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PubMed2006

Confounding asymmetries in evolutionary diversification and character change.

Studies of character evolution often assume that a phylogeny's shape is determined independently of the characters, which then evolve as mere passengers along the tree's branches. However, if the characters help shape the tree, but this is not considered, biased inferences can result. Simulations of asymmetrical speciation (i.e., one character state conferring a higher rate of speciation than another) result in data that are interpreted to show a higher rate of change toward the diversification-enhancing state, even though the rates to and from this state were in fact equal. Conversely, simulations of asymmetrical character change yield data that could be misinterpreted as showing asymmetrical rates of speciation. Studies of biased diversification and biased character change need to be unified by joint models and estimation methods, although how successfully the two processes can be teased apart remains to be seen.

Biological Evolution↗
PubMed2006

Comparative phylogeography of three codistributed stomatopods: origins and timing of regional lineage diversification in the Coral Triangle.

The Indonesian-Australian Archipelago is the center of the world's marine biodiversity. Although many biogeographers have suggested that this region is a "center of origin," criticism of this theory has focused on the absence of processes promoting lineage diversification in the center. In this study we compare patterns of phylogeographic structure and gene flow in three codistributed, ecologically similar Indo-West Pacific stomatopod (mantis shrimp) species. All three taxa show evidence for limited gene flow across the Maluku Sea with deep genetic breaks between populations from Papua and Northern Indonesia, suggesting that limited water transport across the Maluku Sea may limit larval dispersal and gene flow across this region. All three taxa also show moderate to strong genetic structure between populations from Northern and Southern Indonesia, indicating limited gene flow across the Flores and Java Seas. Despite the similarities in phylogeographic structure, results indicate varied ages of the genetic discontinuities, ranging from the middle Pleistocene to the Pliocene. Concordance of genetic structure across multiple taxa combined with temporal discordance suggests that regional genetic structures have arisen from the action of common physical processes operating over extended time periods. The presence in all three species of both intraspecific genetic structure as well as deeply divergent lineages that likely represent cryptic species suggests that these processes may promote lineage diversification within the Indonesian-Australian Archipelago, providing a potential mechanism for the center of origin. Efforts to conserve biodiversity in the Coral Triangle should work to preserve both existing biodiversity as well as the processes creating the biodiversity.

Animals↗
PubMed1992

Dynamic diversification: hospitals pursue physician alliances, 'seamless' care.

In the 1980s, "diversification" in health care meant creating new corporate entities to boost revenues. In the 1990s, in places like New Ulm, MN, Long Beach, CA, and Boston, hospitals and physicians are exploring diversifications that utilize their core patient care strengths. This is creating new entities that benefit patient care and help prepare for health care delivery in the future. In fact, despite predictions that RBRVS would drive physicians into competition with hospitals, the opposite is taking place, as the new "seamless" delivery systems take advantage of pooled resources and economies of scale.

Community-Institutional Relations↗
PubMed1988

Diversification and corporate restructuring revisited. Back to square one?

An historical overview of corporate restructuring in the health care industry is presented. Initial reasons for forming multicorporate structures centered on avoiding regulations governing certified home health agencies and maximizing third party payer reimbursement. As competition increased, home care agencies employed diversification strategies for survival and reorganized their single corporate structures to launch new businesses and engage in profit-making activities. Corporate restructuring is a time-consuming and complex endeavor that should only be undertaken as a part of an agency's strategic plan. Evaluating an agency's corporate structure is a continual process and the criteria for evaluating change over time. The current experience with diversification in the health care industry suggests that the proliferation of multicorporate structures is stemming as health care providers begin to refocus on their core business.

Cost Control↗
PubMed1987

Hospital diversification: corporate restructuring as a survival strategy.

Corporate restructuring of hospitals as a strategy for survival and continued success is described. Health-care providers' traditional orientation has been toward service and mission; now, profits and new markets in health care must be considered also. To remain competitive, hospitals must be prepared to act rapidly on opportunities. Corporate reorganization, the creation of new corporate entities that perform diversified medical and nonmedical functions, may provide the flexibility needed for quick action. Legal and accounting costs will be incurred by corporate reorganization. Tax issues, staff morale, community support, and effect on hospital managers and board members should be considered. Hospitals can cut costs through vertical integration of existing services; in this system-building strategy, new services can be added to broaden the patient base. Corporate reorganization is more important for diversification--the extension of a hospital's medical and health businesses--than for system building. Guidelines for diversification are offered. Corporate reorganization is a technique that should be considered in an institution's planning process.

Hospital Administration↗
PubMed1988

Corporate diversification: expectations and outcomes.

A review of the research concerning the diversification experience of firms in other industries shows that expectations of higher profit rates and lower risk are not entirely realistic. However, there are many ways in which the probability of financially successful diversification may be increased.

Evaluation Studies as Topic↗
PubMedDate not supplied

Assessing B cell diversification by antigen receptor and precursor cell analysis.

A major element in the understanding of B cell specificity diversification is the extent of diversity present in mature and in developing B cell populations. Two general methods are currently used for assessing the specificity repertoire: (a) the enumeration of cells whose receptors can bind a specific antigen, and (b) the enumeration of cells which can respond to antigenic stimulation by antibody-forming cell clone production. Our laboratory has utilized the latter method to establish the frequency of B cells responsive to a wide variety of antigenic determinants. The findings indicate that: (a) the primary murine B cell specificity repertoire probably includes more than 10(7) clonotypes; (b) some clonotypes are represented by numerous B cells (40,000 TEPC 15 precursors per BALB/c mouse) while most are represented by fewer than to B cells per mouse; (c) the acquisition of the repertoire is apparently antigen-independent since germfree mice have repertoires similar to conventional mice and secondary B cells are easily distinguished from primary B cells; (d) the neonatal repertoire appears to contain only 10(4) clonotypes at birth, each represented by perhaps 200-400 cells; (e) the diversification process from neonatal to adult repertorie appears highly ordered and reproducible. Antigen binding cell studies have now used in conjunction with the splenic focus assay in an attempt to correlate these two techniques. The results indicate that the efficiency of the splenic focus assay used for precursor cell anlysis it 4-5% for both primary and secondary B cells and is similar to the percent of donor B cells lodged in recipient spleens. For certain antigens (DNP-BSA) the number of antigen-binding cells can represent 4% of the total B cells, and this number directly correlates with the concentration of antigen used; stimulation, on the other hand, appears to have an affinity threshold achieved by only 0,02% of the DNP-specific B cells. In contrast, PC-BSA antigen-binding cell and splenic focus precursor cell frequencies are identical. These findings are interpreted to indicate that antigen-binding cell analyses confirm the validity of the calculations used to estimate precursor frequencies in the splenic focus technique. However, for some antigens binding to cell receptors, one detects a large number of cells belonging either to a nonstimulatable B cell subclass or whose receptor affinity is too low to permit stimulation.

Animals↗
PubMed1984

Diversification strategies for hospital pharmacies.

Several ways used by the pharmacy department of a large university hospital to generate revenue through diversification are described. The department offers its facilities and staff as a resource in training medical service representatives for several pharmaceutical manufacturers, which is projected to provide $85,000 in net income for fiscal year (FY) 1983-84. The pharmacy department also conducts a six-month program for training pharmacy technicians, which yields a small net profit. The pharmacy department actively participates in educational programs such as college courses and clerkships earning extra income. An apothecary-style outpatient pharmacy was set up under a for-profit corporation. Services have been expanded to include the preparation of i.v. solutions that support home care. A durable medical equipment (DME) business is planned. The ambulatory and home-care programs are expected to generate approximately $165,000 in net profit next year. Contract pharmaceutical services are provided to another hospital. The net income generated through diversification in this pharmacy department will exceed $250,000 in FY 1983-84.

Allied Health Personnel↗
PubMed1983

Analysis of the relationship between the variation in intercleavage times and cell diversification during the cleavage stages of the teleost fish Nothobranchius guentheri.

A cell lineage study up to the ninth cleavage of the annual teleost fish Nothobranchius guentheri is presented and analysed with respect to a possible relationship between cell diversification and intercleavage times. The cleavage pattern contains both regular aspects (formation of the external yolk syncytial layer) and irregular aspects (formation of the deep cells and the enveloping layer cells). Cells that generate cells which divide again have a similar intercleavage time independent of the cell type of their daughters. Peripheral blastomeres with a shorter intercleavage time, that are situated near the centre of the blastoderm, contribute more to the formation of the deep cell population than those blastomeres with a longer intercleavage time, that lie closer to the margin of the blastoderm. No evidence was found for a relationship between the duration of the cell cycle and the cell type(s) a cell generates, nor for the involvement of mitotic gradients in cell diversification.

Animals↗
PubMed1998

Fetal mouse NK cell clones are deficient in Ly49 expression, share a common broad lytic specificity, and undergo continuous and extensive diversification in vitro.

NK cells obtained by exposing mouse fetal thymocytes to appropriate combinations of IL-4, IL-2, and PMA are phenotypically indistinguishable from cultured adult splenic NK cells with the exception that they generally lack measurable expression of all of the inhibitory Ly49 molecules that can currently be detected with Abs (Ly49A, -C, -G, and -I) and of the activating molecule Ly49D. Despite this deficiency, fetal NK cells have a similar specificity to Ly49-expressing adult splenic NK cells. Individual fetal NK cell clones display an essentially invariant and broad specificity similar to that of polyclonal populations of fetal or adult NK cells, although significant differences in the fine specificity of clones can occasionally be detected. Most remarkably, cloned fetal NK cell lines display heterogeneous expression of a restricted set of surface molecules that includes 10A7, Ly6C, 3C2, CD8, certain isoforms of CD45, and also, occasionally, Ly49 molecules. This heterogeneity is not related to the cell cycle or activation status of the cells, and micromanipulation recloning demonstrates unambiguously that it is not due to a lack of a single cell origin. Diversity is generated rapidly and the capacity for diversification appears to persist indefinitely in vitro. The expression of individual variable Ags is independent and stochastic, resulting in fetal NK "clones" being potentially composed of hundreds of phenotypically distinct cells. We hypothesize that fetal NK cells behave as progenitor cells that are undergoing a process of rapid, extensive, and continuous diversification and that are individually capable of generating and regenerating a complex NK cell repertoire.

Animals↗
PubMed1996

Segmental diversification of an identified leech neuron correlates with the segmental domain in which it expresses Lox2, a member of the Hox gene family.

The cellular colocalization of LOX2 protein and small cardioactive peptide (SCP)-like immunoreactivity was studied in the nerve cord of the glossiphoniid leech Helobdella triserialis. Of the six neurons that express SCP in the midbody segments 7 to 17, only one, the MPS neuron, expresses LOX2 protein. The medial paired SCP (MPS) neurons are segmentally repeated and can be divided into three contiguous segmental domains according to cell body size and the timing and level of SCP expression. MPS neurons located in the anterior and middle segmental domains express LOX2 protein. In the middle domain, large MPS neurons begin to accumulate SCP shortly after the end of embryonic development, whereas in the anterior domain the MPS neurons are smaller and begin to express SCP at a later stage. In the posterior domain the MPS neurons exhibit a third phenotype -- they have large cell bodies, express low levels of SCP starting from the midjuvenile stage, and do not show detectable LOX2 expression. Lineage tracer injections showed that the MPS neurons arise from a stereotyped cell lineage and are descended from the O teloblast stem cell. In midbody ganglia 2 to 6 and 18 to 21, there are lineally homologous neurons that do not express either LOX2 protein or SCP. Thus, the boundaries of LOX2 expression coincide precisely with two of the segmental boundaries of MPS differentiation, suggesting that expression of LOX2 at the level of this single identified neuron governs some, but not all, aspects of the neuron's segmental diversification.

Animals↗
PubMed2026

Tandem Duplication-Driven Neofunctionalization of UDP-Glycosyltransferases Shapes the Diversification of Triterpenoid Saponins in the Cucurbitaceae.

Tandem duplication of tailoring enzymes allows evolutionary innovation that diversifies plant specialized metabolism. Here, we present an interesting example of how tandem duplicated UDP-glycosyltransferases undergo neofunctionalization and shape the chemical diversity of triterpenoid saponins in the Cucurbitaceae family. A chromosome-level genome of Siraitia grosvenorii was assembled and aligned with multiple cucurbit genomes, revealing a specific UGT73AM tandem duplication responsible for regio-selective glycosylation (e.g. the rare 1,4-linked disaccharide) of diverse saponins such as mogrosides, ginsenosides, and momordicines. Comparative genomics depicted the evolutionary trajectory of a universal saponin-biosynthesizing UGT73 tandem arrays syntenously preserved across core eudicots, where lineage-specific UGT copies contribute to distinct metabolic phenotypes. A crystal structure of SgUGT73AM30 (mogrol 25-O-glycosyltransferase) in complex with UDP and mogrol was obtained to elucidate the molecular basis of the regio-specific decoration on vicinal diol of the substrates. Altogether, these findings provide insights into tandem duplication-driven diversification of glycosyltransferases and lay the foundation for engineered glycosylation of valuable triterpenoid saponins.

Saponins↗
PubMed2007

On the time scale of New World primate diversification.

New World primates comprise a diverse group of neotropical mammals that suddenly appeared in the Late Oligocene deposits of South America at around 26 million years ago (MYA). Platyrrhines seem to have separated from Old World anthropoids ca. 35 MYA, and their subsequent diversfication is not well documented in the fossil record. Therefore, molecular clock studies were conducted to unveil the temporal scenario for the evolution of the group. In this study, divergence times of all splits within platyrrhines until the generic level were investigated, using two different gene data sets under relaxed molecular clocks. Special attention was paid to the basal diversification of living platyrrhines and to the basal split of the modern Cebidae family, since these nodes were reported to be phylogenetically difficult to resolve. The results showed that analyses from various genomic regions are similar to estimates obtained by early single-gene studies. Living New World primates are descendants of ancestors that lived in the Early Miocene, at around 20 MYA, and modern Cebidae and Pitheciidae appeared ca. 16.9 and 15.6 MYA, respectively. The last common ancestor of living Atelidae is 12.4 million years old, making this clade the youngest New World primate family; at approximately the same time, modern Callitrichinae was evolving (11.8 MYA). The gap between the Platyrrhini/Catarrhini separation and the last common ancestor of living Platyrrhini may be as big as 20 million years. Paleontological and geoclimatological evidence corroborates that the sudden appearance of modern families may be a consequence of environmental changes during the Miocene.

Animal Migration↗
PubMed1987

Immunoglobulin heavy chain gene diversification in the long-term bone marrow culture of normal mice and mice with severe combined immunodeficiency.

The change of immunoglobulin heavy (H) chain gene configuration during the differentiation of B cells from their early precursors was investigated in long-term cultures of bone marrow cells (LTBC). Hemopoietic stem cells are maintained in LTBC described by Dexter et al. (J. Cell. Physiol. 1977. 91: 335; LTBC-D), which supports the differentiation of myeloid lineage cells but not B lineage cells. By simply shifting the culture condition to that devised by Whitlock and Witte (Proc. Natl. Acad. Sci. USA 1982. 79: 3608; LTBC-B) to support the development of B lineage cells, surface IgM-bearing (sIgM+) B cells became detectable by the 2nd week after the shift and the number quickly increased thereafter, while the number of polymorphonuclear cells and granulocyte-macrophage colony-forming cell (CFU-c) decreased rapidly. H chain gene configuration of the developing cells in the culture was examined by Southern blot analysis of Eco RI-digested DNA with a JH probe. Whereas rearranged JH gene configuration was not detectable in the DNA from LTBC-D cells, it first appeared 2 weeks after the shift, and the level of the rearrangement rapidly increased thereafter as the intensity of JH band of germ-line configuration decreased. Almost all the cells in the culture had undergone H chain gene rearrangement in both chromosomes by the 6th week after the shift. During 2 to 4 weeks after the shift, a cluster of bands spanning around 4.5-5.5 kb appeared dominant among the rearranged configurations of JH gene and then it decreased in intensity as the pattern of JH band became a more homogeneous smear. The distribution of rearranged JH bands observed during 3-4 weeks after the shift was strikingly similar to that observed in normal spleen B cells. By semi-quantitative analysis of the intensity of JH and DSP2 bands remaining in germ-line configuration, it was found that the loss of germ-line JH band was far more rapid than that of germ-line DSP2 bands in the developing B cells in vitro. This result is consistent with the conclusion obtained in B cell tumor lines that D to J assembly occurred first and was followed by V to DJ assembly in this culture system. Taken together, it is likely that the process of H chain gene diversification in this culture system may represent the actual process during B cell differentiation in vivo. Differentiative capacity of bone marrow stem cells from mouse with severe combined immunodeficiency (SCID) was also analyzed in the same culture system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Analysis of the natural human IgG antibody repertoire: life-long stability of reactivities towards self antigens contrasts with age-dependent diversification of reactivities against bacterial antigens.

We used a quantitative immunoblotting technique to analyze the repertoires of IgG antibody reactivities in the serum of healthy young children, young adult males and aged males with self and non-self antigens. Densitometric patterns of reactivity of purified IgG with self antigens were highly conserved between individuals within a given age group and across age groups. Inter-individual differences were observed, however, upon analysis of self reactivities of IgG in whole serum. A striking heterogeneity between individuals within a given age group and across age groups characterized the reactivity of purified IgG and of IgG in whole serum with bacterial antigens. Inter-individual differences were more marked among aged individuals than among individuals of other age groups. Analysis of variances of reactivities of IgG with bacterial antigens further demonstrated an increased diversity of repertoires of aged donors compared with those of young adults and children. Our results document the stability of the self-reactive repertoires of IgG throughout life, which contrasts with the diversification of the repertoire of IgG antibody reactivities directed toward foreign antigens with aging. These findings support the concept that self-reactive antibody repertoires are positively selected throughout life by a restricted set of self antigens shared by all individuals.

Adult↗
PubMed2005

Variety of antimicrobial peptides in the Bombina maxima toad and evidence of their rapid diversification.

Antimicrobial peptides secreted by the skin of many amphibians play an important role in innate immunity. From two skin cDNA libraries of two individuals of the Chinese red belly toad (Bombina maxima), we identified 56 different antimicrobial peptide cDNA sequences, each of which encodes a precursor peptide that can give rise to two kinds of antimicrobial peptides, maximin and maximin H. Among these cDNA, we found that the mean number of nucleotide substitution per non-synonymous site in both the maximin and maximin H domains significantly exceed the mean number of nucleotide substitution per synonymous site, whereas the same pattern was not observed in other structural regions, such as the signal and propiece peptide regions, suggesting that these antimicrobial peptide genes have been experiencing rapid diversification driven by Darwinian selection. We cloned and sequenced seven genes amplified from skin or liver genomic DNA. These genes have three exons and share the same gene structure, in which both maximin and maximin H are encoded by the third exon. This suggests that alternative splicing and somatic recombination are less likely to play a role in creating the diversity of maximins and maximin Hs. The gene trees based on different domain regions revealed that domain shuffling or gene conversion among these genes might have happened frequently.

Amino Acid Sequence↗
PubMed2003

Differentiation and diversification of the follicular cells in flies: insight from the studies of the lower brachycerans' ovaries.

Although all dipteran species have ovaries of the same meroistic-polytrophic type, the structure of individual ovarian follicles (egg chambers) as well as the course of oogenesis in major dipteran taxa are highly diversified and often significantly different from the widely known Drosophila model. In this report we present results of the morphological studies of the ovary structure in the representatives of three families of lower brachycerans (Orthorrhapha) and compare them with the present knowledge of the processes that lead to the formation of a mature egg cell in the model dipteran, the cyclorrhaphan fruit fly, Drosophila melanogaster. The most conspicuous and developmentally significant differences between Drosophila and lower brachycerans were found in the events that accompany the differentiation and diversification of somatic follicular cells. Our observations indicate that the directed migrations of some follicular cells within the egg chamber and the ability of border cells to invade the nurse cell compartment can be considered as evolutionary novelties that evolved in the ancestors of higher brachycerans.

Animals↗
PubMed1991

Diversification of glial lineages: a novel method to clone brain cells in vitro on nitrocellulose substratum.

We have developed a novel in vitro method to analyze the diversification of glial cells during development. The primary advantage of the approach is that glial lineages are formed in discrete clones on a nitrocellulose substratum where the relationship of the progeny is strictly defined. This method facilitates the comparison of a large complement of astrocyte and oligodendrocyte lineages under controlled conditions. Clones were formed by plating a brain dissociate on nitrocellulose at very low density (5,000-40,000 cells/154 mm2). However, growth depended on diffusible factors produced by brain cells growing under the nitrocellulose support at high density (feeder layer). The cloning efficiency of cells from mouse forebrain (P0) was 1-3%. This means we can detect 100,000 to 300,000 clonal progenitors in the dissociate (10(7) cells per forebrain) using the clonal culture technique. Cell phenotypes were determined by immunocytochemical staining with anti-glial fibrillary acidic protein (GFAP) to label astrocytes and anti-galactocerebroside (GC) and anti-myelin basic protein (MBP) to label oligodendrocytes. There was a remarkable diversity of glia represented in different lineages. The number of astrocyte clones was greater than the number of oligodendrocyte clones but combined their total was 90%. Clone sizes were distributed over a wide range, which indicated that growth rates varied. Clones appeared compact or dispersed but astrocyte clones exhibited three different morphologies-fibroblast-like, stellate, and elongated. Oligodendrocytes had different morphologies distinct from astrocytes. Although there were different glial lineages the cells in most clones were homogeneous, indicating the progeny had the same fate. However, a small number of the clones, approximately 2%, were heterogeneous and contained both astrocytes and oligodendrocytes. The application of this technique to glial lineages demonstrates that intrinsic factors have a role in determining cell fate since different clones formed under the same external conditions. Finally, these results are consistent with the existence of multiple glial progenitors or the continued presence of multipotential progenitors at the time of birth.

Animals↗