CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation

Cytoplasmic polyadenylation-induced translation controls germ cell development, neuronal synaptic plasticity and cellular senescence, a tumour-suppressor mechanism that limits the replicative lifespan of cells. The cytoplasmic polyadenylation element binding protein (CPEB) promotes polyadenylation by nucleating a group of factors including defective in germline development 2 (Gld2), a non-canonical poly(A) polymerase, on specific messenger RNA (mRNA) 3' untranslated regions (UTRs). Because CPEB regulation of p53 mRNA polyadenylation/translation is necessary for cellular senescence in primary human diploid fibroblasts, we surmised that Gld2 would be the enzyme responsible for poly(A) addition. Here we show that depletion of Gld2 surprisingly promotes rather than inhibits p53 mRNA polyadenylation/translation, induces premature senescence and enhances the stability of CPEB mRNA. The CPEB 3' UTR contains two miR-122 binding sites, which when deleted, elevate mRNA translation, as does an antagomir of miR-122. Although miR-122 is thought to be liver specific, it is present in primary fibroblasts and destabilized by Gld2 depletion. Gld4, a second non-canonical poly(A) polymerase, was found to regulate p53 mRNA polyadenylation/translation in a CPEB-dependent manner. Thus, translational regulation of p53 mRNA and cellular senescence is coordinated by Gld2/miR-122/CPEB/Gld4.     

Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia.

Developmental dyslexia is defined as a specific and significant impairment in reading ability that cannot be explained by deficits in intelligence, learning opportunity, motivation or sensory acuity. It is one of the most frequently diagnosed disorders in childhood, representing a major educational and social problem. It is well established that dyslexia is a significantly heritable trait with a neurobiological basis. The etiological mechanisms remain elusive, however, despite being the focus of intensive multidisciplinary research. All attempts to map quantitative-trait loci (QTLs) influencing dyslexia susceptibility have targeted specific chromosomal regions, so that inferences regarding genetic etiology have been made on the basis of very limited information. Here we present the first two complete QTL-based genome-wide scans for this trait, in large samples of families from the United Kingdom and United States. Using single-point analysis, linkage to marker D18S53 was independently identified as being one of the most significant results of the genome in each scan (P< or =0.0004 for single word-reading ability in each family sample). Multipoint analysis gave increased evidence of 18p11.2 linkage for single-word reading, yielding top empirical P values of 0.00001 (UK) and 0.0004 (US). Measures related to phonological and orthographic processing also showed linkage at this locus. We replicated linkage to 18p11.2 in a third independent sample of families (from the UK), in which the strongest evidence came from a phoneme-awareness measure (most significant P value=0.00004). A combined analysis of all UK families confirmed that this newly discovered 18p QTL is probably a general risk factor for dyslexia, influencing several reading-related processes. This is the first report of QTL-based genome-wide scanning for a human cognitive trait.     

Label-free immunodetection with CMOS-compatible semiconducting nanowires

Semiconducting nanowires have the potential to function as highly sensitive and selective sensors for the label-free detection of low concentrations of pathogenic microorganisms. Successful solution-phase nanowire sensing has been demonstrated for ions, small molecules, proteins, DNA and viruses; however, 'bottom-up' nanowires (or similarly configured carbon nanotubes) used for these demonstrations require hybrid fabrication schemes, which result in severe integration issues that have hindered widespread application. Alternative 'top-down' fabrication methods of nanowire-like devices produce disappointing performance because of process-induced material and device degradation. Here we report an approach that uses complementary metal oxide semiconductor (CMOS) field effect transistor compatible technology and hence demonstrate the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response. This approach eliminates the need for hybrid methods and enables system-scale integration of these sensors with signal processing and information systems. Additionally, the ability to monitor antibody binding and sense the cellular immune response in real time with readily available technology should facilitate widespread diagnostic applications.     

Prediction from the regression model with two‐way error components

In this paper we extend the Baillie and Baltagi ( 1999 ) paper (Prediction from the regression model with one‐way error components. In Analysis of Panels and Limited Dependent Variables Models, Hsiao C, Lahiri K, Lee LF, Pesaran H (eds). Cambridge University Press, Cambridge, UK). In particular, we derive six predictors for the two‐way error components model, as well as their associated asymptotic mean squared error (AMSE) of multi‐step prediction. In addition, we also provide both theoretical and simulation evidence as to the relative efficiency of our six alternative predictors. The adequacy of the prediction AMSE formula is also investigated by the use of Monte Carlo methods which indicate that the ordinary optimal predictors perform well for various accuracy criteria. Copyright © 2010 John Wiley & Sons, Ltd.     

Effects of Douglas-fir beetle (Coleoptera: Scolytidae) infestations on forest overstory and understory conditions in western Wyoming

Douglas-fir beetle ( Dendroctonus pseudotsugae Hopk.) infestations frequently result from disturbance events that create large volumes of weakened Douglas-fir trees, Pseudotsuga menziesii (Mirb.) Franco. Previous research has focused on determining susceptibility of forest stands to Douglas-fir beetle and predicting the amount of tree mortality from Douglas-fir beetle infestations following disturbance events. Little work has been done on consequent changes in the forest overstory and understory. In the early 1990s, populations of Douglas-fir beetle increased in fire-scorched trees, subsequently infesting undamaged neighboring stands in the Rocky Mountains of western Wyoming, USA. In 1999 transect sampling and 25 pairs of previously infested and uninfested plots were used to quantify changes in forest stand conditions and ensuing responses in the understory caused by Douglas-fir beetle infestations. Significant effects of the Douglas-fir beetle infestation comprised 3 general categories: (1) overstory effects: basal area was reduced by 40%-70%, average tree diameter decreased by 8%-40%, and the Douglas-fir component of the overstory decreased by more than 12%; (2) regeneration effects: conifer seedling regeneration increased nearly fourfold in infested plots and 90% of the regeneration was Douglas-fir; (3) understory effects: understory vegetation (forbs, grass, and shrubs) had a threefold increase in infested compared with uninfested plots. In addition, basal area of Douglas-fir killed by the Douglas-fir beetle was significantly correlated with initial Douglas-fir basal area and percentage of Douglas-fir, but not with stand density index, tree diameter, or trees per hectare. Significant inverse relationships also were found between post-infestation basal area and abundance of forbs, grass, and shrubs, and understory height. Thus, we found that Douglas-fir beetle infestations cause significant short-term effects in both the overstory and understory and contribute to an altered mosaic in forest structure.     

Rapid Manufacturing of Non-Assembly Complex Micro-Devices by Microstereolithography

This paper introduces a non-assembly manufacturing case with microstereolithography technology. The design and manufacturing process of a pneumatic thrust bearing is described, and a special tessellation method is developed to further improve the capability of the manufacturing system thus bigger products can also be easily manufactured. Implemented in a layer-by-layer fashion, stereolithography has been used for the rapid manufacturing of complex devices, and it avoids the expensive assembly process in the traditional manufacturing. This paper presents that microstereolithography can produce high-resolution products with intricate details, small openings, and smooth surfaces. The potential of the microstereolithograhy technique is explored for the rapid manufacturing of small and complex objects.     

Transthyretin: the servant of many masters

Transthyretin (TTR) (formerly, thyroxine binding prealbumin) is an evolutionarily conserved serum and cerebrospinal fluid protein that transports holo-retinol-binding protein and thyroxine. Its serum concentration has been widely used to assess clinical nutritional status. It is also well known that wild-type transthyretin and approximately 100 different mutants give rise to a variety of forms of systemic amyloid deposition. It has been suspected and recently established that TTR can suppress the Alzheimer’s disease phenotype in transgenic animal models of cerebral Aβ deposition. Thus, while TTR is a systemic amyloid precursor, in the brain it seems to have an anti-amyloidogenic effect. TTR is found in other organs as a result of local synthesis or transport, suggesting that it may have other, as yet undiscovered, functions. It is possible that its capacity to bind many classes of compounds allows it to serve as an endogenous detoxifier of molecules with potential pathologic effects.     

Mechanism of urea nitrogen binding by proposed oxidized starch gastrointestinal absorbents.

By use of 14-C label it was demonstrated that apparent binding of urea N to polyaldehyde starch was probably preceeded by hydrolysis to ammonium ion. Thus direct urea binding was not the mechanism through which ingested polyaldehyde starch might increase fecal N excretion in uremic patients.