A temperature sensitive live-attenuated canine influenza virus H3N8 vaccine

Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo. The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV. Importance: Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs

An Early CD4+ T Cell–dependent Immunoglobulin A Response to Influenza Infection in the Absence of Key Cognate T–B Interactions

Contact-mediated interactions between CD4+ T cells and B cells are considered crucial for T cell–dependent B cell responses. To investigate the ability of activated CD4+ T cells to drive in vivo B cell responses in the absence of key cognate T–B interactions, we constructed radiation bone marrow chimeras in which CD4+ T cells would be activated by wild-type (WT) dendritic cells, but would interact with B cells that lacked expression of either major histocompatibility complex class II (MHC II) or CD40. B cell responses were assessed after influenza virus infection of the respiratory tract, which elicits a vigorous, CD4+ T cell–dependent antibody response in WT mice. The influenza-specific antibody response was strongly reduced in MHC II knockout and CD40 knockout mice. MHC II–deficient and CD40-deficient B cells in the chimera environment also produced little virus-specific immunoglobulin (Ig)M and IgG, but generated a strong virus-specific IgA response with virus-neutralizing activity. The IgA response was entirely influenza specific, in contrast to the IgG2a response, which had a substantial nonvirus-specific component. Our study demonstrates a CD4+ T cell–dependent, antiviral IgA response that is generated in the absence of B cell signaling via MHC II or CD40, and is restricted exclusively to virus-specific B cells

Mcl-1 dynamics influence mitotic slippage and death in mitosis

Microtubule-binding drugs such as taxol are frontline treatments for a variety of cancers but exactly how they yield patient benefit is unclear. In cell culture, inhibiting microtubule dynamics prevents spindle assembly, leading to mitotic arrest followed by either apoptosis in mitosis or slippage, whereby a cell returns to interphase without dividing. Myeloid cell leukaemia-1 (Mcl-1), a pro-survival member of the Bcl-2 family central to the intrinsic apoptosis pathway, is degraded during a prolonged mitotic arrest and may therefore act as a mitotic death timer. Consistently, we show that blocking proteasome-mediated degradation inhibits taxol-induced mitotic apoptosis in a Mcl-1-dependent manner. However, this degradation does not require the activity of either APC/C-Cdc20, FBW7 or MULE, three separate E3 ubiquitin ligases implicated in targeting Mcl-1 for degradation. This therefore challenges the notion that Mcl-1 undergoes regulated degradation during mitosis. We also show that Mcl-1 is continuously synthesized during mitosis and that blocking protein synthesis accelerates taxol induced death-in-mitosis. Modulating Mcl-1 levels also influences slippage; overexpressing Mcl-1 extends the time from mitotic entry to mitotic exit in the presence of taxol, while inhibiting Mcl-1 accelerates it. We suggest that Mcl-1 competes with Cyclin B1 for binding to components of the proteolysis machinery, thereby slowing down the slow degradation of Cyclin B1 responsible for slippage. Thus, modulating Mcl-1 dynamics influences both death-in-mitosis and slippage. However, because mitotic degradation of Mcl-1 appears not to be under the control of an E3 ligase, we suggest that the notion of network crosstalk is used with caution

Influence of Parenting Practices on Eating Behaviors of Early Adolescents during Independent Eating Occasions: Implications for Obesity Prevention

Among early adolescents (10–14 years), poor diet quality along with physical inactivity can contribute to an increased risk of obesity and associated biomarkers for chronic disease. Approximately one-third of United States (USA) children in this age group are overweight or obese. Therefore, attention to factors affecting dietary intake as one of the primary contributors to obesity is important. Early adolescents consume foods and beverages during eating occasions that occur with and without parental supervision. Parents may influence eating behaviors of early adolescents during eating occasions when they are present or during independent eating occasions by engaging in practices that affect availability of foods and beverages, and through perceived normative beliefs and expectations for intake. Therefore, the purpose of this article was to describe the influence of parenting practices on eating behaviors in general and when specifically applied to independent eating occasions of early adolescents. This information may be helpful to inform parenting interventions targeting obesity prevention among early adolescents focusing on independent eating occasions

Days of Future Past: Why Race Matters in Metadata

While marginalized as a juvenile medium, comics serve as an archive of our collective experience. Emerging with the modern city and deeply affected by race, class, and gender norms, comics are a means to understand the changes linked to identity and power in the United States. For further investigation, we turn to one such collective archive: the MSU Library Comics Art Collection (CAC), which contains over 300,000 comics and comic artifacts dating as far back as 1840. As noted on the MSU Special Collections’ website, “the focus of the collection is on published work in an effort to present a complete picture of what the American comics readership has seen, especially since the middle of the 20th century”. As one of the world’s largest publicly accessible comics archives, a community of scholars and practitioners created the Comics as Data North America (CaDNA) dataset, which comprises library metadata from the CAC to explore the production, content, and creative communities linked to comics in North America. This essay will draw on the Comics as Data North America (CaDNA) dataset at Michigan State University to visualize patterns of racial depiction in North American comics from 1890–2018. Our visualizations highlight how comics serve as a visual record of representation and serve as a powerful marker of marginalization central to popular cultural narratives in the United States. By utilizing data visualization to explore the ways we codify and describe identity, we seek to call attention to the constructed nature of race in North America and the continuing work needed to imagine race beyond the confines of the established cultural legacy