Characterization of the expressed immunoglobulin IGHV repertoire in the New World marmoset Callithrix jacchus

The common marmoset (Callithrix jacchus jacchus) is a member of the Callithrichinae, a family of outbred New World primates with limited MHC polymorphisms and a propensity to develop spontaneous or experimentally induced autoimmunity. C. jacchus marmosets are susceptible to experimental allergic encephalomyelitis (EAE), and spontaneously develop autoimmune colitis and thyroiditis. Such disease models approximate the complexity of human autoimmune disorders, and allow an investigation of the respective roles of T-cell and antibody responses to self-antigens in outbred species. A key issue for further definition of the pathogenic antibody responses in human autoimmunity is to understand the diversity of the immunoglobulin repertoire in primate models. Here, we characterized the expressed immunoglobulin IGHV repertoire of the C. jacchus marmoset. Six IGHV subgroups were identified which show a high degree of sequence similarity to their human IGHV counterparts (IGHV1, IGHV3, IGHV4, IGHV5, IGHV6, and IGHV7). As in the expressed human IGHV repertoire, the framework regions are more conserved when compared to the complementarity-determining regions (CDRs), with the greatest degree of variability located in CDR3. Predicted structural features are highly conserved between C. jacchus and human IGHV. This information now provides a framework for studies of the antigen-specific repertoire of pathogenic antibodies in EAE and other immune-mediated diseases.     

Low affinity of the receptor for 1 alpha,25-dihydroxyvitamin D3 in the marmoset, a New World monkey

Circulating levels of 1,25-dihydroxyvitamin D are 10-fold higher in the marmoset, a New World monkey, than in man; to assess hormone receptors, we evaluated interactions of 1,25-dihydroxyvitamin D3 with virus-transformed lymphocytes. Soluble extracts of transformed lymphocytes from humans showed hormone binding with affinity and capacity similar to that of receptors for 1,25-dihydroxyvitamin D from other human tissues. However, soluble extracts of transformed lymphocytes from the marmoset showed a strikingly lower affinity for 1,25-dihydroxyvitamin D (Kd 2.2 vs 0.27 nM in marmoset vs human) and a mildly lower binding capacity (6.9 vs 16 fmol/mg protein). A defective receptor for 1,25-dihydroxyvitamin D3 could account for resistance of target tissues to this hormone in the marmoset.     

Micromorphological characters and generic delimitation of some New World Senecioneae (Asteraceae)

Some recent systematic investigations have placed great reliance on micromorphological floral features in generic delimitation in the Senecioneae. In order to test the taxonomic value of those features, 31 species of New World “Cacalioid” and “Senecionoid” Senecioneae were examined for five micromorphological characters: 1) configuration and distribution of the stigmatic area on the style branches, 2) stylopodial structure, 3) cellular structure of the carpopodium, 4) configuration of the anther collar, and 5) form of the endothecial cells in the anther. LM or SEM photographs were made for each character for each species. Variation was found to exist with age and geographical range for each of these characters and sometimes between florets on one capitulum. Differences in these five microcharacters were found between the “Cacalioid” and “Senecionoid” genera, but they were no more consistent than the differences in traditional characters employed in generic delimitation.     

Effective antigen-specific immunotherapy in the marmoset model of multiple sclerosis

Mature T cells initially respond to Ag by activation and expansion, but high and repeated doses of Ag cause programmed cell death and can suppress T cell-mediated diseases in rodents. We evaluated repeated systemic Ag administration in a marmoset model of experimental allergic encephalomyelitis that closely resembles the human disease multiple sclerosis. We found that treatment with MP4, a chimeric, recombinant polypeptide containing human myelin basic protein and human proteolipid protein epitopes, prevented clinical symptoms and did not exacerbate disease. CNS lesions were also reduced as assessed in vivo by magnetic resonance imaging. Thus, specific Ag-directed therapy can be effective and nontoxic in primates.     

The marmoset as a model of aging and age-related diseases

The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16? years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change--for example, reduced neurogenesis, ?-amyloid deposition in the cerebral cortex, loss of calbindin D(28k) binding, and evidence of presbycusis--appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age.     

LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing

Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS)-induced inflammation model was established in marmoset monkeys (Callithrix jacchus) to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS) were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4) inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and macrophage inflammatory protein-1 beta (MIP-1β) were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL) was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-α, and MIP-1β. TNF-α release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-α secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC(50)). LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-α and MIP-1β levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.     

A new model for cellulose architecture in some plant cell walls

Summary A new model of rotating fibre components (helicoidal model) is proposed to explain the architecture of some plant cell walls. On the basis of tilting observations under the electron microscope, we establish the validity of this model for the cell wall ofChara vulgaris oospores. We suggest that this model explains the architecture seen in a number of published micrographs from a variety of different plant cell walls. Helicoidal architecture is shown to be distinct from the previously established crossed polylamellate architecture. The diagnostic features of helicoidal architecture are given. Morphogenesis of plant cell walls is discussed, with particular reference to self assembly in cholesteric liquid crystals.     

Antimutagenicity profiles for some model compounds

The concept of activity profile listings and plots, already applied successfully to the display of mutagenicity data, has been modified for application to antimutagenicity data. The activity profiles are bar graphs that have been organized in two general ways: for antimutagens that have been tested in combination with a given mutagen and for mutagens that have been tested in combination with a given antimutagen. Doses from both the mutagen and the antimutagen are displayed and plotted together with results on enhancement or inhibition of mutagenic activity. The short-term tests that have been used extensively to identify mutagens and potential carcinogens are increasingly being used to identify antimutagens and potential anticarcinogens. Three model mutagens, N-methyl-N'-nitro-N-nitrosoguanidine, aflatoxin B1 and benzo[a]pyrene, and 4 model antimutagens, butylated hydroxyanisole, butylated hydroxytoluene, glutathione and disulfiram, were selected from the data surveyed in the published literature. It is not clear at the present time whether the inhibition of carcinogen-induced mutation is a good indicator of anticarcinogenic properties, and further research is needed. Nevertheless, the activity profiles are useful for the assessment of the available antimutagenesis data by providing rapid visualization of considerable dose information and experimental results.     

Makiko's New World

Makiko's New World. 1999. 57 minutes, color. film by the Media Production Group of the Asian Educational Media Service, University of Illinois at Urbana Champaign. Distributed by Documentary Educational Resources, 101 Morse Street, Water town, MA 02472.     

New World Bats Harbor Diverse Influenza A Viruses

Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.     

A restraint system for the common marmoset (Callithrix jacchus)

A method for restraining the marmoset in a primate chair is described. The device is inexpensive to construct, is reliable, and the majority of animals can be habituated to its use. The chair has been used in neurobiological studies employing electrophysiological recordings, with or without concurrent collection of serial blood samples.     

A multilocus phylogeny of New World jay genera

We studied phylogenetic relationships of the New World Jays (NWJs) based on DNA sequences from three mitochondrial and two nuclear loci. Sampling included at least two individuals from each of the seven NWJ genera and four outgroups of closely related corvids, as well as six of the 16 Cyanocorax species (including two representatives of the previously recognized "Cissilopha"). Phylogenetic analyses were conducted using maximum parsimony, maximum likelihood, and Bayesian analyses for individual genes and a combined dataset. The combined phylogenetic analysis supports the basal position of Cyanolyca to all other NWJs, a (Cyanocorax (Calocitta, Psilorhinus)) clade, and a ((Cyanocitta, Aphelocoma) Gymnorhinus) clade that agrees with a novel morphological synapomorphy uniting Cyanocitta and Aphelocoma. Within Cyanocorax, C. yncas (former "Xanthoura") is basal to a split among former "Cyssilopha" species and the rest of the Cyanocorax species. To explore implications for the historical biogeography of the NJWs, we used Dispersal-Vicariance Analysis, which indicated that NWJs originated either in Mesoamerica or North America+Mesoamerica, with South American NWJs dispersing three times independently from Mesoamerica.     

Preparing New World monkeys for laboratory research

New World monkeys represent an important but often poorly understood research resource. The relatively small size and low zoonotic risk of these animals make them appealing as research subjects in a number of areas. However, historic portrayal of many of these species as difficult to manage and handle is one of the factors that has limited their use. Basic guidelines are provided on management and handling approaches for the New World monkeys most commonly used in research: marmosets, squirrel monkeys, owl monkeys, and titi monkeys. Topics include transport and acclimation to a new facility, location changes within a facility, diet changes, removal from and return to social groups, capture and restraint, handling for anesthesia, postprocedural monitoring, and staff training.     

A New World With AIDS—Health Promotion as a Catalyst for Change

Preventing the acquired immunodeficiency syndrome (AIDS) requires an unprecedented response from public health professionals, particularly educators and communicators involved with health promotion. Health promotion is defined and discussed in the light of recent experience in a broad range of public health programs. Increased sophistication is needed in the application of social science within health promotion and increased facility in mobilizing cross-sectorial resources to achieve public health objectives and generate confidence in approaching AIDS prevention.