Gene transfer engineering for astrocyte-specific silencing in the CNS.

Cell-type-specific gene silencing is critical to understand cell functions in normal and pathological conditions, in particular in the brain where strong cellular heterogeneity exists. Molecular engineering of lentiviral vectors has been widely used to express genes of interest specifically in neurons or astrocytes. However, we show that these strategies are not suitable for astrocyte-specific gene silencing due to the processing of small hairpin RNA (shRNA) in a cell. Here we develop an indirect method based on a tetracycline-regulated system to fully restrict shRNA expression to astrocytes. The combination of Mokola-G envelope pseudotyping, glutamine synthetase promoter and two distinct microRNA target sequences provides a powerful tool for efficient and cell-type-specific gene silencing in the central nervous system. We anticipate our vector will be a potent and versatile system to improve the targeting of cell populations for fundamental as well as therapeutic applications

The Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes.

Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expression of the Cas9 protein and high editing efficiency. In the first application, the gene responsible for Huntington's disease (HD) was targeted in adult mouse neuronal and glial cells. Mutant huntingtin (HTT) was efficiently inactivated in mouse models of HD, leading to an improvement in key markers of the disease. Sequencing of potential off-targets with the constitutive Cas9 system in differentiated human iPSC revealed a very low incidence with only one site above background level. This off-target frequency was significantly reduced with the KamiCas9 system. These results demonstrate the potential of the self-inactivating CRISPR/Cas9 editing for applications in the context of neurodegenerative diseases

Study of the Acute Stress Effects on Decision Making Using Electroencephalography and Functional Near-Infrared Spectroscopy: A Systematic Review

This systematic review provides a comprehensive analysis of studies that use electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to investigate how acute stress affects decision-making processes. The primary goal of this systematic review was to examine the influence of acute stress on decision making in challenging or stressful situations. Furthermore, we aimed to identify the specific brain regions affected by acute stress and explore the feature extraction and classification methods employed to enhance the detection of decision making under pressure. Five academic databases were carefully searched and 27 papers that satisfied the inclusion criteria were found. Overall, the results indicate the potential utility of EEG and fNIRS as techniques for identifying acute stress during decision-making and for gaining knowledge about the brain mechanisms underlying stress reactions. However, the varied methods employed in these studies and the small sample sizes highlight the need for additional studies to develop more standardized approaches for acute stress effects in decision-making tasks. The implications of the findings for the development of stress induction and technology in the decision-making process are also explained

SCA8 CAG/CTG Expansions, a Tale of Two TOXICities: A Unique or Common Case?

International audienc

Combined Characterisation of GOME and TOMS Total Ozone Using Ground-Based Observations from the NDSC

Several years of total ozone measured from space by the ERS-2 GOME, the Earth Probe Total Ozone Mapping Spectrometer (TOMS), and the ADEOS TOMS, are compared with high-quality ground-based observations associated with the Network for the Detection of Stratospheric Change (NDSC), over an extended latitude range and a variety of geophysical conditions. The comparisons with each spaceborne sensor are combined altogether for investigating their respective solar zenith angle (SZA) dependence, dispersion, and difference of sensitivity. The space- and ground-based data are found to agree within a few percent on average. However, the analysis highlights for both Global Ozone Monitoring Experiment (GOME) and TOMS several sources of discrepancies, including a dependence on the SZA at high latitudes and internal inconsistencies

Frontal Electroencephalogram Alpha Asymmetry during Mental Stress Related to Workplace Noise

This study aims to investigate the effects of workplace noise on neural activity and alpha asymmetries of the prefrontal cortex (PFC) during mental stress conditions. Workplace noise exposure is a pervasive environmental pollutant and is negatively linked to cognitive effects and selective attention. Generally, the stress theory is assumed to underlie the impact of noise on health. Evidence for the impacts of workplace noise on mental stress is lacking. Fifteen healthy volunteer subjects performed the Montreal imaging stress task in quiet and noisy workplaces while their brain activity was recorded using electroencephalography. The salivary alpha-amylase (sAA) was measured before and immediately after each tested workplace to evaluate the stress level. The results showed a decrease in alpha rhythms, or an increase in cortical activity, of the PFC for all participants at the noisy workplace. Further analysis of alpha asymmetry revealed a greater significant relative right frontal activation of the noisy workplace group at electrode pairs F4-F3 but not F8-F7. Furthermore, a significant increase in sAA activity was observed in all participants at the noisy workplace, demonstrating the presence of stress. The findings provide critical information on the effects of workplace noise-related stress that might be neglected during mental stress evaluations.Ministry of Higher Education Malaysia under the Higher Institutional Centre of Excellence (HICoE) Schem

Effect of Interruptions and Cognitive Demand on Mental Workload: A Critical Review

Worker safety and productivity are crucial for effective job management. Interruptions to an individual’s work environment and their impact on mental health can have adverse effects. One prospective instrument for assessing and calculating an individual’s mental state in an interrupted scenario and cognitive demand levels is the use of physiological computing devices in conjunction with behavioral and subjective measurements. This study sought to address how to gather and compute data on individuals’ cognitive states in interrupted work settings through critical analysis. Thirty-three papers were considered after the literature search and selection procedure. This descriptive study is conducted from three perspectives: parameter measurement, research design, and data analysis. The variables evaluated were working memory, stress, emotional state, performance, and resumption lag. The subject recruitment, experimental task design, and measurement techniques were examined from the standpoint of the experimental design. Data analysis included computing and cognitive pre-processing. Four future research directions are suggested to address the shortcomings of the present studies. This study offers suggestions for researchers on experiment planning and using computing to analyze individuals’ cognitive states during interrupted work scenarios. Additionally, it offers helpful recommendations for organizing and conducting future research

Priority use cases for antibody-detecting assays of recent malaria exposure as tools to achieve and sustain malaria elimination

Measurement of malaria specific antibody responses represents a practical and informative method for malaria control programs to assess recent exposure to infection. Technical advances in recombinant antigen production, serological screening platforms, and analytical methods have enabled the identification of several target antigens for laboratory based and point-of-contact tests. Questions remain as to how these serological assays can best be integrated into malaria surveillance activities to inform programmatic decision-making. This report synthesizes discussions from a convening at Institut Pasteur in Paris in June 2017 aimed at defining practical and informative use cases for serology applications and highlights five programmatic uses for serological assays including: documenting the absence of transmission; stratification of transmission; measuring the effect of interventions; informing a decentralized immediate response; and testing and treating P. vivax hypnozoite carriers