Theta-phase dependent neuronal coding during sequence learning in human single neurons

This work was supported by grants from the French Agence Nationale de la Recherche (ANR-12-JSH2-0004-01 and ANR AI-REPS–18-CE37-0007-01), the Fyssen foundation, and the Université Paul Sabatier, Toulouse, France (BQR, 2009 and Appel à Projets de Recherche Labellisés, 2013), to L.R., the European Research Council (ERC Consolidator Grant P-Cycles number 614244), the French Agence Nationale de la Recherche (ANR OSCI-DEEP ANR-19-NEUC-0004), and an ANITI (Artificial and Natural Intelligence Toulouse Institute) Research Chair (ANR-19-PI3A-0004) to R.V., the Studienstiftung des Deutschen Volkes (German Academic Scholarship Foundation) to B.Z., the European Union (ERC Grant Agreement n. 339490 “Cortic_al_gorithms” and grant agreements 720270 and 785907 “Human Brain Project SGA1 and SGA2’) and the Friends Foundation of the Netherlands Institute for Neuroscience to P.R.R.The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.Publisher PDFPeer reviewe

Mouse visual cortex contains a region of enhanced spatial resolution.

The representation of space in mouse visual cortex was thought to be relatively uniform. Here we reveal, using population receptive-field (pRF) mapping techniques, that mouse visual cortex contains a region in which pRFs are considerably smaller. This region, the "focea," represents a location in space in front of, and slightly above, the mouse. Using two-photon imaging we show that the smaller pRFs are due to lower scatter of receptive-fields at the focea and an over-representation of binocular regions of space. We show that receptive-fields of single-neurons in areas LM and AL are smaller at the focea and that mice have improved visual resolution in this region of space. Furthermore, freely moving mice make compensatory eye-movements to hold this region in front of them. Our results indicate that mice have spatial biases in their visual processing, a finding that has important implications for the use of the mouse model of vision

A haploid pseudo-chromosome genome assembly for a keystone sagebrush species of western North American rangelands

Increased ecological disturbances, species invasions, and climate change are creating severe conservation problems for several plant species that are widespread and foundational. Understanding the genetic diversity of these species and how it relates to adaptation to these stressors are necessary for guiding conservation and restoration efforts. This need is particularly acute for big sagebrush (Artemisia tridentata; Asteraceae), which was once the dominant shrub over 1,000,000 km2 in western North America but has since retracted by half and thus has become the target of one of the largest restoration seeding efforts globally. Here, we present the first reference-quality genome assembly for an ecologically important subspecies of big sagebrush (A. tridentata subsp. tridentata) based on short and long reads, as well as chromatin proximity ligation data analyzed using the HiRise pipeline. The final 4.2-Gb assembly consists of 5,492 scaffolds, with nine pseudo-chromosomal scaffolds (nine scaffolds comprising at least 90% of the assembled genome; n = 9). The assembly contains an estimated 43,377 genes based on ab initio gene discovery and transcriptional data analyzed using the MAKER pipeline, with 91.37% of BUSCOs being completely assembled. The final assembly was highly repetitive, with repeat elements comprising 77.99% of the genome, making the Artemisia tridentata subsp. tridentata genome one of the most highly repetitive plant genomes to be sequenced and assembled. This genome assembly advances studies on plant adaptation to drought and heat stress and provides a valuable tool for future genomic research.This research was made possible by 2 NSF Idaho EPSCoR grants (award numbers OIA-1757324 and OIA-1826801), as well as a Dovetail Genomics Tree of Life Award.Introduction Materials and methods Sample collection, in vitro tissue propagation, and biomass production Flow cytometry and genome complexity analysis PacBio and Omni-C sequence data generation PacBio long-read de novo assembly and validation Pseudomolecule construction with HiRise Genome annotation RNA sequencing Repeat identification Functional annotation Results and discussion Validation of genome assembly and annotation Genome complexity and evidence of past polyploidization Comparing the A. tridentata and A. annua genome assemblies Applications of the sagebrush reference genome Data availability Acknowledgments Literature cite

Who is a credible source of preventive advice? An experimental vignette study of general public attitudes towards role expansion in health and social care

© 2020 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society Objectives: To investigate the general public’s source credibility attitudes towards health and social care professionals when giving advice associated with their ‘traditional role’ versus an ‘expanded health behaviour change’ role, to facilitate the implementation of the health behaviour change agenda. Design: A 3x3 experimental between-subjects vignette questionnaire study with nine scenarios in which a general practitioner (GP), health visitor, or firefighter offered advice on either stopping smoking, preventing cot death, or fire safety. Combinations were either congruent with a traditional role (e.g., health visitor and cot death) or an expanded role (e.g., firefighter and stopping smoking). Methods: Adults were recruited from metropolitan locations in northern England. Participants were randomized to one scenario and complete a validated 18-item source credibility questionnaire. Factor analysis explored source credibility components; ratings for traditional and expanded role scenarios were compared using Mann–Whitney tests. Results: 369 participants completed the questionnaire (49.3% women, 64% White British, age range: 16–83). Factor analysis confirmed three source credibility dimensions: competence, caring, and trustworthiness. Ratings were generally high across professions and scenarios; participants rated professionals as significantly more ‘competent’ where scenarios related to their traditional roles than expanded roles (U 9778.5, p <.001) but equally as caring (U = 14467.5, p<.485) and trustworthy (U 14250.5, p.348). Conclusions: GPs, health visitors, and firefighters were all perceived as credible sources of health behaviour change advice, but may be viewed as ‘less competent’ sources of messages associated with an expanded job role. Effective professional training and public engagement regarding the role expansion agenda are needed to support policy implementation. Statement of Contribution What is already known on this subject? Source credibility surrounds people’s perceptions of the source of advice and includes competence, caring, and trustworthiness dimensions. This may have an important influence on people’s attitudes and behaviour, especially when messages are complex or emotive. A wide range of public sector workers is now expected to routinely offer preventive health and safety advice, as part of role expansion. What does this study add? This experimental survey study compared source credibility perceptions of GPs, health visitors, and firefighters giving advice on topics associated with a traditional or expanded role. Professionals were perceived as less ‘competent’ when giving advice on ‘expanded role’ topics, such as a firefighter discussing smoking, with a small reduction in source credibility. This highlights that source credibility may be specific to professional identities. Policymakers may need to explore this further as part of implementing role expansion for prevention and self-management in health and social care

In vivo kinetic approach reveals slow SOD1 turnover in the CNS

Therapeutic strategies that target disease-associated transcripts are being developed for a variety of neurodegenerative syndromes. Protein levels change as a function of their half-life, a property that critically influences the timing and application of therapeutics. In addition, both protein kinetics and concentration may play important roles in neurodegeneration; therefore, it is essential to understand in vivo protein kinetics, including half-life. Here, we applied a stable isotope-labeling technique in combination with mass spectrometric detection and determined the in vivo kinetics of superoxide dismutase 1 (SOD1), mutation of which causes amyotrophic lateral sclerosis. Application of this method to human SOD1-expressing rats demonstrated that SOD1 is a long-lived protein, with a similar half-life in both the cerebral spinal fluid (CSF) and the CNS. Additionally, in these animals, the half-life of SOD1 was longest in the CNS when compared with other tissues. Evaluation of this method in human subjects demonstrated successful incorporation of the isotope label in the CSF and confirmed that SOD1 is a long-lived protein in the CSF of healthy individuals. Together, the results of this study provide important insight into SOD1 kinetics and support application of this technique to the design and implementation of clinical trials that target long-lived CNS proteins

Hepatitis C infection: eligibility for antiviral therapies

peer reviewedBackground Current treatments of chronic hepatitis C virus (HCV) are effective, but expensive and susceptible to induce significant side effects. Objectives To evaluate the proportion of HCV patients who are eligible for a treatment. Methods In a database comprising 1726 viraemic HCV patients, the files of 299 patients who presented to the same hepatologist for an initial appointment between 1996 and 2003 were reviewed. Results Patients' characteristics were age 43.1 +/- 15.6 years, 53% male and 92% Caucasian. The main risk factors were transfusion (43%) and drug use (22%). Genotypes were mostly genotype 1 (66%), genotype 3 (12%) and genotype 2 (10%). These characteristics were not different from those of the whole series of 1726 patients. A total of 176 patients (59%) were not treated, the reasons for non-treatment being medical contraindications (34%), non-compliance (25%) and normal transaminases (24%). In addition, 17% of patients declined therapy despite being considered as eligible, mainly due to fear of adverse events. Medical contraindications were psychiatric (27%), age (22%), end-stage liver disease (15%), willingness for pregnancy (13%), cardiac contraindication (7%) and others (16%). Only 123 patients (41%) were treated. A sustained viral response was observed in 41%. The treatment was interrupted in 16% for adverse events. Conclusions The majority of HCV patients are not eligible for treatment. This implies that, with current therapies, only 17% of patients referred for chronic HCV become sustained responders. Some modifications of guidelines could extend the rate of treatment (patients with normal transaminases), but an important barrier remains the patients' and the doctors' fear of adverse events