Novel insights into RNAi off-target effects using C. elegans paralogs

<p>Abstract</p> <p>Background</p> <p>In the few years since its discovery, RNAi has turned into a very powerful tool for the study of gene function by allowing post-transcriptional gene silencing. The RNAi mechanism, which is based on the introduction of a double-stranded RNA (dsRNA) trigger whose sequence is similar to that of the targeted messenger RNA (mRNA), is subject to off-target cross-reaction.</p> <p>Results</p> <p>We use a novel strategy based on phenotypic analysis of paralogs and predict that, in <it>Caenorhabditis elegans</it>, off-target effects occur when an mRNA sequence shares more than 95% identity over 40 nucleotides with the dsRNA. Interestingly, our results suggest that the minimum length necessary of a high-similarity stretch between a dsRNA and its target in order to observe an efficient RNAi effect varies from 30 to 50 nucleotides rather than 22 nucleotides, which is the length of siRNAs in <it>C. elegans</it>.</p> <p>Conclusion</p> <p>Our predictive methods would improve the design of dsRNA and ultimately the use of RNAi as a therapeutic tool upon experimental verification.</p

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Hardware Fault Injection

ISBN :2010 ISBN 978-1-4419-6992-7; e-ISBN 978-1-4419-6993-4Hardware fault injection is the widely accepted approach to evaluate the behavior of a circuit in the presence of faults. Thus, it plays a key role in the design of robust circuits. This chapter presents a comprehensive review of hardware fault injection techniques, including physical and logical approaches. The implementation of effective fault injection systems is also analyzed. Particular emphasis is made on the recently developed emulation-based techniques, which can provide large flexibility along with unprecedented levels of performance. These capabilities provide a way to tackle reliability evaluation of complex circuits