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PubMedDate not supplied

Molecular cell biology of renal diseases.

Molecular biology and cell biology of the kidney have seen remarkable development in recent years. Three major cell lineages, endothelial, epithelial, and fibroblastic, can be traced in the kidney, with high degrees of functional specialization in the different nephron segments. Ischemic, toxic or immunological damage has varying impact on glomerular, tubular and interstitial cell populations, often with a major contribution from infiltrating leukocytes. Inflammatory, proliferative, repair and degenerative processes previously recognized and studied in renal biopsies are now interpreted at a molecular level, with implications for the diagnosis and treatment of kidney diseases. A host of cellular mediators have been identified, allowing preliminary testing of inhibitors, antagonists and novel pharmacological agents. Gene targeting and manipulation hold promise for the treatment of disorders until now believed to be relentlessly progressive, including new approaches to renal allograft and xenograft.

Endothelium↗
PubMed2003

Systematic family screening for familial hypercholesterolemia in Iceland.

OBJECTIVE: This study compares a novel approach using systematic family screening for patients in Iceland who have familial hypercholesterolemia (FH) with conventional proband screening and assesses the sensitivity and specificity of diagnosing FH by cholesterol measurements compared with mutational testing of family members. METHODS AND RESULTS: Probands with the I4T+2C mutation were traced to common ancestors. A downtracing of each family lineage was performed back to the oldest living offspring (key individuals); these individuals were recruited for cholesterol measurement and mutation testing. The sensitivity and specificity of cholesterol measurements was assessed against mutational analysis. Eleven probands clustered into 4 families. There were 364 key individuals identified among their descendants. Eighty-four percent responded, and 11% were positive for the mutation. There were 78 offspring of the positive key individuals, and 40 of those were carriers. Compared with use of the conventional first-degree relative approach, an additional 19% of FH individuals, including key individuals and their descendants, were identified. As diagnostic criteria, cholesterol measurements in the families had 95% specificity and 94% sensitivity. CONCLUSIONS: Tracing FH probands to common ancestors and screening the oldest offspring in each family lineage adds considerably to the conventional method of FH screening (testing first-degree relatives). This may have relevance in other founder populations.

Adolescent↗
PubMed1999

A glial cell arises from an additional division within the mechanosensory lineage during development of the microchaete on the Drosophila notum.

We have used different cell markers to trace the development of the sensory cells of the thoracic microchaete. Our results dictate a revision in the currently accepted model for cell lineage within the mechanosensory bristle. The sensory organ progenitor divides to form two secondary progenitors: PIIa and PIIb. PIIb divides first to give rise to a tertiary progenitor-PIII and a glial cell. This is followed by division of PIIa to form the shaft and socket cells as described before. PIII expresses high levels of Elav and low levels of Prospero and divides to produce neuron and sheath. Its sibling cell expresses low Elav and high Prospero and is recognized by the glial marker, Repo. This cell migrates away from the other cells of the lineage following differentiation. The proposed modification in lineage has important implications for previous studies on sibling cell fate choice and cell fate specification in sensory systems.

Animals↗
PubMed1981

Functional ontogeny of human lymphoid cells as a factor in maternal-fetal tolerance.

The development of immunocompetence during gestation depends upon the sequential differentiation of antigen-specific lymphoid cells in the context of epithelial inducing microenvironments. These early intrauterine events, which appear to be antigen-independent, include clonal diversification of idiotypes and isotypes as well as commitment to B or T cell lineages. The steps in cellular maturation can be traced through the use of lymphocyte differentiation markers. Cooperation among lymphoid subsets, as well as from nonlymphoid cells and possibly other cofactors, is necessary for the effective function of this array of lymphocytes. The rate of expansion of functional immunity may be limited as much by the ontogeny of these collaborating influences as by the intrinsic immaturity of the B and T cells themselves.

Animals↗
PubMed1988

Proliferation kinetics and cell lineages can be studied in whole mounts and macerates by means of BrdU/anti-BrdU technique.

S-phase cells in intact animals of the coelenterate species Eirene viridula, Hydractinia echinata, Hydra attenuata, and Hydra magnipapillata incorporate the thymidine analogue bromodeoxyuridine (BrdU) into newly synthesized DNA. BrdU-labelled nuclei divide and cells appear to undergo normal differentiation. Whole-mount preparations and macerated tissues were screened for S-phase cells by means of immunocytochemical detection of BrdU (Gratzner, 1982). It is demonstrated that spatial patterns of DNA replication can be evaluated easily. Cell lineages and pathways of cell migration could be traced.

Animals↗
PubMed2003

Genealogy and genes: tracing the founding fathers of Tristan da Cunha.

The island population of Tristan da Cunha has a well-documented genealogy that dates to its first permanent settlement in 1816. The current population is thought to have descended from only seven females and eight males. Today, there are seven family names in use, corresponding to the number of founding fathers with present-day male descendents. Y chromosome polymorphisms have previously been shown to be reliable tools for tracing patrilineal genealogies. Here, we studied Y chromosome polymorphisms in a sample from Tristan da Cunha together with genealogical records to (i) infer the haplotypes of the seven founders and (ii) test if the Y chromosome transmission is consistent with the documented patrilineal history of the island community. We observed nine Y chromosome haplotypes of which seven could be traced to the known ancestors. Of the two additional lineages, one probably evolved from a founder haplotype due to a single-step microsatellite mutation, while the other had an obvious non-island origin. Its introduction, however, is not reflected in the records. Four more instances of non-paternity were identified, with the "new" chromosomes matching other island haplotypes. The Y chromosome data presented here question the validity of some of the genealogical documentation and emphasise the value of genetic studies in tracing ancestry.

Atlantic Islands↗
PubMed2006

Evolution of glutamine synthetase in heterokonts: evidence for endosymbiotic gene transfer and the early evolution of photosynthesis.

Although the endosymbiotic evolution of chloroplasts through primary and secondary associations is well established, the evolutionary timing and stability of the secondary endosymbiotic events is less well resolved. Heterokonts include both photosynthetic and nonphotosynthetic members and the nonphotosynthetic lineages branch basally in phylogenetic reconstructions. Molecular and morphological data indicate that heterokont chloroplasts evolved via a secondary endosymbiosis, involving a heterotrophic host cell and a photosynthetic ancestor of the red algae and this endosymbiotic event may have preceded the divergence of heterokonts and alveolates. If photosynthesis evolved early in this lineage, nuclear genomes of the nonphotosynthetic groups may contain genes that are not essential to photosynthesis but were derived from the endosymbiont genome through gene transfer. These genes offer the potential to trace the evolutionary history of chloroplast gains and losses within these lineages. Glutamine synthetase (GS) is essential for ammonium assimilation and glutamine biosynthesis in all organisms. Three paralogous gene families (GSI, GSII, and GSIII) have been identified and are broadly distributed among prokaryotic and eukaryotic lineages. In diatoms (Heterokonta), the nuclear-encoded chloroplast and cytosolic-localized GS isoforms are encoded by members of the GSII and GSIII family, respectively. Here, we explore the evolutionary history of GSII in both photosynthetic and nonphotosynthetic heterokonts, red algae, and other eukaryotes. GSII cDNA sequences were obtained from two species of oomycetes by polymerase chain reaction amplification. Additional GSII sequences from eukaryotes and bacteria were obtained from publicly available databases and genome projects. Bayesian inference and maximum likelihood phylogenetic analyses of GSII provided strong support for the monophyly of heterokonts, rhodophytes, chlorophytes, and plants and strong to moderate support for the Opisthokonts. Although the phylogeny is reflective of the unikont/bikont division of eukaryotes, we propose based on the robustness of the phylogenetic analyses that the heterokont GSII gene evolved via endosymbiotic gene transfer from the nucleus of the red-algal endosymbiont to the nucleus of the host. The lack of GSIII sequences in the oomycetes examined here further suggests that the GSIII gene that functions in the cytosol of photosynthetic heterokonts was replaced by the endosymbiont-derived GSII gene.

Amino Acid Sequence↗
PubMed2002

Tracing the LINEs of human evolution.

The amplification of DNA by LINE-1 (L1) retrotransposons has created a large fraction of the human genome. To better understand their role in human evolution we endeavored to delineate the L1 elements that have amplified since the emergence of the hominid lineage. We used an approach based on shared sequence variants to trace backwards from the currently amplifying Ta subfamily. The newly identified groups of insertions account for much of the molecular evolution of human L1s. We report the identification of a L1 subfamily that amplified both before and after the divergence of humans from our closest extant relatives. Progressively more modern groups of L1s include greater numbers of insertions. Our data are consistent with the hypothesis that the rate of L1 amplification has been increasing during recent human evolution.

Animals↗
PubMed1989

Analysis of the first two waves of thymus homing stem cells and their T cell progeny in chick-quail chimeras.

Chick-quail chimeras were used to study precursor/progeny relationships of hemopoietic stem cells (SC) that enter the embryonic thymus in waves to give rise sequentially to the TCR-1+, TCR-2+, and TCR-3+ lineages of T cells. The first wave of SC and their progeny were examined by grafting thymus from 9-d chick embryos (E9) into E3 quails. mAbs specific for chick T cell antigens were used to trace the development of T cells in the recipients. All three lineages of TCR-bearing cells were generated from the first wave of SC. The cortico-medullary transit time was several day shorter for the TCR-1 subpopulation than for the TCR-2 subpopulation, and the peripheral seeding of TCR-2 cells also occurred later in development. The duration of thymocyte production from the first wave of SC that entered the thymus was approximately 3 wk, during which gradual cortical to medullary replacement by second wave SC progeny occurred. When the latter was examined, after transplantation of E7 quail thymus into E3 chick embryos, a sequential generation pattern for the TCR-1 and TCR-2 cell progeny was not evident. Finally, recirculation of T cells to the thymus medulla was defined in this avian model.

Age Factors↗
PubMed2005

Diaspora, a large family of Ty3-gypsy retrotransposons in Glycine max, is an envelope-less member of an endogenous plant retrovirus lineage.

BACKGROUND: The chromosomes of higher plants are littered with retrotransposons that, in many cases, constitute as much as 80% of plant genomes. Long terminal repeat retrotransposons have been especially successful colonizers of the chromosomes of higher plants and examinations of their function, evolution, and dispersal are essential to understanding the evolution of eukaryotic genomes. In soybean, several families of retrotransposons have been identified, including at least two that, by virtue of the presence of an envelope-like gene, may constitute endogenous retroviruses. However, most elements are highly degenerate and are often sequestered in regions of the genome that sequencing projects initially shun. In addition, finding potentially functional copies from genomic DNA is rare. This study provides a mechanism to surmount these issues to generate a consensus sequence that can then be functionally and phylogenetically evaluated. RESULTS: Diaspora is a multicopy member of the Ty3-gypsy-like family of LTR retrotransposons and comprises at least 0.5% of the soybean genome. Although the Diaspora family is highly degenerate, and with the exception of this report, is not represented in the Genbank nr database, a full-length consensus sequence was generated from short overlapping sequences using a combination of experimental and in silico methods. Diaspora is 11,737 bp in length and contains a single 1892-codon ORF that encodes a gag-pol polyprotein. Phylogenetic analysis indicates that it is closely related to Athila and Calypso retroelements from Arabidopsis and soybean, respectively. These in turn form the framework of an endogenous retrovirus lineage whose members possess an envelope-like gene. Diaspora appears to lack any trace of this coding region. CONCLUSION: A combination of empirical sequencing and retrieval of unannotated Genome Survey Sequence database entries was successfully used to construct a full-length representative of the Diaspora family in Glycine max. Diaspora is presently the only fully characterized member of a lineage of putative plant endogenous retroviruses that contains virtually no trace of an extra coding region. The loss of an envelope-like coding domain suggests that non-infectious retrotransposons could swiftly evolve from infectious retroviruses, possibly by anomalous splicing of genomic RNA.

Arabidopsis↗
PubMed1996

Significance of MUC1 and MUC2 mucin expression in colorectal cancer.

AIMS: To compare the lineage specific distribution of MUC1 and MUC2 mucins in normal colorectal mucosa and adenocarcinoma and to identify pathological correlations. METHODS: Paraffin wax sections from 51 colorectal cancers were examined for the expression of MUC1 and MUC2, non-O-acetyl sialic acid and the carbohydrate epitopes Lex, Ley, sialosyl-Lex, sialosyl-Tn, and Tn using standard histochemical methods. RESULTS: MUC1, Lex and Ley co-localised with columnar cell secretions, whereas MUC2, mild periodic acid Schiff and sialosyl-Tn co-localised with goblet cell mucin in both normal and malignant tissues. Sialosyl-Lex and Tn were associated with both lineages. In normal tissues MUC1, Lex and Ley showed only trace expression by crypt base columnar cells. Cancers could be classified into four phenotypes (MUC2+/MUC1-, MUC2+/MUC1+, MUC2-/MUC1+, MUC2-/MUC1-). Particular phenotypes showed significant correlations with cancer type, lymph node spread and peritumoral lymphocytic infiltration and trends falling short of significance in relation to grade of differentiation and contiguous adenoma. CONCLUSIONS: Classification of colorectal cancer by means of lineage specific function may be relevant to both pathogenesis and prognosis.

Adenocarcinoma↗
PubMed2006

Time-lapse tracing of mitotic cell divisions in the early Xenopus embryo using microscopic MRI.

Mitotic cell division is a highly regulated cellular event in all organisms, but its direct visualization in the vertebrates is limited to animals with transparent embryos. Here, we report on the use of microscopic magnetic resonance imaging (mMRI) to noninvasively observe mitotic cell division of early blastomeres in the optically opaque Xenopus laevis embryo. Due to intrinsic tissue contrast, cell nuclei can be directly visualized without the need for contrast enhancing labeling. By taking two-dimensional in vivo time-lapse image sequences, the karyokinesis of a blastomere is followed. Timing and orientation of the cleavages can be traced for five cell divisions to establish a cell lineage tree, including orientation and timing of the mitosis. This work demonstrates for the first time the use of MRI for the visualization of cell divisions and expands the experimental scope of the Xenopus embryo.

Animals↗
PubMed2000

Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells.

In situ detection of neural progenitor cells including stem-like cells is essential for studying the basic mechanisms of the generation of cellular diversity in the CNS, upon which therapeutic treatments for CNS injuries, degenerative diseases, and brain tumors may be based. We have generated rat monoclonal antibodies (Mab 14H1 and 14B8) that recognize an RNA-binding protein Musashi1, but not a Musashi1-related protein, Musashi2. The amino acid sequences at the epitope sites of these anti-Musashi1 Mabs are remarkably conserved among the human, mouse, and Xenopus proteins. Spatiotemporal patterns of Musashi1 immunoreactivity in the developing and/or adult CNS tissues of frogs, birds, rodents, and humans indicated that our anti-Musashi1 Mabs reacted with undifferentiated, proliferative cells in the CNS of all the vertebrates tested. Double or triple immunostaining of embryonic mouse brain cells in monolayer cultures demonstrated strong Musashi1 expression in Nestin(+)/RC2(+) cells. The relative number of Musashi1(+)/Nestin(+)/RC2(+) cells increased fivefold when embryonic forebrain cells were cultured to form 'neurospheres' in which stem-like cells are known to be enriched through their self-renewing mode of growth. Nestin(+)/RC2(-) cells, which included Talpha1-GFP(+) neuronal progenitor cells and GLAST(+) astroglial precursor cells, were also Musashi1(+), as were GFAP(+) astrocytes. Young neurons showed a trace of Musashi1 expression. Cells committed to the oligodendroglial lineage were Musashi(-). Musashi1 was localized to the perikarya of CNS stem-like cells and non-oligodendroglial progenitor cells without shifting to cell processes or endfeet, and is therefore advantageous for identifying each cell and counting cells in situ.

Amino Acid Sequence↗
PubMed2006

Neonatal imitation in rhesus macaques.

The emergence of social behaviors early in life is likely crucial for the development of mother-infant relationships. Some of these behaviors, such as the capacity of neonates to imitate adult facial movements, were previously thought to be limited to humans and perhaps the ape lineage. Here we report the behavioral responses of infant rhesus macaques (Macaca mulatta) to the following human facial and hand gestures: lip smacking, tongue protrusion, mouth opening, hand opening, and opening and closing of eyes (control condition). In the third day of life, infant macaques imitate lip smacking and tongue protrusion. On the first day of life, the model's mouth openings elicited a similar matched behavior (lip smacking) in the infants. These imitative responses are present at an early stage of development, but they are apparently confined to a narrow temporal window. Because lip smacking is a core gesture in face-to-face interactions in macaques, neonatal imitation may serve to tune infants' affiliative responses to the social world. Our findings provide a quantitative description of neonatal imitation in a nonhuman primate species and suggest that these imitative capacities, contrary to what was previously thought, are not unique to the ape and human lineage. We suggest that their evolutionary origins may be traced to affiliative gestures with communicative functions.

Animals↗
PubMed1992

Mhc-DQB repertoire variation in hominoid and Old World primate species.

Comparison of 87 distinct Mhc-DQB sequences, obtained from 13 primate species, demonstrates that five out of eight trans-species Mhc-DQB allele lineages are at least 30 million years old and predate divergence of hominoid and Old World primate species. One lineage may be much older because its members are not only traced back in higher primates, but also are present in a New World primate species. Comparing Mhc-DQB repertoire variation in distinct species, allows one to pinpoint when certain polymorphisms were lost or gained in primate evolution. Heterogeneity observed among members of trans-species Mhc-DQB allele lineages can be explained in major part by point mutations, whereas intraexonic crossing-over is a potent mechanism in generating new allele lineages. The stability of Mhc-DQB polymorphisms is influenced by selective forces because distinct allele lineages appear to have accumulated nucleotide substitutions and amino acid replacements at different rates.

Alleles↗
PubMed1982

Ontogeny and distribution of cells in B lineage in the American leopard frog, Rana pipiens.

Two-color immunofluorescence techniques were used in order to trace the development and distribution of cells expressing immunoglobulin in Rana pipiens. Evidence is provided which suggests that (i) embryo-larval urogenital tissues are sites of generation of cells in B lineage, (ii) during ontogeny, there is a sequential expression of immunoglobulin isotypes on B cell surfaces, (iii) larvae are able to produce the full range of immunoglobulin clases found in adults, and (iv) at least two subpopulations of lymphocytes exist in Rana pipiens, sIg+ and sIg-; thymocytes and presumably peripheral T cells lack conventional surface immunoglobulin. Some ontogenetic and phylogenetic implications are discussed.

Animals↗
PubMed1990

Novel origins of lineage founder cells in the direct-developing sea urchin Heliocidaris erythrogramma.

The lineage and fate of each blastomere in the 32-cell embryo of the direct-developing sea urchin Heliocidaris erythrogramma have been traced by microinjection of tetramethylrhodamine-dextran. The results reveal substantive evolutionary modifications of the ancestral cell lineage pattern of indirect sea urchin development. Significant among these modifications are changes in the time and order of cell lineage segregation: vegetal ectodermal founder cells consistently arise earlier than during indirect development, while internal founder cells generally segregate later and in a different sequence. Modifications have also arisen in proportions of the embryo fated to become various cell types and larval structures. Ectodermal fates, particularly vestibular ectoderm, comprise a greater proportion of the total cellular volume in H. erythrogramma. Among internal cell types, coelom consumes more and endoderm less of the remaining cellular volume than during indirect sea urchin development. Evolutionary modifications are also apparent in the positional origin of larval cell types and structures in H. erythrogramma. These include an apparent tilt in the axis of prospective cell fate relative to the animal-vegetal axis as defined by cleavage planes. Together these evolutionary changes in the cell lineage of H. erythrogramma produce an accelerated loss of dorsoventral symmetry in cell fate relative to indirect development. The extent and diversity of rearrangements in its cell lineage indicate that the non-feeding larva of H. erythrogramma is a highly modified, novel form rather than a degenerate pluteus larva. These same modifications underscore the evolutionarily flexible relationship between cell lineage, gene expression, and larval morphology in sea urchin development.

Animals↗
PubMed1995

Mobilization of an ERV9 human endogenous retroviral element during primate evolution.

ERV9 is a low repeated family of human endogenous retroviral elements, which has close to 50 members, in addition to at least 4000 solitary LTRs. Previous work has shown that randomly selected LTRs can promote transcription of reporter genes, raising the possibility that these sequences may affect the expression of adjacent cellular genes. We report here the structural organization in different primate species of a zinc-finger coding gene whose expression is driven in humans by a solitary ERV9-LTR promoter. Using a PCR strategy and library screening, we were able to trace the origin of the insertion event in the primate lineage and to evaluate the impact of this event on gene structure. Our findings indicate that the integration of the ERV9 element occurred after the split of orangutang from the great apes, but before the divergence of the gorilla lineage. These results suggest that ERV9 elements have been mobile within the primate lineages and may still be active in humans.

Amino Acid Sequence↗