54 research outputs found
Lack of correlation between predicted and actual off-target effects of short-interfering RNAs targeting the human papillomavirus type 16 E7 oncogene.
BACKGROUND: When designing therapeutic short-interfering RNAs (siRNAs), off-target effects (OTEs) are usually predicted by computational quantification of messenger RNAs (mRNAs) that contain matches to the siRNA seed sequence in their 3' UTRs. It is assumed that the higher the number of predicted transcriptional OTEs, the greater the size of the actual OTE signature and the more detrimental the phenotypic consequences in target-negative cells. METHODS: We tested this general assumption by investigating the OTEs of potential therapeutic siRNAs targeting the human papillomavirus (HPV) type-16 E7 oncogene. We studied HPV-negative squamous epithelial cells, from normal cervix (NCx) and skin (HaCaT), which would be vulnerable to 'bystander' OTEs following transfection in vivo. RESULTS: We observed no correlation between the number of computationally predicted OTEs and the actual number of seed-dependent OTEs (P=0.76). On average only 20.5% of actual transcriptional OTEs were seed-dependent (i.e., predicted). The unpredicted OTEs included stimulation of innate immune pathways, as well as indirect (downstream) effects of other OTEs, which affected important cancer-associated pathways. Although most significant OTEs observed were seen in both NCx and HaCaT cells, only 0-5.9% of differentially expressed genes overlapped between the two cell types. CONCLUSION: These data do not support the assumption that actual OTEs correlate well with predicted OTEs
Disorder Effects on Exciton-Polariton Condensates
The impact of a random disorder potential on the dynamical properties of Bose
Einstein condensates is a very wide research field. In microcavities, these
studies are even more crucial than in the condensates of cold atoms, since
random disorder is naturally present in the semiconductor structures. In this
chapter, we consider a stable condensate, defined by a chemical potential,
propagating in a random disorder potential, like a liquid flowing through a
capillary. We analyze the interplay between the kinetic energy, the
localization energy, and the interaction between particles in 1D and 2D
polariton condensates. The finite life time of polaritons is taken into account
as well. In the first part, we remind the results of [G. Malpuech et al. Phys.
Rev. Lett. 98, 206402 (2007).] where we considered the case of a static
condensate. In that case, the condensate forms either a glassy insulating phase
at low polariton density (strong localization), or a superfluid phase above the
percolation threshold. We also show the calculation of the first order spatial
coherence of the condensate versus the condensate density. In the second part,
we consider the case of a propagating non-interacting condensate which is
always localized because of Anderson localization. The localization length is
calculated in the Born approximation. The impact of the finite polariton life
time is taken into account as well. In the last section we consider the case of
a propagating interacting condensate where the three regimes of strong
localization, Anderson localization, and superfluid behavior are accessible.
The localization length is calculated versus the system parameters. The
localization length is strongly modified with respect to the non-interacting
case. It is infinite in the superfluid regime whereas it is strongly reduced if
the fluid flows with a supersonic velocity.Comment: chapter for a book "Exciton Polaritons in Microcavities: New
Frontiers" by Springer (2012), the original publication is available at
http://www.springerlink.co
Is functional dependence of Duchenne muscular dystrophy patients determinant of the quality of life and burden of their caregivers?
Reduction of the contaminant fraction of DNA obtained from an ancient giant panda bone
Objective: A key challenge in ancient DNA research is massive microbial DNA contamination from the deposition site which accumulates post mortem in the study organism’s remains. Two simple and cost-effective methods to enrich the relative endogenous fraction of DNA in ancient samples involve treatment of sample powder with either bleach or Proteinase K pre-digestion prior to DNA extraction. Both approaches have yielded promising but varying results in other studies. Here, we contribute data on the performance of these methods using a comprehensive and systematic series of experiments applied to a single ancient bone fragment from a giant panda (Ailuropoda melanoleuca).
Results: Bleach and pre-digestion treatments increased the endogenous DNA content up to ninefold. However, the absolute amount of DNA retrieved was dramatically reduced by all treatments. We also observed reduced DNA damage patterns in pre-treated libraries compared to untreated ones, resulting in longer mean fragment lengths and reduced thymine over-representation at fragment ends. Guanine–cytosine (GC) contents of both mapped and total reads are consistent between treatments and conform to general expectations, indicating no obvious biasing effect of the applied methods. Our results therefore confirm the value of bleach and pre-digestion as tools in palaeogenomic studies, providing sufficient material is available
Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019
Five insights from the Global Burden of Disease Study 2019
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe
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