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At least 757 records · Page 42Linked to original sources
PubMed2000

Transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development.

During limb development, chondrocytes located at the epiphyseal tip of long bone models give rise to articular tissue, whereas the more numerous chondrocytes in the shaft undergo maturation, hypertrophy, and mineralization and are replaced by bone cells. It is not understood how chondrocytes follow these alternative pathways to distinct fates and functions. In this study we describe the cloning of C-1-1, a novel variant of the ets transcription factor ch-ERG. C-1-1 lacks a short 27-amino acid segment located approximately 80 amino acids upstream of the ets DNA binding domain. We found that in chick embryo long bone anlagen, C-1-1 expression characterizes developing articular chondrocytes, whereas ch-ERG expression is particularly prominent in prehypertrophic chondrocytes in the growth plate. To analyze the function of C-1-1 and ch-ERG, viral vectors were used to constitutively express each factor in developing chick leg buds and cultured chondrocytes. We found that virally driven expression of C-1-1 maintained chondrocytes in a stable and immature phenotype, blocked their maturation into hypertrophic cells, and prevented the replacement of cartilage with bone. It also induced synthesis of tenascin-C, an extracellular matrix protein that is a unique product of developing articular chondrocytes. In contrast, virally driven expression of ch-ERG significantly stimulated chondrocyte maturation in culture, as indicated by increases in alkaline phosphatase activity and deposition of a mineralized matrix; however, it had modest effects in vivo. The data show that C-1-1 and ch-ERG have diverse biological properties and distinct expression patterns during skeletogenesis, and are part of molecular mechanisms by which limb chondrocytes follow alternative developmental pathways. C-1-1 is the first transcription factor identified to date that appears to be instrumental in the genesis and function of epiphyseal articular chondrocytes.

Alkaline Phosphatase↗
PubMed1977

In vitro tolerance induction of neonatal murine B cells as a probe for the study of B-cell diversification.

The susceptibility to in vitro tolerance induction has been implicated as a characteristic of B cells early in their development, since DNP-reactive B cells are tolerizable only during the first days after birth, and 25% of adult bone marrow cells are tolerizable. In the present study, a modification of the in vitro splenic focus technique was utilized to determine if PC-specific B cells, by virtue of their late expression (approximately 1 wk post-parturition), also display susceptibility to tolerance induction. The results demonstrate that at 7-10 days after birth, when over 90% of the DNP-specific splenic B cells are resistant to tolerance induction, the majority of PC-specific B cells are tolerizable. These results re-emphasize tolerance susceptibility as a characteristic of developing clones, confirm the late acquisition of PC-specific B cells, and support the contention that the acquisition of the specificity repertoire is a highly ordered, specifically predetermined process which is independent of antigen-driven events.

Animals↗
PubMed1993

Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome.

Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire.

Antibody Diversity↗
PubMed1998

Diversification of subtype E human immunodeficiency virus type 1 env in heterosexual seroconverters from Northern Thailand.

The C2-V3 region of the human immunodeficiency virus (HIV)-1 env was determined from 15 northern Thailand seroconverters between 1993 and 1995. Similar sequences were also determined from 18 seroconverting injection drug users in Baltimore. All seroconverters from northern Thailand were infected with subtype E HIV-1 on the basis of env sequences. Intersubject viral DNA distances increased from 2.3% in asymptomatic HIV-1-infected subjects characterized between 1990 and 1992 to 7.8% in these more recent seroconverters from Thailand. On the other hand, sequences from 18 seroconverters from Baltimore had a mean intersubject distance of 13.2%. The genetic diversity within HIV-1 subtype E in seroconverters in Thailand has increased significantly but is still less than that observed in HIV-1 from seroconverters in the United States, where the epidemic of HIV-1 infection is more mature. These results suggest that continued monitoring of the molecular epidemiology of HIV-1 infection in Thailand will be important for HIV vaccine development and evaluation.

Amino Acid Sequence↗
PubMed2003

Molecular systematic analysis reveals cryptic tertiary diversification of a widespread tropical rain forest tree.

The broad geographic range of many Neotropical rain forest tree species implies excellent dispersal abilities or range establishment that preceded the formation of current dispersal barriers. In order to initiate historical analyses of such widespread Neotropical trees, we sequenced the nuclear ribosomal spacer (ITS) region of Symphonia globulifera L. f. (Clusiaceae) from populations spanning the Neotropics and western Africa. This rain forest tree has left unmistakable Miocene fossils in Mesoamerica (15.5-18.2 Ma) and in South America ( approximately 15 Ma). Although marine dispersal of S. globulifera is considered improbable, our study establishes three marine dispersal events leading to the colonization of Mesoamerica, the Amazon basin, and the West Indies, thus supporting the paleontological data. Our phylogeographic analysis revealed the spatial extent of the three Neotropical S. globulifera clades, which represent trans-Andes (Mesoamerica+west Ecuador), cis-Andes (Amazonia+Guiana), and the West Indies. Strong phylogeographic structure found among trans-Andean populations of S. globulifera stands in contrast to an absence of ITS nucleotide variation across the Amazon basin and indicates profound regional differences in the demographic history of this rain forest tree. Drawing from these results, we provide a historical biogeographic hypothesis to account for differences in the patterns of beta diversity within Mesoamerican and Amazonian forests.

Africa↗
PubMed2005

Initial diversification of living amphibians predated the breakup of Pangaea.

The origin and divergence of the three living orders of amphibians (Anura, Caudata, Gymnophiona) and their main lineages are one of the most hotly debated topics in vertebrate evolution. Here, we present a robust molecular phylogeny based on the nuclear RAG1 gene as well as results from a variety of alternative independent molecular clock calibrations. Our analyses suggest that the origin and early divergence of the three living amphibian orders dates back to the Palaeozoic or early Mesozoic, before the breakup of Pangaea, and soon after the divergence from lobe-finned fishes. The resulting new biogeographic scenario, age estimate, and the inferred rapid divergence of the three lissamphibian orders may account for the lack of fossils that represent plausible ancestors or immediate sister taxa of all three orders and the heretofore paradoxical distribution of some amphibian fossil taxa. Furthermore, the ancient and rapid radiation of the three lissamphibian orders likely explains why branch lengths connecting their early nodes are particularly short, thus rendering phylogenetic inference of implicated relationships especially difficult.

Amphibians↗
PubMed2005

Diversification of transmission modes and the evolution of mutualism.

In order for mutualism to evolve, some force must align the interests of the two interacting partners. Vertical transmission can fill this role, but it is still unknown whether mutualism can be stable when vertically transmitted symbionts can evolve toward horizontal transmission. In this article, we investigate how symbionts' transmission mode and virulence should evolve, depending on the relationship between these two traits. We show that pathogens that reduce their host's fecundity can have more complex evolutionary dynamics than those that increase mortality. In some cases, runaway evolution of virulence can drive the host population extinct. In most cases, evolutionary branching results in the differentiation of avirulent, vertically transmitted symbionts from virulent, contagious pathogens. The population of symbionts then becomes polymorphic, and because the least virulent symbionts are the most frequent, the average virulence of symbionts is much lower than it would be in a monomorphic population. When the link between transmission and virulence results from correlated mutational changes and not from fixed constraints, vertically transmitted symbionts do not simply lose virulence; they evolve toward mutualism. We show that the force that stabilizes mutualism in such situations is the competition for transmission between symbionts.

Evolution, Molecular↗
PubMed2006

The effects of switching behavior on the evolutionary diversification of generalist consumers.

Mathematical models of consumer-resource systems explore the evolution of a morphological trait that determines two resource acquisition rates in a generalist consumer. The consumer also has the ability to adjust its relative consumption of the two resources via behavioral (or developmental) plasticity subject to a trade-off. The analysis examines both stable systems and those with sustained fluctuations in abundance. In both cases, it seeks to determine how the behavioral choice affects the evolution of the morphological characters. The presence of adaptive switching behavior transforms the shape of the relationship between the morphological character and fitness in a manner that usually leads to evolution of two or more morphological types. As in models without switching, the presence of sustained cycles in resource densities often allows the evolution of a generalist as well as two specialists. However, switching expands and shifts the parameter regions yielding this outcome and in some cases allows the evolution and coexistence of at least two generalists as well as the two specialists. This level of diversity supported by only two resources is not seen in the absence of behavioral choice and resource cycles. The results suggest major roles for both behavior and environmental variation in adaptive radiation.

Adaptation, Physiological↗
PubMed2002

Enhancement and diversification of IFN induction by IRF-7-mediated positive feedback.

Interferons (IFN) are potent components of the innate immune response to microbial infection. The genes for type I IFN (IFN-alpha and IFN-beta) are rapidly induced in response to viral infection through a mechanism that involves latent cellular transcription factors that are activated in response to innate recognition of viral components. IFN regulatory factor (IRF) proteins are key to this regulation, and their conversion from latent to active involves virus-induced serine phosphorylation. Differential utilization of distinct IRF proteins by different members of the type I IFN gene family produces a graded induction of gene expression, resulting in tight control of these cytokines through a positive feedback mechanism. Early response to virus causes secretion of a subset of IFN genes through the action of IRF-3 in conjunction with additional transcription factors, such as NF-kappaB and activator protein-1 (AP-1) (c-jun/ATF). This early IFN acts in an autocrine manner to stimulate production of IRF-7, a transcription factor capable of activating the many additional members of the IFN-alpha gene family. The dependence of IRF-7 on virus-induced phosphorylation for its activity insures that IFN production is limited to virus-infected cells. Characterization of the cellular components involved in viral detection and IRF activation will further delineate this vital mechanism of innate immune response.

Amino Acid Sequence↗
PubMed2005

Genetic diversification and recombination of HIV type 1 group M in Kinshasa, Democratic Republic of Congo.

As the HIV-1 pandemic becomes increasingly complex, the genetic characterization of HIV strains bears important implications for vaccine research. To better understand the molecular evolution of HIV-1 viral diversity, we performed a comparative molecular analysis of HIV strains collected from high-risk persons in Kinshasa, Democratic Republic of Congo (DRC). Analysis of the gag-p24, env-C2V3 and -gp41 regions from 83 specimens collected in 1999-2000 revealed that 44 (53%) had concordant subtypes in the three regions (14 subsubtype A1, 10 subtype G, 8 subtype D, 5 subtype C, 2 each subsubtype F1 and CRF01_AE, and one each of subtypes H and J, and subsubtype A2, while the remaining 39 (47%) had mosaic genomes comprising multiple subtype combinations. Similar multisubtype patterns were also observed in 24 specimens collected in 1985. Sequence analysis of the gag-pol region (2.1 kb) from 21 discordant specimens in the gag-p24, env-C2V3 and -gp41 regions in 1985 and 1999-2000 further confirmed the complex recombinant patterns. Despite the remarkable similarity in overall subtype distribution, the intra- and intersubtype distances of major subtypes A1 and G increased significantly from 1985 to 1999-2000 (p=0.018 and p=0.0016, respectively). Given the complexity of HIV-1 viruses circulating in DRC, efforts should focus on the development of vaccines that result in cross-clade immunity.

Democratic Republic of the Congo↗
PubMed1994

Diversification of antisense research and development: review of the Ringberg meeting, April 1994. Mechanisms of antisense-mediated gene silencing.

Antisense technology has established itself as a new and vibrant entrant into the discipline of molecular biology. As such, it has contributed to basic research by providing tools for the molecular dissection of diverse experimental systems. In applied research, antisense approaches have contributed to development of agricultural products (D. Grierson) now coming to market and to the design of a number of oligonucleotide drugs, now in clinical trials. However, few activities to date have focused on the study of antisense per se. Further, few conceptual perspectives have regarded antisense as an integral part of cellular function and genetic regulation. The Ringberg conference showcased a number of systems that would seem unrelated if we regard antisense as a superficial tool to be imposed on nature. On the other hand, if we want to begin to regard antisense as a field of its own with deeper biological and genetic rationales, the Ringberg meeting provided much tantalizing evidence to do so.

Antisense Elements (Genetics)↗
PubMed2003

Group II intron splicing factors derived by diversification of an ancient RNA-binding domain.

Group II introns are ribozymes whose catalytic mechanism closely resembles that of the spliceosome. Many group II introns have lost the ability to splice autonomously as the result of an evolutionary process in which the loss of self-splicing activity was compensated by the recruitment of host-encoded protein cofactors. Genetic screens previously identified CRS1 and CRS2 as host-encoded proteins required for the splicing of group II introns in maize chloroplasts. Here, we describe two additional host-encoded group II intron splicing factors, CRS2-associated factors 1 and 2 (CAF1 and CAF2). We show that CRS2 functions in the context of intron ribonucleoprotein particles that include either CAF1 or CAF2, and that CRS2-CAF1 and CRS2-CAF2 complexes have distinct intron specificities. CAF1, CAF2 and the previously described group II intron splicing factor CRS1 are characterized by similar repeated domains, which we name here the CRM (chloroplast RNA splicing and ribosome maturation) domains. We propose that the CRM domain is an ancient RNA-binding module that has diversified to mediate specific interactions with various highly structured RNAs.

Amino Acid Sequence↗
PubMed2025

Evolutionary Diversification and Functions of the Candidate Male Killing Gene wmk.

Symbiont-mediated male killing (MK) is a mechanism that selectively eliminates male offspring, often by disrupting sex-specific developmental processes. In Drosophila melanogaster, the WO-mediated killing gene wmk from Wolbachia prophage WO transgenically reproduces the MK phenotype, yet how the gene evolves and functions across diverse Wolbachia has not been systematically investigated. We analyzed 32 Wolbachia genomes available in the NCBI database to study wmk homologs across different arthropod hosts, reproductive parasitism functions, and Wolbachia supergroups. First, we report at least five distinct wmk phylogenetic clusters (Types I to V), often organized in multigenic dyads or triads. Second, among MK Wolbachia, there is a significantly higher number of wmk genes and diversity in Lepidoptera strains than in Drosophila strains, which exclusively harbor wmk Types I and III. Third, there are three patterns of wmk sequence and genomic organizational changes in Drosophila MK strains that associate with different evolutionary trajectories underpinning the MK phenotype. Fourth, single and combinatory transgenic expression of Types I and III in D. melanogaster uncovers male-biased lethality associated with Type I; however, dual expression of the Types together elicits a major reduction in offspring number. Fifth, wmk genes have low expression level across D. melanogaster developmental stages relative to the cifA and cifB genes, which could explain why cytoplasmic incompatibility is expressed in this system. These findings establish a complex and phylogenetically informed genetic basis of wmk-induced lethality, highlighting the role of gene copy number and expression, wmk Types, and host background in shaping the phenotype.

Animals↗