Nest predation by cowbirds and its consequences for passerine demography.

Brood parasitism by brown-headed cowbirds (Molothrus ater) reduces reproductive success in many passerines that nest in fragmented habitats and ecological edges, where nest predation is also common. We tested the hypothesis that parasitism and predation are often linked because cowbirds depredate nests discovered late in the host's nesting cycle to enhance future opportunities for parasitism. Over a 20-year study period, brood parasitism by cowbirds was a prerequisite to observing marked inter- and intraannual variation in the rate of nest failure in an insular song sparrow (Melospiza melodia) population. Nest failure increased with the arrival and laying rate of cowbirds and declined when cowbirds ceased laying. The absence or removal of cowbirds yielded the lowest nest failure rates recorded in the study. The absence of cowbirds also coincided with the absence of an otherwise strong positive correlation between host numbers and the annual rate of nest failure. Host numbers, cowbird parasitism, and nest failure may be correlated because cowbirds facilitate nest failure rather than cause it directly. However, an experiment mimicking egg ejection by cowbirds did not affect nest failure, and, contrary to the main prediction of the predation facilitation hypothesis, naturally parasitized nests failed less often than unparasitized nests. Higher survival of parasitized nests is expected under the cowbird predation hypothesis when female cowbirds defend access to hosts because cowbirds should often depredate unparasitized nests but should not depredate nests they have laid in. Where female cowbirds have overlapping laying areas, we expect parasitized nests to fail more often than others if different cowbirds often discover the same nests. We suggest that nest predation by cowbirds represents an adaptation for successful parasitism and that cowbirds influence host demography via nest predation.

Phenotypic variation and intracellular parasitism by Histoplasma capsulatum

The success of Histoplasma capsulatum as an intracellular pathogen depends completely on successful conversion of the saprophytic mycelial (mold) form of this fungus to a parasitic yeast form. It is therefore not surprising that yeast phase-specific genes and gene products are proving to be important for survival and proliferation of H. capsulatum within macrophages. In this study, we have focused on the role and regulation of two yeast-specific characteristics: α-(1,3)-glucan, a cell wall polysaccharide modulated by cell-density (quorum) sensing, and a secreted calcium-binding protein (CBP) that is essential for pathogenicity.

Somatic and germ cell parasitism in a colonial ascidian: Possible role for a highly polymorphic allorecognition system

A colonial protochordate, Botryllus schlosseri, undergoes a natural transplantation reaction in the wild that results alternatively in colony fusion (chimera formation) or inflammatory rejection. A single, highly polymorphic histocompatibility locus (called Fu/HC) is responsible for rejection versus fusion. Gonads are seeded and gametogenesis can occur in colonies well after fusion, and involves circulating germ-line progenitors. Buss proposed that colonial organisms might develop self/non-self histocompatibility systems to limit the possibility of interindividual germ cell “parasitism” (GCP) to histocompatible kin [Buss, L. W. (1982) Proc. Natl. Acad. Sci. USA 79, 5337–5341 and Buss, L. W. (1987) The Evolution of Individuality (Princeton Univ. Press, Princeton]. Here we demonstrate in laboratory and field experiments that both somatic cell and (more importantly) germ-line parasitism are a common occurrence in fused chimeras. These experiments support the tenet in Buss’s hypothesis that germ cell and somatic cell parasitism can occur in fused chimeras and that a somatic appearance may mask the winner of a gametic war. They also provide an interesting challenge to develop formulas that describe the inheritance of competing germ lines rather than competing individuals. The fact that fused B. schlosseri have higher rates of GCP than unfused colonies additionally provides a rational explanation for the generation and maintenance of a high degree of Fu/HC polymorphism, largely limiting GCP to sibling offspring.

Antiretroviral resistance during successful therapy of HIV type 1 infection

HIV type 1 (HIV-1) drug resistance mutations were selected during antiretroviral therapy successfully suppressing plasma HIV-1 RNA to <50 copies/ml. New resistant mutant subpopulations were identified by clonal sequencing analyses of viruses cultured from blood cells. Drug susceptibility tests showed that biological clones of virus with the mutations acquired during successful therapy had increased resistance. Each of the five subjects with new resistant mutants had evidence of some residual virus replication during highly active antiretroviral therapy (HAART), based on transient episodes of plasma HIV-1 RNA > 50 copies/ml and virus env gene sequence changes. Each had received a suboptimal regimen before starting HAART. Antiretroviral-resistant HIV-1 can be selected from residual virus replication during HAART in the absence of sustained rebound of plasma HIV-1 RNA.

Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging

Allostatic load (AL) has been proposed as a new conceptualization of cumulative biological burden exacted on the body through attempts to adapt to life's demands. Using a multisystem summary measure of AL, we evaluated its capacity to predict four categories of health outcomes, 7 years after a baseline survey of 1,189 men and women age 70–79. Higher baseline AL scores were associated with significantly increased risk for 7-year mortality as well as declines in cognitive and physical functioning and were marginally associated with incident cardiovascular disease events, independent of standard socio-demographic characteristics and baseline health status. The summary AL measure was based on 10 parameters of biological functioning, four of which are primary mediators in the cascade from perceived challenges to downstream health outcomes. Six of the components are secondary mediators reflecting primarily components of the metabolic syndrome (syndrome X). AL was a better predictor of mortality and decline in physical functioning than either the syndrome X or primary mediator components alone. The findings support the concept of AL as a measure of cumulative biological burden.

Toward a successful multinational crop plant genome initiative

Plant genome research is needed as the foundation for an entirely new level of efficiency and success in the application of genetics and breeding to crop plants and products from crop plants. Genetic improvements in crop plants beyond current capabilities are needed to meet the growing world demand not only for more food, but also a greater diversity of food, higher-quality food, and safer food, produced on less land, while conserving soil, water, and genetic resources. Plant biology research, which is poised for dramatic advances, also depends fundamentally on plant genome research. The current Arabidopsis Genome Project has proved of immediate value to plant biology research, but a much greater effort is needed to ensure the full benefits of plant biology and especially plant genome research to agriculture. International cooperation is critical, both because genome projects are too large for any one country and the information forthcoming is of benefit to the world and not just the countries that do the work. Recent research on grass genomes has revealed that, because of extensive senteny and colinearity within linkage groups that make up the chromosomes, new information on the genome of one grass can be used to understand the genomes and predict the location of genes on chromosomes of the other grasses. Genome research applied to grasses as a group thereby can increase the efficiency and effectiveness of breeding for improvement of each member of this group, which includes wheat, corn, and rice, the world’s three most important sources of food.

Factors associated with successful answering of clinical questions using an information retrieval system*

Objectives: Despite the growing use of online databases by clinicians, there has been very little research documenting how effectively they are used. This study assessed the ability of medical and nurse-practitioner students to answer clinical questions using an information retrieval system. It also attempted to identify the demographic, experience, cognitive, personality, search mechanics, and user-satisfaction factors associated with successful use of a retrieval system.

Successful external fertilization in turbulent environments.

Mathematical and experimental simulations predict that external fertilization is unsuccessful in habitats characterized by high water motion. A key assumption of such predictions is that gametes are released in hydrodynamic regimes that quickly dilute gametes. We used fucoid seaweeds to examine whether marine organisms in intertidal and subtidal habitats might achieve high levels of fertilization by restricting their release of gametes to calm intervals. Fucus vesiculosus L. (Baltic Sea) released high numbers of gametes only when maximal water velocities were below ca. 0.2 m/s immediately prior to natural periods of release, which occur in early evening in association with lunar cues. Natural fertilization success measured at two sites was always close to 100%. Laboratory experiments confirmed that (i) high water motion inhibits gamete release by F. vesiculosus and by the intertidal fucoids Fucus distichus L. (Maine) and Pelvetia fastigiata (J. Ag.) DeToni (California), and (ii) showed that photosynthesis is required for high gamete release. These data suggest that chemical changes in the boundary layer surrounding adults during photosynthesis and/or mechanosensitive channels may modulate gamete release in response to changing hydrodynamic conditions. Therefore, sensitivity to environmental factors can lead to successful external fertilization, even for species living in turbulent habitats.

Successful expression of human factor IX following repeat administration of adenoviral vector in mice.

Adenoviral vectors can direct high-level expression of a transgene, but, due to a host immune response to adenoviral antigens, expression is of limited duration, and repetitive administration has generally been unsuccessful. Exposure to foreign proteins beginning in the neonatal period may alter or ablate the immune response. We injected adult and neonatal (immunocompetent) CD-1 mice intravenously with an adenoviral vector expressing human blood coagulation factor IX. In both groups of mice, expression of human factor IX persisted for 12-16 weeks. However, in mice initially injected as adults, repeat administration of the vector resulted in no detectable expression of the transgene, whereas in mice initially injected in the neonatal period, repeat administration resulted in high-level expression of human factor IX. We show that animals that fail to express the transgene on repeat administration have developed high-titer neutralizing antibodies to adenovirus, whereas those that do express factor IX have not. This experimental model suggests that newborn mice can be tolerized to adenoviral vectors and demonstrates that at least one repeat injection of the adenoviral vector is possible; the model will be useful in elucidating the immunologic mechanisms underlying successful repeat administration of adenoviral vectors.

Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination.

Although both CD4+ and CD8+ T cells are clearly required to generate long-lasting anti-tumor immunity induced by s.c. vaccination with interleukin 2 (IL-2)-transfected, irradiated M-3 clone murine melanoma cells, some controversy continues about the site and mode of T-cell activation in this system. Macrophages, granulocytes, and natural killer cells infiltrate the vaccination site early after injection into either syngeneic euthymic DBA/2 mice or athymic nude mice and eliminate the inoculum within 48 hr. We could not find T cells at the vaccination site, which argues against the concept that T-cell priming by the IL-2-secreting cancer cells occurs directly at that location. However, reverse transcription-PCR revealed transcripts indicative of T-cell activation and expansion in the draining lymph nodes of mice immunized with the IL-2-secreting vaccine but not in mice vaccinated with untransfected, irradiated M-3 cells. We therefore propose that the antigen-presenting cells, which invade the vaccination site, process tumor-derived antigens and, subsequently, initiate priming of tumor-specific T lymphocytes in lymphoid organs. These findings suggest a three-stage process for the generation of effector T cells after vaccination with IL-2-secreting tumor cells: (i) tumor-antigen uptake and processing at the site of injection by antigen-presenting cells, (ii) migration of antigen-presenting cells into the regional draining lymph nodes, where T-cell priming occurs, and (iii) circulation of activated T cells that either perform or initiate effector mechanisms leading to tumor cell destruction.