Microbial light-activatable proton pumps as neuronal inhibitors to functionally dissect neuronal networks in C. elegans

Essentially any behavior in simple and complex animals depends on neuronal network function. Currently, the best-defined system to study neuronal circuits is the nematode Caenorhabditis elegans, as the connectivity of its 302 neurons is exactly known. Individual neurons can be activated by photostimulation of Channelrhodopsin-2 (ChR2) using blue light, allowing to directly probe the importance of a particular neuron for the respective behavioral output of the network under study. In analogy, other excitable cells can be inhibited by expressing Halorhodopsin from Natronomonas pharaonis (NpHR) and subsequent illumination with yellow light. However, inhibiting C. elegans neurons using NpHR is difficult. Recently, proton pumps from various sources were established as valuable alternative hyperpolarizers. Here we show that archaerhodopsin-3 (Arch) from Halorubrum sodomense and a proton pump from the fungus Leptosphaeria maculans (Mac) can be utilized to effectively inhibit excitable cells in C. elegans. Arch is the most powerful hyperpolarizer when illuminated with yellow or green light while the action spectrum of Mac is more blue-shifted, as analyzed by light-evoked behaviors and electrophysiology. This allows these tools to be combined in various ways with ChR2 to analyze different subsets of neurons within a circuit. We exemplify this by means of the polymodal aversive sensory ASH neurons, and the downstream command interneurons to which ASH neurons signal to trigger a reversal followed by a directional turn. Photostimulating ASH and subsequently inhibiting command interneurons using two-color illumination of different body segments, allows investigating temporal aspects of signaling downstream of ASH

Polygenic risk for schizophrenia is associated with cognitive change between childhood and old age

We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS)

Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population

Acknowledgements Generation Scotland has received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. For the Lothian Birth Cohorts (LBC1921 and LBC1936), we thank Paul Redmond for database management assistance; Alan Gow, Martha Whiteman, Alison Pattie, Michelle Taylor, Janie Corley, Caroline Brett and Caroline Cameron for data collection and data entry; nurses and staff at the Wellcome Trust Clinical Research Facility, where blood extraction and genotyping was performed; staff at the Lothian Health Board; and the staff at the SCRE Centre, University of Glasgow. The research was supported by a program grant from Age UK (Disconnected Mind) and by grants from the Biotechnology and Biological Sciences Research Council (BBSRC). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Medical Research Council (MRC) and BBSRC is gratefully acknowledged. DJM is an NRS Career Research Fellow funded by the CSO. BATS were funded by the Australian Research Council (A79600334, A79906588, A79801419, DP0212016, DP0664638, and DP1093900) and the National Health and Medical Research Council (389875) Australia. MKL is supported by a Perpetual Foundation Wilson Fellowship. SEM is supported by a Future Fellowship (FT110100548) from the Australian Research Council. GWM is supported by a National Health and Medical Research Council (NHMRC), Australia, Fellowship (619667). We thank the twins and siblings for their participation, Marlene Grace, Ann Eldridge and Natalie Garden for cognitive assessments, Kerrie McAloney, Daniel Park, David Smyth and Harry Beeby for research support, Anjali Henders and staff in the Molecular Epidemiology Laboratory for DNA sample processing and preparation and Scott Gordon for quality control and management of the genotypes. This work is supported by a Stragetic Award from the Wellcome Trust, reference 104036/Z/14/Z.Peer reviewedPublisher PD

Basic comparison of particle size distribution measurements of pigments and fillers using commonly available industrial methods

The Nanobiosciences Unit of the Joint Research Centre’s Institute for Health and Consumer Protection and Eurocolour, the association of European pigments, dyes and fillers industry, have carried out a program of work to evaluate a number of instrumental methods of measuring particle size distributions as required for assessing compliance versus the EU Recommendation for the definition on nanomaterials. The study has examined the use of five instrumental methods applied to a range of eight widely different but industrially relevant powder pigments. The techniques examined were Laser Diffraction (LD), Dynamic Light Scattering (DLS), Centrifugal Liquid Sedimentation (CLS), Volume Specific Surface Area (VSSA) and Electron Microscopy (EM). This report describes the materials studied and the preparative and analytical methods used. Individual chapters provide an overview of the single analytical methods used together with a summary of the results obtained using each particular method. In considering the results of this study it is important to note that the aim was not to determine the optimum conditions for every individual sample but rather to produce and evaluate data which could be considered representative of that obtainable in industrial laboratories using existing instrumental facilities operated by experienced but not specialised operators. The report discusses the challenges of using these instrumental methods to obtain a simple unambiguous classification of the test materials according to the EC definition.JRC.I.4-Nanobioscience

Comparative Analysis of English Language Learners\u27 Experiences in Public School at the Third and Eighth Grade Levels

The field of education is one that endeavors constant change of fluctuating degrees. Most recently and drastically, the educational field has experienced and responded to changes in the cultural and linguistic diversity that is rapidly increasing in classrooms across the United States. Congruently, current legislation holds both educators and students accountable for their standardized performance and accomplishments, although teachers of ethnically diverse students are not required to be certified in the teaching of these learners. As a result, it was the purpose of this study to identify and analyze the themes evident from a series of observations and interviews conducted on two culturally and linguistically diverse participants by two teacher candidates. Ultimately, the study unveiled themes of self-concept, cultural behavioral expectations, language brokering, and social interactions of the two culturally and linguistically diverse participants. A discussion of the results are included, as well as the inclusion of best practices in classrooms comprised of culturally and linguistically diverse students

Deary-Liewald Reaction time

Reaction time tasks are used widely in basic and applied psychology, including in much of the research carried out at CCACE. CCACE Director Ian Deary and Database Manager Dave Liewald have developed a new method of measuring reaction time that is an easy-to-use and freely available programme. The new task was tested on 150 participants aged 18 to 80 years old and compared against existing technology. The new task's parameters are reliable, have very high correlations with the existing task parameters and perform as expected with respect to age and intelligence differences

Transfer characteristics of a thermosensory synapse in Caenorhabditis elegans

Caenorhabditis elegans is a compact, attractive system for neural circuit analysis. An understanding of the functional dynamics of neural computation requires physiological analyses. We undertook the characterization of transfer at a central synapse in C. elegans by combining optical stimulation of targeted neurons with electrophysiological recordings. We show that the synapse between AFD and AIY, the first stage in the thermotactic circuit, exhibits excitatory, tonic, and graded release. We measured the linear range of the input-output curve and estimate the static synaptic gain as 0.056 (<0.1). Release showed no obvious facilitation or depression. Transmission at this synapse is peptidergic. The AFD/AIY synapse thus seems to have evolved for reliable transmission of a scaled-down temperature signal from AFD, enabling AIY to monitor and integrate temperature with other sensory input. Combining optogenetics with electrophysiology is a powerful way to analyze C. elegans’ neural function