The Bovine HapMap Consortium* The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.T he emergence of modern civilization was accompanied by adaptation, assimilation, and interbreeding of captive animals. In cattle (Bos taurus), this resulted in the development of individual breeds differing in, for example, milk yield, meat quality, draft ability, and tolerance or resistance to disease and pests. However, despite mapping and diversity studies (1-5) and the identification of mutations affecting some quantitative phenotypes (6-8), the detailed genetic structure and history of cattle are not known.Cattle occur as two major geographic types, the taurine (humpless-European, African, and Asian) and indicine (humped-South Asian, and East African), which diverged >250 thousand years ago (Kya) (3). We sampled individuals representing 14 taurine (n = 376), three indicine (n = 73) (table S1), and two hybrid breeds (n = 48), as well as two individuals each of Bubalus quarlesi and Bubalus bubalis, which diverged from Bos taurus~1.25 to 2.0 Mya (9, 10). All breeds except Red Angus (n = 12) were represented by at least 24 individuals. We preferred individuals that were unrelated for ≥4 generations; however, each breed had one or two sire, dam, and progeny trios to allow assessment of genotype quality.Single-nucleotide polymorphisms (SNPs) that were polymorphic in many populations were primarily derived by comparing whole-genome sequence reads representing five taurine and one indicine breed to the reference genome assembly obtained from a Hereford cow (10) (table S2). This led to the ascertainment of SNPs with high minor allele frequencies (MAFs) within the discovery breeds (table S5). Thus, as expected, with trio progeny removed, SNPs discovered within the taurine breeds had higher average MAFs

Background: Mesenchymal stem cells (MSCs) have been recently investigated for their potential use in regenerative medicine. MSCs, in particular, have great potential, as in various reports they have shown pluripotency for differentiating into many different cell types. However, the ability of MSCs to differentiate into tendon cells in vitro has not been fully investigated.

PURPOSE The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) -positive locally recurrent/metastatic breast cancer (LR/MBC). PATIENTS AND METHODS Patients with measurable/evaluable HER2-positive LR/MBC who had not received trastuzumab or chemotherapy for LR/MBC were stratified by prior adjuvant trastuzumab, prior (neo)adjuvant taxane, hormone receptor status, and measurable disease and were randomly assigned to receive docetaxel 100 mg/m(2) plus trastuzumab 8 mg/kg loading dose followed by 6 mg/kg either with bevacizumab 15 mg/kg or without bevacizumab, all administered every 3 weeks. The primary end point was progression-free survival (PFS). Additional end points included overall survival, response rate (RR), safety, quality of life, and translational research. Results Baseline characteristics of the 424 patients were balanced between treatment arms. Most patients had visceral metastases, 43% had a disease-free interval less than 12 months, and 85% had measurable disease. Median follow-up was 26 months. The hazard ratio for investigator-assessed PFS was 0.82 (95% CI, 0.65 to 1.02; P = .0775; median PFS, 13.7 v 16.5 months in the non-bevacizumab and bevacizumab arms, respectively; PFS events in 72%). The Independent Review Committee-assessed PFS hazard ratio was 0.72 (95% CI, 0.54 to 0.94; P = .0162; median PFS, 13.9 v 16.8 months, respectively; PFS events in 53%). The RR was 70% versus 74%, respectively (P = .3492). Grade ≥ 3 febrile neutropenia and hypertension were more common with bevacizumab-containing therapy. High baseline plasma vascular endothelial growth factor A (VEGF-A) concentrations were associated with greater bevacizumab benefit (not statistically significant). CONCLUSION Combining bevacizumab with docetaxel and trastuzumab did not significantly improve investigator-assessed PFS. The potential predictive value of plasma VEGF-A is consistent with findings in HER2-negative LR/MBC, warranting prospective evaluation.

The implication of calcium as intracellular messenger in the arbuscular mycorrhizal (AM) symbiosis has not yet been directly demonstrated, although often envisaged. We used soybean (Glycine max) cell cultures stably expressing the bioluminescent Ca 21 indicator aequorin to detect intracellular Ca 21 changes in response to the culture medium of spores of Gigaspora margarita germinating in the absence of the plant partner. Rapid and transient elevations in cytosolic free Ca 21 were recorded, indicating that diffusible molecules released by the mycorrhizal fungus are perceived by host plant cells through a Ca 21 -mediated signaling. Similar responses were also triggered by two Glomus isolates. The fungal molecules active in generating the Ca 21 transient were constitutively released in the medium, and the induced Ca 21 signature was not modified by the coculture of germinating spores with plant cells. Even ungerminated spores were able to generate the signaling molecules, as proven when the germination was blocked by a low temperature. The fungal molecules were found to be stable to heat treatment, of small molecular mass (,3 kD), and, on the basis of extraction with an organic solvent, partially lipophilic. Evidence for the specificity of such an early fungal signal to the AM symbiosis is suggested by the lack of a Ca 21 response in cultured cells of the nonhost plant Arabidopsis (Arabidopsis thaliana) and by the up-regulation in soybean cells of genes related to Medicago truncatula DMI1, DMI2, and DMI3 and considered essential for the establishment of the AM symbiosis.

alpha-1,4-linked oligogalacturonides (OGs) are pectic fragments of plant cell walls that are able to induce defence and developmental responses. To understand plant responses to OGs at the transcriptional level, changes in gene expression were examined using oligonucleotide-based microarrays that cover almost the entire Arabidopsis transcriptome. In suspension-cultured Arabidopsis thaliana (L.) Columbia hypocotyl cells, approximately 4% of the total transcriptome exhibited significant change in abundance in response to treatment with OGs for 2 h. Steady-state changes in the abundance of transcripts encoding stress- and disease-related proteins, signalling components, and transcription factors were particularly noteworthy. As in other plant cell types, OGs elicit a rapid, but transient, elevation in cytosolic free Ca(2+). The Ca(2+) transient can be abolished by the protein kinase inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) and by the Ca(2+) channel inhibitor La(3+), thereby facilitating a distinction between Ca(2+)-dependent and -independent transcriptional responses. Among the 244 transcripts that were up-regulated by OGs, the response of 93 (38%) was selectively sensitive to abolition of the Ca(2+) transient. These OG-up-regulated, Ca(2+)-dependent transcripts included two noteworthy classes, the first comprising genes involved in cell wall modification following pathogen attack, and the second consisting of genes involved in the biosynthesis of jasmonate and C6 volatile compounds. These results support the notion of an important role for cytosolic Ca(2+) signalling in jasmonate biosynthesis following OG perception. Promoter analysis of OG-induced, inhibitor-sensitive and -insensitive genes identified several putative cis-elements that might be involved specifically in Ca(2+)-dependent transcriptional regulation.