Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation.

Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. Two glycoproteins coordinate the infection of host cells, an attachment protein (G), which binds to cell surface receptors, and a fusion (F) protein, which carries out the process of virus-cell membrane fusion. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding. Using an optical approach based on second harmonic generation, we show that monomeric and dimeric receptors activate distinct conformational changes in G. The monomeric receptor-induced changes are not detected by conformation-sensitive monoclonal antibodies or through electron microscopy analysis of G:ephrinB2 complexes. However, hydrogen/deuterium exchange experiments confirm the second harmonic generation observations and reveal allosteric changes in the G receptor binding and F-activating stalk domains, providing insights into the pathway of receptor-activated virus entry.Nipah virus causes encephalitis in humans. Here the authors use a multidisciplinary approach to study the binding of the viral attachment protein G to its host receptor ephrinB2 and show that monomeric and dimeric receptors activate distinct conformational changes in G and discuss implications for receptor-activated virus entry

Transcriptomics of CD29+/CD44+ cells isolated from hPSC retinal organoids reveals a single cell population with retinal progenitor and Müller glia characteristics

Müller glia play very important and diverse roles in retinal homeostasis and disease. Although much is known of the physiological and morphological properties of mammalian Müller glia, there is still the need to further understand the profile of these cells during human retinal development. Using human embryonic stem cell-derived retinal organoids, we investigated the transcriptomic profiles of CD29+/CD44+ cells isolated from early and late stages of organoid development. Data showed that these cells express classic markers of retinal progenitors and Müller glia, including NFIX, RAX, PAX6, VSX2, HES1, WNT2B, SOX, NR2F1/2, ASCL1 and VIM, as early as days 10-20 after initiation of retinal differentiation. Expression of genes upregulated in CD29+/CD44+ cells isolated at later stages of organoid development (days 50-90), including NEUROG1, VSX2 and ASCL1 were gradually increased as retinal organoid maturation progressed. Based on the current observations that CD24+/CD44+ cells share the characteristics of early and late-stage retinal progenitors as well as of mature Müller glia, we propose that these cells constitute a single cell population that upon exposure to developmental cues regulates its gene expression to adapt to functions exerted by Müller glia in the postnatal and mature retina

Embedded Machine-Learning For Variable-Rate Fertiliser Systems: A Model-Driven Approach To Precision Agriculture

Efficient use of fertilisers, in particular the use of Nitrogen (N), is one of the rate-limiting factors in meeting global food production requirements. While N is a key driver in increasing crop yields, overuse can also lead to negative environmental and health impacts. It has been suggested that Variable-Rate Fertiliser (VRF) techniques may help to reduce excessive N applications. VRF seeks to spatially vary fertiliser input based on estimated crop requirements, however a major challenge in the operational deployment of VRF systems is the automated processing of large amounts of sensor data in real-time. Machine Learning (ML) algorithms have shown promise in their ability to process these large, high-velocity data streams, and to produce accurate predictions. The newly developed Fuzzy Boxes (FB) algorithm has been designed with VRF applications in mind, however no publicly available software implementation currently exists. Therefore, development of a prototype implementation of FB forms a component of this work. This thesis will also employ a Hardware-in-the-Loop (HWIL) testing methodology using a potential target device in order to simulate a real-world VRF deployment environment. By using this environment simulation, two existing ML algorithms (Artificial Neural Network (ANN) and Support Vector Machine (SVM)) can be compared against the prototype implementation of FB for applicability to VRF applications. It will be shown that all tested algorithms could potentially be suitable for high-speed VRF when measured on prediction time and various accuracy metrics. All algorithms achieved higher than 84.5% accuracy, with FB20 reaching 87.21%. Prediction times were highly varied; the fastest average predictor was an ANN (16.64μs), while the slowest was FB20(502.77μs). All average prediction times were fast enough to achieve a spatial resolution of 31 mm when operating at 60 m/s, making all tested algorithms fast enough predictors for VRF applications

Cell-Based Therapies for Glaucoma

Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of GON are retinal ganglion cell (RGC) degeneration and characteristic cupping of the optic nerve head (ONH) due to tissue remodeling, while intraocular pressure remains the only modifiable GON risk factor currently targeted by approved clinical treatment strategies. Efforts to understand the mechanisms that allow species such as the zebrafish to regenerate their retinal cells have greatly increased our understanding of regenerative signaling pathways. However, proper integration within the retina and projection to the brain by the newly regenerated neuronal cells remain major hurdles. Meanwhile, a range of methods for in vitro differentiation have been developed to derive retinal cells from a variety of cell sources, including embryonic and induced pluripotent stem cells. More recently, there has been growing interest in the implantation of glial cells as well as cell-derived products, including neurotrophins, microRNA, and extracellular vesicles, to provide functional support to vulnerable structures such as RGC axons and the ONH. These approaches offer the advantage of not relying upon the replacement of degenerated cells and potentially targeting earlier stages of disease pathogenesis. In order to translate these techniques into clinical practice, appropriate cell sourcing, robust differentiation protocols, and accurate implantation methods are crucial to the success of cell-based therapy in glaucoma. Translational Relevance: Cell-based therapies for glaucoma currently under active development include the induction of endogenous regeneration, implantation of exogenously derived retinal cells, and utilization of cell-derived products to provide functional support

Fate of the lower extremity in patients with VA-ECMO via femoral cannulation

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a salvage therapy in patients with severe cardiopulmonary failure. Femoral cannulation is associated with limb complications including ischemia, limb loss, arterial infections and wound infections. This study aims to evaluate these complications and management related to successful outcomes. Methods: A retrospective review was conducted in 17 patients requiring VA- ECMO support via femoral cannulation from 1/ 2010 till 4/2012. After cannulation, all patients had near infared spectroscopy (NIRS) monitoring after cannula placement and most had placement of distal arterial perfusion catheters (DPC). At decannulation, all patients had femoral cutdown with closure of arteriotomies by primary repair or patch angioplasty with bovine pericardium. Primary study endpoints included ischemia, limb loss, arterial infection; secondary endpoints were wound infection and post-discharge symptoms. Results: Seventeen patients were supported with VA-ECMO during the study period with arterial cannula size of 16-20 French. All patients had NIRS monitoring after cannula placement and 13/17 patients had DPC placement, with no subsequent ischemia. Two of 4 patients without DPC developed ischemia; one was decannulated and the other resolved spontaneously. At decannulation, open arterial repair was performed as described. In this study population, simple wound infection occurred in 3/17with Vacuum Assisted Closure (VAC) devices were placed at the timed if appropriate. There were no arterial infections and no instances of limb ischemia requiring amputation. There were no complaints of rest pain during outpatient follow-up. Conclusions: Limb complications related to femoral cannulation for VA-ECMO can lead to prolonged morbidity and limb loss. NIRS and placement of DPC, primary repair of arteriotomy or patch angioplasty, along with aggressive wound care, can dramatically decrease rates of limb ischemia, limb loss and infection

ROSIsat

As the cost of sending satellites into space continues to drive down, the use of CubeSats for orbital missions continues to rise. Even though these satellites are smaller than traditional satellites, they still provide the ability to take on important science-based missions at a fraction of the cost. The Radiation Orbital Shielding Investigation satellite (ROSIsat) otherwise known as Project Hermes, will be the first student-built satellite for Embry-Riddle’s Daytona Beach campus. The main research mission of Project Hermes consists of shielding onboard flight computer memory modules from space radiation using various materials and substances. These materials include simulated Martian and Lunar regolith. To send a student-built CubeSat to space, the Hermes team is designing and integrating the majority of the satellite’s components in-house. These in-house components include the CubeSat’s electronics system, avionics, payload bay, and magnetorquer. Project Hermes will provide students with educational, technical, scientific, and legal knowledge that can be applied in their respective futures

Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases.

Using expression profiles from postmortem prefrontal cortex samples of 624 dementia patients and non-demented controls, we investigated global disruptions in the co-regulation of genes in two neurodegenerative diseases, late-onset Alzheimer's disease (AD) and Huntington's disease (HD). We identified networks of differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242-gene subnetwork enriched for independent AD/HD signatures. This subnetwork revealed a surprising dichotomy of gained/lost correlations among two inter-connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases, DNMT1 and DNMT3A, of which we predicted the former but not latter as a key regulator. To validate the inter-connection of these two processes and our key regulator prediction, we generated two brain-specific knockout (KO) mice and show that Dnmt1 KO signature significantly overlaps with the subnetwork (P = 3.1 × 10(-12)), while Dnmt3a KO signature does not (P = 0.017)