Inhibition of type I interferon induction and signalling by mosquito-borne flaviviruses

The Flavivirus genus (Flaviviridae family) contains a number of important human pathogens, including dengue and Zika viruses, which have the potential to cause severe disease. In order to efficiently establish a productive infection in mammalian cells, flaviviruses have developed key strategies to counteract host immune defences, including the type I interferon response. They employ different mechanisms to control interferon signal transduction and effector pathways, and key research generated over the past couple of decades has uncovered new insights into their abilities to actively decrease interferon antiviral activity. Given the lack of antivirals or prophylactic treatments for many flaviviral infections, it is important to fully understand how these viruses affect cellular processes to influence pathogenesis and disease outcome. This review will discuss the strategies mosquito-borne flaviviruses have evolved to antagonise type I interferon mediated immune responses

Checked Out: How U.S. Supermarkets Fail to Make the Grade in Reducing Food Waste

Supermarkets have an enormous influence on the food system. That influence extends to the environmental footprint of food waste — from farm to fork. As the primary place where most Americans purchase food, supermarkets influence what makes it from farms to shelves, what happens to unsold food and even how much and what types of food shoppers buy (Escaron, A. 2013). Food waste has become a critical issue in recent decades. Roughly 40 percent of the food produced in the United States goes uneaten — costing more than $200 billion each year and creating unnecessary impacts on water supplies, clean air, climate and wildlife (ReFED, 2016). This report analyzes key food-waste reduction commitments, policies and actions across the top supermarket chains in the United States. Using publicly available information and details provided by company officials, we evaluated and graded 10 companies — Ahold Delhaize, Albertsons, ALDI, Costco, Kroger, Publix, Target, Trader Joe's, Walmart and Whole Foods Market — that operate a combined total of more than 13,000 grocery stores across the country. The analysis was also applied to Tesco U.K. as an example of a major European supermarket that has adopted effective food-waste reduction policies.Our key findings:Nine out of America's 10 largest grocery companies fail to publicly report their total volume of food waste. Ahold Delhaize was the only company that publicly reported its total food-waste volume.The four companies that earned a C grade or higher overall were the only ones with specific food-waste reduction commitments. Kroger leads the way with a commitment of zero food waste by 2025.Four of the 10 companies have no "imperfect-produce initiatives," which can prevent the waste of fruits and vegetables considered too "imperfect" for retail sale.Walmart was the only company with a variety of clear in-store efforts to reduce food waste, such as improving store fixtures, standardizing date labels, and educating associates and shoppers.All 10 of the companies have food-donation programs, with the majority operating company-wide. ALDI was the only company that did not report a food-recycling program (e.g., composting or a program to reuse unsold food as animal feed or for other industrial uses)

Oligotyping reveals stronger relationship of organic soil bacterial community structure with N-amendments and soil chemistry in comparison to that of mineral soil at Harvard Forest, MA, USA

The impact of chronic nitrogen amendments on bacterial communities was evaluated at Harvard Forest, Petersham, MA, USA. Thirty soil samples (3 treatments × 2 soil horizons × 5 subplots) were collected in 2009 from untreated (control), low nitrogen-amended (LN; 50 kg NH4NO3 ha-1 yr-1) and high nitrogen-amended (HN; 150 kg NH4NO3 ha-1 yr-1) plots. PCR-amplified partial 16S rRNA gene sequences made from soil DNA were subjected to pyrosequencing (Turlapati et al., 2013) and analyses using oligotyping. The parameters M (the minimum count of the most abundant unique sequence in an oligotype) and s (the minimum number of samples in which an oligotype is expected to be present) had to be optimized for forest soils because of high diversity and the presence of rare organisms. Comparative analyses of the pyrosequencing data by oligotyping and operational taxonomic unit clustering tools indicated that the former yields more refined units of taxonomy with sequence similarity of ≥99.5%. Sequences affiliated with four new phyla and 73 genera were identified in the present study as compared to 27 genera reported earlier from the same data (Turlapati et al., 2013). Significant rearrangements in the bacterial community structure were observed with N-amendments revealing the presence of additional genera in N-amended plots with the absence of some that were present in the control plots. Permutational MANOVA analyses indicated significant variation associated with soil horizon and N treatment for a majority of the phyla. In most cases soil horizon partitioned more variation relative to treatment and treatment effects were more evident for the organic (Org) horizon. Mantel test results for Org soil showed significant positive correlations between bacterial communities and most soil parameters including NH4 and NO3. In mineral soil, correlations were seen only with pH, NH4, and NO3. Regardless of the pipeline used, a major hindrance for such a study remains to be the lack of reference databases for forest soils

The Time Has Come...To Build, Reflect, and Analyze Connections Between Qualitative and Quantitative Data

This poster will address the development process of a qualitative evaluation tool to aid in the thorough analysis of library resources at the University of Maryland. Specifically, our project looks at the use and added value of this tool for the building, reflecting, and analyzing connections between qualitative and quantitative data. This will allow for more meaningful justifications of budgetary decisions than compared to cost and use metrics alone. Given the necessity for meticulous review of continuing resources, our project addresses a request for enhanced transparency from the university faculty and library oversight body and serves as a useful tool for accountability and justification of impactful decisions for stakeholders internally and externally. We will discuss the extant literature and the need for this type of tool, the development process including the output planning and data input format, the initial reception of the project, and future goals and planning for our initial usag

Temporal and Spatial Variation of Nitrogen in Wyoming Big Sagebrush

Sagebrush steppe systems represent one of North America’s greatest conservation challenges. Shrinking habitat and declining animal populations have prompted researchers to fill gaps in our understanding of the ecology of this system, particularly at a scale relevant to individual animals. What animals eat and why are fundamental questions linked to habitat quality and use. We investigated the temporal and spatial heterogeneity of the dietary quality of food to better understand habitat use by a sagebrush specialist, the pygmy rabbit (Brachylagus idahoensis). Within a foraging patch, pygmy rabbits selectively browse on individual Wyoming big sagebrush (Artemisia tridentata wyomingensis) that are high in nitrogen. Therefore, we hypothesized that variation in nitrogen would influence habitat use by pygmy rabbits at the patch scale. As a first step to test this hypothesis, we investigated the temporal and spatial variation in nitrogen content of patches of sagebrush within a study site in southcentral Idaho. Nitrogen concentration was determined using the Kjeldahl method. We used multivariate analysis of variance to test for differences in nitrogen content among three months within the winter season (November, January, and March) and between patches of sagebrush on mounds with deeper soils where pygmy rabbits burrow (on-mound) versus patches of sagebrush in shallower soils adjacent to mounds (off-mound). We found that nitrogen content of sagebrush was temporally and spatially dynamic. For both on- and off-mound plants, nitrogen content was significantly higher in March than November. Regardless of season, nitrogen content was significantly higher in plants on mounds compared to off-mound plants. Understanding the phenology and spatial heterogeneity of nitrogen content will help ecologists better assess diet quality and habitat quality within and among landscapes and seasons. Moreover, effective management and restoration efforts of sagebrush depend upon understanding patterns in nutrient availability to pygmy rabbits and other sagebrush specialists

The Use of a Quantitative Fusion Assay to Evaluate HN–Receptor Interaction for Human Parainfluenza Virus Type 3

AbstractSialic acid is the receptor determinant for the human parainfluenza virus type 3 (HPF3) hemagglutinin–neuraminidase (HN) glycoprotein, the molecule responsible for binding of the virus to cell surfaces. In order for the fusion protein (F) of HPF3 to promote membrane fusion, HN must interact with its receptor. In addition to its role in receptor binding and fusion promotion, the HPF3 HN molecule contains receptor-destroying (sialidase) activity. The putative active sites are in the extracellular domain of this type II integral membrane protein. However, HN is not available in crystalline form; the exact locations of these sites, and the structural requirements for binding to the cellular receptor, which has not yet been isolated, are unknown. Nor have small molecular synthetic inhibitors of attachment or fusion that would provide insight into these processes been identified. The strategy in the present study was to develop an assay system that would provide a measure of a specific step in the viral cycle—functional interaction between viral glycoproteins and the cell during attachment and fusion—and serve to screen a variety of substances for inhibitory potential. The assay is based on our previous finding that CV-1 cells persistently infected (p.i.) with HPF3 do not fuse with one another but that the addition of uninfected CV-1 cells, supplying the critical sialic acid containing receptor molecules that bind HN, results in rapid fusion. In the present assay two HeLa cell types were used: we persistently infected HeLa-LTR-βgal cells, assessed their fusion with uninfected HeLa-tat cells, and then quantitated the β-galactosidase (βgal) produced as a result of this fusion. The analog α-2-S-methyl-5-N-thioacetylneuraminic acid (α-Neu5thioAc2SMe) interfered with fusion, decreasing βgal production by 84% at 50 mM and by 24% at 25 mM. In beginning to extend our studies to different types of molecules, we tested an unsaturated derivative of sialic acid, 2,3-dehydro-2-deoxy-n-acetyl neuraminic acid (DANA), which is known to inhibit influenza neuraminidase by virtue of being a transition-state analog. We found that 10 mM DANA inhibited neuraminidase activity in HPF3 viral preparations. More significantly, this compound was active in our assay of HN–receptor interaction; 10 mM DANA completely blocked fusion and βgal production, and hemadsorption inhibition by DANA suggested that DANA blocks attachment. In plaque reduction assays performed with the compounds, the active analog α-Neu5thioAc2SMe reduced plaque formation by 50% at a 50 mM concentration; DANA caused a 90% inhibition in the plaque reduction assay at a concentration of 25 mM. Our results indicate that specific sialic acid analogs that mimic the cellular receptor determinant of HPF3 can block virus cell interaction and that an unsaturated n-acetyl-neuraminic acid derivative with affinity to the HN site responsible for neuraminidase activity also interferes with HN–receptor binding. Strategies suggested by these findings are now being pursued to obtain information regarding the relative locations of the active sites of HN and to further elucidate the relationship between the receptor-binding and receptor-destroying activities of HN during the viral life cycle. The quantitative assay that we describe is of immediate applicability to large-scale screening for potential inhibitors of HPF3 infection in vivo