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.     

Genetic structure of human populations

We studied human population structure using genotypes at 377 autosomal microsatellite loci in 1056 individuals from 52 populations. Within-population differences among individuals account for 93 to 95% of genetic variation; differences among major groups constitute only 3 to 5%. Nevertheless, without using prior information about the origins of individuals, we identified six main genetic clusters, five of which correspond to major geographic regions, and subclusters that often correspond to individual populations. General agreement of genetic and predefined populations suggests that self-reported ancestry can facilitate assessments of epidemiological risks but does not obviate the need to use genetic information in genetic association studies.     

Single-molecule kinetics of lambda exonuclease reveal base dependence and dynamic disorder

We used a multiplexed approach based on flow-stretched DNA to monitor the enzymatic digestion of lambda-phage DNA by individual bacteriophage lambda exonuclease molecules. Statistical analyses of multiple single-molecule trajectories observed simultaneously reveal that the catalytic rate is dependent on the local base content of the substrate DNA. By relating single-molecule kinetics to the free energies of hydrogen bonding and base stacking, we establish that the melting of a base from the DNA is the rate-limiting step in the catalytic cycle. The catalytic rate also exhibits large fluctuations independent of the sequence, which we attribute to conformational changes of the enzyme-DNA complex.     

Deferring flowering of nobile dendrobium hybrids by holding plants under low temperature after vernalization

Orchids are currently the most valuable potted crop in the United States. To date, no studies focused on making possible the year-round greenhouse production of flowering nobile dendrobium orchids. This experiment was aimed at developing a strategy to defer flowering of nobile dendrobium orchids by holding them under low temperature. Mature Den. Red Emperor ‘Prince’ and Den. Sea Mary ‘Snow King’ were held at 10 °C for various durations (0, 4, 8, 12 or 16 weeks) after vernalization (4 weeks at 10 °C). Plants were forced in a greenhouse after holding. Time to flower, flower differentiation (flowering node percentage, number of aerial shoot and aborted bud) and flower quality (total flower number, flower diameter, flower number per flowering node and flower longevity) were determined. Increase of low temperature holding duration from 0 to 16 weeks extended time to flower up to 3 months and did not affect parameters of flower except producing larger flowers and reducing flower number per flowering node for Den. Red Emperor ‘Prince’. Notably, the flower longevity was not adversely affected. Defoliation was aggravated in Den. Red Emperor ‘Prince’ by longer duration of cooling and was considered a detrimental effect of low temperature holding.     

Soil variability through spatial scales in a permanently disturbed natural spruce-fir-beech forest

Soil variability was assessed in a 74.2-ha area within the Žofínsky prales natural forest. Parameters evaluated for 1765 soil profiles inside 353 graticule plots were as follows: (1) thickness of organic horizons, (2) thickness and form of mineral horizons, (3) humus form (HF), (4) soil taxonomic unit (STU) and (5) anomalies. In addition, soil reaction (pH_KCl) and oxidizable carbon content (C_ox) were measured in the laboratory for 734 samples from the upper mineral (A) and lower mineral (B) horizons. The most frequently occurring humus form was mor followed by moder, hydromor and peaty T-horizon. Entic Podzols, Dystric Cambisols, Haplic Cambisols, Albic Podzols, Histic (or Haplic) Gleysols, Endogleyic Stagnosols, Fibric or Hemic or Sapric Histosols and Stagnic Gleysols were all present at the site despite its homogeneous geological bedrock. Overall coefficient of variance (CV) was lower in terrestrial soils compared with (semi-)hydromorphic soils. Overall variance decreased in both soil groups with increasing depth, as did CV differences between the fine (up to 10 m) and the locality scales. The lowest CV values occurred for C_ox and pH_KCl. The CV values differed between STUs as well. Compared to lower horizons, variograms of upper horizons showed greater autocorrelation at the intermediate spatial scale (10–320 m)—ranging from 50 to 150 m. Semivariance values, however, reached 70–80% of sill already at a distance of 10 m. The most significant factor of variability at all studied spatial scales is presumably the soil disturbance regime, followed by terrain micro-topography and the effect of tree species.     

Measuring Eastern Redcedar (Juniperus virginiana L.) Mass With the Use of Satellite Imagery

Eastern redcedar (Juniperus virginiana L.) is an aggressively spreading native species in Oklahoma grasslands. It decreases rangeland forage production, and has been implicated in reducing stream flow and groundwater recharge. Industrial-scale plans to use redcedar as a biofuel source are being considered. Optimal placement of redcedar-based industries requires determination of redcedar availability. Such large-area inventories of redcedar mass can be practically addressed via aircraft or satellite remote sensing. Therefore, we conducted a study in central and western Oklahoma to develop and test a remote-sensing–based allometric equation relating redcedar canopy area to aboveground dry mass (AGM). We used automated methods to measure tree canopy area from georectified, pan-sharpened, multispectral QuickBird images having a spatial resolution of 0. 45 m² per pixel ground sample area. We also measured the canopy area and fresh and dry mass of these trees with the use of destructive sampling techniques. Regression analysis showed that satellite-derived measurements of canopy coverage explained about 85% of field-measured redcedar dry AGM in the study plots. The resulting allometric equation was applied to an independent data set, yielding dry AGM of 38.2 metric tons ? ha^?1, which was well within the field-measured range of 36–43 metric tons ? ha^?1. The allometric equation was then applied to Natural Resources Conservation Service measurements of redcedar canopy coverage for 17 counties in Oklahoma, to determine that the area of interest contains a median value of about 11.5 million metric tons of redcedar AGM. These results indicate that 0.45-m² spatial resolution multispectral imagery can be a useful tool for rapid and reliable measurement of redcedar dry AGM.     

A new species of Acanthochondria (Copepoda: Chondracanthidae) parasitizing the flounder Xystreurys rasile (Pleuronectiformes: Paralichthyidae) from Argentina

A new copepod species, Acanthochondria sagitta sp. n., is described based on specimens collected from the flounder Xystreurys rasile (Jordan) (Pleuronectiformes, Paralichthyidae), caught in the coastal waters off Necochea, Buenos Aires Province, Argentina. The new species differs from its congeners by the following combination of characters: presence of three pairs of cephalic outgrowths; the triangular shape of the trunk with diverging postero-lateral processes; leg 2 of an intermediate shape between Types C and D, which projects laterally from the trunk, and Type B-V antennule bearing two proximal processes (one ventral and one dorsal) on the swollen basal portion.     

Reduced metribuzin pollution with phosphatidylcholine-clay formulations

BACKGROUND: Metribuzin is a widely used herbicide that has been identified as a groundwater contaminant. In this study, slow‐release formulations of metribuzin were designed by encapsulating the active ingredient in phosphatidylcholine (PC) vesicles and adsorbing the vesicles onto montmorillonite. RESULTS: The maximum active ingredient content in the slow‐release formulations was 246 g kg^?1. Infrared spectroscopy results revealed that the hydrophobic interactions between metribuzin and the alkyl chains on PC were necessary for encapsulation. In addition, water bridges connecting the herbicide and the PC headgroup enhanced the solubility of metribuzin in PC. Adsorption experiments in soils were performed to evaluate the relationship between sorption and leaching. Funnel experiments in a sandy soil revealed that the herbicide was not irreversibly retained in the formulation matrix. In soil column experiments, PC–clay formulations enhanced herbicide accumulation and biological activity in the top soil layer relative to a commercial formulation. PC–clay formulations also reduced the dissipation of metribuzin by a factor of 1.6–2.5. CONCLUSIONS: A reduction in the recommended dose of metribuzin can be achieved by employing PC–clay formulations, which reduces the environmental risk associated with herbicide applications. Moreover, PC and montmorillonite are non‐toxic and do not negatively affect the environment. Copyright © 2010 Society of Chemical Industry     

Characterization of nematode colonization and succession in disturbed soil using the Maturity Index

Nematode colonization and succession were studied over 60 weeks in field plots which had been disturbed by combinations of fumigation and manuring. It was expected that the Maturity Index, which is based on the composition of the nematode fauna, would decrease after disturbance, and subsequently increase with recovery and succession. The results showed that in all treatments, the initial colonization and growth were due to taxa scaled in colonizer-persister (c-p) group 1, resulting in a low Maturity Index. An increase in this index followed when these taxa were gradually replaced by c-p group 2 which thereafter remained the dominant group. C-p groups 3–5 developed only in the non-fumigated treatment. Manuring caused characteristic changes in the nematode fauna which could be described as a cycle, starting with an increase in enrichment opportunists (c-p 1), which were succeeded by general opportunists (c-p 2) which, in turn, were supplemented with persisters (c-p 3–5). It is expected that the same cycle will be observed as a result of other disturbances that cause temporary increase in food supply.