Multiple tandem splicing silencer elements suppress aberrant splicing within the long exon 26 of the human Apolipoprotein B gene.

ABSTRACT: BACKGROUND: Apolipoprotein B (APOB) is an integral component of the chylomicron and the atherogenic lipoproteins LDL and Lp(a). Exon 26 of the APOB pre-mRNA is unusually long at 7,572 nt and is constitutively spliced. It is also subject to RNA editing in the intestine, which generates a shortened isoform, APOB48, assembled exclusively into chylomicrons. Due to its length, exon 26 contains multiple pseudo splice sites which are not spliced, but which conform to the degenerate splice site consensus. RESULTS: We demonstrate that these pseudo splice sites are repressed by multiple, tandem splicing silencers distributed along the length of exon 26. The distribution of these elements appears to be heterogeneous, with a greater frequency in the middle 4,800 nt of the exon. CONCLUSION: Repression of these splice sites is key to maintaining the integrity of exon 26 during RNA splicing and therefore the correct expression of both isoforms of APOB

An evaluation of strategies used by the Landscapes and Policy Hub to achieve interdisciplinary and transdisciplinary research

The report presents an evaluation of the Landscapes and Policy Hub's approach to interdisciplinary and transdisciplinary research. The hub was a national, four year, $15 million collaborative research program. The focus of the evaluation was for researchers to reflect on the effectiveness of strategies used by the hub to facilitate interdisciplinarity (where researchers from different disciplines work together to solve problems) and transdisciplinarity (where researchers from different disciplines work in partnership with research users to solve problems). The evaluation was commissioned in the final phase of the hub’s life in the interests of improving performance of future interdisciplinary and transdisciplinary research. It was based on a number of strategies that had been implemented by the hub to encourage and facilitate interdisciplinary research occurring in partnership with research users. The aim of the evaluation was to improve performance of future interdisciplinary and transdisciplinary research. Six recommendations are presented

Broken rotational symmetry in the pseudogap phase of a high-Tc superconductor

The nature of the pseudogap phase is a central problem in the quest to understand high-Tc cuprate superconductors. A fundamental question is what symmetries are broken when that phase sets in below a temperature T*. There is evidence from both polarized neutron diffraction and polar Kerr effect measurements that time- reversal symmetry is broken, but at temperatures that differ significantly. Broken rotational symmetry was detected by both resistivity and inelastic neutron scattering at low doping and by scanning tunnelling spectroscopy at low temperature, but with no clear connection to T*. Here we report the observation of a large in-plane anisotropy of the Nernst effect in YBa2Cu3Oy that sets in precisely at T*, throughout the doping phase diagram. We show that the CuO chains of the orthorhombic lattice are not responsible for this anisotropy, which is therefore an intrinsic property of the CuO2 planes. We conclude that the pseudogap phase is an electronic state which strongly breaks four-fold rotational symmetry. This narrows the range of possible states considerably, pointing to stripe or nematic orders.Comment: Published version. Journal reference and DOI adde

The pseudogap: friend or foe of high Tc?

Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic

Estimating the burden of disease attributable to four selected environmental risk factors in South Africa

The first South African National Burden of Disease study quantified the underlying causes of premature mortality and morbidity experienced in South Africa in the year 2000. This was followed by a Comparative Risk Assessment to estimate the contributions of 17 selected risk factors to burden of disease in South Africa. This paper describes the health impact of exposure to four selected environmental risk factors: unsafe water, sanitation and hygiene; indoor air pollution from household use of solid fuels; urban outdoor air pollution and lead exposure.The study followed World Health Organization comparative risk assessment methodology. Population-attributable fractions were calculated and applied to revised burden of disease estimates (deaths and disability adjusted life years, [DALYs]) from the South African Burden of Disease study to obtain the attributable burden for each selected risk factor. The burden attributable to the joint effect of the four environmental risk factors was also estimated taking into account competing risks and common pathways. Monte Carlo simulation-modeling techniques were used to quantify sampling, uncertainty.Almost 24 000 deaths were attributable to the joint effect of these four environmental risk factors, accounting for 4.6% (95% uncertainty interval 3.8-5.3%) of all deaths in South Africa in 2000. Overall the burden due to these environmental risks was equivalent to 3.7% (95% uncertainty interval 3.4-4.0%) of the total disease burden for South Africa, with unsafe water sanitation and hygiene the main contributor to joint burden. The joint attributable burden was especially high in children under 5 years of age, accounting for 10.8% of total deaths in this age group and 9.7% of burden of disease.This study highlights the public health impact of exposure to environmental risks and the significant burden of preventable disease attributable to exposure to these four major environmental risk factors in South Africa. Evidence-based policies and programs must be developed and implemented to address these risk factors at individual, household, and community levels

d+idd+id Holographic Superconductors

A holographic model of $d+id$ superconductors based on the action proposed by Benini, Herzog, and Yarom [arXiv:1006.0731] is studied. This model has a charged spin two field in an AdS black hole spacetime. Working in the probe limit, the normalizable solution of the spin two field in the bulk gives rise to a $d+id$ superconducting order parameter at the boundary of the AdS. We calculate the fermion spectral function in this\ superconducting background and confirm the existence of fermi arcs for non-vanishing Majorana couplings. By changing the relative strength $\gamma$ of the $d$ and $id$ condensations, the position and the size of the fermi arcs are changed. When $\gamma =1$, the spectrum becomes isotropic and the spectral function is s-wave like. By changing the fermion mass, the fermi momentum is changed. We also calculate the conductivity for these holographic $d+id$ superconductors where time reversal symmetry has been broken spontaneously. A non-vanishing Hall conductivity is obtained even without an external magnetic field.Comment: 24 pages,17 figures, Add more discussions on hall conductivity, two new figures, Matched with published versio