Acetylcholine release in mouse hippocampal CA1 preferentially activates inhibitory-selective interneurons via α4β2* nicotinic receptor activation

Acetylcholine (ACh) release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were assessed on both pyramidal neurons and different interneuron subtypes via whole cell patch clamp methods. Vasoactive intestinal peptide (VIP)-expressing interneurons that selectively innervate other interneurons (VIP/IS) were excited by ACh through the activation of nicotinic receptors containing α4 and β2 subunits (α4β2*). ACh release onto VIP/IS was presynaptically inhibited by M2 muscarinic autoreceptors. ACh release produced spontaneous inhibitory postsynaptic current (sIPSC) barrages blocked by dihydro-β-erythroidine in interneurons but not pyramidal neurons. Optogenetic suppression of VIP interneurons did not inhibit these sIPSC barrages suggesting other interneuron-selective interneurons were also excited by α4β2* nicotinic receptor activation. In contrast, interneurons that innervate pyramidal neuron perisomatic regions were not activated by ACh release onto nicotinic receptors. Therefore, we propose ACh release in CA1 facilitates disinhibition through activation of α4β2* nicotinic receptors on interneuron-selective interneurons whereas interneurons that innervate pyramidal neurons are less affected by nicotinic receptor activation

Preprotachykinin A (PPTA) is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli

The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined three non-overlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B (NKB) and gastrin-releasing peptide (GRP). Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ~14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ~15% of the excitatory neurons in this region. They are different from the neurotensin, NKB or GRP neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli, and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1Cre), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P-expressing excitatory neurons is likely to play an important role in transmission of signals that are perceived as pain and itch

Fast classification of drones and birds with an LSTM network applied to 1D phase data

Funding: Science and Technology Facilities Council under grant ST/N006569/1.This study investigates a new type of drone classifier based on Long Short-Term Memory (LSTM) networks. As a real-time surveillance system, the classification time of a drone detection radar is crucial. The motivation for this work is to develop a classification framework which has low latency in terms of data processing for the algorithm input. Theoretical modeling of a rotary wing drone and a bird wing flapping returns were done first to exhibit the difference in the patterns of the respective phase progressions. Then, 94 GHzexperimental trial data containing 4800 sequences of drones, birds, noise and clutter were used to create a diverse training dataset of 1D phase data for supervised learning. A stackedLSTM network with tuned hyperparameters was generated to reduce the possible overfitting from a simple LSTM model. Validation accuracy of 98.1% was achieved for 2-class classification of drone and non-drone. Further performance assessment was then done with 30 unseen test data, where the network was able to correctly classify all the sequences. It is ascertained that this method can be ~10 times faster than a spectrogram based classification model, which requires additional Fast Fourier Transform (FFT) operations

Multi-scale chemistry modelling for spacecraft atmospheric re-entry

We aim to develop a model capable of simulating the surface chemistry and material erosion involved when a re-entry vehicle descends through the atmosphere. Our starting point is to simulate the erosion of a fcc crystal slab due to cluster bombardment, using the model Lennard-Jones potential. From this, we plan to scale up towards Direct Monte Carlo Simulation approaches for the gas dynamics above the surface

Mapping low-latitude stellar substructure with SEGUE photometry

Encircling the Milky Way at low latitudes, the Low Latitude Stream is a large stellar structure, the origin of which is as yet unknown. As part of the SEGUE survey, several photometric scans have been obtained that cross the Galactic plane, spread over a longitude range of 50 to 203 degrees. These data allow a systematic study of the structure of the Galaxy at low latitudes, where the Low Latitude Stream resides. We apply colour-magnitude diagram fitting techniques to map the stellar (sub)structure in these regions, enabling the detection of overdensities with respect to smooth models. These detections can be used to distinguish between different models of the Low Latitude Stream, and help to shed light on the nature of the system.Comment: To appear in the proceedings of IAU Symposium 254 "The Galaxy disk in a cosmological context", Copenhagen, June 200

Assessment of Magnetic Resonance Imaging Artefacts Caused By Equine Anaesthesia Equipment:A Cadaver Study

Acquisition of magnetic resonance images of the equine limb is still sometimes conducted under general anaesthesia. Despite low-field systems allow the use of standard anaesthetic equipment, possible interferences of the extensive electronic componentry of advanced anaesthetic machines on image quality is unknown. This prospective, blinded, cadaver study investigated the effects of 7 standardised conditions [Tafonius positioned as in clinical cases, Tafonius on the boundaries of the controlled area, anaesthetic monitoring only, Mallard anaesthetic machine, Bird ventilator, complete electronic silence in the room (negative control), source of electronic interference (positive control)] on image quality through the acquisition of 78 sequences using a 0.31T equine MRI scanner. Images were graded with a 4-point scoring system, where 1 denoted absence of artefacts and 4 major artefacts requiring repetition in a clinical setting. A lack of STIR fat suppression was commonly reported (16/26). Ordinal logistic regression showed no statistically significant differences in image quality between the negative control and either the non-Tafonius or the Tafonius groups (p = 0.535 and p = 0.881, respectively), and with the use of Tafonius compared to the other anaesthetic machines (p = 0.578). The only statistically significant differences in scores were observed between the positive control and the non-Tafonius (p = 0.006) and the Tafonius groups (p = 0.017). Our findings suggest that anaesthetic machines and monitoring do not appear to affect MRI scan quality and support the use of Tafonius during acquisition of images with a 0.31T MRI system in a clinical context

In Vivo Biotinylation of the Toxoplasma Parasitophorous Vacuole Reveals Novel Dense Granule Proteins Important for Parasite Growth and Pathogenesis.

UnlabelledToxoplasma gondii is an obligate intracellular parasite that invades host cells and replicates within a unique parasitophorous vacuole. To maintain this intracellular niche, the parasite secretes an array of dense granule proteins (GRAs) into the nascent parasitophorous vacuole. These GRAs are believed to play key roles in vacuolar remodeling, nutrient uptake, and immune evasion while the parasite is replicating within the host cell. Despite the central role of GRAs in the Toxoplasma life cycle, only a subset of these proteins have been identified, and many of their roles have not been fully elucidated. In this report, we utilize the promiscuous biotin ligase BirA* to biotinylate GRA proteins secreted into the vacuole and then identify those proteins by affinity purification and mass spectrometry. Using GRA-BirA* fusion proteins as bait, we have identified a large number of known and candidate GRAs and verified localization of 13 novel GRA proteins by endogenous gene tagging. We proceeded to functionally characterize three related GRAs from this group (GRA38, GRA39, and GRA40) by gene knockout. While Δgra38 and Δgra40 parasites showed no altered phenotype, disruption of GRA39 results in slow-growing parasites that contain striking lipid deposits in the parasitophorous vacuole, suggesting a role in lipid regulation that is important for parasite growth. In addition, parasites lacking GRA39 showed dramatically reduced virulence and a lower tissue cyst burden in vivo Together, the findings from this work reveal a partial vacuolar proteome of T. gondii and identify a novel GRA that plays a key role in parasite replication and pathogenesis.ImportanceMost intracellular pathogens reside inside a membrane-bound vacuole within their host cell that is extensively modified by the pathogen to optimize intracellular growth and avoid host defenses. In Toxoplasma, this vacuole is modified by a host of secretory GRA proteins, many of which remain unidentified. Here we demonstrate that in vivo biotinylation of proximal and interacting proteins using the promiscuous biotin ligase BirA* is a powerful approach to rapidly identify vacuolar GRA proteins. We further demonstrate that one factor identified by this approach, GRA39, plays an important role in the ability of the parasite to replicate within its host cell and cause disease

Bounds on Quantum Correlations in Bell Inequality Experiments

Bell inequality violation is one of the most widely known manifestations of entanglement in quantum mechanics; indicating that experiments on physically separated quantum mechanical systems cannot be given a local realistic description. However, despite the importance of Bell inequalities, it is not known in general how to determine whether a given entangled state will violate a Bell inequality. This is because one can choose to make many different measurements on a quantum system to test any given Bell inequality and the optimization over measurements is a high-dimensional variational problem. In order to better understand this problem we present algorithms that provide, for a given quantum state, both a lower bound and an upper bound on the maximal expectation value of a Bell operator. Both bounds apply techniques from convex optimization and the methodology for creating upper bounds allows them to be systematically improved. In many cases these bounds determine measurements that would demonstrate violation of the Bell inequality or provide a bound that rules out the possibility of a violation. Examples are given to illustrate how these algorithms can be used to conclude definitively if some quantum states violate a given Bell inequality.Comment: 13 pages, 1 table, 2 figures. Updated version as published in PR

Non-Equilibrium Quantum Dissipation

Dissipative processes in non-equilibrium many-body systems are fundamentally different than their equilibrium counterparts. Such processes are of great importance for the understanding of relaxation in single molecule devices. As a detailed case study, we investigate here a generic spin-fermion model, where a two-level system couples to two metallic leads with different chemical potentials. We present results for the spin relaxation rate in the nonadiabatic limit for an arbitrary coupling to the leads, using both analytical and exact numerical methods. The non-equilibrium dynamics is reflected by an exponential relaxation at long times and via complex phase shifts, leading in some cases to an "anti-orthogonality" effect. In the limit of strong system-lead coupling at zero temperature we demonstrate the onset of a Marcus-like Gaussian decay with {\it voltage difference} activation. This is analogous to the equilibrium spin-boson model, where at strong coupling and high temperatures the spin excitation rate manifests temperature activated Gaussian behavior. We find that there is no simple linear relationship between the role of the temperature in the bosonic system and a voltage drop in a non-equilibrium electronic case. The two models also differ by the orthogonality-catastrophe factor existing in a fermionic system, which modifies the resulting lineshapes. Implications for current characteristics are discussed. We demonstrate the violation of pair-wise Coulomb gas behavior for strong coupling to the leads. The results presented in this paper form the basis of an exact, non-perturbative description of steady-state quantum dissipative systems

Online tools for assessing the climatology and predictability of rainfall and temperature in the Indo-Gangetic plains based on observed datasets and seasonal forecast models

Rainfall in the Northern India-Nepal-Bangladesh region is crucial for farmers, water managers and others in the region. Most precipitation falls predominantly during the south Asian summer monsoon season. The phase of El Niño-Southern Oscillation (ENSO) affects the monsoon as well as winter rainfall in some of the region, but the spring predictability barrier and weakness of ENSO-monsoon relationships lead to relatively low-to-moderate seasonal forecast skill in the region during summer. This report documents a set of tools developed to facilitate the analysis of the mean climate and the predictability of seasonal climate in the region and presents preliminary results for the summer monsoon season. These tools advance the tailoring of historical and forecast climate information for agriculture and increase the accessibility of the information via online map rooms to benefit stakeholders throughout the region