Efficient Cre-loxP-induced mitotic recombination in mouse embryonic stem cells.

FLP/FRT-induced mitotic recombination provides a powerful method for creating genetic mosaics in Drosophila and for discerning the function of recessive genes in a heterozygous individual. Here we show that mitotic recombination can be reproducibly induced in mouse embryonic stem (ES) cells, by Cre/loxP technology, at frequencies ranging from 4.2 x 10(-5) (Snrpn) to 7.0 x 10(-3) (D7Mit178) for single allelic loxP sites, and to 5.0 x 10(-2) (D7Mit178) for multiple allelic lox sites, after transient Cre expression. Notably, much of the recombination occurs in G2 and is followed by X segregation, where the recombinant chromatids segregate away from each other during mitosis. It is X segregation that is useful for genetic mosaic analysis because it produces clones of homozygous mutant daughter cells from heterozygous mothers. Our studies confirm the predictions made from studies in Drosophila that suggest that X segregation will not be limited to organisms with strong mitotic pairing, because the forces (sister-chromatid cohesion) responsible for X segregation are an elemental feature of mitosis in all eukaryotes. Our studies also show that genetic mosaic analysis in mice is feasible, at least for certain chromosomal regions.     

Modeling large reversible electric-field-induced strain in ferroelectric materials using 90° orientation switching

Reversible large electric-field-induced strain caused by reversible orientation switchings in BaTiO3 is modeled using the Landau's theory of phase transition.A triple well free energy function is constructed.Each of its minima is associated with one of the polarization orientations involved.Nonlinear constitutive laws accounting for reversible orientation switchings and electrostriction effects are obtained by using thermodynamic equilibrium conditions.Hysteretic dynamics of onedimensional structures is des...     

Comparing the effects of granivorous rodents on persistence of Indian ricegrass ( Oryzopsis hymenoides ) seeds in mixed and monospecific seed patches

In desert environments seeds are often heterogeneously distributed in small patches that vary in number of seed species and in seed density. Because seed harvest by rodents is often density dependent (a larger proportion of seeds is removed from high-density seed patches than from low-density patches), the proportion of residual or post-harvest seeds should be greater in low-density patches. In addition, seed preference can affect harvest. We tested whether the residual proportion of a highly preferred seed (Indian ricegrass, Oryzopsis hymenoides ) was less when in a seed patch with a 2nd species (mixed-species patch) than when in a monospecific seed patch. We predicted that the increased overall seed density due to the presence of 2 species in a patch would result in a lower residual proportion of ricegrass seeds in the mixed-species seed patches than in the monospecific patches. As predicted, the residual proportions of Indian ricegrass seeds were less each time ricegrass was paired with one of 6 other species in mixed-species patches. Similarly, the residual proportion of each of those 6 species was less when paired with ricegrass than when in a monospecific patch. We speculate on the potential implications of these results for the population dynamics of plant species and the physical structure of plant communities.     

The influence of fallen tree timing on spruce beetle brood production

This study compared brood production of the spruce beetle ( Dendroctonus rufipennis Kirby [Coleoptera: Curculionidae, Scolytinae]) in downed host material felled during summer and spring seasons on the Wasatch Plateau in south central Utah. Thirty-three matched pairs of Engelmann spruce ( Picea engelmannii Parry ex Engelm.) trees were selected for study in spring 1996. One tree of each pair was cut during August 1996 (summer-felled), and the other tree was cut in early April 1997 (spring-felled), so that trees would be colonized by spruce beetles of the same flight period. Brood adults were collected and counted from bark samples, which were removed from the top, bottom, and sides of all sample trees in October 1998. The number of emergent adults produced in June 1999 was determined from exit holes counted in bark samples removed from these same locations. Mixed-model procedures were used to compare differences in the mean number of adults produced in summer-felled versus spring-felled trees in each year. The results indicated that significantly fewer spruce beetles were produced in summer-felled trees than in spring-felled trees. More brood adults were also present in, or emerged from, unexposed bole aspects (bottom, north, and east) of sample trees than exposed aspects (top, south, and west). These findings suggest that disturbances providing spruce beetles with an abundance of fresh host material in the spring result in the greatest potential for spruce beetle production, particularly beneath unexposed bark aspects. Examples of such disturbances include snow avalanches, blowdown, and snow and ice damage.     

Engelmann spruce cone losses caused by insects in northern Utah in a year of low cone production

The impacts and timing of insect infestation were determined in developing Engelmann spruce cones throughout the summer of a year of low cone production in northern Utah. The major insects found were the western spruce budworm, Choristoneura occidentalis Freeman (Lepidoptera: Tortricidae); fir coneworm, Dioryctria abietivorella Grote (Lepidoptera: Pyralidae); and the spruce seed moth, Laseyresia youngana Kearfott (Lepidoptera: Olethreutidae). Insects reduced the survival of cones to 11.48 cones out of 100. The high percentage of seeds and cones lost to insect predation supported previous studies of a similar nature.     

Genetic variation of woodrats ( Neotoma cinerea ) and deer mice ( Peromyscus maniculatus ) on montane habitat islands in the Great Basin

Seventeen loci were examined for polymorphism in four populations of Neotoma cinerea and Peromyscus maniculatus on isolated mountain ranges in the Great Basin, one population of each in the Sierra Nevada, and one of each in the Rocky Mountains. All Peromyscus populations had higher levels of heterozygosity than syntopic Neotoma populations.     

Ancestrular morphology in cyclostome bryozoans and the quest for phylogenetically informative skeletal characters

Cyclostomes are an ancient order of bryozoans with more than 500 living species. Traditionally, cyclostome taxonomy has depended almost entirely on characters of the calcareous skeletons of mature colonies. However, the taxonomic distribution of these characters is largely incongruent with well-supported molecular phylogenetic trees, implying the need for major revisions if cyclostome taxonomy is to reflect phylogeny. While far more taxa must be sequenced to ascertain their molecular relationships, there is also a need to discover morphological characters that can be used to support molecular clades, not least to allow these clades to be inferred among fossil cyclostomes for which molecular data will never be available. Here we survey the skeletal morphology of the first-formed part of the skeleton – the protoecium of the founding zooid (ancestrula) – in a variety of Recent and well-preserved fossil cyclostomes, motivated by the recent discovery of a morphologically disparate molecular clade that can be distinguished by protoecial characters. The distribution of pseudopores on the protoecium is shown to vary between species, with eight patterns recognizable, offering a new source of skeletal characters in both living and fossil taxa. However, the patterns seem not to be fully congruent with the cyclostome molecular tree and more data and analyses are required before these patterns can be used to recognize cyclostome clades.     

Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila

Discriminating among sensory stimuli is critical for animal survival. This discrimination is particularly essential when evaluating whether a stimulus is noxious or innocuous. From insects to humans, transient receptor potential (TRP) channels are key transducers of thermal, chemical and other sensory cues. Many TRPs are multimodal receptors that respond to diverse stimuli, but how animals distinguish sensory inputs activating the same TRP is largely unknown. Here we determine how stimuli activating Drosophila TRPA1 are discriminated. Although Drosophila TRPA1 responds to both noxious chemicals and innocuous warming, we find that TRPA1-expressing chemosensory neurons respond to chemicals but not warmth, a specificity conferred by a chemosensory-specific TRPA1 isoform with reduced thermosensitivity compared to the previously described isoform. At the molecular level, this reduction results from a unique region that robustly reduces the channel's thermosensitivity. Cell-type segregation of TRPA1 activity is critical: when the thermosensory isoform is expressed in chemosensors, flies respond to innocuous warming with regurgitation, a nocifensive response. TRPA1 isoform diversity is conserved in malaria mosquitoes, indicating that similar mechanisms may allow discrimination of host-derived warmth--an attractant--from chemical repellents. These findings indicate that reducing thermosensitivity can be critical for TRP channel functional diversification, facilitating their use in contexts in which thermal sensitivity can be maladaptive.     

Large-scale prediction and testing of drug activity on side-effect targets

Discovering the unintended 'off-targets' that predict adverse drug reactions is daunting by empirical methods alone. Drugs can act on several protein targets, some of which can be unrelated by conventional molecular metrics, and hundreds of proteins have been implicated in side effects. Here we use a computational strategy to predict the activity of 656 marketed drugs on 73 unintended 'side-effect' targets. Approximately half of the predictions were confirmed, either from proprietary databases unknown to the method or by new experimental assays. Affinities for these new off-targets ranged from 1 nM to 30 μM. To explore relevance, we developed an association metric to prioritize those new off-targets that explained side effects better than any known target of a given drug, creating a drug-target-adverse drug reaction network. Among these new associations was the prediction that the abdominal pain side effect of the synthetic oestrogen chlorotrianisene was mediated through its newly discovered inhibition of the enzyme cyclooxygenase-1. The clinical relevance of this inhibition was borne out in whole human blood platelet aggregation assays. This approach may have wide application to de-risking toxicological liabilities in drug discovery.     

Discovery of a previously unrecognized microdeletion syndrome of 16p11.2-p12.2

We have identified a recurrent de novo pericentromeric deletion in 16p11.2-p12.2 in four individuals with developmental disabilities by microarray-based comparative genomic hybridization analysis. The identification of common clinical features in these four individuals along with the characterization of complex segmental duplications flanking the deletion regions suggests that nonallelic homologous recombination mediated these rearrangements and that deletions in 16p11.2-p12.2 constitute a previously undescribed syndrome.