Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain

The severe acute respiratory syndrome (SARS) epidemic was caused by the spread of a previously unrecognized infectious agent, the SARS-associated coronavirus (SARS-CoV). Here we show that SARS-CoV could inhibit both virus- and interferon (IFN)-dependent signaling, two key steps of the antiviral response. We mapped a strong inhibitory activity to SARS-CoV nonstructural protein 1 (nsp1) and show that expression of nsp1 significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nsp1 significantly inhibited IFN-dependent signaling by decreasing the phosphorylation levels of STAT1 while having little effect on those of STAT2, JAK1, and TYK2. We engineered an attenuated mutant of nsp1 in SARS-CoV through reverse genetics, and the resulting mutant virus was viable and replicated as efficiently as wild-type virus in cells with a defective IFN response. However, mutant virus replication was strongly attenuated in cells with an intact IFN response. Thus, nsp1 is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication

Drug repositioning of Clopidogrel or Triamterene to inhibit influenza virus replication in vitro

Influenza viruses cause respiratory tract infections and substantial health concerns. Infection may result in mild to severe respiratory disease associated with morbidity and some mortality. Several anti-influenza drugs are available, but these agents target viral components and are susceptible to drug resistance. There is a need for new antiviral drug strategies that include repurposing of clinically approved drugs. Drugs that target cellular machinery necessary for influenza virus replication can provide a means for inhibiting influenza virus replication. We used RNA interference screening to identify key host cell genes required for influenza replication, and then FDA-approved drugs that could be repurposed for targeting host genes. We examined the effects of Clopidogrel and Triamterene to inhibit A/WSN/33 (EC(50) 5.84 uM and 31.48 uM, respectively), A/CA/04/09 (EC(50) 6.432 uM and 3.32 uM, respectively), and B/Yamagata/16/1988 (EC(50) 0.28 uM and 0.11 uM, respectively) replication. Clopidogrel and Triamterene provide a druggable approach to influenza treatment across multiple strains and subtypes

Sustainable Mobility for Rural Small University Towns

How can all of the emerging changes in transportation affect a small rural University town? This panel will discuss the opportunities and the drawbacks to automated vehicles, shared vehicles, electric, and solar powered vehicles. The panel will be comprised of various academics and professionals involved with these new transportation changes

MicroRNAs affect GPCR and Ion channel genes needed for influenza replication

Influenza virus causes seasonal epidemics and sporadic pandemics resulting in morbidity, mortality, and economic losses worldwide. Understanding how to regulate influenza virus replication is important for developing vaccine and therapeutic strategies. Identifying microRNAs (miRs) that affect host genes used by influenza virus for replication can support an antiviral strategy. In this study, G-protein coupled receptor (GPCR) and ion channel (IC) host genes in human alveolar epithelial (A549) cells used by influenza virus for replication (Orr-Burks et al., 2021) were examined as miR target genes following A/CA/04/09- or B/Yamagata/16/1988 replication. Thirty-three miRs were predicted to target GPCR or IC genes and their miR mimics were evaluated for their ability to decrease influenza virus replication. Paired miR inhibitors were used as an ancillary measure to confirm or not the antiviral effects of a miR mimic. Fifteen miRs lowered influenza virus replication and four miRs were found to reduce replication irrespective of virus strain and type differences. These findings provide evidence for novel miR disease intervention strategies for influenza viruses

Linear Current-Mode Active Pixel Sensor

A current mode CMOS active pixel sensor (APS) providing linear light-to-current conversion with inherently low fixed pattern noise (FPN) is presented. The pixel features adjustable-gain current output using a pMOS readout transistor in the linear region of operation. This paper discusses the pixel’s design and operation, and presents an analysis of the pixel’s temporal noise and FPN. Results for zero and first-order pixel mismatch are presented. The pixel was implemented in a both a 3.3 V 0.35 µm and a 1.8 V 0.18 µm CMOS process. The 0.35 µm process pixel had an uncorrected FPN of 1.4%/0.7% with/without column readout mismatch. The 0.18 µm process pixel had 0.4% FPN after delta-reset sampling (DRS). The pixel size in both processes was 10 X 10 µm2, with fill factors of 26% and 66%, respectively

The Changing of the Guard: The New American Labor Leader

This article analyzes recent changes in the leadership of international unions. There has been a trend toward leaders who are lifetime bureaucrats rather than rank-and-file members with charisma. This change toward more technocratic leadership is due to the different environment and new challenges that labor currently faces. The United Mine Workers is a good example of a union that has had many changes in the type of person who has become president, from the labor giant John L. Lewis to the 33-year-old lawyer Richard Trumka. The United Auto Workers is an example of a union whose leadership has been consistently drawn from the union hierarchy. The AFL-CIO has made a change in leadership from George Meany to the labor bureaucrat Lane Kirkland. There will probably be an increase in the number of women and minorities in top leadership positions in unions, but this will be a gradual increase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66627/2/10.1177_000271628447300107.pd

‘It's all the way you look at it, you know’: reading Bill ‘Bojangles’ Robinson's film career

This paper engages with a major paradox in African American tap dancer Bill ‘Bojangles’ Robinson's film image – namely, its concurrent adherences to and contestations of dehumanising racial iconography – to reveal the complex and often ambivalent ways in which identity is staged and enacted. Although Robinson is often understood as an embodiment of popular cultural imagery historically designed to dehumanise African Americans, this paper shows that Robinson's artistry displaces these readings by providing viewing pleasure for black, as much as white, audiences. Robinson's racially segregated scenes in Dixiana (1930) and Hooray for Love (1935) illuminate classical Hollywood's racial codes, whilst also showing how his inclusion within these otherwise all-white films provides grounding for creative and self-reflexive artistry. The films' references to Robinson's stage image and artistry overlap with minstrelsy-derived constructions of ‘blackness’, with the effect that they heighten possible interpretations of his cinematic persona by evading representational conclusion. Ultimately, Robinson's films should be read as sites of representational struggle that help to uncover the slipperiness of performances of African American identities in 1930s Hollywood

Understanding continent-wide variation in vulture ranging behavior to assess feasibility of Vulture Safe Zones in Africa: Challenges and possibilities

Protected areas are intended as tools in reducing threats to wildlife and preserving habitat for their long-term population persistence. Studies on ranging behavior provide insight into the utility of protected areas. Vultures are one of the fastest declining groups of birds globally and are popular subjects for telemetry studies, but continent-wide studies are lacking. To address how vultures use space and identify the areas and location of possible vulture safe zones, we assess home range size and their overlap with protected areas by species, age, breeding status, season, and region using a large continent-wide telemetry datasets that includes 163 individuals of three species of threatened Gyps vulture. Immature vultures of all three species had larger home ranges and used a greater area outside of protected areas than breeding and non-breeding adults. Cape vultures had the smallest home range sizes and the lowest level of overlap with protected areas. Rüppell\u27s vultures had larger home range sizes in the wet season, when poisoning may increase due to human-carnivore conflict. Overall, our study suggests challenges for the creation of Vulture Safe Zones to protect African vultures. At a minimum, areas of 24,000 km2 would be needed to protect the entire range of an adult African White-backed vulture and areas of more than 75,000 km2 for wider-ranging Rüppell\u27s vultures. Vulture Safe Zones in Africa would generally need to be larger than existing protected areas, which would require widespread conservation activities outside of protected areas to be successful

The role of gene expression in ecological speciation

Ecological speciation is the process by which barriers to gene flow between populations evolve due to adaptive divergence via natural selection. A relatively unexplored area in ecological speciation is the role of gene expression. Gene expression may be associated with ecologically important phenotypes not evident from morphology and play a role during colonization of new environments. Here we review two potential roles of gene expression in ecological speciation: (1) its indirect role in facilitating population persistence and (2) its direct role in contributing to genetically based reproductive isolation. We find indirect evidence that gene expression facilitates population persistence, but direct tests are lacking. We also find clear examples of gene expression having effects on phenotypic traits and adaptive genetic divergence, but links to the evolution of reproductive isolation itself remain indirect. Gene expression during adaptive divergence seems to often involve complex genetic architectures controlled by gene networks, regulatory regions, and “eQTL hotspots.” Nonetheless, we review how approaches for isolating the functional mutations contributing to adaptive divergence are proving to be successful. The study of gene expression has promise for increasing our understanding ecological speciation, particularly when integrative approaches are applied