Analysis of cilia dysfunction phenotypes in zebrafish embryos depleted of origin recognition complex factors

Meier–Gorlin syndrome (MGS) is a rare, congenital primordial microcephalic dwarfism disorder. MGS is caused by genetic variants of components of the origin recognition complex (ORC) consisting of ORC1–6 and the pre-replication complex, which together enable origin firing and hence genome replication. In addition, ORC1 has previously been shown to play a role in ciliogenesis. Here, we extend this work and investigate the function of ORC1 and two other members of the complex on cilia at an organismal level. Knockdown experiments in zebrafish confirmed the impact of ORC1 on cilia. ORC1-deficiency confers defects anticipated to arise from impaired cilia function such as formation of oedema, kidney cysts, curved bodies and left–right asymmetry defects. We found ORC1 furthermore required for cilium formation in zebrafish and demonstrate that ciliopathy phenotypes in ORC1-depleted zebrafish could not be rescued by reconstitution with ORC1 bearing a genetic variant previously identified in MGS patients. Loss-of-function of Orc4 and Orc6, respectively, conferred similar ciliopathy phenotypes and cilium shortening in zebrafish, suggesting that several, if not all, components of the ORC regulate ciliogenesis downstream to or in addition to their canonical function in replication initiation. This study presents the first in vivo evidence of an influence of the MGS genes of the ORC family on cilia, and consolidates the possibility that cilia dysfunction could contribute to the clinical manifestation of ORC-deficient MGS

Internet-based psychoeducation for bipolar disorder: a qualitative analysis of feasibility, acceptability and impact

<p>Background: In a recent exploratory randomised trial we found that a novel, internet-based psychoeducation programme for bipolar disorder (Beating Bipolar) was relatively easy to deliver and had a modest effect on psychological quality of life. We sought to explore the experiences of participants with respect to feasibility, acceptability and impact of Beating Bipolar.</p> <p>Methods: Participants were invited to take part in a semi-structured interview. Thematic analysis techniques were employed; to explore and describe participants’ experiences, the data were analysed for emerging themes which were identified and coded.</p> <p>Results: The programme was feasible to deliver and acceptable to participants where they felt comfortable using a computer. It was found to impact upon insight into illness, health behaviour, personal routines and positive attitudes towards medication. Many participants regarded the programme as likely to be most beneficial for those recently diagnosed.</p> <p>Conclusions: An online psychoeducation package for bipolar disorder, such as Beating Bipolar, is feasible and acceptable to patients, has a positive impact on self-management behaviours and may be particularly suited to early intervention. Alternative (non-internet) formats should also be made available to patients.</p&gt

Relation between composition and vacant oxygen sites in the mixed ionicelectronic conductors La5.4W1 yMyO12 delta M Mo, Re; 0 lt; y lt; 0.2 and their mother compound La6 xWO12 delta 0.4 lt; x lt; 0.8

A detailed analysis of specimen composition, water uptake and their interrelationship in the systems La6 xWO12 amp; 948; 0.4 amp; 8804; x amp; 8804;0.8 and La6 xW1 yMyO12 amp; 948; 0 amp; 8804;y amp; 8804;0.2; M Mo, Re is presented. The three specimen series were investigated in dry and wet D2O conditions. A systematic trend in mass loss and onset temperature variation was observed in La6 xWO12 amp; 948; 0.4 amp; 8804;x amp; 8804;0.8 . Even very small amounts lt; 1 wt of secondary phases were found to notably modify the specimen s water uptake and onset temperature of mass loss. The theoretical model for vacancy concentration available was used to calculate the vacant oxygen sites starting from mass loss values determined by thermogravimetry. A discrepancy between the calculated and observed concentration of vacant oxygen sites is observed for all three systems. The effect of substitution of W by Re or Mo on the vacancy amount is explained taking into account diffraction measurements and information on the oxidation state of the substituting elements Mo and R

Clinical effectiveness of online computerised cognitive-behavioural therapy without support for depression in primary care: randomised trial

BACKGROUND: Computerised cognitive-behavioural therapy (CCBT) might offer a solution to the current undertreatment of depression. AIMS: To determine the clinical effectiveness of online, unsupported CCBT for depression in primary care. METHOD: Three hundred and three people with depression were randomly allocated to one of three groups: Colour Your Life; treatment as usual (TAU) by a general practitioner; or Colour Your Life and TAU combined. Colour Your Life is an online, multimedia, interactive CCBT programme. No assistance was offered. We had a 6-month follow-up period. RESULTS: No significant differences in outcome between the three interventions were found in the intention-to-treat and per protocol analyses. CONCLUSIONS: Online, unsupported CCBT did not outperform usual care, and the combination of both did not have additional effects. Decrease in depressive symptoms in people with moderate to severe depression was moderate in all three interventions. Online CCBT without support is not beneficial for all individuals with depressio

Theory of Magneto--Acoustic Transport in Modulated Quantum Hall Systems Near ν=1/2\nu=1/2

Motivated by the experimental results of Willett et al [Phys.Rev. Lett., {\bf 78}, 4478 (1997)] we develop a magneto-transport theory for the response of a two dimensional electron gas (2DEG) in the Fractional Quantum Hall Regime near Landau level filling factor $\nu = 1/2$ to the surface acoustic wave (SAW) in the presence of an added periodic density modulation. We assume there exists a Composite Fermion Fermi Surface (CF-FS) at $\nu = 1/2$, and we show that the deformation of the (CF-FS) due to the density modulation can be at the origin of the observed transport anomalies for the experimental conditions. Our analysis is carried out particularly for the non-local case which corresponds to the SAW experiments. We introduce a new model of a deformed CF-FS. The model permits us to explain anomalous features of the response of the modulated 2DEG to the SAW near $\nu = 1/2:$ namely the nonlinear wave vector dependence of the electron conductivity, the appearance of peaks in the SAW velocity shift and attenuation and the anisotropy of the effect, all of which originate from contributions to the conductivity tensor due to the regions of the CF-FS which are flattened by the applied modulation.Comment: 13 pages, 4 figures, the published versio

Remarkable high efficiency of red emitters using Eu(III) ternary complexes

We have synthesized Eu(iii) ternary complexes possessing record photoluminescence yields up to 90%. This high luminescence performance resulted from the absence of quenching moieties in the Eu coordination environment and an efficient energy transfer between ligands, combined with a particular symmetry of the coordination environment

Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA

Deep-inelastic positron-proton interactions at low values of Bjorken-x down to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons are studied with the H1 experiment at HERA. The inclusive cross section for pi^0 mesons produced at small angles with respect to the proton remnant (the forward region) is presented as a function of the transverse momentum and energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x. Measurements are also presented of the transverse energy flow in events containing a forward pi^0 meson. Hadronic final state calculations based on QCD models implementing different parton evolution schemes are confronted with the data.Comment: 27 pages, 8 figures and 3 table

Al13H−: Hydrogen atom site selectivity and the shell model

Using a combination of anion photoelectron spectroscopy and density functional theory calculations, we explored the influence of the shell model on H atom site selectivity in Al13H−. Photoelectron spectra revealed that Al13H− has two anionic isomers and for both of them provided vertical detachment energies (VDEs). Theoretical calculations found that the structures of these anionic isomers differ by the position of the hydrogen atom. In one, the hydrogen atom is radially bonded, while in the other, hydrogen caps a triangular face. VDEs for both anionic isomers as well as other energetic relationships were also calculated. Comparison of the measured versus calculated VDE values permitted the structure of each isomer to be confirmed and correlated with its observed photoelectron spectrum. Shell model, electron-counting considerations correctly predicted the relative stabilities of the anionic isomers and identified the stable structure of neutral Al13H