Neocortical Layer 6, A Review

This review attempts to summarise some of the major areas of neocortical research as it pertains to neocortical layer 6. After a brief summary of the development of this intriguing layer, the major pyramidal cell classes to be found in layer 6 are described and compared. The connections made and received by these different classes of neurones are then discussed and the possible functions of these connections, with particular reference to the shaping of responses in visual cortex and thalamus. Inhibition in layer 6 is discussed where appropriate, but not in great detail. Many types of interneurones are to be found in each cortical layer and layer 6 is no exception, but the functions of each type remain to be elucidated (Gonchar et al., 2007)

Functional Maps of Neocortical Local Circuitry

This review aims to summarize data obtained with different techniques to provide a functional map of the local circuit connections made by neocortical neurones, a reference for those interested in cortical circuitry and the numerical information required by those wishing to model the circuit. A brief description of the main techniques used to study circuitry is followed by outline descriptions of the major classes of neocortical excitatory and inhibitory neurones and the connections that each layer makes with other cortical and subcortical regions. Maps summarizing the projection patterns of each class of neurone within the local circuit and tables of the properties of these local circuit connections are provided

Development of Cortical GABAergic Innervation

The mature neocortex contains many different classes of GABAergic inhibitory interneurons, distributed, with some degree of selectivity, through six layers, and through many different regions. Some of the events in the early lives of these neurones that may determine their ultimate destination, their maturation and their selective innervation of targets appropriate for each subtype, are discussed. Both time and place of birth influence the class of interneuron that an early post-mitotic interneuronal precursor will become, driven by the selective expression of different combinations of transcription factors in different regions of their birth places in the ganglionic eminence and ventricular zone. The long distance migration of these precursors along tangential routes in marginal, subventricular, and intermediate zones and their final radial movement, into the developing cortex, is regulated by chemical cues, both attractant and repellent. Once they arrive at their final destination, they must integrate into the developing circuitry. As they mature within the cortex, their axons grow and branch in highly specific patterns that may be partially determined by the genetic blueprint for each interneuronal class and partly by the environment in which they find themselves. Finally, as each interneuron class begins to form synapses with only certain postsynaptic targets, cell–cell recognition, most probably via protein–protein interactions across the synaptic cleft, facilitate the formation of appropriate synapses

Wave breaking turbulence at the offshore front of the Columbia River Plume

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Geophysical Research Letters 41 (2014): 8987–8993, doi:10.1002/2014GL062274.Observations at the Columbia River plume show that wave breaking is an important source of turbulence at the offshore front, which may contribute to plume mixing. The lateral gradient of current associated with the plume front is sufficient to block (and break) shorter waves. The intense whitecapping that then occurs at the front is a significant source of turbulence, which diffuses downward from the surface according to a scaling determined by the wave height and the gradient of wave energy flux. This process is distinct from the shear-driven mixing that occurs at the interface of river water and ocean water. Observations with and without short waves are examined, especially in two cases in which the background conditions (i.e., tidal flows and river discharge) are otherwise identical.This work was supported by the Office of Naval Research, as part of the Data Assimilation and Remote Sensing for Littoral Applications (DARLA) project and in coordination with the Rivers and Inlets (RIVET) program

Patients with naproxen-induced liver injury display T-cell memory responses toward an oxidative (S)-O-Desmethyl Naproxen metabolite but not the acyl glucuronide

Background Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (IBU) and naproxen (NAP) is associated with idiosyncratic drug-induced liver injury (DILI). Carboxylate bioactivation into reactive metabolites (e.g., acyl glucuronides, AG) and resulting T-cell activation is hypothesized as causal for this adverse event. However, conclusive evidence supporting this is lacking. Methods In this work, we identify CD4+ and CD8+ T-cell hepatic infiltration in a biopsy from an IBU DILI patient. Lymphocyte transformation test and IFN-γ ELIspot, conducted on peripheral blood mononuclear cells (PBMCs) of patients with NAP-DILI, were used to explore drug-specific T-cell activation. T-cell clones (TCC) were generated and tested for drug specificity, phenotype/function, and pathways of T-cell activation. Cells were exposed to NAP, its oxidative metabolite 6-O-desmethyl NAP (DM-NAP), its AG or synthesized NAP-AG human-serum albumin adducts (NAP-AG adduct). Results CD4+ and CD8+ T-cells from patients expressing a range of different Vβ receptors were stimulated to proliferate and secrete IFN-γ and IL-22 when exposed to DM-NAP, but not NAP, NAP-AG or the NAP-AG adduct. Activation of the CD4+ TCC was HLA-DQ-restricted and dependent on antigen presenting cells (APC); most TCC were activated with DM-NAP-pulsed APC, while fixation of APC blocked the T-cell response. Cross-reactivity was not observed with structurally-related drugs. Conclusion Our results confirm hepatic T-cell infiltrations in NSAID-induced DILI, and show a T-cell memory response toward DM-NAP indicating an immune-mediated basis for the adverse event. Whilst bioactivation at the carboxylate group is widely hypothesized to be pathogenic for NSAID associated DILI, we found no evidence of this with NAP

Imaging Electronic Correlations in Twisted Bilayer Graphene near the Magic Angle

Twisted bilayer graphene with a twist angle of around 1.1{\deg} features a pair of isolated flat electronic bands and forms a strongly correlated electronic platform. Here, we use scanning tunneling microscopy to probe local properties of highly tunable twisted bilayer graphene devices and show that the flat bands strongly deform when aligned with the Fermi level. At half filling of the bands, we observe the development of gaps originating from correlated insulating states. Near charge neutrality, we find a previously unidentified correlated regime featuring a substantially enhanced flat band splitting that we describe within a microscopic model predicting a strong tendency towards nematic ordering. Our results provide insights into symmetry breaking correlation effects and highlight the importance of electronic interactions for all filling factors in twisted bilayer graphene.Comment: Main text 9 pages, 4 figures; Supplementary Information 25 page

The Global Magneto-Ionic Medium Survey (GMIMS): The brightest polarized region in the Southern sky at 75cm and its implications for Radio Loop II

Using the Global Magneto-Ionic Medium Survey (GMIMS) Low-Band South (LBS) southern sky polarization survey, covering 300 to 480 MHz at 81 arcmin resolution, we reveal the brightest region in the Southern polarized sky at these frequencies. The region, G150-50, covers nearly 20deg$^2$, near (l,b)~(150 deg,-50 deg). Using GMIMS-LBS and complementary data at higher frequencies (~0.6--30 GHz), we apply Faraday tomography and Stokes QU-fitting techniques. We find that the magnetic field associated with G150-50 is both coherent and primarily in the plane of the sky, and indications that the region is associated with Radio Loop II. The Faraday depth spectra across G150-50 are broad and contain a large-scale spatial gradient. We model the magnetic field in the region as an expanding shell, and we can reproduce both the observed Faraday rotation and the synchrotron emission in the GMIMS-LBS band. Using QU-fitting, we find that the Faraday spectra are produced by several Faraday dispersive sources along the line-of-sight. Alternatively, polarization horizon effects that we cannot model are adding complexity to the high-frequency polarized spectra. The magnetic field structure of Loop II dominates a large fraction of the sky, and studies of the large-scale polarized sky will need to account for this object. Studies of G150-50 with high angular resolution could mitigate polarization horizon effects, and clarify the nature of G150-50.Comment: 25 pages, 14 figures. Accepted for publication in MNRA

The domesticated transposase ALP2 mediates formation of a novel Polycomb protein complex by direct interaction with MSI1, a core subunit of Polycomb Repressive Complex 2 (PRC2)

A large fraction of plant genomes is composed of transposable elements (TE), which provide a potential source of novel genes through "domestication"-the process whereby the proteins encoded by TE diverge in sequence, lose their ability to catalyse transposition and instead acquire novel functions for their hosts. In Arabidopsis, ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN 1 (ALP1) arose by domestication of the nuclease component of Harbinger class TE and acquired a new function as a component of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a histone H3K27me3 methyltransferase involved in regulation of host genes and in some cases TE. It was not clear how ALP1 associated with PRC2, nor what the functional consequence was. Here, we identify ALP2 genetically as a suppressor of Polycomb-group (PcG) mutant phenotypes and show that it arose from the second, DNA binding component of Harbinger transposases. Molecular analysis of PcG compromised backgrounds reveals that ALP genes oppose silencing and H3K27me3 deposition at key PcG target genes. Proteomic analysis reveals that ALP1 and ALP2 are components of a variant PRC2 complex that contains the four core components but lacks plant-specific accessory components such as the H3K27me3 reader LIKE HETEROCHROMATION PROTEIN 1 (LHP1). We show that the N-terminus of ALP2 interacts directly with ALP1, whereas the C-terminus of ALP2 interacts with MULTICOPY SUPPRESSOR OF IRA1 (MSI1), a core component of PRC2. Proteomic analysis reveals that in alp2 mutant backgrounds ALP1 protein no longer associates with PRC2, consistent with a role for ALP2 in recruitment of ALP1. We suggest that the propensity of Harbinger TE to insert in gene-rich regions of the genome, together with the modular two component nature of their transposases, has predisposed them for domestication and incorporation into chromatin modifying complexes

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus