A researcher’s guide to the galaxy of IRESs

The idea of internal initiation is frequently exploited to explain the peculiar translation properties or unusual features of some eukaryotic mRNAs. In this review, we summarize the methods and arguments most commonly used to address cases of translation governed by internal ribosome entry sites (IRESs). Frequent mistakes are revealed. We explain why “cap-independent” does not readily mean “IRES-dependent” and why the presence of a long and highly structured 5′ untranslated region (5′UTR) or translation under stress conditions cannot be regarded as an argument for appealing to internal initiation. We carefully describe the known pitfalls and limitations of the bicistronic assay and artefacts of some commercially available in vitro translation systems. We explain why plasmid DNA transfection should not be used in IRES studies and which control experiments are unavoidable if someone decides to use it anyway. Finally, we propose a workflow for the validation of IRES activity, including fast and simple experiments based on a single genetic construct with a sequence of interest.     

Asymmetry in the link between the yield spread and industrial production: threshold effects and forecasting

We analyse the nonlinear behaviour of the information content in the spread for future real economic activity. The spread linearly predicts one‐year‐ahead real growth in nine industrial production sectors of the USA and four of the UK over the last 40 years. However, recent investigations on the spread–real activity relation have questioned both its linear nature and its time‐invariant framework. Our in‐sample empirical evidence suggests that the spread–real activity relationship exhibits asymmetries that allow for different predictive power of the spread when past spread values were above or below some threshold value. We then measure the out‐of‐sample forecast performance of the nonlinear model using predictive accuracy tests. The results show that significant improvement in forecasting accuracy, at least for one‐step‐ahead forecasts, can be obtained over the linear model. Copyright © 2004 John Wiley & Sons, Ltd.     

LaConf:A Localized Address Autoconfiguration Scheme for Wireless Ad Hoc Networks

We propose a localized address autoconfiguration (LaConf) scheme for wireless ad hoc networks.Address allocation information is maintained on the network border nodes,called addressing agents (AAs),which are locally identified by a geographic routing protocol GFG (Greedy-FACE-Greedy).When a node joins the network,it acquires an address from a neighboring AA (if any exists) by local communication or from the head AA (a geographic extreme AA) by GFG-based multi-hop communication.A Geographic Hash Table (GHT) ...     

Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice

Reactive aldehydes are common carcinogens. They are also by-products of several metabolic pathways and, without enzymatic catabolism, may accumulate and cause DNA damage. Ethanol, which is metabolised to acetaldehyde, is both carcinogenic and teratogenic in humans. Here we find that the Fanconi anaemia DNA repair pathway counteracts acetaldehyde-induced genotoxicity in mice. Our results show that the acetaldehyde-catabolising enzyme Aldh2 is essential for the development of Fancd2(-/-) embryos. Nevertheless, acetaldehyde-catabolism-competent mothers (Aldh2(+/-)) can support the development of double-mutant (Aldh2(-/-)Fancd2(-/-)) mice. However, these embryos are unusually sensitive to ethanol exposure in utero, and ethanol consumption by postnatal double-deficient mice rapidly precipitates bone marrow failure. Lastly, Aldh2(-/-)Fancd2(-/-) mice spontaneously develop acute leukaemia. Acetaldehyde-mediated DNA damage may critically contribute to the genesis of fetal alcohol syndrome in fetuses, as well as to abnormal development, haematopoietic failure and cancer predisposition in Fanconi anaemia patients.