Optimizing purebred selection for crossbred performance using QTL with different degrees of dominance

A method was developed to optimize simultaneous selection for a quantitative trait with a known QTL within a male and a female line to maximize crossbred performance from a two-way cross. Strategies to maximize cumulative discounted response in crossbred performance over ten generations were derived by optimizing weights in an index of a QTL and phenotype. Strategies were compared to selection on purebred phenotype. Extra responses were limited for QTL with additive and partial dominance effects, but substantial for QTL with over-dominance, for which optimal QTL selection resulted in differential selection in male and female lines to increase the frequency of heterozygotes and polygenic responses. For over-dominant QTL, maximization of crossbred performance one generation at a time resulted in similar responses as optimization across all generations and simultaneous optimal selection in a male and female line resulted in greater response than optimal selection within a single line without crossbreeding. Results show that strategic use of information on over-dominant QTL can enhance crossbred performance without crossbred testing.     

Animal housing influences the response of bone to spaceflight in juvenile rats.

The rat has been used extensively as an animal model to study the effects of spaceflight on bone metabolism. The results of these studies have been inconsistent. On some missions, bone formation at the periosteal bone surface of weight-bearing bones is impaired and on others it is not, suggesting that experimental conditions may be an important determinant of bone responsiveness to spaceflight. To determine whether animal housing can affect the response of bone to spaceflight, we studied young growing (juvenile) rats group housed in the animal enclosure module and singly housed in the research animal holding facility under otherwise identical flight conditions (Spacelab Life Science 1). Spaceflight reduced periosteal bone formation by 30% (P < 0.001) and bone mass by 7% in single-housed animals but had little or no effect on formation (-6%) or mass (-3%) in group-housed animals. Group housing reduced the response of bone to spaceflight by as much as 80%. The data suggest that housing can dramatically affect the skeletal response of juvenile rats to spaceflight. These observations explain many of the discrepancies in previous flight studies and emphasize the need to study more closely the effects of housing (physical-social interaction) on the response of bone to the weightlessness of spaceflight.     

Infectious disease and the Unesco basic education initiative

As part of a Basic Education for All campaign, Unesco is exploring ways to improve health and nutrition in school-age children in order to help them take advantage of the only schooling they may ever receive. At the first international Unesco working meeting on health, nutrition and school performance, intestinal helminths were identified as more appropriate immediate targets than malaria and other infectious diseases. Prevalence and intensity of infection in school-age children, the schools as vehicles of intervention, and the availability of interventions contributed to this choice. However, there are still many gaps in our knowledge of the effects of infectious diseases in schoolchildren. Through the improvement of understanding in this area, the parasitology community may be able to contribute to the Unesco project.     

Effect of postnatal development on calcium currents and slow charge movement in mammalian skeletal muscle

Single- (whole-cell patch) and two-electrode voltage-clamp techniques were used to measure transient (Ifast) and sustained (Islow) calcium currents, linear capacitance, and slow, voltage-dependent charge movements in freshly dissociated fibers of the flexor digitorum brevis (FDB) muscle of rats of various postnatal ages. Peak Ifast was largest in FDB fibers of neonatal (1-5 d) rats, having a magnitude in 10 mM external Ca of 1.4 +/- 0.9 pA/pF (mean +/- SD; current normalized by linear fiber capacitance). Peak Ifast was smaller in FDB fibers of older animals, and by approximately 3 wk postnatal, it was so small as to be unmeasurable. By contrast, the magnitudes of Islow and charge movement increased substantially during postnatal development. Peak Islow was 3.6 +/- 2.5 pA/pF in FDB fibers of 1-5-d rats and increased to 16.4 +/- 6.5 pA/pF in 45-50-d-old rats; for these same two age groups, Qmax, the total mobile charge measurable as charge movement, was 6.0 +/- 1.7 and 23.8 +/- 4.0 nC/microF, respectively. As both Islow and charge movement are thought to arise in the transverse-tubular system, linear capacitance normalized by the area of fiber surface was determined as an indirect measure of the membrane area of the t-system relative to that of the fiber surface. This parameter increased from 1.5 +/- 0.2 microF/cm2 in 2-d fibers to 2.9 +/- 0.4 microF/cm2 in 44-d fibers. The increases in peak Islow, Qmax, and normalized linear capacitance all had similar time courses. Although the function of Islow is unknown, the substantial postnatal increase in its magnitude suggests that it plays an important role in the physiology of skeletal muscle.     

Changes in Ia expression in mouse kidney during acute graft-vs-host disease

We induced graft-vs-host disease (GVHD) in mice to determine whether immunologic stimuli could alter renal Ia expression. Two strain combinations were used: B6.C-H-2bm12 into C57BL/6, an I-A mutation difference, and A.SW into A.TL, differing in the I and D regions of H-2. By day 10 after allogeneic reconstitution of lethally irradiated recipients with bone marrow and spleen cells, the recipients had developed acute GVHD, as measured by their spleen to body weight ratio. Histologic examination revealed focal interstitial infiltrates of mononuclear cells in the kidneys. The expression of host Ia in these kidneys was increased up to 10-fold, as measured by absorption, and indirect immunofluorescence indicated that certain renal tubule cells had become strongly positive, suggesting that these were the principal sites of the increase in Ia expression. Similar increases were not observed in donor Ia. Tubule cells may have become Ia positive by passive uptake, or more probably, by the increase of Ia biosynthesis in cells that usually synthesize little or no Ia. Lethal irradiation without reconstitution tended to decrease renal Ia expression, as assessed by absorption and immunofluorescence. The results indicate that renal Ia expression, particularly in renal tubules, can be altered by changes in the immune system, raising the possibility of a role for such altered Ia expression in autoimmune or alloimmune responses involving the kidney.     

Modeling malaria vaccines. I: New uses for old ideas

Starting from a modification of the model of malaria transmission developed for the Garki project, this paper develops a model containing variables relevant to the stimulation of malaria vaccination programs. Modifications include (1) integration of maintenance of immunity dependent on boosting and the possibility of loss of immunity; (2) introduction of a boosting factor distinct from susceptibility to infection; (3) reinterpretation of the epidemiological compartments of positive immunes and nonimmunes in terms of severity of disease rather than just infection; (4) interpretation of the different stage-specific levels of immunity; (5) discrimination between different susceptibilities for the immune and nonimmune classes; (6) reformulation of the expression for acquisition of immunity to be biologically more acceptable. Simulations using the Garki model, Nedelman's modification of it, and our Basic model compare the similarities and differences in the predictive behavior of the models. Simulations using the Basic model reproduce observed periodic fluctuations of malaria attributed to the interplay of transmission-blocking immunity and loss of immunity in the absence of boosting in areas of unstable malaria transmission.     

Nesting Behaviour of Abert Squirrels (Sciurus aberti)

Nesting behaviour of Abert squirrels (Sciurus aberti), including site selection and use, was studied in the foothills of the Rocky Mountains in Boulder County, Colorado. Only females were observed building nests, although both males and females maintained nests once they were built. Communal nesting by Abert squirrels was rare, but the majority of observed nest sharings involved unrelated male and female pairs. A total of 14 variables were used to evaluate the nests (n = 49) inhabited by Abert squirrels from May 1988 to Jun. 1991. All nests were located in Ponderosa pine (Pinus ponderosa) trees. The majority of nests were constructed of twigs and located in the upper one-third of the canopy, near the trunk, on the south-east side of the tree. Trees with nests were predominantly located in closed stands. Nest trees, when compared with unused control trees that were equally accessible to squirrels, were significantly different from control trees in five of nine variables. Nest tree crowns intertwined with a larger number of adjacent tree crowns than did control tree crowns. Nest trees were also significantly taller than control trees, but subdominant to adjacent trees within a stand. Seasonal and diurnal patterns of nest use indicate that Abert squirrels do not choose nest locations on the south-east sides of trees to facilitate behavioural thermoregulation. Rather, Abert squirrels select nest site locations to (1) maximize accessibility and (2) maximize structural stability which may provide protection from wind and rain.