A population model of deep brain stimulation in movement disorders from circuits to cells

Copyright © 2020 Yousif, Bain, Nandi and Borisyuk.For more than 30 years, deep brain stimulation (DBS) has been used to target the symptoms of a number of neurological disorders and in particular movement disorders such as Parkinson's disease (PD) and essential tremor (ET). It is known that the loss of dopaminergic neurons in the substantia nigra leads to PD, while the exact impact of this on the brain dynamics is not fully understood, the presence of beta-band oscillatory activity is thought to be pathological. The cause of ET, however, remains uncertain, however pathological oscillations in the thalamocortical-cerebellar network have been linked to tremor. Both of these movement disorders are treated with DBS, which entails the surgical implantation of electrodes into a patient's brain. While DBS leads to an improvement in symptoms for many patients, the mechanisms underlying this improvement is not clearly understood, and computational modeling has been used extensively to improve this. Many of the models used to study DBS and its effect on the human brain have mainly utilized single neuron and single axon biophysical models. We have previously shown in separate models however, that the use of population models can shed much light on the mechanisms of the underlying pathological neural activity in PD and ET in turn, and on the mechanisms underlying DBS. Together, this work suggested that the dynamics of the cerebellar-basal ganglia thalamocortical network support oscillations at frequency range relevant to movement disorders. Here, we propose a new combined model of this network and present new results that demonstrate that both Parkinsonian oscillations in the beta band and oscillations in the tremor frequency range arise from the dynamics of such a network. We find regions in the parameter space demonstrating the different dynamics and go on to examine the transition from one oscillatory regime to another as well as the impact of DBS on these different types of pathological activity. This work will allow us to better understand the changes in brain activity induced by DBS, and allow us to optimize this clinical therapy, particularly in terms of target selection and parameter setting.Peer reviewe

Integrated dataset on acute phase protein response in chicken challenged with Escherichia coli lipopolysaccharide endotoxin

Data herein describe the quantitative changes in the plasma proteome in chickens challenged with lipopolysaccharide (LPS), a bacterial endotoxin known to stimulate the host innate immune system obtained by shotgun quantitative proteomic tandem mass tags approach using high-resolution Orbitrap technology. Statistical and bioinformatic analyses were performed to specify the effect of bacterial endotoxin. Plasma from chicken (N=6) challenged with Escherichia coli (LPS) (2 mg/kg body weight) was collected pre (0 h) and at 12, 24, 48, and 72 h post injection along with plasma from a control group (N=6) challenged with sterile saline. Protein identification and relative quantification were performed using Proteome Discoverer, and data were analysed using R. Gene Ontology terms were analysed by the Cytoscape application ClueGO based on Gallus gallus GO Biological Process database, and refined by REVIGO. Absolute quantification of several acute phase proteins, e.g. alpha-1-acid glycoprotein (AGP), serum amyloid A (SAA) and ovotrensferrin (OVT) was performed by immunoassays to validate the LC-MS results. The data contained within this article are directly related to our research article”Quantitative proteomics using tandem mass tags in relation to the acute phase protein response in chicken challenged with Escherichia coli lipopolysaccharide endotoxin” [1]. The raw mass spectrometric data generated in this study were deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD009399 (http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD009399)

Aspects of Transit Map Design

A printed transit system map is a specific representation of a transportation network, typically covering an entire urban area. In comparison to interactive guides offered by services such as Google, such a transit system map is subject to limitations of scale and range of information for users. Transit maps from London, New York, and Paris show evidence of consensus by designers and map publishers on what information is required and how to graphically convey it. Indications of streets and surface geography show some divergence and reveal conceptions of local identity and wayfinding. In addition to their functional role subway or metro system maps have attracted attention as design artifacts. The design approach taken by Henry Beck and later adapted by Massimo Vignelli restricted the complex reality of transit lines to a limited number of angles. Advocates for network maps based on this technique claim greater understanding by users. Writers of books on transit have been gathering rules of thumb and formulating design guidelines. Separately, design guidelines for bus system maps have been produced. Both these guidelines and individual maps produced by transit map publishers are good candidates for further investigation concerning the user-centered design process. Given the growing use of interactive itineraries and other tools, the role of printed maps should be evaluated from the perspective of a diverse group of users. These users benefit from public information systems and should not be forced to adopt unnecessary technology

Typocurious, and how to stay that way

Introductory notes with a bibliography, aimed at students and professionals seeking to learn more about typographic design. Published as part of a series of directories to independently created digital typefaces

Design for Conspicuous Transit

My creative project explores design for transit advocacy; aimed at shifting a car-dependent society into one where transit helps meet climate change, energy, and land-use challenges. It incorporates my research into aspects of designing for transit, an understanding of urbanism in Richmond and New York, and an appreciation of planning

Identification of putative nuclear receptors and steroidogenic enzymes in Murray-Darling rainbowfish (Melanotaenia fluviatilis) using RNA-Seq and de novo transcriptome assembly

Murray-Darling rainbowfish (Melanotaenia fluviatilis [Castelnau, 1878]; Atheriniformes: Melanotaeniidae) is a small-bodied teleost currently under development in Australasia as a test species for aquatic toxicological studies. To date, efforts towards the development of molecular biomarkers of contaminant exposure have been hindered by the lack of available sequence data. To address this, we sequenced messenger RNA from brain, liver and gonads of mature male and female fish and generated a high-quality draft transcriptome using a de novo assembly approach. 149,742 clusters of putative transcripts were obtained, encompassing 43,841 non-redundant protein-coding regions. Deduced amino acid sequences were annotated by functional inference based on similarity with sequences from manually curated protein sequence databases. The draft assembly contained protein-coding regions homologous to 95.7% of the complete cohort of predicted proteins from the taxonomically related species, Oryzias latipes (Japanese medaka). The mean length of rainbowfish protein-coding sequences relative to their medaka homologues was 92.1%, indicating that despite the limited number of tissues sampled a large proportion of the total expected number of protein-coding genes was captured in the study. Because of our interest in the effects of environmental contaminants on endocrine pathways, we manually curated subsets of coding regions for putative nuclear receptors and steroidogenic enzymes in the rainbowfish transcriptome, revealing 61 candidate nuclear receptors encompassing all known subfamilies, and 41 putative steroidogenic enzymes representing all major steroidogenic enzymes occurring in teleosts. The transcriptome presented here will be a valuable resource for researchers interested in biomarker development, protein structure and function, and contaminant-response genomics in Murray-Darling rainbowfish

Acute phase proteins and stress markers in the immediate response to a combined vaccination against Newcastle disease and infectious bronchitis viruses in specific pathogen free (SPF) layer chicks

Vaccination is an important tool in poultry health, but is itself a stressor often resulting in a reduction in feed intake, body weight gain, and nutrient digestibility. In other species, vaccination is associated with an immediate acute-phase response. As an important immune parameter, the circulating heterophil/lymphocyte (H/L) ratio is a well-recognized parameter of stress in poultry. In this study, the effects of a routinely used commercial poultry vaccine on the acute phase response (APR) and H/L ratios in specific pathogen-free (SPF) layer chicks was examined to determine if post vaccination (PV) stress and an APR occur. A combined Newcastle disease and infectious bronchitis vaccine (Nobalis Ma5+Clone 30) was administered to SPF chicks by the intraocular route at age 7 d. Acute phase proteins (APP), alpha-1 acid glycoprotein (AGP) and serum amyloid A (SAA) were measured by enzyme-linked immunosorbent assays at d 0 (pre-vaccination) and d 0.5, 1, 2, 3, 4, 5, 6, and 21 PV. Stress was determined in the chicks by measurement of the H/L ratio. The immune response to the vaccine was estimated by measurement of the antibody (IgY) response to the vaccine at d 21. The antibody titer was significantly (P < 0.05) higher in the vaccinated group at 21 d PV, confirming stimulation of the immune system. The H/L ratio was also significantly higher in the vaccinated group at 1 to 2 d (P < 0.01) and at 3 d (P < 0.05) PV. The concentration of SAA increased by 2.8-fold, from 63.7 μg/mL in controls to 181 μg/mL in the vaccinated group, (P < 0.05) at 1 d PV. AGP increased 1.6-fold at 2 d PV, (from 0.75 g/mL in the control group to 1.24 g/mL in the vaccinated group, P < 0.05). In conclusion an immediate but mild APR occurred in the chicks following intraocular vaccination, whereas the stress response as measured by H/L ratio seemed to be more specific and sensitive. Measurement of these biomarkers of the host response could be a tool in vaccine development

Apprenticeship standard: Building Services Engineering Service and Maintenance Engineer

Differential abundance analysis results, functional annotations and putative descriptions of transcripts passing the minimum abundance threshold. (XLSX 2717 kb

Magnetic nanostructures by adaptive twinning in strained epitaxial films

We exploit the intrinsic structural instability of the Fe70Pd30 magnetic shape memory alloy to obtain functional epitaxial films exhibiting a self-organized nanostructure. We demonstrate that coherent epitaxial straining by 54% is possible. The combination of thin film experiments and large-scale first-principles calculations enables us to establish a lattice relaxation mechanism, which is not expected for stable materials. We identify a low twin boundary energy compared to a high elastic energy as key prerequisite for the adaptive nanotwinning. Our approach is versatile as it allows to control both, nanostructure and intrinsic properties for ferromagnetic, ferroelastic and ferroelectric materials.Comment: Final version. Supplementary information available on request or at the publisher's websit