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At least 127 records · Page 7Linked to original sources
PubMed2006

Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity.

BACKGROUND: Umbilical cord blood (CB) is a promising source of hematopoietic stem cells for allogeneic transplantation. However, delayed engraftment and impaired immune reconstitution remain major limitations. Enrichment of donor grafts with CB T cells expanded ex vivo might facilitate improved T-cell immune reconstitution post-transplant. We hypothesized that CB T cells could be expanded using paramagnetic microbeads covalently linked to anti-CD3 and anti-CD28 Ab. METHODS: CB units were divided into three fractions: (1) cells cultured without beads, (2) cells cultured with beads and (3) cells cultured with beads following CD3+ magnetic enrichment. All fractions were cultured for 14 days in the presence of IL-2 (200 IU/mL). RESULTS: A mean 100-fold expansion (range 49-154) of total nucleated cells was observed in the CD3+ magnetically enriched fraction. Following expansion, CB T cells retained a naive and/or central memory phenotype and contained a polyclonal TCR diversity demonstrated by spectratyping. DISCUSSION: Our data provide evidence that naive and diverse CB T cells may be expanded ex vivo and warrant additional studies in the setting of human CB transplantation.

Antigens, CD↗
PubMed2006

Mitochondrial DNA reveals a mosaic pattern of phylogeographical structure in Atlantic and Mediterranean populations of anchovy (Engraulis encrasicolus).

This study extends the geographic coverage of a previous study of mitochondrial DNA restriction fragment length polymorphism in European anchovy. Both studies together include 24 samples representing 17 localities extending from the Black Sea, through the Mediterranean Sea to the eastern Atlantic as far south as Dakar, Senegal. Eighty-eight haplotypes define two clades (A and B) separated by 3.2% sequence divergence. Clade A has a star-like genealogy indicative of a recent population expansion. Clade B has a more complex genealogy, consisting of several haplotypes at intermediate frequencies. The distributions of these clades consist of a mosaic with abrupt changes between some areas and gradients between other areas. Clade A predominates the Black and Aegean seas, but is present throughout the Mediterranean. Unexpectedly, new data show that clade A is also at a high frequency in the Atlantic, from Portugal to at least Senegal. Overall, the level of genetic differentiation among populations is high (F(ST)=0.148, p<0.0001), with the greatest differences between basins. AMOVA reveals four main geographical groups: Atlantic, central Mediterranean, Aegean Sea, and Black Sea. Mismatch distribution clearly indicates historical bottleneck and population expansion for clade A, while for clade B such evidence is equivocal. This difference may reflect a range expansion for both clades, but with higher gene flow (Nm values) between demes for clade A. Both contemporary and historical processes are important in shaping the complex genetic population structure of European anchovy.

Animals↗
PubMed2002

Using nested clade analysis to assess the history of colonization and the persistence of populations of an Iberian Lizard.

The distribution of the lizard Lacerta schreiberi is likely to have been severely affected by the climatic cycles that have influenced the Iberian Peninsula. Information about the species ecology and Iberian physiogeography was used to generate specific hypotheses about episodes of colonization and subsequent population persistence. These hypotheses generated predictions about the distribution of genetic variation, which were tested using nested clade analysis (NCA) supplemented by analysis of molecular variance (amova). Two predictions were confirmed by NCA; that is those that specified multiple and allopatric refugia. However, the remaining three predictions were not corroborated by the analyses. Firstly, a simple analysis of the distribution of genetic variability failed to detect an expected difference in the pattern of colonization between the inland mountain system and the coastal region. Moreover, while NCA did detect the expected genetic pattern in southern coastal populations, it was explained in terms of long-distance migration, which seems implausible because of the extent of unsuitable habitat. A more likely cause of the pattern is population fragmentation and a reduction in population size caused during the Holocene. Finally, NCA also failed to detect a northwestern population expansion, which is supported by other evidence. We conclude that NCA has a limited ability to detect range expansion led by individuals with more ancestral (interior) haplotypes.

Animals↗
PubMed2004

Molecular systematics and phylogeography of the Plethodon elongatus species group: combining phylogenetic and population genetic methods to investigate species history.

Plethodon elongatus and P. stormi (Caudata: Plethodontidae) are Pacific Northwest endemic species which occur in northwestern California and southwestern Oregon. Studies on these salamanders have resulted in differing taxonomic conclusions, but the underlying historical hypotheses, at both inter- and intraspecific levels, have never been examined in a molecular framework. Here, representatives of 81 populations from throughout the range of both taxa are sequenced. Portions of three mitochondrial protein-coding genes (cytochrome b, NADH dehydrogenase subunit 4, and ATPase 6) were sequenced. Four haplotype groups with nonoverlapping geographical ranges were recovered in separate and combined analyses of the data. One clade corresponds to the distribution of P. stormi, while the remaining three comprise P. elongatus. Phylogenetic relationships among haplotype groups differ in separate analyses of the genes but converge on a well-supported topology, with P. elongatus and P. stormi as monophyletic sister taxa, in combined Maximum Parsimony and Maximum Likelihood analyses. Population genetic analyses of mismatch distributions and Tajima's D-statistic are consistent with range expansion for the largest clade within P. elongatus, covering the northern two-thirds of the species range. In contrast, the P. stormi haplotype clade and the P. elongatus clade from the southern third of the species range may have been relatively stable. Morphological boundaries between P. elongatus and P. stormi are largely congruent with mitochondrial DNA breaks and continued treatment as sister taxa is supported. Although mitochondrial DNA haplotype groups may reflect historical separation within P. elongatus, genetic barriers are incongruent with intraspecific patterns of morphological variation.

Animals↗
PubMed1999

Genetic diversity and differentiation of Taxodium in the south-eastern United States using cleaved amplified polymorphic sequences.

Two taxa of Taxodium, bald cypress and pond cypress, occur in the south-eastern United States. The ranges of these taxa overlap in the south-eastern Coastal Plain, with the range of the latter being more restricted. Although these taxa co-occur throughout a portion of the more expansive range of bald cypress (Taxodium distichum (L.) L. C. Rich), the habitats of the two taxa appear to differ. Consequently, considerable debate has occurred regarding the taxonomic status of pond cypress. Some authors recognize pond cypress as a distinct species (Taxodium ascendens Brongn.), whereas others recognize it as a variety/ecotype (Taxodium distichum var. imbricarium (Nutt.) Croom). In this study, the genetic diversity of these two taxa was investigated using 10 DNA markers based on sequences from cDNA clones of Cryptomeria japonica. Cryptomeria is a monospecific genus native to Japan, and is a close relative of Taxodium. These markers were codominant in Cryptomeria and were presumed to be codominant in Taxodium. DNA was extracted from leaf tissue collected from six populations of bald cypress and seven populations of pond cypress throughout Florida and Georgia. The average heterozygosities of bald cypress and pond cypress were 0.386 (SE 0.040) and 0.380 (SE 0.040), respectively. Most of the genetic variation (91.9%) was found within populations, 4.9% was found between populations and 3.2% between taxa. Results of DNA analysis using cleaved amplified polymorphic sequences (CAPS) in this study did not suggest that pond cypress was a species distinct from bald cypress. Our conclusion is that the two taxa of Taxodium should be given varietal status.

Base Sequence↗
PubMed2000

Dynamics of speciation and diversification in a metapopulation.

We develop a simple framework for modeling speciation and diversification as a continuous process of accumulation of genetic (or morphological) differences accompanied by species and subpopulation extinction and/or range expansion. This framework can be used to approach a number of questions such as species-area distribution, species-range size distribution, the rate of ecological turnover, asymmetries of range division between sister species, waiting time until speciation and extinction, the relationship between the geographic range size and the probability of speciation, the relationships between subpopulation-level parameters and metapopulation-level parameters, and the effects of taxonomic level on these rates, distributions, and parameters. We illustrate some of these applications using numerical simulations. We develop approximations describing the dependence of the number of different taxonomic units, their average range size, and the rate of their turnover on the system size, the rate of fixation of genetic (or morphological) changes in local demes, and the rate of local extinction and colonization.

Algorithms↗
PubMed1997

[Structural analysis of 16 different coronary stent systems].

Parallel with the increasing number of coronary stent implantation procedures, new or more elaborate coronary stents were introduced into clinical use almost every month in 1996. We have studied the architecture, surface-morphology, and shape-conversion of 16 different coronary stent systems. The objective of our study was to detect possible specific design and surface features which might influence the healing process in stent restenosis and stent thrombosis. Using electron microscopy we found ultrasmooth surfaces on 5 stents. All other coronary stents revealed individually varying and partly sharp-edged surface irregularities. Video-based morphometry showed covering between 8.3% and 26.4%. Stent shortening after in-vitro expansion ranged from 0% up to 10.5% of the initial stent length. In some stent systems balloon dilation lead to over-expansion of the stent margin. This over-expansion amounted up to 20% of the balloon diameter and the stents revealed a rather biconcave than homogeneous expansion pattern. This phenomenon was also found after postmortal stent implantation in 20 autopsied hearts.

Angioplasty, Balloon, Coronary↗
PubMed2000

The retroviral transduction of HOXC4 into human CD34(+) cells induces an in vitro expansion of clonogenic and early progenitors.

OBJECTIVE: +HOX genes are expressed in the hematopoietic system and increasing data point to their involvement in the control of proliferation and/or differentiation. Genes belonging to the C cluster are preferentially expressed in developing and differentiated lymphoid lineages. However, recent studies demonstrated, by RT-PCR, that the HOXC4 gene is also actively transcribed in the most undifferentiated hematopoietic cells (CD34(+)38(low)) and in more mature myeloid and erythroid progenitors. We evaluated the expression of HOXC4 protein on human CD34(+) cells and the in vitro effect of its overexpression on proliferation and differentiation. MATERIALS AND METHODS: We assessed the expression of HOXC4 on human CD34(+) cells using a polyclonal antibody raised against the C-terminal portion of the protein expressed using the baculovirus system. Overexpression of HOXC4 in human CD34(+) cells was obtained by retroviral gene transfer; its effect on clonogenic (CFU-GM, BFU-E, and CFU-GEMM) and early progenitors (LTC-IC) was evaluated. RESULTS: The HOXC4 protein is indeed expressed in human CD34(+) cells, and its overexpression in human CD34(+) cells increases the proliferation potential of clonogenic and early progenitors. CFU-GM showed a median threefold expansion (range: 1.1-19.4; p < 0.002) compared with control transduced with the vector alone. The increment of BFU-E was higher (median ninefold, range 2.5-35; p < 0. 0009) and erythroid colonies presented a larger size with normal morphology. An even more marked effect was observed on LTC-IC (median 13, onefold; range 4.1-102.1, p < 0.0001). CONCLUSION: We demonstrate that HOXC4 is expressed in CD34(+) cells and that its overexpression induces an in vitro expansion of committed as well as very early hematopoietic progenitors. The most striking effect was obtained on LTC-IC with an expansion of 13.1-fold. The enforced expression of HOXC4 induced a significant increase (p < 0.009) in the number of erythroid colonies compared with CFU-GM, although without perturbing, at least in vitro, the maturation program of the cells. On the other hand, the effect of the gene overexpression did not induce any skewing in the colony types derived from the myeloid lineage.

Antigens, CD34↗
PubMed1992

Changes in population density and distribution of Ixodes dammini (Acari: Ixodidae) in Wisconsin during the 1980s.

Changes in the density and distribution of Ixodes dammini, Spielman Clifford, Piesman & Corwin were assessed in Wisconsin by examining hunter-killed deer for ticks in 1981 and 1989. Deer examination sites were distributed widely across the state and included 23 sites in 1981 and 15 sites in 1989; 10 sites were visited both years. Between 1981 and 1989, I. dammini became more abundant throughout its range, and I. dammini range expanded into the southwestern portion of Wisconsin. I. dammini was not found in the eastern one-third of the state. When compared with 1981, the 1989 survey revealed significant increases in the proportion of infested deer in the southwest (Arena), higher levels of infestation of individual deer (number of ticks per individual deer) in the central west (Bangor-W. Salem), and significantly less disparity between the proportions of infested male deer and infested female deer in the north (Spooner) compared with sites farther south. These results are consistent with a pattern of I. dammini range expansion from north to south, followed by an increase in population density in the colonized areas. Dermacentor albipictus Packard was present throughout the range of I. dammini and at sites in the northeastern quadrant of Wisconsin where I. dammini was not found. The range of D. albipictus did not change between the survey years, but its population density increased significantly at sites in the north. There is no evidence for interaction between the two tick species that might affect tick distribution or population density, nor can the greater number of I. dammini found in 1989 be attributed to increased tick activity because of warmer weather; temperatures were cooler in 1989 than 1981.

Animals↗
PubMed2000

Clinical and genetic findings in Finnish ataxia patients with the spinocerebellar ataxia 8 repeat expansion.

Spinocerebellar ataxia 8 (SCA8) is caused by a CTG repeat expansion in an untranslated region of a recently cloned gene on 13q21. The pathogenic role of this trinucleotide repeat was evaluated by examining 154 Finnish ataxia patients and 448 controls. Expansions ranging from 100 to 675 repeats were present in 9 (6%) unrelated patients and in 13 (3%) controls. There was a threefold excess of shorter expansions (<204 repeats) in the ataxia series, and the expansions tended to cluster in patients with a family history for the disease. Clinical and genetic data were subsequently collected from 15 patients. Common initial symptoms included gait instability, dysarthria, and tremor. A marked cerebellar atrophy in magnetic resonance imaging or computed tomography was found in all patients. Pyramidal affection was often seen, and various kinds of cognitive impairment were evident in 40% of patients. Disease progression was slow, and fluctuation of symptoms was commonly observed. A maternal penetrance bias was not seen, nor was there any clear-cut negative correlation between age of onset and repeat number. Meiotic but not mitotic instability of the repeat expansion was evident. Haplotype analysis suggests multiple origins for the Finnish spinocerebellar ataxia 8 repeat expansions.

Adolescent↗
PubMed2002

A single mitochondrial lineage is shared by morphologically and allozymatically distinct freshwater Corbicula clones.

Despite that the exotic invasion and rapid range expansion of Asian freshwater Corbicula into new environments have been of intensive research topic in freshwater ecology, the genetic structures of freshwater Corbicula in its native range remain poorly understood. In this study, the genetic structures of two Korean freshwater Corbicula clonal lineages were characterized by cross-referencing the nuclear genomic structures with mtDNA sequence analysis. In spite of substantial genetic differences (Nei's D = 0.363-0.372) and a pronounced level of fixed allelic distinctions (in six of 20 allozyme loci) between Corbicula lineages, no lineage-specific mtDNA differentiation was observed. The evident disjunction between mtDNA sequences and nuclear genomes is a compelling evidence for the existence of interspecific nuclear hybrid genome structures, comprising different combinations of paternal and maternal contributions. This unusual novel finding is the first case demonstrating that morphologically and allozymatically distinct, yet mitochondrially identical clonal lineages exist in the genus Corbicula. However, we could not find the ancestral species for these two clonal lineages in the present study, and the answer for this question must wait until the genetic structure of Asian Corbicula taxa is fully characterized.

Animals↗
PubMed2003

CTG repeat instability and size variation timing in DNA repair-deficient mice.

Type 1 myotonic dystrophy is caused by the expansion of an unstable CTG repeat in the DMPK gene. We have investigated the molecular mechanisms underlying the CTG repeat instability by crossing transgenic mice carrying >300 unstable CTG repeats in their human chromatin environment with mice knockout for genes involved in various DNA repair pathways: Msh2 (mismatch repair), Rad52 and Rad54 (homologous recombination) and DNA-PKcs (non-homologous end-joining). Genes of the non-homologous end-joining and homologous recombination pathways did not seem to affect repeat instability. Only lack of Rad52 led to a slight decrease in expansion range. Unexpectedly, the absence of Msh2 did not result in stabilization of the CTG repeats in our model. Instead, it shifted the instability towards contractions rather than expansions, both in tissues and through generations. Furthermore, we carefully analyzed repeat transmissions with different Msh2 genotypes to determine the timing of intergenerational instability. We found that instability over generations depends not only on parental germinal instability, but also on a second event taking place after fertilization.

Animals↗
PubMed1997

Reconstruction of head and neck hemangiomas with tissue expansion in the pediatric population.

A retrospective study of 245 patients with 299 hemangiomas treated from May 1981 to April 1994 was done. A subset of 175 of these patients (58.5%) had hemangiomas of the head and neck. Six of the 175 (3%) required reconstruction following laser therapy. Tissue expansion was chosen for each of these reconstructions. Five females and 1 male underwent tissue expansion. The age of the patients at the time of tissue expansion ranged from 2.5 to 12 years, with an average of 6 years. Tissue expander sizes were 50 cc and 100 cc. Infection was seen during the course of expansion in 1 patient. Satisfactory results were achieved after reconstruction in all cases. Tissue expansion is the treatment of choice for reconstruction of head and neck hemangioma deformities following laser or other surgical procedures as well as involution.

Child↗
PubMed2004

Huntington's Disease-like 2 (HDL2) in North America and Japan.

Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of r2=0.29, p=0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.

Adult↗
PubMed2003

A molecular phylogeny of the neotropical butterfly genus Anartia (Lepidoptera: Nymphalidae).

While Anartia butterflies have served as model organisms for research on the genetics of speciation, no phylogeny has been published to describe interspecific relationships. Here, we present a molecular phylogenetic analysis of Anartia species relationships, using both mitochondrial and nuclear genes. Analyses of both data sets confirm earlier predictions of sister species pairings based primarily on genital morphology. Yet both the mitochondrial and nuclear gene phylogenies demonstrate that Anartia jatrophae is not sister to all other Anartia species, but rather that it is sister to the Anartia fatima-Anartia amathea lineage. Traditional biogeographic explanations for speciation across the genus relied on A. jatrophae being sister to its congeners. These explanations invoked allopatric divergence of sister species pairs and multiple sympatric speciation events to explain why A. jatrophae flies alongside all its congeners. The molecular phylogenies are more consistent with lineage divergence due to vicariance, and range expansion of A. jatrophae to explain its sympatry with congeners. Further interpretations of the tree topologies also suggest how morphological evolution and eco-geographic adaptation may have set species range boundaries.

Animals↗
PubMed2005

Bayesian estimation of recent migration rates after a spatial expansion.

Approximate Bayesian computation (ABC) is a highly flexible technique that allows the estimation of parameters under demographic models that are too complex to be handled by full-likelihood methods. We assess the utility of this method to estimate the parameters of range expansion in a two-dimensional stepping-stone model, using samples from either a single deme or multiple demes. A minor modification to the ABC procedure is introduced, which leads to an improvement in the accuracy of estimation. The method is then used to estimate the expansion time and migration rates for five natural common vole populations in Switzerland typed for a sex-linked marker and a nuclear marker. Estimates based on both markers suggest that expansion occurred <10,000 years ago, after the most recent glaciation, and that migration rates are strongly male biased.

Animals↗
PubMed2005

Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak.

Genealogy can illuminate the evolutionary path of important human pathogens. In some microbes, strict clonal reproduction predominates, as with the worldwide dissemination of Mycobacterium leprae, the cause of leprosy. In other pathogens, sexual reproduction yields clones with novel attributes, for example, enabling the efficient, oral transmission of the parasite Toxoplasma gondii. However, the roles of clonal or sexual propagation in the origins of many other microbial pathogen outbreaks remain unknown, like the recent fungal meningoencephalitis outbreak on Vancouver Island, Canada, caused by Cryptococcus gattii. Here we show that the C. gattii outbreak isolates comprise two distinct genotypes. The majority of isolates are hypervirulent and have an identical genotype that is unique to the Pacific Northwest. A minority of the isolates are significantly less virulent and share an identical genotype with fertile isolates from an Australian recombining population. Genotypic analysis reveals evidence of sexual reproduction, in which the majority genotype is the predicted offspring. However, instead of the classic a-alpha sexual cycle, the majority outbreak clone appears to have descended from two alpha mating-type parents. Analysis of nuclear content revealed a diploid environmental isolate homozygous for the major genotype, an intermediate produced during same-sex mating. These studies demonstrate how cryptic same-sex reproduction can enable expansion of a human pathogen to a new geographical niche and contribute to the ongoing production of infectious spores. This has implications for the emergence of other microbial pathogens and inbreeding in host range expansion in the fungal and other kingdoms.

Animals↗
PubMed2006

Inferring the population structure and demographic history of the tick, Amblyomma americanum Linnaeus.

A hierarchial population genetic study was conducted on 703 individual Amblyomma americanum from nine populations in Georgia, U.S.A. Populations were sampled from the Coastal Plain, midland Piedmont region, and the upper Piedmont region. Twenty-nine distinct haplotypes were found. A minimum spanning tree was constructed that indicated these haplotypes comprised two lineages, the root of which was distinctly star-like. The majority of the variation found was among ticks within each population, indicating high amounts of gene flow and little genetic differentiation between the three regions. An overall F(ST) value of 0.006 supported the lack of genetic structuring between collection sites in Georgia. Mantel regression analysis revealed no isolation by distance. Signatures of population expansion were detected in the shapes of the mismatch distribution and tests of neutrality. The absence of genetic differentiation combined with the rejection of the null model of isolation by distance may indicate recent range expansion in Georgia or insufficient time to reach an equilibrium where genetic drift may have affected allele frequencies. Alternatively, the high degree of panmixia found within A. americanum in Georgia may be due to bird-mediated dispersal of ticks increasing the genetic similarity between geographically separated populations.

Animals↗