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At least 415 records · Page 23Linked to original sources
PubMed1994

Sustained human hematopoiesis in immunodeficient mice by cotransplantation of marrow stroma expressing human interleukin-3: analysis of gene transduction of long-lived progenitors.

We have developed a novel cotransplantation system in which gene-transduced human CD34+ progenitor cells are transplanted into immunodeficient (bnx) mice together with primary human bone marrow (BM) stromal cells engineered to produce human interleukin-3 (IL-3). The IL-3-secreting stroma produced sustained circulating levels of human IL-3 for at least 4 months in the mice. The IL-3-secreting stroma, but not control stroma, supported human hematopoiesis from the cotransplanted human BM CD34+ progenitors for up to 9 months, such that an average of 6% of the hematopoietic cells removed from the mice were of human origin (human CD45+). Human multilineage progenitors were readily detected as colony-forming units from the mouse marrow over this time period. Retroviral-mediated transfer of the neomycin phosphotransferase gene or a human glucocerebrosidase cDNA into the human CD34+ progenitor cells was performed in vitro before cotransplantation. Human multilineage progenitors were recovered from the marrow of the mice 4 to 9 months later and were shown to contain the transduced genes. Mature human blood cells marked by vector DNA circulated in the murine peripheral blood throughout this time period. This xenograft system will be useful in the study of gene transduction of human hematopoietic stem cells, by tracing the development of individually marked BM stem cells into mature blood cells of different lineages.

Animals↗
PubMed1993

Trypanosoma and Leishmania have clonal population structures of epidemiological significance.

This paper presents three results concerning the population structure of Trypanosoma cruzi, the agent of Chagas disease: (1) The mode of propagation of T. cruzi in nature is clonal; sexual reproduction is either totally absent or so rare that it leaves no traces in the population structure of the parasite. (2) The genetic diversity of the clonal lineages is large: extant T. cruzi represent lineages of descent that have evolved independently for long time spans (up to 40 million years). (3) Some genetically identical clonal lineages ("clonets") are geographically widespread ("ubiquitous"). However, most clonets are endemic, restricted in geographic distribution. These results have each in turn consequences of epidemiological significance: (1) In a sexually-reproducing organism the individual genotype is ephemeral; the entity that persists and evolves is the species ("gene pool"), and a few individuals contain most of the genetic variability of the species. In a clonally-propagating organism, the entity that persists and evolves is the clonal lineage; the genetic diversity of the species can only be captured by extensive sampling of distinct lineages. (2) The extensive genetic divergence among clonal lineages implies proportionally diverse biological characteristics, which are likely to include pathological effects, host propensity, vulnerability to drugs and vaccines, and other medically significant attributes. The extant T. cruzi lineages diverged much before human origins; hence, specific adaptation to human hosts, to whichever extent it exists, has evolved independently in separate lineages, and may not have evolved at all in some T. cruzi. (3) Epidemiological surveys and medical characterization, including search for specific vaccines and drugs, should not proceed randomly; rather, preliminary surveys must identify those clonets that are ubiquitous and target them for investigation. Review of published literature shows that Leishmania (and other parasitic protozoa) also has a clonal population structure. We advance a taxonomic and nomenclatural proposal that is appropriate for clonal organisms, yet simple.

Americas↗
PubMed2006

The internalized CdSe/ZnS quantum dots impair the chondrogenesis of bone marrow mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are capable of differentiating into multiple cell lineages and are useful for therapeutic applications. Labeling the MSCs with fluorescent probes is beneficial in tracing the fate of MSCs after implantation. We have introduced the CdSe/ZnS quantum dots (QDs) into the human bone marrow MSCs and examined the effects of QDs on the proliferation and chondrogenesis of the cells. The internalized QDs were found localized in perinuclear regions and remained there after a number of cell passages. The presence of QDs did not affect the proliferation of cells or the size of chondrospheres formed, when subjected to chondrogenesis induction. However, the expression of mRNA and protein of type II collagen and aggrecan in the chondrospheres was significantly inhibited in cells labeled with QDs, suggesting impaired chondrogenesis. Our results that the presence of QDs interferes with the chondrogenic differentiation of MSCs raise concerns in using the QDs as fluorescence tracers for stem cells.

Biocompatible Materials↗
PubMed2007

Erosion of interaction networks in reduced and degraded genomes.

Unlike eukaryotes, which often recruit duplicated genes into existing protein-protein interaction (PPI) networks, the low levels of gene duplication coupled with the high probability of lateral transfer of novel genes alters the manner in which PPI networks can evolve in bacteria. By inferring the PPIs present in the ancestor to contemporary Gammaproteobacteria, we were able to trace the changes in gene repertoires, and their consequences on PPI network evolution, in several bacterial lineages that have independently undergone reductions in genome size and genome contents. As genomes degrade, virtually all multi-partner proteins have lost interactors; however, the overall average number of connections increases due to the preferential elimination of proteins that interact with only one other protein partner. We also studied the effect of lateral gene transfer on PPI network evolution by analyzing the connectivity of genes that have been gained along the Escherichia coli lineage, as well as those acquired genes subsequently silenced in Shigella flexneri, since diverging from the gammaproteobacterial ancestor. The situation in PPI networks, in which newly acquired genes preferentially attach to the hubs of the network, contrasts that observed in metabolic networks, which evolve by the peripheral gain and loss of genes, and in regulatory networks, in which high connectivity increases the propensity of loss.

Gammaproteobacteria↗
PubMed2006

Labelling of human adipose-derived stem cells for non-invasive in vivo cell tracking.

Human adipose-derived stem cells (ASC) can be expanded in an undifferentiated state or differentiated along the osteogenic, chondrogenic, adipogenic, myogenic, endothelial and neurogenic lineage. To test their in vivo and in situ regenerative potential, their fate needs to be traced after application in suitable defect models. Non-invasive imaging systems allow for real time tracking of labelled cells in the living animal. We have evaluated a bioluminescence cell tracking approach to visualise ASC labelled with luciferase in the living animal. Two procedures have been tested to efficiently label human stem cells with a reporter gene (luciferase, green fluorescent protein), namely lipofection with Lipofectamine 2000 and electroporation with a Nucleofector device. With both lipofection and nucleofection protocols, we have reached transfection efficiencies up to 60%. Reporter gene expression was detectable for 3 weeks in vitro and did not interfere with the phenotype and the stem cell properties of the cells. By means of a highly sensitive CCD camera, we were able to achieve real time imaging of cell fate for at least 20 days after application (intravenous, intramuscular, intraperitoneal, subcutaneous) in nude mice. Moreover, we were able to influence cell mobility by choosing different modes of application such as enclosure in fibrin matrix. The optical imaging system with transient transfection is an elegant cell-tracking concept to follow survival and fate of human stem cells in small animals.

Adipose Tissue↗
PubMed2004

Anticodon and wobble evolution.

The location of the root of life within the Archaea domain close to Methanopyrus kandleri and Aeropyrum pernix on the basis of tRNA sequence clustering has allowed the tracing of evolutionary change in anticodon usages and the wobble rules governing them among different living lineages. Analysis suggests that the primitive Archaea employed simple modes of wobble of anticodon-codon pairing that enable the reading of standard one-amino acid and two-amino acid odon boxes with the uniform use of GNN and UNN anticodons, or the uniform use of GNN, UNN and CNN anticodons, together with the use of a modified C to read the AUA codon of isoleucine. Later on, evolution of tRNA sequences and posttranscriptional modifications brought about in the Bacteria and Eukarya the more complex anticodon usages as described by the Crick Rules of wobble, often with different codon boxes being read with dissimilar anticodon combinations. Still later, the use of a single anticodon to read all four codons in a codon box appeared, both in free living organisms and in organelles. The striking simplicity of the uniform anticodon combinations used by the Archaea to read all standard one- and two-amino acid codon boxes provides strong confirmation for an archaeal root of life.

Animals↗
PubMed2006

Hot crenarchaeal viruses reveal deep evolutionary connections.

The discovery of archaeal viruses provides insights into the fundamental biochemistry and evolution of the Archaea. Recent studies have identified a wide diversity of archaeal viruses within the hot springs of Yellowstone National Park and other high-temperature environments worldwide. These viruses are often morphologically unique and code for genes with little similarity to other known genes in the biosphere, a characteristic that has complicated efforts to trace their evolutionary history. Comparative genomics combined with structural analysis indicate that spindle-shaped virus lineages might be unique to the Archaea, whereas other icosahedral viruses might share a common lineage with viruses of Bacteria and Eukarya. These studies provide insights into the evolutionary history of viruses in all three domains of life.

Archaeal Viruses↗
PubMed2005

Ribonuclease H evolution in retrotransposable elements.

Eukaryotic and prokaryotic genomes encode either Type I or Type II Ribonuclease H (RNH) which is important for processing RNA primers that prime DNA replication in almost all organisms. This review highlights the important role that Type I RNH plays in the life cycle of many retroelements, and its utility in tracing early events in retroelement evolution. Many retroelements utilize host genome-encoded RNH, but several lineages of retroelements, including some non-LTR retroposons and all LTR retrotransposons, encode their own RNH domains. Examination of these RNH domains suggests that all LTR retrotransposons acquired an enzymatically weak RNH domain that is missing an important catalytic residue found in all other RNH enzymes. We propose that this reduced activity is essential to ensure correct processing of the polypurine tract (PPT), which is an important step in the life cycle of these retrotransposons. Vertebrate retroviruses appear to have reacquired their RNH domains, which are catalytically more active, but their ancestral RNH domains (found in other LTR retrotransposons) have degenerated to give rise to the tether domains unique to vertebrate retroviruses. The tether domain may serve to control the more active RNH domain of vertebrate retroviruses. Phylogenetic analysis of the RNH domains is also useful to "date" the relative ages of LTR and non-LTR retroelements. It appears that all LTR retrotransposons are as old as, or younger than, the "youngest" lineages of non-LTR retroelements, suggesting that LTR retrotransposons arose late in eukaryotes.

Animals↗
PubMed1988

Descending pathways to the spinal cord: a comparative study of 22 mammals.

In order to estimate the qualitative commonalities and range of variation among major descending spinal pathways relevant to mankind's ancestral lineage, the supraspinal cell groups originating fibers descending directly to the spinal cord were examined in 22 mammalian species. In a standardized retrograde tract-tracing procedure, flakes of raw HRP were applied directly to the freshly cut fibers of the spinal cord after it had been hemisected at the C1-C2 junction. After a 72-hour survival period, brain and spinal cord tissues were processed by conventional HRP-processing techniques. This procedure was performed on 94 individual animals. Of this total, 41 individual cases were eliminated by a rigorous culling procedure. The results are based on 53 individuals representing 15 species selected for their successive kinship with mankind and seven species in two other lineages selected for the convergence of their visual or sensorimotor systems with anthropoids. The 22 species represent 19 genera, 14 families, eight orders, and two subclasses of Mammalia. The results show that at least 27 supraspinal cell groups, each containing intensely labeled cells, can be readily identified in each of the species. Despite vast quantitative differences in cell number and cell size, this qualitative uniformity among the relatively large number of diverse taxa suggests that the same pathways were probably present in the extinct ancestors throughout mankind's mammalian lineage and are probably still present in extant viviparous mammals as well. If so, these pathways are as old in phylogenetic history as the last common ancestor of marsupial and placental mammals--dating from the late Jurassic to early Cretaceous, perhaps 145-120 million years ago. Further comparison of the results with similar experimental findings in members of other vertebrate classes supports the notion that several of these same pathways can be traced to even more remote ancestry, with some possibly as old as the entire vertebrate subphylum--dating from the early Devonian or before, perhaps 430 million years ago. Within mankind's ancestral lineage, from the appearance of vertebrates to the appearance of mammals, there seems to have been an irregular stepwise augmentation of the set of descending pathways until the full mammalian complement was finally attained with the appearance of the corticospinal tract.

Animals↗
PubMed2005

A common somitic origin for embryonic muscle progenitors and satellite cells.

In the embryo and in the adult, skeletal muscle growth is dependent on the proliferation and the differentiation of muscle progenitors present within muscle masses. Despite the importance of these progenitors, their embryonic origin is unclear. Here we use electroporation of green fluorescent protein in chick somites, video confocal microscopy analysis of cell movements, and quail-chick grafting experiments to show that the dorsal compartment of the somite, the dermomyotome, is the origin of a population of muscle progenitors that contribute to the growth of trunk muscles during embryonic and fetal life. Furthermore, long-term lineage analyses indicate that satellite cells, which are known progenitors of adult skeletal muscles, derive from the same dermomyotome cell population. We conclude that embryonic muscle progenitors and satellite cells share a common origin that can be traced back to the dermomyotome.

Animals↗
PubMed2006

Positive selection on the nonhomologous end-joining factor Cernunnos-XLF in the human lineage.

BACKGROUND: Cernunnos-XLF is a nonhomologous end-joining factor that is mutated in patients with a rare immunodeficiency with microcephaly. Several other microcephaly-associated genes such as ASPM and microcephalin experienced recent adaptive evolution apparently linked to brain size expansion in humans. In this study we investigated whether Cernunnos-XLF experienced similar positive selection during human evolution. RESULTS: We obtained or reconstructed full-length coding sequences of chimpanzee, rhesus macaque, canine, and bovine Cernunnos-XLF orthologs from sequence databases and sequence trace archives. Comparison of coding sequences revealed an excess of nonsynonymous substitutions consistent with positive selection on Cernunnos-XLF in the human lineage. The hotspots of adaptive evolution are concentrated around a specific structural domain, whose analogue in the structurally similar XRCC4 protein is involved in binding of another nonhomologous end-joining factor, DNA ligase IV. CONCLUSION: Cernunnos-XLF is a microcephaly-associated locus newly identified to be under adaptive evolution in humans, and possibly played a role in human brain expansion. We speculate that Cernunnos-XLF may have contributed to the increased number of brain cells in humans by efficient double strand break repair, which helps to prevent frequent apoptosis of neuronal progenitors and aids mitotic cell cycle progression. REVIEWERS: This article was reviewed by Chris Ponting and Richard Emes (nominated by Chris Ponting), Kateryna Makova, Gáspár Jékely and Eugene V. Koonin.

Journal Article↗
PubMed2025

Uncovering new lineages in the Sunda pangolin (Manis javanica) with museum mitogenomics.

Accurately identifying evolutionarily significant units (ESUs) is crucial for conservation planning, especially for species like pangolins threatened by overhunting and habitat loss. ESUs help categorize different pangolin populations, aiding in understanding their genetic diversity and distribution, which is vital for targeted conservation efforts. This research generated mitochondrial genomes from historical museum specimens of Sunda pangolins (Manis javanica) from underrepresented locations, uncovering a new evolutionary lineage from the Mentawai Islands that diverged from Indochina and west Sundaland populations around 760 000 years ago. This population thereby represents a divergent ESU with a small distribution, important for conservation planning. The novel sequences provide resources for forensic labs tracing the origin of confiscated scales and shed light into the potential distribution of the 'mysterious pangolin'. Additionally, this research confirmed the presence of the two major M. javanica lineages in Java and extended the known distribution of the eastern clade to Bali and East Kalimantan. Our findings potentially suggest a recent bottleneck and postglacial expansion of pangolins across Indochina and west Sundaland. Further investigation with genomic and morphological evidence, contact area sampling and type sequencing will be required to evaluate the taxonomic status of different M. javanica lineages and M. culionensis.

Genomics↗
PubMed1993

Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients.

The contribution of infused bone marrow cells to long-term haemopoietic recovery in patients undergoing autologous bone marrow transplantation is unknown. Such information would help to clarify the role of this procedure in cancer therapy and would aid in the development of strategies to reduce the risk of subsequent aplasia. By transferring a neomycin resistance marker gene into the marrow cells of 20 patients before transplantation, we were able to trace the pattern of haemopoietic reconstitution postinfusion. The marker gene was present and expressed in all haemopoietic lineages in vivo in 15 of 18 evaluable patients at 1 month post-transplantation, in 8 of 9 patients at 6 months, and in 5 of 5 at 1 year. The marker has remained detectable for up to 18 months--the duration of our study. Our findings indicate that harvested bone marrow consistently contributes to long-term multilineage recovery of haemopoiesis after autologous marrow transplantation in cancer patients. These results provide a rationale for the continued exploration of more ablative preparative regimens with single or sequential autologous marrow transplants.

Adolescent↗
PubMed2006

An evolutionary perspective on the regulation of carpel development.

The carpel, or female reproductive organ enclosing the ovules, is one of the major evolutionary innovations of the flowering plants. The control of carpel development has been intensively studied in the model eudicot species Arabidopsis thaliana. This review traces the evolutionary history of genes involved in carpel development by surveying orthologous genes in taxa whose lineages separated from that of A. thaliana at different levels of the phylogenetic tree of the seed plants. Some aspects of the control of female reproductive development are conserved between the flowering plants and their sister group, the gymnosperms, indicating the presence of these in the common ancestor of the extant seeds plants, some 300 million years ago. Gene duplications that took place in the pre-angiosperm lineage, before the evolution of the first flowering plants, provided novel gene clades of potential importance for the origin of the carpel. Subsequent to the appearance of the first flowering plants, further gene duplications have led to sub-functionalization events, in which pre-existing reproductive functions were shared between paralogous gene clades. In some cases, fluidity in gene function is evident, leading to similar functions in carpel development being controlled by non-orthologous genes in different taxa. In other cases, gene duplication events have created sequences that evolved novel functions by the process of neo-functionalization, thereby generating biodiversity in carpel and fruit structures.

Biological Evolution↗
PubMed2005

Detecting active methanogenic populations on rice roots using stable isotope probing.

Methane is formed on rice roots mainly by CO2 reduction. The present study aimed to identify the active methanogenic populations responsible for this process. Soil-free rice roots were incubated anaerobically under an atmosphere of H2/(13CO2) or N2/(13CO2) with phosphate or carbonate (marble) as buffer medium. Nucleic acids were extracted and fractionated by caesium trifluoroacetate equilibrium density gradient centrifugation after 16-day incubation. Community analyses were performed for gradient fractions using terminal restriction fragment polymorphism analysis (T-RFLP) and sequencing of the 16S rRNA genes. In addition, rRNA was extracted and analysed at different time points to trace the community change during the 16-day incubation. The Methanosarcinaceae and the yet-uncultured archaeal lineage Rice Cluster-I (RC-I) were predominant in the root incubations when carbonate buffer and N2 headspace were used. The analysis of [13C]DNA showed that the relative 16S rRNA gene abundance of RC-I increased whereas that of the Methanosarcinaceae decreased with increasing DNA buoyant density, indicating that members of RC-I were more active than the Methanosarcinaceae. However, an unexpected finding was that RC-I was suppressed in the presence of high H2 concentrations (80%, v/v), which during the early incubation period caused a lower CH4 production compared with that with N2 in the headspace. Eventually, however, CH4 production increased, probably because of the activity of Methanosarcinaceae, which became prevalent. Phosphate buffer appeared to inhibit the activity of the Methanosarcinaceae, resulting in lower CH4 production as compared with carbonate buffer. Under these conditions, Methanobacteriaceae were the prevalent methanogens. Our study suggests that the active methanogenic populations on rice roots change in correspondence to the presence of H2 (80%, v/v) and the type of buffer used in the system.

Carbon Isotopes↗
PubMed2005

Efficient differentiation and integration of lineage-restricted neural precursors in the traumatically injured adult cat spinal cord.

Several recent studies have shown that highly undifferentiated neural stem cells (NSCs) grafted into the intact or injured adult spinal cord of animal either remain undifferentiated or show fate restriction to a astrocytic lineage. This indicates that functionally diverse roles expected of cellular replacement cannot be performed by the transplantation of highly immature precursors; rather, more differentiated or appropriate mixtures of more restricted neural precursors may be important in replacement strategies. In this study, we investigated the ability of lineage-restricted neural progenitors derived from adult mouse periventricular subependymal zone (SEZ) to integrate and differentiate into the chronically injured adult spinal cord. To this end, NSCs were grown as adherent cultures followed by expansion in non-adhesive dishes. This allowed us to grow NSCs as colonies of restricted neural precursors, illustrated by NCAM, nestin, Sox-2, A2B5, and GFAP immunostaining. The mixture of lineage-restricted precursors was directly implanted into the chronically injured spinal cord of immunosuppressed cats. The fate of the cells was traced with GFP fluorescence and immunocytochemistry for neural markers such as beta-III-tubulin, GFAP, and Ng2. After four weeks, transplanted cells survived, giving rise to neurons and in addition to cells with an astrocytic phenotype. We conclude that a mixture of more restricted neural precursors may be better suited than highly immature NSCs for neural replacement strategies after central nervous system (CNS) injuries.

Animals↗
PubMed1999

Polarity of the mouse embryo is anticipated before implantation.

In most species, the polarity of an embryo underlies the future body plan and is determined from that of the zygote. However, mammals are thought to be an exception to this; in the mouse, polarity is generally thought to develop significantly later, only after implantation. It has not been possible, however, to relate the polarity of the preimplantation mouse embryo to that of the later conceptus due to the lack of markers that endure long enough to follow lineages through implantation. To test whether early developmental events could provide cues that predict the axes of the postimplantation embryo, we have used the strategy of injecting mRNA encoding an enduring marker to trace the progeny of inner cell mass cells into the postimplantation visceral endoderm. This tissue, although it has an extraembryonic fate, plays a role in axis determination in adjacent embryonic tissue. We found that visceral endoderm cells that originated near the polar body (a marker of the blastocyst axis of symmetry) generally became distal as the egg cylinder formed, while those that originated opposite the polar body tended to become proximal. It follows that, in normal development, bilateral symmetry of the mouse blastocyst anticipates the polarity of the later conceptus. Moreover, our results show that transformation of the blastocyst axis of symmetry into the axes of the postimplantation conceptus involves asymmetric visceral endoderm cell movement. Therefore, even if the definitive axes of the mouse embryo become irreversibly established only after implantation, this polarity can be traced back to events before implantation.

Animals↗
PubMed1984

Quantitative lineage analysis of the frog's nervous system. I. Lineages of Rohon-Beard neurons and primary motoneurons.

After injection of horseradish peroxidase into single blastomeres in Xenopus embryos at 2- to 512-cell stages, all of the descendants could be traced and counted at tailbud stages. Progenitors of Rohon-Beard neurons and of primary spinal motoneurons were identified, and all neurons of each type that originated from individual progenitors were counted. From these data were derived the geometric mean of the number (N) of Rohon-Beard neurons (or primary motoneurons) that descended from a single progenitor at each generation from the first to ninth, the mean number of progenitors of each generation, and the probability that, following mitosis, daughter cells continue in the Rohon-Beard (or primary motoneuron) lineages (the continuation probability). On a log-log plot a straight line fitted to the N values intercepts the abscissa at the 13th generation for Rohon-Beard progenitors and the 16th generation for primary motoneuron progenitors. This indicates the number of generations before the entire set of each type of neuron is finally produced. The Rohon-Beard neurons and primary motoneurons each originated from a separate group of progenitors at the 9th generation (512-cell stage), but those progenitors gave rise to mesodermal, endodermal, and ectodermal cells in addition to neurons. Nevertheless, the continuation probability significantly greater than 0.5 shows that there is a bias toward recruitment of progenitors into lineages leading to production of those two types of neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗