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PubMed1998

Neuronal diversification: development of motor neuron subtypes.

Recent progress has been made in defining the developmental mechanisms that contribute to the diversification of motor neuron subtypes, which differ in transcription factor gene expression and synaptic connections. These studies suggest that progenitor cells acquire specific motor neuron identities through the coordinate actions of multiple factors. Current evidence suggests that Sonic hedgehog initiates a common pathway for motor neuron differentiation, while positionally distributed factors act to assign subtype identities.

Animals↗
PubMed2000

Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV protease inhibitor library.

An efficient combination solution-phase/solid-phase route enabling the diversification of the P1', P2', and P3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates.

Animals↗
PubMed2003

Diversification of sympatric Sapromyza (Diptera: Lauxaniidae) from Madeira: six morphological species but only four mtDNA lineages.

A series of recent studies on speciation of insects within the Canary Islands have indicated considerable within-island diversification, similar to that described in the Hawaiian islands. Little work has yet been carried out on the neighboring Madeiran archipelago, which is also volcanic. This study examines relationships among all known Lauxaniid flies of the genus Sapromyza from Madeira (including six newly described morphological species) based on mitochondrial gene trees constructed from cytochrome c oxidase (subunit I) and 16S rRNA partial sequences. Phylogenies based on maximum likelihood distances, a Bayesian method based on Markov chain Monte Carlo sampling from the posterior probability distribution, and maximum parsimony show that eight of the nine Madeiran species comprise a single monophyletic group. This clade is also split into two subclades representing black- and yellow/orange-bodied forms. The latter mtDNA clade corresponds to only two species (Sapromyza imitans and Sapromyza indigena) which are not reciprocally monophyletic. Monophyly is strongly supported within four of the six black-bodied species but not for the species pair (Sapromyza inconspicua, Sapromyza laurisilvae). We discuss the double occurrence (at least) of introgressive hybridization/incomplete lineage sorting within this group and suggest that recent speciation is the most likely explanation. The remaining species on the island, Sapromyza madeirensis, is very divergent from the aforementioned group, occupying a more basal position in the tree than the other Atlantic island and continental Sapromyza that were included in the analysis. At least two speciation events for Madeiran Sapromyza appear to correspond to quite ancient periods relative to the age of the island, while others are more recent. This suggests that a combination of island colonization and within-island sympatric and/or vicariance-mediated speciation may explain the observed diversity.

Animals↗
PubMed2003

Molecular phylogeography reveals island colonization history and diversification of western Indian Ocean sunbirds (Nectarinia: Nectariniidae).

We constructed a phylogenetic hypothesis for western Indian Ocean sunbirds (Nectarinia) and used this to investigate the geographic pattern of their diversification among the islands of the Indian Ocean. A total of 1309 bp of mitochondrial sequence data was collected from the island sunbird taxa of the western Indian Ocean region, combined with sequence data from a selection of continental (African and Asian) sunbirds. Topological and branch length information combined with estimated divergence times are used to present hypotheses for the direction and sequence of colonization events in relation to the geological history of the Indian Ocean region. Indian Ocean sunbirds fall into two well-supported clades, consistent with two independent colonizations from Africa within the last 3.9 million years. The first clade contains island populations representing the species Nectarinia notata, while the second includes Nectarinia souimanga, Nectarinia humbloti, Nectarinia dussumieri, and Nectarinia coquereli. With respect to the latter clade, application of Bremer's [Syst. Biol. 41 (1992) 436] ancestral areas method permits us to posit the Comoros archipelago as the point of initial colonization in the Indian Ocean. The subsequent expansion of the souimanga clade across its Indian Ocean range occurred rapidly, with descendants of this early expansion remaining on the Comoros and granitic Seychelles. The data suggest that a more recent expansion from Anjouan in the Comoros group led to the colonization of Madagascar by sunbirds representing the souimanga clade. In concordance with the very young geological age of the Aldabra group, the sunbirds of this archipelago have diverged little from the Madagascar population; this is attributed to colonization of the Aldabra archipelago in recent times, in one or possibly two or more waves originating from Madagascar. The overall pattern of sunbird radiation across Indian Ocean islands indicates that these birds disperse across ocean barriers with relative ease, but that their subsequent evolutionary success probably depends on a variety of factors including prior island occupation by competing species.

Animals↗
PubMed1997

Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification.

Mice carrying transgenic rearranged V region genes in their IgH and Igkappa loci to encode an autoreactive specificity direct the emerging autoreactive progenitors into a pre-B cell compartment, in which their receptors are edited by secondary Vkappa-Jkappa rearrangements and RS recombination. Editing is an efficient process, because the mutant mice generate normal numbers of B cells. In a similar nonautoreactive transgenic strain, neither a pre-B cell compartment nor receptor editing was seen. Thus, the pre-B cell compartment may have evolved to edit the receptors of autoreactive cells and later been generally exploited for efficient antibody diversification through the invention of the pre-B cell receptor, mimicking an autoreactive antibody to direct the bulk of the progenitors into that compartment.

Animals↗
PubMed2003

Transcriptional control of neuronal diversification in the retina.

During embryonic development, the array of vastly different neuronal types that are incorporated into the functional architecture of the mature neuroretina derives from a common population of multipotent retinal progenitor cells (RPCs). Retinogenesis proceeds in a precise chronological order, with the seven principal cell classes generated in successive phases. Cell biological experiments established that this histogenetic order, at least in part, reflects intrinsic changes within the RPC pool. In recent years a number of molecules controlling various aspects of cell fate specification from RPCs have been identified. However, few attempts have been made to integrate previous concepts that emerged from cell biological studies and more recent results based on molecular genetic experiments. This review aims at providing an overview of recent advances in our understanding of the cellular and molecular mechanisms underlying retinal neuronal diversification, with a particular focus on cell-intrinsic factors.

Animals↗
PubMed2002

Missing links: the genetic architecture of flowers [correction of flower] and floral diversification.

To understand the genetic architecture of floral development, including the origin and subsequent diversification of the flower, data are needed not only for a few model organisms but also for gymnosperms, basal angiosperm lineages and early-diverging eudicots. We must link what is known about derived model plants such as Arabidopsis, snapdragon and maize with other angiosperms. To this end, we suggest a massive evolutionary genomics effort focused on the identification and expression patterns of floral genes and elucidation of their expression patterns in 'missing-link' taxa differing in the arrangement, number and organization of floral parts.

Cycadopsida↗
PubMed2004

Redefining health technology assessment in Canada: diversification of products and contextualization of findings.

OBJECTIVES: While strategies for enhancing the dissemination and impact of Health Technology Assessment (HTA) are now being increasingly examined, the characteristics of HTA production have received less attention. METHODS: This study presents the results of a content analysis of the HTA documents (n = 187) produced by six Canadian agencies from 1995 to 2001, supplemented by interviews with chief executive officers and researchers (n = 40). The goal of this analysis was to characterize the agencies' portfolios and to analyze the challenges these agencies face in responding to the increased demand for HTA. RESULTS: On average, thirty HTA products were issued annually by the agencies. While the bulk of documents produced were full HTA reports (76 percent), two agencies showed significant diversification in their products. Three agencies in particular actively supported the publication of results in scientific journals. Three agencies showed evidence of adapting to different institutional environments by specializing in certain areas (drugs, health services). Overall, a significant portion of the agencies' HTAs contained data on costs (37 percent) and effectiveness (48 percent), whereas ethical and social issues were rarely addressed (17 percent). Most agencies addressed issues and outcomes that did not strictly fall under the typical definition of HTA but that increased the "contextualization" of their findings. CONCLUSIONS: Our discussion highlights four paradoxes and reflects further on challenges raised by the coordination of HTA within large countries and among European states. This study concludes that HTA is being redefined in Canada as HTA agencies offer a more contextualized informational basis, an approach that may prove more compatible with the increased demand for HTA.

Canada↗
PubMedDate not supplied

Natural products as scaffolds for chemical diversification: solution-phase parallel synthesis of a series of naringin analogues.

The flavanone glycoside naringin hydrate is widely abundant in various citrus plants. As an ongoing effort toward the exploitation of natural products as scaffolds for chemical diversification at readily accessible positions, we have prepared a series of analogues of naringin in which the 6-hydroxyl group of the beta-d-glucopyranosyl subunit was converted to sulfonamides, amides, urethanes, and secondary and tertiary amines via the corresponding 6-amino derivative using a solution-phase parallel array protocol.

Journal Article↗
PubMed2005

Organolithium-mediated diversification of peptide thiazoles.

[Reaction: see text] We report a one-step, racemization-free method for the diversification of peptide thiazoles via direct lithiation of the thiazole ring. The method is compatible with N-Boc, N-trityl, carboxylic ester, and carboxamide protecting groups and has been used to directly functionalize the thiazole ring of cyclopeptide natural products.

Lithium↗
PubMed2005

Identification of a tunable site in bryostatin analogs: C20 Bryologs through late stage diversification.

[structure: see text] The C20 region of our bryostatin analogs was identified as a nonpharmacophoric site that could be varied to tune analogs for function and physical properties without significantly affecting their binding affinity for PKC. The use of this site in a late-stage diversification strategy has enabled the facile synthesis of a variety of new C20 analogs, all of which retain nanomolar affinity for PKC, in agreement with our pharmacophore hypothesis.

Animals↗
PubMed2006

Active methylene phosphinic peptides: a new diversification approach.

[reaction: see text] Simple, rapid, and efficient methods for P(1)' diversification of phosphinic peptides have been developed, employing alkylation and Knoevenagel-type condensation reactions with active methylene phosphinic scaffolds, thus leading to a wide variety of diversified phosphinic and dehydrophosphinic peptides.

Alkylation↗
PubMed1999

The diversification of psychology: a multicultural revolution.

The National Multicultural Conference and Summit was held in January 1999 in Newport Beach, California. Hosted by Divisions 17 (Counseling Psychology), 35 (Society for the Psychology of Women), and 45 (Society for the Psychological Study of Ethnic Minority Issues), the event drew support from many American Psychological Association (APA) divisions and other major organizations and sponsors. Approximately 550 psychologists and graduate students attended the conference, which was intended to (a) examine state-of-the-art issues in ethnic minority psychology, (b) identify barriers to becoming a multicultural profession, and (c) forge alliances for political action and advocacy. The summit participants unanimously endorsed resolutions aimed at implementing cultural competence in all psychological endeavors. Multicultural themes arising from the summit included the diversification of the United States; the facilitation of difficult dialogues on race, gender, and sexual orientation; spirituality as a basic dimension of the human condition; the invisibility of monoculturalism and Whiteness; and the teaching of multiculturalism and diversity. APA was strongly encouraged to take the lead in seeing that multicultural competence becomes a defining feature of psychological practice, education and training, and research.

Cultural Diversity↗
PubMed1995

Hox genes and the diversification of insect and crustacean body plans.

Crustaceans and insects share a common origin of segmentation, but the specialization of trunk segments appears to have arisen independently in insects and various crustacean subgroups. Such macroevolutionary changes in body architecture may be investigated by comparative studies of conserved genetic markers. The Hox genes are well suited for this purpose, as they determine positional identity along the body axis in a wide range of animals. Here we examine the expression of four Hox genes in the branchiopod crustacean Artemia franciscana, and compare this with Hox expression patterns from insects. In Artemia the three 'trunk' genes Antp, Ubx and abdA are expressed in largely overlapping domains in the uniform thoracic region, whereas in insects they specify distinct segment types within the thorax and abdomen. Our comparisons suggest a multistep process for the diversification of these Hox gene functions, involving early differences in tissue specificity and the later acquisition of a role in defining segmental differences within the trunk. We propose that the branchiopod thorax may be homologous to the entire pregenital (thoracic and abdominal) region of the insect trunk.

Amino Acid Sequence↗
PubMed2004

Cladogenesis and morphological diversification in passerine birds.

Morphological diversity tends to increase within evolving lineages over time, but the relative roles of gradual evolutionary change (anagenesis) and abrupt shifts associated with speciation events (cladogenesis, or 'punctuated equilibrium') have not been resolved for most groups of organisms. However, these two modes of evolution can be distinguished by the fact that morphological variance increases in proportion to time under anagenesis, and in proportion to the logarithm of the number of species under cladogenesis. Although species and time are themselves correlated, multiple regression analysis provides a statistical framework for partitioning their relative contributions. In this study, I use multiple regressions to evaluate the effects of time and species number on morphological diversity within clades of passerine birds. The results show clearly that number of species exerts a strong influence on morphological variance independent of time, but that time has no unique effect. Thus, morphological evolution in birds seems to be associated with cladogenesis. How lineage splitting promotes morphological diversification poses an important challenge to ecologists and evolutionary biologists.

Animals↗
PubMed2005

Evolutionary diversification of TTX-resistant sodium channels in a predator-prey interaction.

Understanding the molecular genetic basis of adaptations provides incomparable insight into the genetic mechanisms by which evolutionary diversification takes place. Whether the evolution of common traits in different lineages proceeds by similar or unique mutations, and the degree to which phenotypic evolution is controlled by changes in gene regulation as opposed to gene function, are fundamental questions in evolutionary biology that require such an understanding of genetic mechanisms. Here we identify novel changes in the molecular structure of a sodium channel expressed in snake skeletal muscle, tsNa(V)1.4, that are responsible for differences in tetrodotoxin (TTX) resistance among garter snake populations coevolving with toxic newts. By the functional expression of tsNa(V)1.4, we show how differences in the amino-acid sequence of the channel affect TTX binding and impart different levels of resistance in four snake populations. These results indicate that the evolution of a physiological trait has occurred through a series of unique functional changes in a gene that is otherwise highly conserved among vertebrates.

Adaptation, Physiological↗
PubMed2006

Bacterial populations as perfect gases: genomic integrity and diversification tensions in Helicobacter pylori.

Microorganisms that persist in single hosts face particular challenges. Helicobacter pylori, an obligate bacterial parasite of the human stomach, has evolved a lifestyle that features interstrain competition and intraspecies cooperation, both of which involve horizontal gene transfer. Microbial species must maintain genomic integrity, yet H. pylori has evolved a complex nonlinear system for diversification that exists in dynamic tension with the mechanisms for ensuring fidelity. Here, we review these tensions and propose that they create a dynamic pool of genetic variants that is sufficiently genetically diverse to allow H. pylori to occupy all of the potential niches in the stomach.

Biological Evolution↗