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The limited host tropism of numerous viruses causing disease in humans remains incompletely understood. One example is Zika virus (ZIKV), an RNA virus that has reemerged in recent years. Here, we demonstrate that ZIKV efficiently infects fibroblasts from humans, great apes, New and Old World monkeys, but not rodents. ZIKV infection in human—but not murine—cells impairs responses to agonists of the cGMP-AMP synthase/stimulator of IFN genes (cGAS/STING) signaling pathway, suggesting that viral mechanisms to evade antiviral defenses are less effective in rodent cells. Indeed, human, but not mouse, STING is subject to cleavage by proteases encoded by ZIKV, dengue virus, West Nile virus, and Japanese encephalitis virus, but not that of yellow fever virus. The protease cleavage site, located between positions 78/79 of human STING, is only partially conserved in nonhuman primates and rodents, rendering these orthologs resistant to degradation. Genetic disruption of STING increases the susceptibility of mouse—but not human—cells to ZIKV. Accordingly, expression of only mouse, not human, STING in murine STING knockout cells rescues the ZIKV suppression phenotype. STING-deficient mice, however, did not exhibit increased susceptibility, suggesting that other redundant antiviral pathways control ZIKV infection in vivo. Collectively, our data demonstrate that numerous RNA viruses evade cGAS/STING-dependent signaling and affirm the importance of this pathway in shaping the host range of ZIKV. Furthermore, our results explain—at least in part—the decreased permissivity of rodent cells to ZIKV, which could aid in the development of mice model with inheritable susceptibility to ZIKV and other flaviviruses.

Mice engrafted with components of a human immune system have become widely-used models for studying aspects of human immunity and disease. However, a defined methodology to objectively measure and compare the quality of the human immune response in different models is lacking. Here, by taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we provide an in-depth comparison of immune responses in human vaccinees, conventional humanized mice, and second generation humanized mice. We demonstrate that selective expansion of human myeloid and natural killer cells promotes transcriptomic responses akin to those of human vaccinees. These enhanced transcriptomic profiles correlate with the development of an antigen-specific cellular and humoral response to YFV-17D. Altogether, our approach provides a robust scoring of the quality of the human immune response in humanized mice and highlights a rational path towards developing better pre-clinical models for studying the human immune response and disease. Humanized mice are an enabling technology to explore human immunity and disease. Here, Douam et al. provide an in-depth comparison of immune responses to yellow fever vaccine in human vaccinees, conventional and second-generation humanized mice and define a workflow to evaluate and refine these models.

The restricted host tropism of hepatitis C virus (HCV) remains incompletely understood, especially post-entry, and has hindered developing an immunocompetent, small animal model. HCV replication in non-permissive species may be limited by incompatibilities between the viral replication machinery and orthologs of essential host factors, like cyclophilin A (CypA). We thus compared the ability of CypA from mouse, tree shrew, and seven non-human primate species to support HCV replication, finding that murine CypA only partially rescued viral replication in Huh7.5-shRNA CypA cells. We determined the specific amino acid differences responsible and generated mutants able to fully rescue replication. We expressed these mutants in engineered murine hepatoma cells and although we observed increases in HCV replication following infection, they remained far lower than those in highly permissive human hepatoma cells, and minimal infectious particle release was observed. Together, these data suggest additional co-factors remain unidentified. Future work to determine such factors will be critical for developing an immunocompetent mouse model supporting HCV replication. Hepatitis C is a life-long disease that begins when a virus infects the cells of the liver. Although the infection is curable, it is expensive to treat, and there is not yet a vaccine to prevent the disease. This is largely because the virus that causes hepatitis C, also known as HCV, naturally only infects humans and chimpanzees, which has made it difficult to generate an effective animal model for developing a vaccine. Mice are frequently used as a model for studying disease and can be genetically altered to allow HCV to enter their liver cells. However, once HCV enters mouse cells, it struggles to replicate. As a result, an infection does not develop, and the immune system’s response to the virus cannot be fully explored. Replication of HCV in humans relies on a protein called cyclophilin A, or CypA for short. Now, Gaska et al. have set out to improve current animal models for HCV by investigating whether HCV can also use CypA from other species, including mice, to replicate. Gaska et al. showed that the mouse form of CypA could help HCV replicate in human liver cells with lower than normal levels of CypA, but only very poorly. Editing the mouse gene for CypA to be more like the human version resulted in higher HCV replication. Putting variants of CypA into the liver cells of mice, which do not normally replicate HCV at high levels, led to an increase in HCV replication. However, replication of HCV in mice was still far lower than in human liver cells, suggesting that the mouse model system could be improved by learning more about which proteins interact with CypA. Injection drug use – one of the main ways hepatitis C spreads – is becoming increasingly common because of the growing opioid epidemic in many countries. A clinically relevant animal model that supports hepatitis C virus infection would be an important milestone towards a vaccine that could prevent the continued spread of this disease.

Inoculants containing Bradyrhizobium japonicum are available for soybean [Glycine max (L.) Merr.] production but may not be necessary in fields where soybean previously has been produced. The objective of this study was to determine yield response and probability of an economic return from inoculants in fields with a recent history of soybean production. Fifty-one inoculant products were evaluated in experiments (n = 73) conducted in Indiana, Iowa, Minnesota, Nebraska, and Wisconsin between 2000 and 2008. Inoculant products were similar and did not produce a yield response relative to an untreated control different from zero (P > 0.05) at 63 environments. Probability for a break-even economic return at a soybean sale price of $0.33 kg–1 was 59% for Nebraska, 36% for Wisconsin, 25% for Minnesota, 25% for Indiana, and 4% for Iowa. Attaining a return on investment of 67 kg ha–1 (a 2:1 return) reduced success to 11, 2, 1, 7, and 0.2%, for the five states, respectively. Data from this range of environments and products indicate that application of an inoculant offers limited success for either a yield increase or improved economic return on soils where soybean has previously been grown in the upper Midwest.

Data quality of the tokamaks diagnostics is often a neglected topic. In literature it is rather rare to find considerations regarding the data quality received from the diagnostic systems’ sensors. The scope of the paper is to provide a discussion regarding systems’ construction and analysis in scope of implementation of data quality monitoring methods for a new generation of diagnostics. Mainly considerations are performed regarding the necessity of DQM (Data Quality Monitoring) implementation, functionality, performance and required system resources. The covered topics are related to basics of system construction including: system layout and construction blocks, data processing stages, signal processing modes, system construction with resource estimation in scope of DQM implementation. Based on the covered points, it is possible to plan the extra resources or specific construction, to provide reliable design with data quality monitoring features. The data quality monitoring aspect is especially important in the modern diagnostics working with a real-time feedback loop. Such approach could be especially interesting for the ITER-like projects, since the quality of the data may directly influence the behavior of the control systems during plasma phenomena. The work is based on experience in design work of various high performance diagnostic systems for plasma physics and high energy physics.

Phenotypic variation among species is a product of evolutionary changes to developmental programs 1 , 2 . However, how these changes generate novel morphological traits remains largely unclear. Here we studied the genomic and developmental basis of the mammalian gliding membrane, or patagium—an adaptative trait that has repeatedly evolved in different lineages, including in closely related marsupial species. Through comparative genomic analysis of 15 marsupial genomes, both from gliding and non-gliding species, we find that the Emx2 locus experienced lineage-specific patterns of accelerated cis -regulatory evolution in gliding species. By combining epigenomics, transcriptomics and in-pouch marsupial transgenics, we show that Emx2 is a critical upstream regulator of patagium development. Moreover, we identify different cis -regulatory elements that may be responsible for driving increased Emx2 expression levels in gliding species. Lastly, using mouse functional experiments, we find evidence that Emx2 expression patterns in gliders may have been modified from a pre-existing program found in all mammals. Together, our results suggest that patagia repeatedly originated through a process of convergent genomic evolution, whereby regulation of Emx2 was altered by distinct cis -regulatory elements in independently evolved species. Thus, different regulatory elements targeting the same key developmental gene may constitute an effective strategy by which natural selection has harnessed regulatory evolution in marsupial genomes to generate phenotypic novelty. Patagia—the mammalian gliding membrane—repeatedly originated through a process of convergent genomic evolution, whereby the regulation of Emx2 was altered by distinct cis -regulatory elements in independently evolved species.

Heterodera glycines continues to be the number one yield limiting factor in soybean [Glycine max (L.) Merr.] across the Midwest. Several genetic and agronomic practices are available to assist growers in maximizing yield in a H. glycines environment. The objectives of this research were to (i) measure yield response to rotation and tillage systems and evaluate whether presence of H. glycines and reaction of cultivars to H. glycines modified this response, and (ii) determine if H. glycines population dynamics were related to source of resistance to H. glycines, rotation, or tillage systems. Field research trials were conducted during 3 yr (2006–2008) near Arlington, WI and Ames, IA. Main plots were no-tillage and conventional tillage systems. Subplots consisted of 10 rotation sequences involving corn (Zea mays L.) and soybean. Sub-subplots were three sources of H. glycines resistance. Crop rotation and source of genetic resistance were the most important factors to consider in maximizing seed yield and managing H. glycines across locations, whereas tillage was the least valuable tool in H. glycines management. Extended rotations decreased H. glycines populations, however this benefit was overcome by first or second year soybean. Results also show that continued reliance on one source of genetic resistance can lead to reproduction of H. glycines, regardless of source. Our results suggest that an integrated approach to H. glycines management that considers rotation, tillage, knowledge of H. glycines (HG)-type, and source of genetic resistance is needed to maximize seed yield and decrease H. glycines populations.

Wheat (Triticum aestivum L.) is the third‐most cultivated field crop in the United States and a very important source of nutrition globally. The economic value of wheat motivates farmers to optimize yield and grain quality, which can be obtained with additional inputs that are often expensive. This study investigated three management intensity levels on grain yield, straw yield, grain test weight, and disease on winter wheat in Wisconsin across 4 yr and 20 varieties. All management practices included a pre‐emergence herbicide and N application, with a mid‐level management strategy adding another N application and a single fungicide application to the current strategy, and a high‐level management intensity strategy adding a growth regulator, two micronutrient applications, and another fungicide application to the mid‐level strategy. Our study revealed that increasing management intensity from current strategies to mid‐ or high levels significantly increased grain yields by 0.81–1.22 kg ha−1, straw yields by 1.2–1.2 t ha−1, and grain test weights by 2.6–3.2 kg hl−1, respectively (P < .05). In addition, the high‐level management intensity led to significant reductions in stripe rust incidence and severity, whereas both mid‐ and high‐level management intensity reduced Fusarium head blight incidence and severity, and mycotoxin contamination (P < .001). The economic considerations of intensified management were also examined, and the mid‐ and high‐level management practices resulted in US $306 and US$ 242 ha−1 greater profit than current management, respectively, as a result of the improved disease protection and yields.

There is little peer‐reviewed information regarding prophylactic use of multiple inputs in soybean [Glycine max (L.) Merr.] production systems as a way to increase seed yield and profitability. Therefore, the objective of this study was to examine the effect of multiple inputs on soybean yield and quality in Wisconsin (WI). Two separate studies were established from 2011 to 2013. The inputs examined included: trait [first (RR1) and second (RR2Y) generation Roundup Ready traits], rhizobia inoculant, fungicide seed treatment, foliar fertilizer, foliar insecticide, and foliar fungicide. In the first experiment, main effects and up to three‐way interactions were evaluated; whereas in the second experiment, all inputs were combined in a high‐management (i.e., intensive) treatment. In the first experiment, soybean yield was not consistently increased due to the used inputs. Trait and foliar fungicide use were significant factors with variable effect on soybean seed yield in three and four of the nine location‐years, respectively. The foliar insecticide effect varied between traits in three location‐years. The (rhizobia inoculant + fungicide seed treatment) × foliar insecticide × foliar fungicide interaction was a significant factor in three of the nine location‐years. None of the examined factors significantly increased yield across all location–years. In the second experiment, high‐management, trait, and their interaction did not consistently increase soybean yield, nor improved seed quality characteristics. Overall, these results suggest that WI growers should continue to use university‐developed integrated pest management principles for making input decisions instead of relying on prophylactic input applications for maximizing soybean yield and profitability. No sole input or interaction consistently increased soybean yield across site‐years. Intensive management had inconsistent and minimal effect on soybean yield. Growers should not rely on prophylactic input applications to maximize soybean yield.

Farmers have been interested in using foliar‐applied nutrient products to increase soybean [Glycine max (L.) Merr.] yield since at least the 1970s, despite limited evidence that these products offer consistent yield increases when used prophylactically. Recently, interest in foliar fertilizer products for soybean production has been renewed, likely related to elevated soybean prices. Over the 2019 and 2020 growing seasons (46 site‐years), agronomists in 16 states collaborated to test six foliar nutrient treatments (commercial mixtures of macro‐ and micro‐nutrients) on soybean grain yield and composition. Soybean grain yield and composition differed among sites but not among foliar fertilizer treatments. Results show that prophylactic foliar fertilization is likely to decrease the profitability of soybean production. Foliar fertilizer products tested in this study and similar products should not be recommended to U.S. soybean farmers in the absence of visual symptoms of nutrient deficiency. Core Ideas The tested prophylactic foliar fertilizers did not increase soybean yield. Foliar fertilizers did not change grain composition. Prophylactic foliar fertilizers tested decreased profitability.