Instability of reconstruction of the low CMB multipoles

We discuss the problem of the bias of the Internal Linear Combination (ILC) CMB map and show that it is closely related to the coefficient of cross-correlation K(l) of the true CMB and the foreground for each multipole l. We present analysis of the cross-correlation for the WMAP ILC quadrupole and octupole from the first (ILC(I)) and the third (ILC(III)) year data releases and show that these correlations are about -0.52-0.6. Analysing 10^4 Monte Carlo simulations of the random Gaussian CMB signals, we show that the distribution function for the corresponding coefficient of the cross-correlation has a polynomial shape P(K,l)\propto(1-K^2)^(l-1). We show that the most probable value of the cross-correlation coefficient of the ILC and foreground quadrupole has two extrema at K ~= +/-0.58$. Thus, the ILC(III) quadrupole represents the most probable value of the coefficient K. We analyze the problem of debiasing of the ILC CMB and pointed out that reconstruction of the bias seems to be very problematic due to statistical uncertainties. In addition, instability of the debiasing illuminates itself for the quadrupole and octupole components through the flip-effect, when the even (l+m) modes can be reconstructed with significant error. This error manifests itself as opposite, in respect to the true sign of even low multipole modes, and leads to significant changes of the coefficient of cross-correlation with the foreground. We show that the CMB realizations, whose the sign of quadrupole (2,0) component is negative (and the same, as for all the foregrounds), the corresponding probability to get the positive sign after implementation of the ILC method is about 40%.Comment: 11 pages, 5 figure

Raman scattering in C_{60} and C_{48}N_{12} aza-fullerene: First-principles study

We carry out large scale {\sl ab initio} calculations of Raman scattering activities and Raman-active frequencies (RAFs) in ${\rm C}_{48}{\rm N}_{12}$ aza-fullerene. The results are compared with those of ${\rm C}_{60}$. Twenty-nine non-degenerate polarized and 29 doubly-degenerate unpolarized RAFs are predicted for ${\rm C}_{48}{\rm N}_{12}$. The RAF of the strongest Raman signal in the low- and high-frequency regions and the lowest and highest RAFs for ${\rm C}_{48}{\rm N}_{12}$ are almost the same as those of ${\rm C}_{60}$. The study of ${\rm C}_{60}$ reveals the importance of electron correlations and the choice of basis sets in the {\sl ab initio} calculations. Our best calculated results for ${\rm C}_{60}$ with the B3LYP hybrid density functional theory are in excellent agreement with experiment and demonstrate the desirable efficiency and accuracy of this theory for obtaining quantitative information on the vibrational properties of these molecules.Comment: submitted to Phys.Rev.

Drebrin-mediated microtubule-actomyosin coupling steers cerebellar granule neuron nucleokinesis and migration pathway selection

Neuronal migration from a germinal zone to a final laminar position is essential for the morphogenesis of neuronal circuits. While it is hypothesized that microtubule-actomyosin crosstalk is required for a neuron's 'two-stroke' nucleokinesis cycle, the molecular mechanisms controlling such crosstalk are not defined. By using the drebrin microtubule-actin crosslinking protein as an entry point into the cerebellar granule neuron system in combination with super-resolution microscopy, we investigate how these cytoskeletal systems interface during migration. Lattice light-sheet and structured illumination microscopy reveal a proximal leading process nanoscale architecture wherein f-actin and drebrin intervene between microtubules and the plasma membrane. Functional perturbations of drebrin demonstrate that proximal leading process microtubule-actomyosin coupling steers the direction of centrosome and somal migration, as well as the switch from tangential to radial migration. Finally, the Siah2 E3 ubiquitin ligase antagonizes drebrin function, suggesting a model for control of the microtubule-actomyosin interfaces during neuronal differentiation.</p

Aphid resistance in wheat varieties

As an environmentally compatible alternative to the use of conventional insecticides to control cereal aphids, we have investigated the possibility to exploit natural resistance to insect pests in wheat varieties. We have tested a wide range of hexaploid (Triticum aestivum), tetraploid (T. durum) and diploid (T. boeoticum and T. monococcum) wheat lines for resistance to the bird cherry oat aphid (Rhopalosiphum padi). Lines tested included Russian wheat aphid (Diuraphis noxia), greenbug (Schizaphis graminum), hessian fly (Mayetiola destructor) and orange wheat blossom midge (Sitodiplosis mosellana) resistant varieties. Antixenosis and antibiosis were determined in the settling and fecundity tests respectively. Since hydroxamic acids (Hx), including the most generally active, 2,4-dihidroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), are biosynthesised in many cereal plants and are implicated in resistance against insects, leaf tissue was analysed for Hx and the glucosides from which they are produced. The hexaploid varieties, which contained relatively low levels of the DIMBOA glucoside, did not deter aphid feeding or reduce nymph production significantly. Reduced settlement and nymph production were recorded on the diploid varieties, but they contained no detectable level of the glucoside or the toxic aglucone

Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix

Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix component collagen type I promotes greater adhesion and decreased migration of CRC cells along with increased expression of characteristic epithelial markers, suggesting a role for citrullination in promoting mesenchymal-to-epithelial transition and liver metastasis. Overall, our study reveals the potential for PAD4-dependant citrullination to drive the progression of CRC liver metastasis

Costs and advance directives at the end of life: a case of the ‘Coaching Older Adults and Carers to have their preferences Heard (COACH)’ trial

Background Total costs associated with care for older people nearing the end of life and the cost variations related with end of life care decisions are not well documented in the literature. Healthcare utilisation and associated health care costs for a group of older Australians who entered Transition Care following an acute hospital admission were calculated. Costs were differentiated according to a number of health care decisions and outcomes including advance directives (ADs). Methods Study participants were drawn from the Coaching Older Adults and Carers to have their preferences Heard (COACH) trial funded by the Australian National Health and Medical Research Council. Data collected included total health care costs, the type of (and when) ADs were completed and the place of death. Two-step endogenous treatment-regression models were employed to test the relationship between costs and a number of variables including completion of ADs. Results The trial recruited 230 older adults with mean age 84 years. At the end of the trial, 53 had died and 80 had completed ADs. Total healthcare costs were higher for younger participants and those who had died. No statistically significant association was found between costs and completion of ADs. Conclusion For our frail study population, the completion of ADs did not have an effect on health care utilisation and costs. Further research is needed to substantiate these findings in larger and more diverse clinical cohorts of older people

Drebrin Regulates Neuroblast Migration in the Postnatal Mammalian Brain

After birth, stem cells in the subventricular zone (SVZ) generate neuroblasts that migrate along the rostral migratory stream (RMS) to become interneurons in the olfactory bulb (OB). This migration is crucial for the proper integration of newborn neurons in a pre-existing synaptic network and is believed to play a key role in infant human brain development. Many regulators of neuroblast migration have been identified; however, still very little is known about the intracellular molecular mechanisms controlling this process. Here, we have investigated the function of drebrin, an actin-binding protein highly expressed in the RMS of the postnatal mammalian brain. Neuroblast migration was monitored both in culture and in brain slices obtained from electroporated mice by time-lapse spinning disk confocal microscopy. Depletion of drebrin using distinct RNAi approaches in early postnatal mice affects neuroblast morphology and impairs neuroblast migration and orientation in vitro and in vivo. Overexpression of drebrin also impairs migration along the RMS and affects the distribution of neuroblasts at their final destination, the OB. Drebrin phosphorylation on Ser142 by Cyclin-dependent kinase 5 (Cdk5) has been recently shown to regulate F-actin-microtubule coupling in neuronal growth cones. We also investigated the functional significance of this phosphorylation in RMS neuroblasts using in vivo postnatal electroporation of phosphomimetic (S142D) or non-phosphorylatable (S142A) drebrin in the SVZ of mouse pups. Preventing or mimicking phosphorylation of S142 in vivo caused similar effects on neuroblast dynamics, leading to aberrant neuroblast branching. We conclude that drebrin is necessary for efficient migration of SVZ-derived neuroblasts and propose that regulated phosphorylation of drebrin on S142 maintains leading process stability for polarized migration along the RMS, thus ensuring proper neurogenesis