Unilateral Administration of Surface-Modified G1 and G4 PAMAM Dendrimers in Healthy Mice to Assess Dendrimer Migration in the Brain.

Polyamidoamine (PAMAM) dendrimers are nanoparticles that have a wide scope in the field of biomedicine. Previous evidence shows that the generation 4 (G4) dendrimers with a 100% amine surface (G4-NH2) are highly toxic to cells in vitro and in vivo due to their positively charged amine groups. To reduce the toxicity, we modified the surface of the dendrimers to have more neutral functional groups, with 10% of the surface covered with -NH2 and 90% of the surface covered with hydroxyl groups (-OH; G4-90/10). Our previous in vitro data show that these modified dendrimers are taken up by cells, neurons, and different types of stem cells in vitro and neurons and glial cells in vivo. The toxicity assay shows that these modified dendrimers are less toxic compared with G4-NH2 dendrimers. Moreover, prolonged dendrimer exposure (G1-90/10 and G4-90/10), up to 3 weeks following unilateral intrastriatal injections into the striatum of mice, showed that dendrimers have the tendency to migrate within the brain via corpus callosum at different rates depending on their size. We also found that there is a difference in migration between the G1 and G4 dendrimers based on their size differences. The G4 dendrimers migrate in the anterior and posterior directions as well as more laterally from the site of injection in the striatum compared to the G1 dendrimers. Moreover, the G4 dendrimers have unique projections from the site of injection to the cortical areas.

Multi-donor × elite-based populations reveal QTL for low-lodging wheat.

KEY MESSAGE: Low-lodging high-yielding wheat germplasm and SNP-tagged novel alleles for lodging were identified in a process that involved selecting donors through functional phenotyping for underlying traits with a designed phenotypic screen, and a crossing strategy involving multiple-donor × elite populations. Lodging is a barrier to achieving high yield in wheat. As part of a study investigating the potential to breed low-lodging high-yielding wheat, populations were developed crossing four low-lodging high-yielding donors selected based on lodging related traits, with three cultivars. Lodging was evaluated in single rows in an early generation and subsequently in plots in 2 years with contrasting lodging environment. A large number of lines lodged less than their recurrent parents, and some were also higher yielding. Heritability for lodging was high, but the genetic correlation between contrasting environments was intermediate-low. Lodging genotypic rankings in single rows did not correlate well with plots. Populations from the highest lodging background were genotyped (90 K iSelect BeadChip array). Fourteen markers on nine chromosomes were associated with lodging, differing under high- versus low-lodging conditions. Of the fourteen markers, ten were found to co-locate with previously identified QTL for lodging-related traits or at homoeologous locations for previously identified lodging-related QTL, while the remaining four markers (in chromosomes 2D, 4D, 7B and 7D) appear to map to novel QTL for lodging. Lines with more favourable markers lodged less, suggesting value in these markers as a selection tool. This study demonstrates that the combination of donor functional phenotyping, screen design and crossing strategy can help identify novel alleles in germplasm without requiring extensive bi-parental populations.

BET 1: Everything in graduation: arterial/end-tidal CO2 gradient and the diagnosis of pulmonary embolism.

A short cut review was carried out to establish the diagnostic characteristics of alveolar dead space fraction (AVDSf) in the diagnosis of pulmonary embolism (PE). This is calculated from the arterial and end-tidal CO2 Three papers were selected to answer the clinical question. The author, study type, relevant outcomes, results and weaknesses are tabulated. It is concluded that there is good evidence to support the use of AVDSf within a clinical prediction model to exclude a PE in patients when there is a low pretest probability. However, the specificity is not sufficient to support it as a 'rule in' test.

Colonization of Durum Wheat (Triticum turgidum L. var. durum) Culms Exhibiting Premature Senescence (Dead Heads) Associated with Fusarium pseudograminearum Crown Rot.

Fusarium crown rot is a significant disease of durum wheat (Triticum turgidum L. var. durum), which exhibits high levels of disease susceptibility. The most extreme symptom of crown rot is a prematurely senescing culm that typically fails to set grain. Individual crown rot-affected durum wheat plants displaying both nonsenescent and prematurely senescent culms were harvested to compare visual discoloration, Fusarium pseudograminearum biomass, and vascular colonization in culm sections sampled at three different heights above the crown. Field samples of EGA Bellaroi were collected at Wellcamp, QLD, in 2011, 2012, 2013, and 2014, and of Hyperno at Narrabri, NSW, in 2014. Prematurely senescent culms exhibited greater visual discoloration, F. pseudograminearum biomass, and vascular colonization than nonsenescent culms in each year they were examined. The extent of these differences varied between environments and timing of collection in each year. Vascular colonization initially occurred in xylem vessels and spread into phloem tissues as disease severity increased. The increased presence of hyphae in vascular bundles of prematurely senescing culms provides strong evidence for the hypothesis that restriction of water and nutrient movement in a diseased culm is a key factor in crown rot severity.