Thermobarometry of the Moine and Sgurr Beag thrust sheets, northern Scotland

In the Caledonides of northern Scotland temperatures of metamorphism (Tm) and deformation (Td) progressively increase structurally up section in the Moine thrust sheet at the foreland edge of the Scandian (mid Silurian) orogenic wedge. However, the thermal history of the structurally overlying, more hinterland positioned thrust sheets is less well known. This study focuses on determining Td and Tm for both the central/upper part of the Moine thrust sheet and the lower part of the overlying Sgurr Beag thrust sheets in the middle of the Northern Highlands Terrane. Preserved microstructures and quartz c-axis fabric opening angles in the Moine and Sgurr Beag thrust sheets imply Td of 460 °C to 605 °C ± 50 °C. Thermobarometry and pseudosection-based P-T constraints, indicate Tm of ∼550–680 °C at 4.8–7.2 kbar in the Moine thrust sheet and Tm of ∼620 °C at 5.6–7.7 kbar in the Sgurr Beag thrust sheet. Together, Td and Tm in the Moine and Sgurr Beag thrust sheets indicate that deformation continued after peak metamorphic conditions in the Sgurr Beag thrust sheet. Monazite and xenotime petrochronology show that Tm, and possibly Td, record Precambrian metamorphism. Peak metamorphism is associated with the Knoydartian orogenic event (840-720 Ma), with possible reworking during Scandian thrusting (430-425 Ma)

Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

A Set of 100 Chloroplast DNA Primer Pairs to Study Population Genetics and Phylogeny in Monocotyledons

Chloroplast DNA sequences are of great interest for population genetics and phylogenetic studies. However, only a small set of markers are commonly used. Most of them have been designed for amplification in a large range of Angiosperms and are located in the Large Single Copy (LSC). Here we developed a new set of 100 primer pairs optimized for amplification in Monocotyledons. Primer pairs amplify coding (exon) and non-coding regions (intron and intergenic spacer). They span the different chloroplast regions: 72 are located in the LSC, 13 in the Small Single Copy (SSC) and 15 in the Inverted Repeat region (IR). Amplification and sequencing were tested in 13 species of Monocotyledons: Dioscorea abyssinica, D. praehensilis, D. rotundata, D. dumetorum, D. bulbifera, Trichopus sempervirens (Dioscoreaceae), Phoenix canariensis, P. dactylifera, Astrocaryum scopatum, A. murumuru, Ceroxylon echinulatum (Arecaceae), Digitaria excilis and Pennisetum glaucum (Poaceae). The diversity found in Dioscorea, Digitaria and Pennisetum mainly corresponded to Single Nucleotide Polymorphism (SNP) while the diversity found in Arecaceae also comprises Variable Number Tandem Repeat (VNTR). We observed that the most variable loci (rps15-ycf1, rpl32-ccsA, ndhF-rpl32, ndhG-ndhI and ccsA) are located in the SSC. Through the analysis of the genetic structure of a wild-cultivated species complex in Dioscorea, we demonstrated that this new set of primers is of great interest for population genetics and we anticipate that it will also be useful for phylogeny and bar-coding studies

VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC

2-Hydroxy-saclofen causes a phaclofen-reversible reduction in population spike amplitude in the rat hippocampal slice

2-Hydroxy-saclofen is known to be active at GABAB receptors in the mammalian central nervous system, and we have investigated its effects on synaptic transmission in the rat hippocampal slice preparation. Orthodromic stimuli were applied to the stratum radiatum, and population spike responses from the CA1 pyramidal cell layer were recorded extracellularly. A second, identical stimulus was applied at a variable interpulse interval (IPI) after the initial conditioning stimulus. GABAergic synaptic inhibition was observed as a decrease in the spike amplitude of the second response compared to the first. Both the GABAB receptor antagonist phaclofen (1 mM) and 2-hydroxy-saclofen (200 µM) prevented a slow phase of inhibition for IPIs of 200–400 ms. However, these agents differed markedly in their effects on overall synaptic transmission. Phaclofen had no effect on the amplitude of the initial conditioning spike amplitude, whereas 2-hydroxy-saclofen reduced it significantly, in a manner similar to baclofen (1 µM). The direct actions of 2-hydroxy-saclofen were unexpected for a pure antagonist of GABAB receptors, but could be prevented by the co-administration of phaclofen (1 mM), but not bicuculline (1 µM). Reduction in conditioning spike amplitude due to antagonism of GABAB autoreceptors on inhibitory interneurones and subsequent enhancement of GABAA tonic inhibition would have been blocked by bicuculline. The blockade of the 2-hydroxy-saclofen effect by phaclofen implies a GABAB receptor partial agonist action. The possible sites of this action are discussed

Brains, Genes, and Primates

One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators, and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive, and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward.Poitras Center for Affective Disorders ResearchStanley Center for Psychiatric ResearchBrain Research Foundation (Science Innovation Award