A chromosome 21 critical region does not cause specific Down syndrome phenotypes

The "Down syndrome critical region" (DSCR) is a chromosome 21 segment purported to contain genes responsible for many features of Down syndrome (DS), including craniofacial dysmorphology. We used chromosome engineering to create mice that were trisomic or monosomic for only the mouse chromosome segment orthologous to the DSCR and assessed dysmorphologies of the craniofacial skeleton that show direct parallels with DS in mice with a larger segmental trisomy. The DSCR genes were not sufficient and were largely not necessary to produce the facial phenotype. These results refute specific predictions of the prevailing hypothesis of gene action in DS.     

Medulloblastoma growth inhibition by hedgehog pathway blockade

Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.     

Control of stress-dependent cardiac growth and gene expression by a microRNA

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of alpha-myosin heavy chain (alphaMHC) and up-regulation of betaMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism. Thus, the alphaMHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.     

Vegetation Response to a One-Time Spent Drilling Mud Application to Semiarid,Mixed-Grass Prairie

Landspraying while drilling (LWD) is an approved disposal method for water-based drilling mud (WBM) systems in western Canada. The mud is applied either on cultivated land, where it is incorporated by cultivation, or on vegetated land where it is not incorporated. This study examined the effects of summer WBM application (0, 15, 20, 40, and 80 m³ · ha^?1) on native vegetation properties. Our results indicated that LWD increased bare ground but decreased lichen cover at the 80 m³ · ha^?1 rate relative to the untreated control. Nitrogen (N), sulfur (S), and magnesium (Mg) concentrations in aboveground plant tissue increased with increasing LWD rate in samples taken 45 d after WBM application, but these differences disappeared 1 yr after treatment. Increase in tissue concentration of phosphorus (P) with LWD rate, however, was only detected 3 yr after LWD. Nonetheless, these changes in tissue chemistry were not associated with significant changes in biomass yield or species composition. Overall, our results suggest that single WBM applications at rates (≤ 20 m³ · ha^?1) commonly used in western Canada, if properly managed, are unlikely to adversely affect native prairie vegetation.     

Phylogenetic history of Phytophthora cryptogea and P. drechsleri isolates from floriculture crops in North Carolina greenhouses

The evolutionary history of Phytophthora cryptogea and P. drechsleri isolates previously collected from floriculture crops in North Carolina commercial greenhouses was explored with coalescent- and parsimony-based analyses. Initially, 68 isolates representing 13 location-host groups were sequenced at multiple loci. Sequences of all isolates within a group were identical. A subset of isolates were selected, cloned to resolve heterozygous sites, and analyzed with SNAP Workbench. The internal transcribed spacer (ITS) region of the ribosomal DNA and cytochrome oxidase II gene genealogies were congruent and indicated that P. cryptogea and P. drechsleri are sister species diverged from a common ancestor with no evidence of gene flow. In contrast, genealogies inferred from β-tubulin (β-tub) and translation elongation factor 1α (EF-1α) genes were in conflict with these loci. Coalescent analysis based on a nonrecombining partition in β-tub and EF-1α showed an initial (older) split between P. cryptogea and P. drechsleri, with a later (recent) event separating the remaining P. cryptogea haplotypes from P. drechsleri. A parsimony-based minimal ancestral recombination graph inferred recombination between P. cryptogea and P. drechsleri isolates in the ITS region and β-tub, suggesting genetic exchange between species. Also, putative recombination between A1 and A2 mating types of P. cryptogea suggests that sexual reproduction has occurred in the history of these P. cryptogea isolates.     

Glyphosate-tolerant corn: the composition and feeding value of grain from glyphosate-tolerant corn is equivalent to that of conventional corn (Zea mays L.)

Glyphosate-tolerant (Roundup Ready) corn line GA21 has been developed by genetic modification to tolerate glyphosate, the active ingredient in Roundup herbicide. The purpose of this study was to evaluate the compositional and nutritional safety of corn line GA21 compared to that of conventional corn. Compositional analyses were conducted to measure proximate, fiber, amino acid, fatty acid, and mineral contents of grain and proximate, fiber, and mineral contents of forage collected from 16 field sites over two growing seasons. The nutritional safety of corn line GA21 was evaluated in a poultry feeding study conducted with 2-day old, rapidly growing broiler chickens, at a dietary concentration of 50-60% w/w. Compositional analysis results showed that, except for a few minor differences that are unlikely to be of biological significance, the grain and forage of GA21 corn were comparable in their composition to that of the control corn line and to conventional corn. Results from the poultry feeding study showed that there were no differences in growth, feed efficiency, adjusted feed efficiency, and fat pad weights between chickens fed with GA21 grain or with parental control grain. These data taken together demonstrate that Roundup Ready corn is as safe and nutritious as conventional corn for food and feed use.     

Aspects of bacteriology and endocrinology of cows with pyometra and retained fetal membranes

In an effort to clarify the pathogenesis of pyometra, 20 cows with retained fetal membranes and 20 without, but with contemporary calving dates were studied. They were palpated and their uteri were subjected to sample collections for bacteriologic cultural examinations twice weekly for 4 weeks. Blood samples were obtained each day and evaluated for serum progesterone concentration. Three cows without and 3 with retained fetal membranes developed pyometra during the study, resulting in 3 groups designated control (CON), cows with retained fetal membranes (RFM), and cows with pyometra (PYO). Bacterial isolations occurred less frequently in the CON group than in the PYO and RFM groups. Growth patterns of bacteria also varied between groups. Coliform and incidental bacteria disappeared from the uterus of the PYO group by the end of the 3rd week. In contrast, heavy growth of Corynebacterium pyogenes and gram-negative anaerobic bacteria developed during this same period in the PYO group. In cows with pyometra, the significant persistent pathogenic bacteria recovered were C pyogenes and gram-negative anaerobic bacteria, especially Fusobacterium necrophorum and Bacteroides melaninogenicus. Anaerobic bacteria were isolated simultaneously with C pyogenes in most cows of the PYO group, but less often in CON and RFM groups, and highest growth levels were present near the time of ovulation. Clinically, pyometra usually developed about 10 days after observation of concurrent ovulation and high growth levels of C pyogenes and gram-negative anaerobic bacteria. A hypothesis is presented for development of pyometra in the cow.