth lower premolar roots. This work provides both empirical and theoretical contexts for investigating patterns of human variation over the last 6 to 8 million years.

Genetic Variation↗
PubMed2002

Haplotype exclusion and receptor editing: irreconcilable differences?

Features of antibody genes and their regulation hinder two properties thought to be critical for clonal selection: haplotype exclusion and receptor diversity. These properties include: (1) the retention of multiple independent L-chain isotypes, which compounds the problem of allelic exclusion with one of isotype exclusion; (2) the process of receptor editing, in which recombination continues in cells already expressing antigen receptors; and (3) non-random associations and quasi-ordered rearrangements of the elements that generate light chain genes, which promote editing at the expense of allelic exclusion and receptor diversification. In contrast, heavy chain gene structure seems to promote haplotype exclusion and receptor diversity. It appears that requirements of receptor selection, such as the need for receptor editing as an immune tolerance mechanism and positive selection as a quality control checkpoint for receptor functionality, impose independent selections that shape the organization and regulation of the antibody genes. Despite these features, B cell development still achieves a significant level of phenotypic haplotype exclusion, suggesting that there is indeed significant selection for antibody monospecificity that is accommodated along with receptor editing. Thus, the immune system achieves both receptor selection and clonal selection, despite their partly antagonistic mechanisms.

Alleles↗
PubMed2006

Novel gain-of-function alleles demonstrate a role for the heterochronic gene lin-41 in C. elegans male tail tip morphogenesis.

To gain an understanding of the genes and mechanisms that govern morphogenesis and its evolution, we have analyzed mutations that disrupt this process in a simple model structure, the male tail tip of the rhabditid nematode C. elegans. During the evolution of rhabditid male tails, there have been several independent changes from tails with rounded tips ("peloderan", as in C. elegans) to those with pointed tips ("leptoderan"). Mutations which produce leptoderan (Lep) tails in C. elegans thus identify candidate genes and pathways in which evolutionary changes could have produced leptoderan tails from peloderan ancestors. Here we report that two novel, gain-of-function (gf) alleles of lin-41 have lesions predicted to affect the N-terminus of the RBCC-domain LIN-41 protein. Both gf alleles cause the tail tip of adult males to retain the pointed shape of the juvenile tails, producing a Lep phenotype that looks like the tails of leptoderan species. Consistent with its role in the heterochronic pathway, we find that lin-41 governs the timing and extent of male tail tip morphogenesis in a dose-dependent manner. Specifically, the Lep phenotype results from a heterochronic delay in the retraction and fusion of the tail tip cells during L4 morphogenesis, such that retraction is not completed before the adult molt. Conversely, we find that tail tip morphogenesis and cell fusions begin precociously at the L3 stage in the reduced-function lin-41 mutant, ma104, resulting in over-retracted male tails in the adult. Because modulated anti-LIN-41 RNAi knockdowns in the gf mutants restore wild-type phenotype, we suggest that the leptoderan phenotype of the gf alleles is due to a higher activity of otherwise normal LIN-41. Additionally, the gf allele is suppressed by the wild-type allele, suggesting that LIN-41 normally regulates itself, possibly by autoubiquitination. We speculate that small changes affecting LIN-41 could have been significant for male tail evolution.

Alleles↗
PubMed1997

Absence of atherosclerosis evolution in the coronary arterial segment covered by myocardial tissue in cholesterol-fed rabbits.

The evolution of atherosclerotic lesions is suppressed in the intima of the human coronary artery, beneath myocardial bridges. To elucidate the mechanism of the protective effect, we investigated morphological changes using the rabbit coronary artery as a model. Rabbit fed a 1%-cholesterol diet were killed at intervals up to 20 weeks. Two short segments of the left coronary arteries running in the epicardial adipose tissue (EpiLAD) and subsequently running in the myocardium (MyoLAD) were compared morphologically. The intima of the EpiLAD had flat endothelial cells with a polygonal shape, and demonstrated raised atherosclerotic lesions with increase in serum cholesterol level. In contrast, the intima of the MyoLAD was free of atherosclerotic lesions throughout the study, and the endothelial cells were spindle-shaped and engorged. While ferritin particles reached only the surroundings of the internal elastic lamina in the MyoLAD, they permeated into the media of the EpiLAD. We suggest that myocardial bridges suppress coronary atherosclerosis by an alteration of endothelial permeability, which may be due to changes in haemodynamic force tending towards a higher shear stress. The data provide an insight into the relationship between haemodynamics and the development of coronary atherosclerosis.

Animals↗
PubMed2003

A comparative study of bchG from green photosynthetic bacteria.

The gene bchG, coding for bacteriochlorophyll a synthase from a variety of green sulfur bacteria and the filamentous anoxygenic phototrophic bacteria, Chloroflexus aurantiacus, Chloronema sp., and Roseiflexus castenholzii HL08, was partially sequenced and compared. The deduced amino acid consensus sequences for green sulfur bacteria and green filamentous anoxygenic phototrophic bacteria were found to belong to the UbiA enzyme family of polyprenyltransferases with the most similar sequences being those of photosynthetic organisms. All deduced amino acid sequences showed a highly conserved region, which includes the motif DRXXD, characteristic of polyprenyltransferases, which was extended to DREVDAINEP for green sulfur bacteria. Neighbor-joining analysis of a protein similitude matrix displayed a relatively high distance between green sulfur bacteria and the other groups. Sequences from green sulfur bacteria were more closely related to those of purple bacteria than to those of filamentous anoxygenic phototrophic bacteria. In addition, internal grouping within green sulfur bacteria was congruent regarding taxonomic features including cell shape, presence of gas vacuoles and NaCl requirement. In addition to bchlG, another gene encoding for a second chlorophyll synthetase, previously tentatively identified as chlG, was also found in Chlorobium tepidum, showing the highest similarities with polyprenyltransferases from chlorophyll- a-containing organisms.

Amino Acid Sequence↗
PubMed2026

Complex evolutionary history of Rosales mediated by extensive incomplete lineage sorting and hybridization.

The angiosperm order Rosales still represents a major challenge for phylogenetic reconstruction. Although its circumscription is now well-defined, phylogenetic relationships among families are still uncertain. Here, we used nuclear, plastid, and mitochondrial genomic data from 33 species representing all nine families to further clarify interfamilial relationships and the group's evolutionary history. We detected significant phylogenetic conflict among the three datasets. Further analyses at the nuclear level identified incomplete lineage sorting (ILS) as the main cause of unstable phylogenetic positions among families. The discordant placements of Rhamnaceae and Elaeagnaceae based on plastid and mitochondrial data are caused by ancient hybridization events, potentially involving differences in organellar inheritance. Our molecular dating confirms earlier suggestions that the ancient rapid diversification of the three Rosaceae subfamilies could be the main reason for the difficulties in resolving their phylogenetic relationships. Our findings provide new insights into the interfamilial relationships of Rosales and demonstrate that the evolutionary history of this order was shaped by ancient and rapid radiation as well as extensive ILS and reticulate evolution. They also suggest that previous attempts to clarify interfamilial relationships in this order were hampered by combining nuclear and organellar sequence data, leading to inconsistent topologies observed across earlier studies.

Phylogeny↗
PubMed1991

Tooth movement.

This article reviews the evolution of concepts regarding the biological foundation of force-induced tooth movement. Nineteenth century hypotheses proposed two mechanisms: application of pressure and tension to the periodontal ligament (PDL), and bending of the alveolar bone. Histologic investigations in the early and middle years of the 20th century revealed that both phenomena actually occur concomitantly, and that cells, as well as extracellular components of the PDL and alveolar bone, participate in the response to applied mechanical forces, which ultimately results in remodeling activities. Experiments with isolated cells in culture demonstrated that shape distortion might lead to cellular activation, either by opening plasma membrane ion channels, or by crystallizing cytoskeletal filaments. Mechanical distortion of collagenous matrices, mineralized or non-mineralized, may, on the other hand, evoke the development of bioelectric phenomena (stress-generated potentials and streaming potentials) that are capable of stimulating cells by altering the electric charge on their membrane or their fluid envelope. In intact animals, mechanical perturbations on the order of about 1 min/d are apparently sufficient to cause profound osteogenic responses, perhaps due to matrix proteoglycan-related "strain memory". Enzymatically isolated human PDL cells respond biochemically to mechanical and chemical signals. The latter include endocrines, autocrines, and paracrines. Histochemical and immunohistochemical studies showed that during the early places of tooth movement, PDL fluids are shifted, and cells and matrix are distorted. Vasoactive neurotransmitters are released from periodontal nerve terminals, causing leukocytes to migrate out of adjacent capillaries. Cytokines and growth factors are secreted by these cells, stimulating PDL cells and alveolar bone lining cells to remodel their related matrices. This remodeling activity facilitates movement of teeth into areas in which bone had been resorbed. This emerging information suggests that in the living mammal, many cell types are involved in the biological response to applied mechanical stress to teeth, and thereby to bone. Essentially, cells of the nervous, immune, and endocrine systems become involved in the activation and response of PDL and alveolar bone cells to applied stresses. This fact implies that research in the area of the biological response to force application to teeth should be sufficiently broad to include explorations of possible associations between physical, cellular, and molecular phenomena. The goals of this investigative field should continue to expound on fundamental principles, particularly on extrapolating new findings to the clinical environment, where millions of patients are subjected annually to applications of mechanical forces to their teeth for long periods of time in an effort to improve their position in the oral cavity.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1993

[Early ultrastructural evolution of murine malaria merozoites after entering red cells].

A TEM study of murine malaria parasites, Plasmodium berghei and P. yoelii was performed by consecutive sampling in vivo to look into the early sequential changes in the ultrastructure of the merozoites after entering red cells. The results showed that once finishing invasion, the merozoite resided in the peripheral cytoplasm of the red cell, creating a bulge at the invasion site, with an additional unit membrane around it (parasitophorous vacuole); apical structures disappeared; the spherical body was degenerative or atrophic and separated from the mitochondrion and nucleus. The mitochondrion became more extended and the nucleus elongated and curved. There were more Er vesicles in the cytoplasm, taking a dilated polyangular shape. The inner double membrane was separated from the outer membrane and got into incomplete, winding, finally disappeared. Sometimes multimembranous bodies could be seen in the peripheral spaces. Once the dedifferentiation process was over, the merozoite was transformed into an early trophozoite, with a single plasma membrane and decreased density. Individual large Er vesicle with acute angles was found in the cytoplasm, and small food pills appeared beneath the plasma membrane; then the shape of the parasite changed from a ball-like one to a pie-like one, gradually the flat cell body rolled up, with its edges met and fused, resulting in the formation of a large food vacuole, with digestive vacuoles and pigment granules around it. Thus, it grew into a middle-aged trophozoite.

Animals↗
PubMed2002

Divergence of mitochondrial dna is not corroborated by nuclear dna, morphology, or behavior in Drosophila simulans.

We ask whether the observed mitochondrial DNA (mtDNA) population subdivision of Drosophila simulans is indicative of organismal structure or of specific processes acting on the mitochondrial genome. Factors either intrinsic or extrinsic to the host genome may influence the evolutionary dynamics of mtDNA. Potential intrinsic factors include adaptation of the mitochondrial genome and of nucleomitochondrial gene complexes specific to the local environment. An extrinsic force that has been shown to influence mtDNA evolution in invertebrates is the bacterial endosymbiont Wolbachia. Evidence presented in this study suggests that mtDNA is not a good indicator of organismal subdivision in D. simulans. Furthermore, there is no evidence to suggest that Wolbachia causes any reduction in nuclear gene flow in this species. The observed differentiation in mtDNA is not corroborated by data from NADH: ubiquinone reductase 75kD subunit precursor or the Alcohol dehydrogenase-related loci, from the shape or size of the male genital arch, or from assortative premating behavior. We discuss these results in relation to a mitochondrial genetic species concept and the potential for Wolbachia-induced incompatibility to be a mechanism of speciation in insects. We conclude with an iterated appeal to include phylogenetic and statistical tests of neutrality as a supplement to phylogenetic and population genetic analyses when using mtDNA as an evolutionary marker.

Animals↗
PubMed2005

Artiodactyl emergence is accompanied by the birth of an extensive pool of diverse germline TRDV1 genes.

Molecular cloning of cDNA from gamma/delta T cells has shown that in sheep, the variable domain of the delta chain is chiefly determined by the expression of the TRDV1 subgroup, apparently composed of a large number of genes. There are three other TRDV subgroups, but these include only one gene each. To evaluate the extent and the complexity of the genomic TRDV repertoire, we screened a sheep liver genomic library from a single individual of the Altamurana breed and sheep fibroblast genomic DNA from a single individual of the Gentile di Puglia breed. We identified a total of 22 TRDV1 genes and the TRDV4 gene. A sequence comparison between germline and the rearranged genes indicates that, in sheep, the TRDV repertoire is generated by the VDJ rearrangement of at least 40 distinct TRDV1 genes. All germline TRDV1 genes present a high degree of similarity in their coding as well as in 5' and 3' flanking regions. However, a systematic analysis of the translation products reveals that these genes present a broadly different and specific repertoire in the complementarity-determining regions or recognition loops, allowing us to organize the TRDV genes into sets. We assume that selection processes operating at the level of ligand recognition have shaped the sheep TRDV germline repertoire. A phylogenetic study based on a sequence analysis of the TRDV genes from different mammalian species shows that the diversification level of these genes is higher in artiodactyl species compared to humans and mice.

Amino Acid Sequence↗
PubMed2004

Heterogeneous cell mechanical properties: an atomic force microscopy study.

Atomic force microscopy (AFM) is a non-invasive microscopy to explore living biological systems like cells in liquid environment. Thus AFM is an appropriate tool to investigate surface chemical modification and its influence on biological systems. In particular, control over biomaterial surface chemistry can result in a regulated cell response. This report investigates the influence of adhesive and non-adhesive surfaces on the cell morphology and the influence of the cytoskeleton structure on the local mechanical properties. In this study, the main work concerns a thorough investigation of the height images obtained with an AFM as therecorded images provide the evolution of the mechanical properties of the cell as function of its local structure. Information on the cell elasticity due to the cytoskeleton organization is deduced when comparing the AFM tip indentation depth versus the distance between the cytoskeleton bundles for the different samples.

Cell Adhesion↗
PubMed2006

New details from the complete life cycle of the red-tide dinoflagellate Noctiluca scintillans (Ehrenberg) McCartney.

Noctilucid protozoans are among the dinoflagellates that cause red tides. Sexual reproduction may occur in this group, as they sometimes undergo gametogenesis. However, the life cycle, in particular the developmental process after gamete fusion, has not been fully elucidated. We have been able to maintain clonal cultures of Noctiluca scintillans throughout the whole life cycle and have revealed new details of various stages. In trophont populations, a small fraction of cells spontaneously transform into gametogenic cells, which undergo two successive nuclear divisions, without cellular division, probably corresponding to meiosis. The products of nuclear division migrate to the cell surface with a small amount of cytoplasm, and there further synchronously divide 6-8 times, during which the division products are connected by thin cytoplasmic bridges. Thus, numerous gametes with a semi-spindle body shape are released from the mother cell ghost. They retain two flagella that differ in length and motion, as is typical of dinoflagellates. The presence of longitudinal and transverse grooves indicates that dinoflagellate-like characteristics are conserved in the gametes, although they are not present in the specialized trophonts. Zygotes with four flagella result from the fusion of two isogametes. The zygotes change shape from spindle to spherical, with a reduction in flagellar number. The developing cell acquires a tentacle and crust, similar to large trophonts, and begins to develop a cytoplasmic network, thus completing the transformation into a miniscule trophont. These early trophonts grow to maturity as cell size increases. Our observations of the life cycle of N. scintillans may provide clues for understanding the evolutionary origin of noctilucae.

Animals↗
PubMed2005

Geometry and topology of diatom shape and surface morphogenesis for use in applications of nanotechnology.

Diatoms have attracted the interest of those involved in nanotechnology and the development of this discipline for research and practical application. These microorganisms exhibit self-assembly of silica on the micrometer scale, with parts of diatoms measuring on the nanometer scale. They exhibit a wide variety of shapes and patterns. An interest in diatom development and the geometry and topology of diatom shapes and gross patterns formed the focus of this study. Diatoms may be theoretically created on the basis of conic sections and quadratic surfaces expressed in parametric two-dimensional (2D) and three-dimensional (3D) functions (as sheets). Recreated diatom shapes, surfaces, and gross patterns based on 3D parametric equations are presented. Changes from one form to another are discussed as changes in magnitude or functional element within a given set of 3D equations for sequences that are phylogenetically or taxonomically related. Topological evolution and combinations of diatom shapes and surfaces are explored. An example shows how diatom forms depicted as 2-manifolds can be subjected to topological gluing to create a form whose surface is topologically different from the original. Topological surgery and gluing of diatoms as geometric forms may be useful in hypotheses about creating nanosubstrates and nanopatterned nanomaterials or in other applications of nanotechnology.

Biomimetics↗
PubMed2026

Defining and managing high-risk acute myeloid leukemia (AML) in 2026.

Acute myeloid leukemia (AML) remains a highly heterogeneous malignancy in which outcomes are particularly poor for patients classified as having high-risk disease. Traditionally, high-risk AML has been defined by adverse baseline genetic features, including complex cytogenetics, TP53 alterations, and mutations associated with secondary or therapy-related disease. However, this static, genetics-centered definition is increasingly insufficient in the modern therapeutic era. Emerging evidence supports a more dynamic and context-dependent model in which risk is shaped not only by molecular architecture but also by treatment intensity, patient fitness, measurable residual disease (MRD), and evolving resistance mechanisms. Advances in genomic profiling have refined risk stratification frameworks, including ELN 2022 for intensively treated patients and the ELN 2024 classification for those receiving less-intensive therapies. In parallel, MRD has emerged as a powerful biomarker that reclassifies patients during treatment, identifying those with persistent, therapy-resistant disease despite morphologic remission. Biologically, high-risk AML is driven by the interplay of clonal evolution, epigenetic plasticity, leukemic stem cell persistence, and protective microenvironmental and immune interactions, all of which contribute to relapse. Therapeutically, the landscape has expanded to include targeted agents, venetoclax-based combinations, and transplantation strategies, yet outcomes remain limited in key high-risk subsets, particularly TP53-mutated disease and post-venetoclax relapse. Accordingly, current strategies emphasize rational combination therapies, MRD-guided treatment adaptation, and approaches targeting both leukemic cells and their supportive niches. In 2026, high-risk AML is best understood as a dynamic, treatment-context-dependent state. Improving outcomes will require integration of precision diagnostics, biologically informed therapy, and adaptive strategies designed to anticipate and overcome resistance.

Humans↗