Dual effect of CTCF loss on neuroprogenitor differentiation and survival

An increasing number of proteins involved in genome organization have been implicated in neurodevelopmental disorders, highlighting the importance of chromatin architecture in the developing CNS. The CCCTC-binding factor (CTCF) is a zinc finger DNA binding protein involved in higher-order chromatin organization, and mutations in the human CTCF gene cause an intellectual disability syndrome associated with microcephaly. However, information on CTCF function in vivo in the developing brain is lacking. To address this gap, we conditionally inactivated the Ctcf gene at early stages of mouse brain development. Cre-mediated Ctcf deletion in the telencephalon and anterior retina at embryonic day 8.5 triggered upregulation of the p53 effector PUMA (p53 upregulated modulator of apoptosis), resulting in massive apoptosis and profound ablation of telencephalic structures. Inactivation of Ctcf several days later at E11 also resulted in PUMA upregulation and increased apoptotic cell death, and the Ctcf-null forebrain was hypocellular and disorganized at birth. Although deletion of both Ctcf and Puma in the embryonic brain efficiently rescued Ctcf-null progenitor cell apoptosis, it failed to improve neonatal hypocellularity due to decreased proliferative capacity of rescued apical and outer radial glia progenitor cells. This was exacerbated by an independent effect of CTCF loss that resulted in depletion of the progenitor pool due to premature neurogenesis earlier in development. Our findings demonstrate that CTCF activities are required for two distinct events in early cortex formation: first, to correctly regulate the balance between neuroprogenitor cell proliferation and differentiation, and second, for the survival of neuroprogenitor cells, providing new clues regarding the contributions of CTCF in microcephaly/intellectual disability syndrome pathologies

Religious diversity, empathy, and God images : perspectives from the psychology of religion shaping a study among adolescents in the UK

Major religious traditions agree in advocating and promoting love of neighbour as well as love of God. Love of neighbour is reflected in altruistic behaviour and empathy stands as a key motivational factor underpinning altruism. This study employs the empathy scale from the Junior Eysenck Impulsiveness Questionnaire to assess the association between empathy and God images among a sample of 5993 religiously diverse adolescents (13–15 years old) attending state maintained schools in England, Northern Ireland, Scotland, Wales, and London. The key psychological theory being tested by these data concerns the linkage between God images and individual differences in empathy. The data demonstrate that religious identity (e.g. Christian, Muslim) and religious attendance are less important than the God images which young people hold. The image of God as a God of mercy is associated with higher empathy scores, while the image of God as a God of justice is associated with lower empathy scores

Non-linear regression models for Approximate Bayesian Computation

Approximate Bayesian inference on the basis of summary statistics is well-suited to complex problems for which the likelihood is either mathematically or computationally intractable. However the methods that use rejection suffer from the curse of dimensionality when the number of summary statistics is increased. Here we propose a machine-learning approach to the estimation of the posterior density by introducing two innovations. The new method fits a nonlinear conditional heteroscedastic regression of the parameter on the summary statistics, and then adaptively improves estimation using importance sampling. The new algorithm is compared to the state-of-the-art approximate Bayesian methods, and achieves considerable reduction of the computational burden in two examples of inference in statistical genetics and in a queueing model.Comment: 4 figures; version 3 minor changes; to appear in Statistics and Computin

Optimisation of the Zr:Ti ratio in bulk lead zirconate titanate for templated grain growth using BaTiO3 seeds

Presented here is a proof of concept demonstration of the templated grain growth (TGG) process for the development of [001]c fibre-textured Pb(ZrxTi1-x)O3 (PZT) ceramics. BaTiO3 platelets (5 and 10 vol.%) were selected to seed growth of highly oriented PZT grains resulting in texture fractions as high as 94%. The TGG process in PZT was observed to be critically dependent upon the addition of excess PbO liquid phase and may be driven by BaTiO3 dissolution into the matrix. Solid solution incorporation of BaTiO3 during sintering resulted in a structural shift away from the PZT morphotropic phase boundary (MPB) and a decrease in Curie temperature (TC) by ~ 40 °C which still exceeded > 300 °C. Modification of the Zr:Ti ratio in untextured ceramic analogues was explored as a strategy to tailor dielectric, ferroelectric, and electromechanical properties. An initial PZT matrix composition of Pb(Zr0.56Ti0.44)O3 resulted in a final bulk Pb0.947Ba0.053(Zr0.531Ti0.469)O3 ceramic having MPB-like properties of d33 = 453 pC/N, tan δ = 0.017, TC = 340 °C, and Ec = 9.3 kV/cm, which was observed to be similar to commercial ‘soft’ PZT-5A1

Sugars of pearl millet [Pennisetum americanum (L.) Leeke] grains

The sugars in the grains of nine pearl millet cultivars were fractionated through a Biogel column. Five different sugars‘(stachyose, raffinose, sucrose, glucose, and fructose) were identified. Sucrose was predominant in all the cultivars. Raffinose content was high as compared to other cereals, and maltose was absen

Identification of a novel MAGT1 mutation supports a diagnosis of XMEN disease

XMEN (X-linked immunodeficiency with magnesium defect) is caused by loss-of-function mutations in MAGT1 which is encoded on the X chromosome. The disorder is characterised by CD4 lymphopenia, severe chronic viral infections and defective T-lymphocyte activation. XMEN patients are susceptible to Epstein-Barr virus infections and persistently low levels of intracellular Mg2+. Here we describe a patient that presented with multiple recurrent infections and a subsequent diffuse B-cell lymphoma. Molecular genetic analysis by exome sequencing identified a novel hemizygous MAGT1 nonsense mutation c.1005T>A (NM_032121.5) p.(Cys335*), confirming a diagnosis of XMEN deficiency. Follow-up immunophenotyping was performed by antibody staining and flow cytometry; proliferation was determined by 3H-thymidine uptake after activation by PHA and anti-CD3. Cytotoxic natural killer cell activity was assessed with K562 target cells using the NKTESTTM assay. While lymphocyte populations were superficially intact, B cells were largely naive with a reduced memory cell compartment. Translated NKG2D was absent on both NK and T cells in the proband, and normally expressed in the carrier mother. In vitro NK cell activity was intact in both the proband and his mother. This report adds to the growing number of identified XMEN cases, raising awareness of a, still rare, X-linked immunodeficiency

The Importance of Time Congruity in the Organisation.

In 1991 Kaufman, Lane, and Lindquist proposed that time congruity in terms of an individual's time preferences and the time use methods of an organisation would lead to satisfactory performance and enhancement of quality of work and general life. The research reported here presents a study which uses commensurate person and job measures of time personality in an organisational setting to assess the effects of time congruity on one aspect of work life, job-related affective well-being. Results show that time personality and time congruity were found to have direct effects on well-being and the influence of time congruity was found to be mediated through time personality, thus contributing to the person–job (P–J) fit literature which suggests that direct effects are often more important than indirect effects. The study also provides some practical examples of ways to address some of the previously cited methodological issues in P–J fit research

Propagator of a Charged Particle with a Spin in Uniform Magnetic and Perpendicular Electric Fields

We construct an explicit solution of the Cauchy initial value problem for the time-dependent Schroedinger equation for a charged particle with a spin moving in a uniform magnetic field and a perpendicular electric field varying with time. The corresponding Green function (propagator) is given in terms of elementary functions and certain integrals of the fields with a characteristic function, which should be found as an analytic or numerical solution of the equation of motion for the classical oscillator with a time-dependent frequency. We discuss a particular solution of a related nonlinear Schroedinger equation and some special and limiting cases are outlined.Comment: 17 pages, no figure

Weather, disease, and wheat breeding effects on Kansas wheat varietal yields, 1985 to 2011.

Wheat (Triticum aestivum L.) yields in Kansas have increased due to wheat breeding and improved agronomic practices, but are subject to climate and disease challenges. The objective of this research is to quantify the impact of weather, disease, and genetic improvement on wheat yields of varieties grown in 11 locations in Kansas from 1985 to 2011. Wheat variety yield data from Kansas performance tests were matched with comprehensive location-specific disease and weather data, including seasonal precipitation, monthly air temperature, air temperature and solar radiation around anthesis, and vapor pressure deficit (VPD). The results show that wheat breeding programs increased yield by 34 kg ha⁻¹ yr⁻¹. From 1985 through 2011, wheat breeding increased average wheat yields by 917 kg ha⁻¹, or 27% of total yield. Weather was found to have a large impact on wheat yields. Simulations demonstrated that a 1°C increase in projected mean temperature was associated with a decrease in wheat yields of 715 kg ha⁻¹, or 21%. Weather, diseases, and genetics all had significant impacts on wheat yields in 11 locations in Kansas during 1985 to 2011