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Wight-Carter, M.

Publications and source records attributed to Wight-Carter, M..

3 recordsLinked to original sources

Time-Restricted Feeding Extends Healthspan in Female and Lifespan in Male C57BL/6J Mice

Time-restricted feeding (TRF) aligned with an organisms circadian rhythm has been shown to improve health, but its long-term effects on healthspan and lifespan in mammals, especially under normal dietary conditions, remain unclear. Here, we examined the impact of 12-hour (h) and 8h nightly TRF windows in male and female mice fed regular chow. TRF improved multiple health measures, including behavioral rhythmicity, body weight and composition, frailty, and disease onset. These effects were most pronounced in the 8h-TRF group, which exhibited voluntary caloric restriction in addition to time restriction. A composite Healthspan Index revealed that TRF extended healthspan in both sexes, though the benefits were more prolonged in females relative to their total lifespan. Median lifespan was significantly extended in males under 8h-TRF by 12%, whereas females showed no significant lifespan extension, highlighting sex-specific responses to TRF.

physiology↗

Effect of shipping on the microbiome of donor mice used to reconstitute germ-free recipients

The gut microbiota (GM) influences multiple processes during host development and maintenance. To study these events, fecal microbiota transfer (FMT) to germ-free (GF) recipients is often performed. Mouse models of disease are also susceptible to GM-dependent effects, and cryo-repositories often store feces from donated mouse strains. Shipping live mice may affect the GM and result in an inaccurate representation of the baseline GM. We hypothesize that the use of such fecal samples for FMT would transfer shipping-induced changes in the donor GM to GF recipients. To test this, donor mice originating from two suppliers were shipped to the University of Missouri. Fecal samples collected pre- and post-shipping were used to inoculate GF mice. Pre- and post-shipping fecal samples from donors, and fecal and/or cecal contents were collected from recipients at one and two weeks post-FMT. 16S rRNA sequencing revealed supplier-dependent effects of shipping on the donor microbiome. FMT efficiency was independent of shipping timepoint or supplier, resulting in transmission of shipping-induced changes to recipient mice, however the effect of supplier-origin microbiome remained evident. While shipping may cause subtle changes in fecal samples collected for FMT, such effects are inconsistent among supplier-origin GMs and minor in comparison to other biological variables.

microbiology↗

LY6E impairs coronavirus fusion and confers immune control of viral disease

Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Host immune responses to CoV are complex and regulated in part through antiviral interferons. However, the interferon-stimulated gene products that inhibit CoV are not well characterized2. Here, we show that interferon-inducible lymphocyte antigen 6 complex, locus E (LY6E) potently restricts cellular infection by multiple CoVs, including SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to murine CoV infection. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic and splenic immune cells and reduction in global antiviral gene pathways. Accordingly, we found that Ly6e directly protects primary B cells and dendritic cells from murine CoV infection. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo, knowledge that could help inform strategies to combat infection by emerging CoV.

microbiology↗