The Gut Microbiome in Neuromyelitis Optica.

Neuromyelitis optica (NMO) is a rare, disabling, sometimes fatal central nervous system inflammatory demyelinating disease that is associated with antibodies ("NMO IgG") that target the water channel protein aquaporin-4 (AQP4) expressed on astrocytes. There is considerable interest in identifying environmental triggers that may elicit production of NMO IgG by AQP4-reactive B cells. Although NMO is considered principally a humoral autoimmune disease, antibodies of NMO IgG are IgG1, a T-cell-dependent immunoglobulin subclass, indicating that AQP4-reactive T cells have a pivotal role in NMO pathogenesis. When AQP4-specific proliferative T cells were first identified in patients with NMO it was discovered that T cells recognizing the dominant AQP4 T-cell epitope exhibited a T helper 17 (Th17) phenotype and displayed cross-reactivity to a homologous peptide sequence within a protein of Clostridium perfringens, a commensal bacterium found in human gut flora. The initial analysis of gut microbiota in NMO demonstrated that, in comparison to healthy controls (HC) and patients with multiple sclerosis, the microbiome of NMO is distinct. Remarkably, C. perfringens was the second most significantly enriched taxon in NMO, and among bacteria identified at the species level, C. perfringens was the one most highly associated with NMO. Those discoveries, along with evidence that certain Clostridia in the gut can regulate the balance between regulatory T cells and Th17 cells, indicate that gut microbiota, and possibly C. perfringens itself, could participate in NMO pathogenesis. Collectively, the evidence linking microbiota to humoral and cellular immunity in NMO underscores the importance for further investigating this relationship

scRNA-seq dropouts serve as a signal for tissue heterogeneity in autism spectrum disorder

Analysis of single-cell RNA-sequencing (scRNA-seq) data is plagued by dropouts, zero counts for mRNA transcripts due to low mRNA in individual cells and inefficient mRNA capture. Dropouts are traditionally treated as an error to be corrected through normalization while performing unsupervised clustering of single cells based on highly expressed, variable transcripts. A novel algorithm, co-occurrence clustering, treats dropouts as a signal and binarizes scRNA-seq data for cell clustering, producing the same clusters as Seurat. Previous application of Seurat to single nuclear RNA-sequencing (snRNA-seq) data taken from the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) of patients with autism spectrum disorder (ASD) found no difference in clusters between brain regions. This seems at odds with literature suggesting tissue-specific emergence of co-expression networks and regional specialization in the brain. We applied co-occurrence clustering to ASD samples to parse interregional heterogeneity between the PFC and ACC and identify novel cell clusters.Undergraduat

Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4.

While it is recognized that aquaporin-4 (AQP4)-specific T cells and antibodies participate in the pathogenesis of neuromyelitis optica (NMO), a human central nervous system (CNS) autoimmune demyelinating disease, creation of an AQP4-targeted model with both clinical and histologic manifestations of CNS autoimmunity has proven challenging. Immunization of wild-type (WT) mice with AQP4 peptides elicited T cell proliferation, although those T cells could not transfer disease to naïve recipient mice. Recently, two novel AQP4 T cell epitopes, peptide (p) 135-153 and p201-220, were identified when studying immune responses to AQP4 in AQP4-deficient (AQP4-/-) mice, suggesting T cell reactivity to these epitopes is normally controlled by thymic negative selection. AQP4-/- Th17 polarized T cells primed to either p135-153 or p201-220 induced paralysis in recipient WT mice, that was associated with predominantly leptomeningeal inflammation of the spinal cord and optic nerves. Inflammation surrounding optic nerves and involvement of the inner retinal layers (IRL) were manifested by changes in serial optical coherence tomography (OCT). Here, we illustrate the approaches used to create this new in vivo model of AQP4-targeted CNS autoimmunity (ATCA), which can now be employed to study mechanisms that permit development of pathogenic AQP4-specific T cells and how they may cooperate with B cells in NMO pathogenesis

The KiHM-9: A Novel Self-Deploying PicoSat Antenna Design for Reflectarray Antennas

Reflectarray antennas are popular on satellites for their ability to achieve similar performance to parabolic antennas in a more compact volume. This project shows how integrating novel technologies achieves the benefits of larger antennas while maintaining the advantages of small satellites. The objective of this research is to create a reflectarray antenna for a holographic metasurface that utilizes the volume surrounding a CubeSat when stowed, incorporates a novel pin-less hinge, includes a self-deploying and stabilizing joint, and is manufactured out of space-grade materials. By using hinges embedded with membranes and magnets, issues with lubrication and outgassing may be avoided, and the same motion and stability of pin-joints may be maintained with no external structure required. These technologies also result in a self-deploying and self-stabilizing design. The Radii Controlled Embedded Lamina (RadiCEL) hinge design was incorporated into the final model and allows the geometry of the hinge joint to be specifically tuned to control the stress in the hinge membrane while minimizing required hinge volume. Metal meshes were used as membrane joints, increasing the durability and robustness of the hinge. Feasibility of the RadiCEL joint is shown through fatigue testing of various materials at a range of hinge radii. The testing shows the viability of metal meshes, as well as other common membranes. Magnets were used in a MaLO configuration, which allowed for a smaller footprint in the antenna and required no external actuation or power source to deploy and stabilize the antenna. Various prototypes of the system were manufactured and are presented. Modeling and testing efforts presented create various opportunities to build on current research to improve mission capability by increasing antenna gain while eliminating peripherals required for antenna deployment

Cost Estimates for the KPipe Experiment

We present estimates for the cost of the KPipe experiment. Excluding the cost of civil engineering, the total cost comes to 4.6 million USD. This report supports statements in arXiv article 1506.05811

Land Use and Habitat Conditions Across the Southwestern Wyoming Sagebrush Steppe: Development Impacts, Management Effectiveness and the Distribution of Invasive Plants

For the past several years, USGS has taken a multi-faceted approach to investigating the condition and trends in sagebrush steppe ecosystems. This recent effort builds upon decades of work in semi-arid ecosystems providing a specific, applied focus on the cumulative impacts of expanding human activities across these landscapes. Here, we discuss several on-going projects contributing to these efforts: (1) mapping and monitoring the distribution and condition of shrub steppe communities with local detail at a regional scale, (2) assessing the relationships between specific, land-use features (for example, roads, transmission lines, industrial pads) and invasive plants, including their potential (environmentally defined) distribution across the region, and (3) monitoring the effects of habitat treatments on the ecosystem, including wildlife use and invasive plant abundance. This research is focused on the northern sagebrush steppe, primarily in Wyoming, but also extending into Montana, Colorado, Utah and Idaho. The study area includes a range of sagebrush types (including, Artemisia tridentata ssp. tridentata, Artemisia tridentata ssp. wyomingensis, Artemisia tridentata ssp. vaseyana, Artemisia nova) and other semi-arid shrubland types (for example, Sarcobatus vermiculatus, Atriplex confertifolia, Atriplex gardneri), impacted by extensive interface between steppe ecosystems and industrial energy activities resulting in a revealing multiple-variable analysis. We use a combination of remote sensing (AWiFS (1 Any reference to platforms, data sources, equipment, software, patented or trade-marked methods is for information purposes only. It does not represent endorsement of the U.S.D.I., U.S.G.S. or the authors), Landsat and Quickbird platforms), Geographic Information System (GIS) design and data management, and field-based, replicated sampling to generate multiple scales of data representing the distribution of shrub communities for the habitat inventory. Invasive plant sampling focused on the interaction between human infrastructure and weedy plant distributions in southwestern Wyoming, while also capturing spatial variability associated with growing conditions and management across the region. In a separate but linked study, we also sampled native and invasive composition of recent and historic habitat treatments. Here, we summarize findings of this ongoing work, highlighting patterns and relationships between vegetation (native and invasive), land cover, landform, and land-use patterns in the sagebrush steppe