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PubMedDate not supplied

Effect of HCV infection on THP-1 monocytoid cells.

Hepatitis C virus (HCV) is the main cause of hepatocellular carcinoma in industrialized countries. HCV-HIV-1 co-infection occurs frequently among users of illicit intravenous drugs, thereby increasing the severity of HIV disease and the evolution of chronic active hepatitis towards cirrhosis and hepatocellular carcinoma. The present work shows that THP-1 monocytoid cells are susceptible to HCV infection, of strain 1b, and that this strain can induce cellular modifications in this cell line. Infection of HCV was demonstrated by positivity for the E2 antigen within THP-1 cells and by indirect immunofluorescence; moreover, HCV-RNA was detected in supernatants of THP-1 cells from day 7 post-inoculation. Cell shape and membrane surface antigens varied upon viral infection, which is also capable of inducing oxygen radicals. In particular we underline the relevant intracellular accumulation of ferritin that paralleled an increase of cell surface expression of the transferrin receptor. Evaluation of cellular events upon HCV infection in THP-1 cells may represent a useful tool with which to identify alteration in monocytes metabolism and to study therapeutic approaches for such alterations.

12E7 Antigen↗
PubMed2001

Immune and artificial selection in the haemagglutinin (H) glycoprotein of measles virus.

We present a maximum likelihood (ML) analysis of the selection pressures that have shaped the evolution of the large (L) protein and the haemagglutinin (H) glycoprotein of measles virus (MV). A number of amino acid sites that have potentially been subject to adaptive evolution were identified in the H protein using sequences from every known genotype of MV. All but one of these putative positively selected sites reside within the ectodomain of the H protein, where they often show an association with positions of potential B-cell epitopes and sites known to interact with the CD46 receptor. This suggests that MV may be under pressure from the immune system, albeit relatively weakly, to alter sites within epitopes and hence evade the humoral immune response. The positive selection identified at amino acid 546 was shown to correlate with the passage history of MV isolates in Vero cells. We reveal that Vero cell passaging has the potential to introduce an artificial signal of adaptive evolution through selection for changes that increase affinity for the CD46 receptor.

Amino Acid Sequence↗
PubMed2004

Phylogeny and regulation of four lipocalin genes clustered in the chicken genome: evidence of a functional diversification after gene duplication.

A novel lipocalin gene is here reported that represents the fourth member of a cluster we have identified in the chicken genome. This cluster also includes Chondrogenesis-Associated Lipocalins beta and gamma (CAL beta, CAL gamma) and Extracellular Fatty Acid Binding Protein (Ex-FABP). The new gene codes for a 22-kDa secreted protein with three cysteine residues and a series of sequence features well conserved in the lipocalin family. All the genes in the cluster are structurally similar presenting comparable exon/intron boundary positions and exon sizes. A phylogenetic analysis indicates the monophyletic grouping of these genes, and their relationship with the lipocalins alpha-1-microglobulin (A1mg), complement factor 8 gamma chain (C8GC), prostaglandin D synthase (PGDS), and neutrophil-gelatinase-associated lipocalin (NGAL). The new cluster gene appears to be the ortholog of the mammalian C8GC and was thus named Ggal-C8GC. This orthology also suggests that this lipocalin was present in the ancestor common to reptiles and mammals. In addition to other expressing tissues, Ex-FABP, CAL beta and CAL gamma genes are highly transcribed in chondrocytes at late stages of chondrogenesis during endochondral bone formation and/or upon inflammatory stimulation. Here, we show that they are also transcriptionally induced when chondrocytes are subjected to various biological events as cell quiescence, cell shape transition, and hormonal stimulation. By contrast, Ggal-C8GC transcripts are only barely detectable in chondrocytes, but are more abundant in liver, kidney, brain, heart, skeletal muscle and particularly in skin. Moreover, no expression induction was observed neither during chondrocyte differentiation, nor upon any of the stimulations mentioned above. This indicates that the Ggal-C8GC gene was co-opted for a novel function after the duplication events that gave rise to the cluster. The peculiar coordinated regulation of Ex-FABP, CAL beta and CAL gamma, and the apparent divergent role of Ggal-C8GC suggest that these gene duplications may have been maintained during evolution by a sub-functionalization mechanism where some common function(s) are shared by several members of the cluster and some other specialized function(s) are unique to other members.

Amino Acid Sequence↗
PubMed1989

In vitro study of translocation t(4;11) acute leukemia. Sequential range of phenotype.

The nature of translocation t(4;11) acute leukemia cells has been widely discussed over the past few years. Many authors report their phenotypic heterogeneity, ranging from apparently common acute lymphoblastic leukemia antigen-positive to monoblastic leukemia, through "promiscuous" phenotype. We studied in vitro phenotypic modulation of three typical cases after induction by 12-O-tetradecanoyl phorbol 13 acetate. The initial phenotype was different in each case, but all of them exhibited changes in morphologic shape, cytochemistry, and immunophenotype; common features appeared after induction by 12-O-tetradecanoyl phorbol 13 acetate, including esterase activity, expression of CD-9, CD-15, and CD-18 surface antigens, and monocyte/macrophage morphology. In all cases a B-associated surface antigen, CD-19, persisted. During clinical evolution, some previously reported cases have shown a karyotypic and phenotypic transformation. In one of our cases this phenomenon correlated with in vitro phenotypic modulation of initial blast population. Furthermore, clinical relapses and in vitro modulation always seem to evolve toward a more "mature" phenotype. Those results support the "promiscuous lineage" hypothesis, and point out the usefulness of in vitro studies to express the myeloid potential of this category of acute leukemia, which can be regarded as a model of early hematopoietic differentiation.

Acute Disease↗
PubMed1976

Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells.

When their growth is arrested in culture, susceptible 3T3 fibroblasts differentiate into adipose cells. Different clones form adipose cells with different frequency, depending upon the proportion of susceptible cells they contain. In cultures grown from small inocula, the fat cells appear in clusters formed by colonies of susceptible cells. Study of these clusters indicates the infrequent occurrence of cellular transitions from insusceptible to susceptible state. Beginning with a clone converting to adipose cells with a vary low frequency, it has been possible, by serial selection, to generate subclones which convert with a high frequency. This evolution is due to spontaneous heritable changes affecting susceptibility to the adipose conversion. Presumably, they involve the control of triglyceride synthesis. Early stages of the adipose conversion may be recognized in stained cultures. When triglyceride first begins to accumulate, the highly extended and flattened processes of the cells are probably similar to those of nonfatty cells in the same cultures. As the adipose conversion proceeds, the processes thicken and retract; the cells eventually acquire the rounded shape of the more mature adipose cells.

Adipose Tissue↗
PubMed1999

Crystal structure of invasin: a bacterial integrin-binding protein.

The Yersinia pseudotuberculosis invasin protein promotes bacterial entry by binding to host cell integrins with higher affinity than natural substrates such as fibronectin. The 2.3 angstrom crystal structure of the invasin extracellular region reveals five domains that form a 180 angstrom rod with structural similarities to tandem fibronectin type III domains. The integrin-binding surfaces of invasin and fibronectin include similarly located key residues, but in the context of different folds and surface shapes. The structures of invasin and fibronectin provide an example of convergent evolution, in which invasin presents an optimized surface for integrin binding, in comparison with host substrates.

Adhesins, Bacterial↗
PubMed2005

Ion transport pathology in the mechanism of sickle cell dehydration.

Polymers of deoxyhemoglobin S deform sickle cell anemia red blood cells into sickle shapes, leading to the formation of dense, dehydrated red blood cells with a markedly shortened life-span. Nearly four decades of intense research in many laboratories has led to a mechanistic understanding of the complex events leading from sickling-induced permeabilization of the red cell membrane to small cations, to the generation of the heterogeneity of age and hydration condition of circulating sickle cells. This review follows chronologically the major experimental findings and the evolution of guiding ideas for research in this field. Predictions derived from mathematical models of red cell and reticulocyte homeostasis led to the formulation of an alternative to prevailing gradualist views: a multitrack dehydration model based on interactive influences between the red cell anion exchanger and two K(+) transporters, the Gardos channel (hSK4, hIK1) and the K-Cl cotransporter (KCC), with differential effects dependent on red cell age and variability of KCC expression among reticulocytes. The experimental tests of the model predictions and the amply supportive results are discussed. The review concludes with a brief survey of the therapeutic strategies aimed at preventing sickle cell dehydration and with an analysis of the main open questions in the field.

Anemia, Sickle Cell↗
PubMed2005

Intestinal bacteria and development of the B-lymphocyte repertoire.

Vertebrates have a large antibody repertoire with diverse antigen specificities, poised to react to invading pathogens, such as bacteria, viruses and helminths. In some species, microbes such as these are required for development of both diverse antibody and B-lymphocyte repertoires. Recent studies demonstrate that B-lymphocyte expansion, selection and somatic diversification of Ig genes are regulated in these species, in part, by the interaction between commensal intestinal bacteria and gut-associated lymphoid tissue (GALT). These findings indicate that the commensal microbiota can shape the repertoire of peripheral B lymphocytes and can potentially influence the health of the host. Here, how the interactions between commensal microbiota and lymphoid cells of GALT might affect the development of the peripheral B-lymphocyte repertoire is discussed.

Animals↗
PubMed1990

A bangiophyte red alga from the Proterozoic of arctic Canada.

Silicified peritidal carbonate rocks of the 1250- to 750-million-year-old Hunting Formation, Somerset Island, arctic Canada, contain fossils of well-preserved bangiophyte red algae. Morphological details, especially the presence of multiseriate filaments composed of radially arranged wedge-shaped cells derived by longitudinal divisions from disc-shaped cells in uniseriate filaments, indicate that the fossils are related to extant species in the genus Bangia. Such taxonomic resolution distinguishes these fossils from other pre-Ediacaran eukaryotes and contributes to growing evidence that multicellular algae diversified well before the Ediacaran radiation of large animals.

Biological Evolution↗
PubMed2003

Evolutionary relationships of the Tas2r receptor gene families in mouse and human.

The early molecular events in the perception of bitter taste start with the binding of specific water-soluble molecules to G protein-coupled receptors (GPCRs) encoded by the Tas2r family of taste receptor genes. The identification of the complete TAS2R receptor family repertoire in mouse and a comparative study of the Tas2r gene families in mouse and human might help to better understand bitter taste perception. We have identified, cloned, and characterized 13 new mouse Tas2r sequences, 9 of which encode putative functional bitter taste receptors. The encoded proteins are between 293 and 333 amino acids long and share between 18% and 54% sequence identity with other mouse TAS2R proteins. Including the 13 sequences identified, the mouse Tas2r family contains approximately 30% more genes and 60% fewer pseudogenes than the human TAS2R family. Sequence and phylogenetic analyses of the proteins encoded by all mouse and human Tas2r genes indicate that TAS2R proteins present a lower degree of sequence conservation in mouse than in human and suggest a classification in five groups that may reflect a specialization in their functional activity to detect bitter compounds. Tas2r genes are organized in clusters in both mouse and human genomes, and an analysis of these clusters and phylogenetic analyses indicates that the five TAS2R protein groups were present prior to the divergence of the primate and rodent lineages. However, differences in subsequent evolutionary processes, including local duplications, interchromosomal duplications, divergence, and deletions, gave rise to species-specific sequences and shaped the diversity of the current TAS2R receptor families during mouse and human evolution.

Amino Acid Sequence↗
PubMed1999

Dynamics of rabies virus quasispecies during serial passages in heterologous hosts.

To understand the mutations and genetic rearrangements that allow rabies virus infections of new hosts and adaptation in nature, the quasispecies structure of the nucleoprotein and glycoprotein genes as well as two noncoding sequences of a rabies virus genome were determined. Gene sequences were obtained from the brain and from the salivary glands of the original host, a naturally infected European fox, and after serial passages in mice, dogs, cats and cell culture. A relative genetic stasis of the consensus sequences confirmed previous results about the stability of rabies virus. At the quasispecies level, the mutation frequency varies, in the following order: glycoprotein region (21.9 x 10(-4) mutations per bp), noncoding sequence nucleoprotein-phosphoprotein region (7.2-7.9 x 10(-4) mutations per bp) and nucleoprotein gene region (2.9-3.7 x 10(-4) mutations per bp). These frequencies varied according to the number, type of heterologous passages and the genomic region considered. The shape of the quasispecies structure was dramatically modified by passages in mice, in which the mutation frequencies increased by 12-31 x 10(-4) mutations per bp, depending on the region considered. Non-synonymous mutations were preponderant particularly in the glycoprotein gene, stressing the importance of positive selection in the maintenance and fixation of substitutions. Two mechanisms of genomic evolution of the rabies virus quasispecies, while adapting to environmental changes, have been identified: a limited accumulation of mutations with no replacement of the original master sequence and a less frequent but rapid selective overgrowth of favoured variants.

Animals↗
PubMed2007

Evidence of positive selection on the Atlantic salmon CD3gammadelta gene.

Atlantic salmon are typically anadromous, spending the majority of their lifetime in oceans and returning to fresh water to breed. This diversity of environments likely results in strong selective forces shaping their genome. In this paper, we present the first genomics approach to detect positive selection operating on the Salmo salar (salmon) lineage, an important aquaculture species. We identify a panel of candidate genes that may have been subject to adaptive evolution in this species. In particular, we identify a robust signature of positive selection operating on the salmon CD3gammadelta gene, which encodes one of the protein chains essential for formation of the T-cell receptor complex and for T-cell activation. Furthermore, we identified the particular codon sites that have been subject to positive selection in fish and highlight two sites flanking an important N-glycosylation site in this molecule.

Amino Acid Sequence↗
PubMed1975

In vitro suppression of segmentation in Echinococcus multilocularis with morphological transformation of protoscoleces into monozoic adults.

When protoscoleces of Echinococcus multilocularis were cultured in vitro, under axenic conditions in either monophasic or diphasic media, segmentation was suppressed in most organisms, some 70-80% of which developed into unsegmented, monozoic forms with a complete set of sexually mature male and female genitalia. The most striking feature of monozoic worms was the large lateral swelling produced by the cirrus sac the effect being to produce organisms with an unusual asymmetric shape. Worms which did not become monozoic either (a) underwent some somatic growth, developed two sets of genitalia and became 'pseudo-segmented', i.e. with the inter-proglottid membranes absent or poorly defined, or (b) became vesicular or abnormal. The mechanisms which could be involved in the suppression of somatic growth and the induction of the monozoic condition, are examined in terms of cell lineage. The possible significance of these results in understanding the evolution of the cestodes is discussed.

Animals↗
PubMed2001

[Basal cell and squamous cell carcinomas of the eyelid in adults under 50 years of age: 13 cases].

PURPOSE: It is widely accepted that exposure to UV light may cause malignant lesions in the eyelid of elderly people. Its occurrence in young adults is much less frequent and requires an early diagnosis and accurate treatment as well. MATERIAL AND METHOD: We have retrospectively reviewed a series of 13 patients younger that 50 years of age who had been surgically treated in our hospital between 1990 and 1997. RESULTS: The pathologic examination revealed 12 basal cell carcinomas and one squamous cell carcinoma. Lesions were small nodular tumors with a previous mean evolution of 34 months (2.6 years). CONCLUSION: Although the periocular area may develop several kinds of malignancies due to the presence of various types of tissues, most of the lesions found in the eyelid are carcinomas. With an early diagnosis and correct treatment, prognosis is good. The purpose of the surgical treatment is not only the excision of the lesion, but also to maintain shape and function of the eyelid and preserve the eye as well.

Adult↗
PubMed1997

Bone marrow mastocytosis associated with an undifferentiated extramedullary tumor of hemopoietic origin.

The case of a 62-year-old man who presented with acute abdominal pain and a widespread tumor involving the retroperitoneum is described. Three weeks after initial presentation, the patient died suddenly of acute cardiac failure with signs of arrhythmia. Autopsy revealed a disseminated tumor with infiltration of the retroperitoneal fat, as well as nodules in the left testis and the right atrium. The tumor cells were reactive for CD45, vimentin, and chloroacetate esterase, but were unreactive with a broad spectrum of antibodies against myelomonocytic and lymphocytic antigens and with antibodies against tryptase and c-kit (CD117), which are characteristic markers for mast cells. However, the bone marrow exhibited the typical picture of mastocytosis, with disseminated clusters of differentiated spindle-shaped cells that stained strongly for tryptase, c-kit, and chloroacetate esterase. No infiltrates of well-differentiated mastocytosis could be detected in any of the extramedullary tissues investigated. A diagnosis of bone marrow mastocytosis with an associated undifferentiated extramedullary tumor of hemopoietic origin was established. By definition, the extramedullary tumor could not be diagnosed as a granulocytic sarcoma or (differentiated) mastocytoma, but the possibility that a mast cell progenitor could be involved in the evolution of both tumors cannot be ruled out.

Bone Marrow Diseases↗
PubMed2004

Emerging functions of BRCA2 in DNA recombination.

Mutations in the breast cancer susceptibility protein BRCA2 cause inherited susceptibility to breast, ovarian and other cancers. There is now compelling experimental evidence that a major biological function of BRCA2 is the maintenance of chromosome structure stability in dividing cells by regulation of steps in recombination between homologous DNA strands. Recent experimental findings shape the current models for BRCA2 function, and structural and biochemical advances shed new light on the interactions between BRCA2, the RAD51 recombinase and single-stranded DNA during DNA recombination.

Animals↗
PubMed2006

Vacillating breathing and tumbling of vesicles under shear flow.

The dynamics of vesicles under a shear flow are analyzed analytically in the small deformation regime. We derive two coupled nonlinear equations which describe the vesicle orientation in the flow and its shape evolution. A new type of motion is found, namely, a "vacillating-breathing" mode: the vesicle orientation undergoes an oscillation around the flow direction, while the shape executes breathing dynamics. This solution coexists with tumbling. Moreover, we provide an explicit expression for the tumbling threshold. A rheological law for a dilute vesicle suspension is outlined.

Cell Physiological Phenomena↗
PubMed2005

Perforin and Fas cytolytic pathways coordinately shape the selection and diversity of CD8+-T-cell escape variants of influenza virus.

Antigenic variation is a viral strategy exploited to promote survival in the face of the host immune response and represents a major challenge for efficient vaccine development. Influenza viruses are pathogens with high transmissibility and mutation rates, enabling viral escape from immunity induced by prior infection or vaccination. Intense selection from neutralizing antibody drives antigenic changes in the surface glycoproteins, resulting in emergence of new strains able to reinfect hosts immune to previously circulating viruses. CD8+ cytotoxic T cells (CTLs) also provide protective immunity from influenza virus infection and may contribute to the antigenic evolution of influenza viruses. Utilizing mice transgenic for an influenza virus NP366-374 peptide-specific T-cell receptor, we demonstrated that the respiratory tract is a suitable site for generation of escape variants of influenza virus selected by CTL in vivo. In this report the contributions of the perforin and Fas pathways utilized by influenza virus-specific CTLs in viral clearance and selection of CTL escape variants have been evaluated. While transgenic CTLs deficient in either perforin- or Fas-mediated pathways are efficient in initial pulmonary viral control, variant virus emergence was observed in all the mice studied, although the spectrum of viral CTL escape variants selected varied profoundly. Thus, a less-restricted repertoire of escape variants was observed in mice with an intact perforin cytotoxic pathway compared with a limited variant diversity in perforin pathway-deficient mice, although maximal variant diversity was observed in mice having both Fas and perforin pathways intact. We conclude that selection of viral CTL escape variants reflects coordinate action between the tightly controlled perforin/granzyme pathway and the more promiscuous Fas/FasL pathway.

Animals↗