New frontiers in translational research: Touchscreens, open science, and the mouse translational research accelerator platform

© 2020 International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd Many neurodegenerative and neuropsychiatric diseases and other brain disorders are accompanied by impairments in high-level cognitive functions including memory, attention, motivation, and decision-making. Despite several decades of extensive research, neuroscience is little closer to discovering new treatments. Key impediments include the absence of validated and robust cognitive assessment tools for facilitating translation from animal models to humans. In this review, we describe a state-of-the-art platform poised to overcome these impediments and improve the success of translational research, the Mouse Translational Research Accelerator Platform (MouseTRAP), which is centered on the touchscreen cognitive testing system for rodents. It integrates touchscreen-based tests of high-level cognitive assessment with state-of-the art neurotechnology to record and manipulate molecular and circuit level activity in vivo in animal models during human-relevant cognitive performance. The platform also is integrated with two Open Science platforms designed to facilitate knowledge and data-sharing practices within the rodent touchscreen community, touchscreencognition.org and mousebytes.ca. Touchscreencognition.org includes the Wall, showcasing touchscreen news and publications, the Forum, for community discussion, and Training, which includes courses, videos, SOPs, and symposia. To get started, interested researchers simply create user accounts. We describe the origins of the touchscreen testing system, the novel lines of research it has facilitated, and its increasingly widespread use in translational research, which is attributable in part to knowledge-sharing efforts over the past decade. We then identify the unique features of MouseTRAP that stand to potentially revolutionize translational research, and describe new initiatives to partner with similar platforms such as McGill\u27s M3 platform (m3platform.org)

Improved adaptability of PEEK by Nb doped graphite-like carbon composite coatings for bio-tribological applications

Polyaryl-ether-ether-ketone (PEEK), an alternative to metal alloys in prosthesis implants, suffers from insufficient elasticity and biocompatibility, and generates wear particulates initiating the destructive osteolysis process. In this study coating the implant with Nb containing graphite-like carbon (GLC) film is performed using the closed field unbalanced magnetron sputtering system, the as-deposited Nb/GLC film is uniform and smooth. The mechanical assessment shows that Nb/GLC film has the strongly adhesive strength and good matching compliance to the flexible PEEK substrates. Especially, the use of GLC film not only effectively reduced the wear-generated debris in simulated body fluids but also exhibited excellently low friction character, as well as the lowest wear of the counterpart. Furthermore, Nb/GLC matrix greatly improved the biocompatibility and osteogenesis of PEEK by the indication of the excellent adherent attachment, proliferation and differentiation of L-929 fibroblast-like cell

Tribological properties of si-doped graphite-like amorphous carbon film of PEEK rubbing with different counterparts in SBF medium

The present investigation has been conducted in order to evaluate the friction and wear behaviors of polyaryl-ether-ether-ketone coated with a Si/GLC film sliding against 100Cr6 steel, Al2O3 and Si3N4 balls in a biological medium of simulated body fluid, using the ball-on-disk tribological tests. The test results show that the wear volume loss of the rubbing pairs is two orders of magnitude greater than that determined for the tribo-pairs in SBF lubrication, coefficient of friction decreases by 50% at least, as compared to that in dry conditions. The friction coefficient showed the same varied trend with Hertzian contact radius. The wear rate showed the inverse varied trend with the contact pressure. The interfacial tribochemically reacted with moisture available in SBF medium plays an effect role of the difference in the wearresistant and lubricating behavior. Furthermore, some indexes including hardness ratio of pair and film were employed to predict the wear behavior of GLC composite films sliding against different counterparts. The Si/GLC nanocomposite films would be a new kind of promising materials applied to artificial heart valves and stents

Cerebellar modulation of anxiety: serotonergic involvement examined via a new 5-HT sensor

Cerebellar involvement in anxiety and anxiety-related behavior is supported by numerous clinical and animal studies (Behav. Brain Res. 112:107). Because the neuromodulator serotonin (5-HT) is well-known to play a role in anxiety (Nature 537:97) and serotonergic axons are amongst the most abundant fibers in the cerebellar cortex (Neuroscience 462:106), we determined whether cerebellar 5-HT is involved in anxiety. We first identified a locus for anxiety within the mouse cerebellum. We found that photostimulation of lobule VII in transgenic mice expressing channelrhodopsin in molecular layer interneurons (Cell Rep. 7:1601) caused a 67% decrease in time spent in the open quadrants of an elevated-zero maze (EZM; n = 8), indicating an anxiogenic effect. This is consistent with a previous observation that inhibiting lobule VII interneurons decreases anxiety (eLife 7: e36401) and indicates that lobule VII output is important for anxiety. To measure 5-HT levels in lobule VII, we expressed a novel fluorescent 5-HT indicator (GRAB5HT2h) with improved sensitivity to 5-HT compared to previous sensors (Nat. Neurosci. 24:746). GRAB5HT2h fiber photometry revealed higher 5-HT levels when mice were in open quadrants of the EZM, compared to the closed quadrants, indicating that 5-HT is higher during a low-anxiety state. To determine whether 5-HT levels affect anxiety, we optogenetically controlled the activity of serotonergic axons in lobule VII of a transgenic mouse line expressing channelrhodopsin or archaerhodopsin in serotonergic neurons (PNAS 102:16472). Photostimulation of 5-HT fibers caused a 106% increase in the amount of time spent in open quadrants of the EZM (n = 8), indicating an anxiolytic effect. Conversely, photoinhibition of 5-HT fibers produced an 81% decrease in the time spent in the open quadrants (n = 4), indicating an anxiogenic effect. Collectively, these results support the hypothesis that 5-HT levels in cerebellar lobule VII regulate anxiety, with higher 5-HT reducing anxiety.Ministry of Education (MOE)Grant/Other Support: : Ministry of Education, Singapore, MOE AcRF Tier 3 Award MOE2017-T3-1-002, MOE AcRF Tier 2 Award MOE2016-T2-1-097 and Interdisciplinary Graduate School bench fees

Effects of Dodonaea viscosa Afforestation on Soil Nutrients and Aggregate Stability in Karst Graben Basin

Dodonaea viscosa is widely cultivated in the karst graben basin and is crucial for recovering land after rocky desertification. However, the effect of long–time D. viscosa afforestation on changes in the quality of soil remains unclear. Soil nutrients and aggregate composition can be used to evaluate the beneficial effects of afforestation of D. viscosa in improving soil functional stability. In this study, soil nutrients and aggregate stability were investigated using cropland, 10–year, 20–year, and 40–year D. viscosa afforestation and secondary succession shrub. Compared to the cropland, D. viscosa afforestation significantly increased the soil water content (WC), soil organic carbon (SOC), and total nitrogen (TN) contents, with an enhanced effect observed with prolonged afforestation. Soil nutrient contents under D. viscosa afforestation rapidly reached the level of the shrub. Dodonaea viscosa afforestation promoted the formation of >2 mm aggregates and decreased the ratio of 0.053–0.25 mm aggregates, which varied with afforestation years. Compared to the cropland, the content of >0.25 mm water–stable aggregates (R>0.25), mean weight diameter (MWD), and geometric mean weight diameter (GMD) of soil increased exponentially. However, soil erodibility factor (K) and unstable aggregates index (EIt) decreased exponentially with prolonged D. viscosa afforestation, and the latter two indicators did not reach the level of the shrub. These results indicated that soil nutrients, aggregate stability, and erosion resistance increased with prolonged D. viscosa afforestation. However, the aggregate stability and erosion resistance exhibited by D. viscosa could not reach the level of secondary shrub for a long time

Genome-Wide Constitutively Expressed Gene Analysis and New Reference Gene Selection Based on Transcriptome Data: A Case Study from Poplar/Canker Disease Interaction

A number of transcriptome datasets for differential expression (DE) genes have been widely used for understanding organismal biology, but these datasets also contain untapped information that can be used to develop more precise analytical tools. With the use of transcriptome data generated from poplar/canker disease interaction system, we describe a methodology to identify candidate reference genes from high-throughput sequencing data. This methodology will improve the accuracy of RT-qPCR and will lead to better standards for the normalization of expression data. Expression stability analysis from xylem and phloem of Populus bejingensis inoculated with the fungal canker pathogen Botryosphaeria dothidea revealed that 729 poplar transcripts (1.11%) were stably expressed, at a threshold level of coefficient of variance (CV) of FPKM < 20% and maximum fold change (MFC) of FPKM < 2.0. Expression stability and bioinformatics analysis suggested that commonly used house-keeping (HK) genes were not the most appropriate internal controls: 70 of the 72 commonly used HK genes were not stably expressed, 45 of the 72 produced multiple isoform transcripts, and some of their reported primers produced unspecific amplicons in PCR amplification. RT-qPCR analysis to compare and evaluate the expression stability of 10 commonly used poplar HK genes and 20 of the 729 newly-identified stably expressed transcripts showed that some of the newly-identified genes (such as SSU_S8e, LSU_L5e, and 20S_PSU) had higher stability ranking than most of commonly used HK genes. Based on these results, we recommend a pipeline for deriving reference genes from transcriptome data. An appropriate candidate gene should have a unique transcript, constitutive expression, CV value of expression < 20% (or possibly 30%) and MFC value of expression <2, and an expression level of 50–1,000 units. Lastly, when four of the newly identified HK genes were used in the normalization of expression data for 20 differential expressed genes, expression analysis gave similar values to Cufflinks output. The methods described here provide an alternative pathway for the normalization of transcriptome data, a process that is essential for integrating analyses of transcriptome data across environments, laboratories, sequencing platforms, and species

Alterations of ileal mucosa-associated microbiota in hypercholesterolemia patients

Many metabolic diseases have been demonstrated to be associated with changes in the microbiome. However, no studies have yet been conducted to examine the characteristics of the mucosal microbiota of patients with hypercholesterolemia. We aimed to examine mucosa-associated microbiota in subjects with hypercholesterolemia. We conducted a case-control study, in which ileal mucosal samples were collected from 13 hypercholesterolemia patients and 13 controls for 16S rRNA gene sequencing. There were differences in the composition of ileal mucosal microbiota based on beta diversity between the hypercholesterolemia and control groups (P < 0.05). Compared with the control group, the phylum Bacteroidetes and the genera Bacteroides, Butyricicoccus, Parasutterella, Candidatus_Soleaferrea, and norank_f__norank_o__Izemoplasmatales were less abundant in the hypercholesterolemia group (P < 0.05), while the genus Anaerovibrio was enriched in the hypercholesterolemia group (P < 0.05). The relative abundance of Bacteroides was negatively correlated with total cholesterol and low-density lipoprotein cholesterol (P < 0.01). The relative abundance of Coprococcus was negatively correlated with triglycerides and body mass index (all P < 0.05). PICRUSt functional prediction analysis showed that pathways related to Glycerophospholipid metabolism, ABC transporters, Phosphotransferase system, and Biofilm formation - Escherichia coli, and infectious diseases of pathogenic Escherichia coli were enriched in the hypercholesterolemia group. This work suggests a potential role of ileal mucosal microbiota in the development of hypercholesterolemia