Characterization of the angular memory effect of scattered light in biological tissues.

This is the final version of the article. Available via open access from Optical Society of America via the DOI in this record.High resolution optical microscopy is essential in neuroscience but suffers from scattering in biological tissues and therefore grants access to superficial brain layers only. Recently developed techniques use scattered photons for imaging by exploiting angular correlations in transmitted light and could potentially increase imaging depths. But those correlations ('angular memory effect') are of a very short range and should theoretically be only present behind and not inside scattering media. From measurements on neural tissues and complementary simulations, we find that strong forward scattering in biological tissues can enhance the memory effect range and thus the possible field-of-view by more than an order of magnitude compared to isotropic scattering for ∼1 mm thick tissue layers.This work was funded by European Research Council Grant 278025 and the Agence Nationale de la Recherche (Investissements d’Avenir ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX- 0001-02 PSL* Research University). We thank Prof. Georg Maret for enabling Sam Schott’s stay at institut Langevin and his support of the project and David Martina for technical help in the development of the experimental setup

Independent and combined influence of healthy lifestyle factors on academic performance in adolescents: DADOS Study

BACKGROUND. Few studies have analyzed the combined effect of lifestyle factors on academic performance (AP) in adolescents. The aim of this study was to analyze the independent and combined effects of weight status, screen time, sleep quality, daily meal frequency, cardiorespiratory fitness and physical activity (PA) on AP in adolescents. METHODS. A total of 262 adolescents (13.9±0.3 years) from the DADOS study were included in the analysis. Weight status was assessed through body mass index (kg/m 2 ). Participants completed questionnaires to evaluate screen time, sleep quality and daily meal frequency. Cardiorespiratory fitness was assessed by the 20-m shuttle run test. PA was evaluated by a wrist-worn GENEActiv accelerometer. AP was assessed through the final academic grades and a validated questionnaire. RESULTS. Non-overweight status, low screen time, good sleep quality and proper meal frequency showed independent, positive influence on AP. Moreover, adolescents achieving at least 3 healthy lifestyles were more likely to be in the high-performance group for academic grades than those achieving ≤ 1 (math OR: 3.02-9.51, language OR: 3.51-6.76 and grade point average OR: 4.22-9.36). CONCLUSIONS. Although individual healthy lifestyles are independently and positively associated with AP, the cumulative effect of multiple healthy lifestyles have a stronger impact

Optimizing the Design of Oligonucleotides for Homology Directed Gene Targeting

BACKGROUND: Gene targeting depends on the ability of cells to use homologous recombination to integrate exogenous DNA into their own genome. A robust mechanistic model of homologous recombination is necessary to fully exploit gene targeting for therapeutic benefit. METHODOLOGY/PRINCIPAL FINDINGS: In this work, our recently developed numerical simulation model for homology search is employed to develop rules for the design of oligonucleotides used in gene targeting. A Metropolis Monte-Carlo algorithm is used to predict the pairing dynamics of an oligonucleotide with the target double-stranded DNA. The model calculates the base-alignment between a long, target double-stranded DNA and a probe nucleoprotein filament comprised of homologous recombination proteins (Rad51 or RecA) polymerized on a single strand DNA. In this study, we considered different sizes of oligonucleotides containing 1 or 3 base heterologies with the target; different positions on the probe were tested to investigate the effect of the mismatch position on the pairing dynamics and stability. We show that the optimal design is a compromise between the mean time to reach a perfect alignment between the two molecules and the stability of the complex. CONCLUSION AND SIGNIFICANCE: A single heterology can be placed anywhere without significantly affecting the stability of the triplex. In the case of three consecutive heterologies, our modeling recommends using long oligonucleotides (at least 35 bases) in which the heterologous sequences are positioned at an intermediate position. Oligonucleotides should not contain more than 10% consecutive heterologies to guarantee a stable pairing with the target dsDNA. Theoretical modeling cannot replace experiments, but we believe that our model can considerably accelerate optimization of oligonucleotides for gene therapy by predicting their pairing dynamics with the target dsDNA

A Very Large Number of GABAergic Neurons Are Activated in the Tuberal Hypothalamus during Paradoxical (REM) Sleep Hypersomnia

We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD67 in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD+, Fos-ir/MCH+, and GAD+/MCH+ double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD+ neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis