DoRGaN: Development of Quality Assurance and Quality Control Systems for High Dose Rate Brachytherapy Based on GaN Dosimetry Probes

Background

Safe High Dose Rate Brachytherapy (HDR-BT) requires quality assurance/quality control (QA/QC) according to IPEM and ESTRO recommendations. Recent advances in real-time dosimetry and related developments of QA, QC and in vivo dosimetry (IVD) systems have offered new possibilities for effective independent treatment verification, and thus for improving the patient safety.

Chemoattractant receptor promotion of Ca2+ influx across the plasma membrane of HL-60 cells. A role for cytosolic free calcium elevations and inositol 1,3,4,5-tetrakisphosphate production

The mechanisms by which the chemotactic peptide formyl-methyl-leucyl-phenyl-alanine stimulates Ca2+ influx across the plasma membrane were investigated in the human promyelocytic cell line HL-60, induced to differentiate with dimethyl sulfoxide. Ca2+ influx was determined: (a) from the initial rate of Mn2+ influx, apparent from the quenching of intracellular quin2 or fura-2 fluorescence; (b) from the rate of the elevation of cytosolic free calcium, [Ca2+]i, upon readdition of Ca2+ to cells previously stimulated in the absence of extracellular Ca2+. [3H]Inositol tris-, tetrakis-, and pentakisphosphates were analyzed by a high performance liquid chromatography procedure which was optimized for the separation of inositol tetrakisphosphates, yielding three predominant isomers: inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), inositol 1,4,5,6-tetrakisphosphate, and inositol 1,3,4, 6-tetrakisphosphate. Both the kinetics and agonist dose dependence of Ca2+ influx stimulation correlated closely with the corresponding receptor-mediated variations of [Ca2+]i either in the presence or in the absence of extracellular Ca2+. Of the different inositol phosphates determined in parallel and under the same conditions, accumulation of [3H]Ins(1,3,4,5)P4 correlated best with Ca2+ influx both temporally and in its dose dependence in the presence or in the absence of extracellular Ca2+; inositol 1,3,4-trisphosphate was also correlated but to a lesser extent. Attenuations of [Ca2+]i elevations by decreasing extracellular Ca2+ or by increasing the cytosolic Ca2+ buffering capacity with quin2 led to parallel inhibition of Ca2+ influx and Ins(1,3,4,5)P4 production. In conclusion: 1) activation of Ca2+ influx by formyl-methionyl-leucyl-phenylalanine depends on the elevation of [Ca2+]i, the latter being initiated by Ca2+ mobilization from intracellular stores; 2) Ins(1,3, 4,5)P4 is a strong candidate for maintaining receptor-mediated activation of Ca2+ influx in differentiated HL-60 cells.     

Marked seasonal variation in the wild mouse gut microbiota

Recent studies have provided an unprecedented view of the microbial communities colonizing captive mice; yet the host and environmental factors that shape the rodent gut microbiota in their natural habitat remain largely unexplored. Here, we present results from a 2-year 16 S ribosomal RNA gene sequencing-based survey of wild wood mice (Apodemus sylvaticus) in two nearby woodlands. Similar to other mammals, wild mice were colonized by 10 bacterial phyla and dominated by the Firmicutes, Bacteroidetes and Proteobacteria. Within the Firmicutes, the Lactobacillus genus was most abundant. Putative bacterial pathogens were widespread and often abundant members of the wild mouse gut microbiota. Among a suite of extrinsic (environmental) and intrinsic (host-related) factors examined, seasonal changes dominated in driving qualitative and quantitative differences in the gut microbiota. In both years examined, we observed a strong seasonal shift in gut microbial community structure, potentially due to the transition from an insect- to a seed-based diet. This involved decreased levels of Lactobacillus, and increased levels of Alistipes (Bacteroidetes phylum) and Helicobacter. We also detected more subtle but statistically significant associations between the gut microbiota and biogeography, sex, reproductive status and co-colonization with enteric nematodes. These results suggest that environmental factors have a major role in shaping temporal variations in microbial community structure within natural populations.     

Focal adhesion size controls tension-dependent recruitment of alpha-smooth muscle actin to stress fibers

Expression of alpha-smooth muscle actin (alpha-SMA) renders fibroblasts highly contractile and hallmarks myofibroblast differentiation. We identify alpha-SMA as a mechanosensitive protein that is recruited to stress fibers under high tension. Generation of this threshold tension requires the anchoring of stress fibers at sites of 8-30-microm-long "supermature" focal adhesions (suFAs), which exert a stress approximately fourfold higher (approximately 12 nN/microm2) on micropatterned deformable substrates than 2-6-microm-long classical FAs. Inhibition of suFA formation by growing myofibroblasts on substrates with a compliance of < or = 11 kPa and on rigid micropatterns of 6-microm-long classical FA islets confines alpha-SMA to the cytosol. Reincorporation of alpha-SMA into stress fibers is established by stretching 6-microm-long classical FAs to 8.1-microm-long suFA islets on extendable membranes; the same stretch producing 5.4-microm-long classical FAs from initially 4-microm-long islets is without effect. We propose that the different molecular composition and higher phosphorylation of FAs on supermature islets, compared with FAs on classical islets, accounts for higher stress resistance.     

The rise to dominance of the angiosperm kingdom: dispersal,habitat widening and evolution during the Late Cretaceous of Europe

Coiffard, C. & Gomez, B. 2009: The rise to dominance of the angiosperm kingdom: dispersal, habitat widening and evolution during the Late Cretaceous of Europe. Lethaia, Vol. 43, pp. 164–169. The earliest fossil records of angiosperms in Europe occur in the Barremian and consist of freshwater wetland plants. From the Barremian onwards, angiosperms show a stepwise widening of their ecological range with the result that they inhabited most environments by the Cenomanian. Nevertheless, most angiosperms had still restricted habitats, while a few angiosperm trees were confined to disturbed environments, such as channel margins. A Wagner’s Parsimony Method analysis performed on a fossil plant and locality database from the Turonian to the Campanian of Europe indicates continued decrease in richness of ferns and gymnosperms compared with angiosperms, turnover between conifer and palm trees in freshwater‐related swamps at about the Cenomanian/Turonian boundary, and spreading of angiosperm trees through the floodplains. The ecological range of angiosperm trees was increased, being recorded in channel margins from the Cenomanian and spreading over floodplains (e.g. Platanaceae) and swamps (e.g. Arecaceae) by the Campanian. These new ecological ranges and successions went with innovative architectures, such as dicot trees and palm trees. Most living core angiosperm families had their earliest representatives in the Late Cretaceous, which should be considered as the dawn of modern angiosperm forests. □Core angiosperms, Europe, Late Cretaceous, palms, Wagner’s Parsimony Method.     

Transforming Growth Factor ��1 Inhibits Cystic Fibrosis Transmembrane Conductance Regulator-dependent cAMP-stimulated Alveolar Epithelial Fluid Transport via a Phosphatidylinositol 3-Kinase-dependent Mechanism

Exogenous or endogenous β₂-adrenergic receptor agonists enhance alveolar epithelial fluid transport via a cAMP-dependent mechanism that protects the lungs from alveolar flooding in acute lung injury. However, impaired alveolar fluid clearance is present in most of the patients with acute lung injury and is associated with increased mortality, although the mechanisms responsible for this inhibition of the alveolar epithelial fluid transport are not completely understood. Here, we found that transforming growth factor β1 (TGF-β1), a critical mediator of acute lung injury, inhibits β₂-adrenergic receptor agonist-stimulated vectorial fluid and Cl⁻ transport across primary rat and human alveolar epithelial type II cell monolayers. This inhibition is due to a reduction in the cystic fibrosis transmembrane conductance regulator activity and biosynthesis mediated by a phosphatidylinositol 3-kinase (PI3K)-dependent heterologous desensitization and down-regulation of the β₂-adrenergic receptors. Consistent with these in vitro results, inhibition of the PI3K pathway or pretreatment with soluble chimeric TGF-β type II receptor restored β₂-adrenergic receptor agonist-stimulated alveolar epithelial fluid transport in an in vivo model of acute lung injury induced by hemorrhagic shock in rats. The results demonstrate a novel role for TGF-β1 in impairing the β- adrenergic agonist-stimulated alveolar fluid clearance in acute lung injury, an effect that could be corrected by using PI3K inhibitors that are safe to use in humans.     

Comparison of marker types and map assumptions using Markov chain Monte Carlo-based linkage analysis of COGA data

We performed multipoint linkage analysis of the electrophysiological trait ECB21 on chromosome 4 in the full pedigrees provided by the Collaborative Study on the Genetics of Alcoholism (COGA). Three Markov chain Monte Carlo (MCMC)-based approaches were applied to the provided and re-estimated genetic maps and to five different marker panels consisting of microsatellite (STRP) and/or SNP markers at various densities. We found evidence of linkage near the GABRB1 STRP using all methods, maps, and marker panels. Difficulties encountered with SNP panels included convergence problems and demanding computations.