Project description:Hearing mediates many behaviors critical for survival in echolocating bats, including foraging and navigation. Although most mammals are susceptible to progressive age-related hearing loss, the evolution of biosonar, which requires the ability to hear low-intensity echoes from outgoing sonar signals, may have selected against the development of hearing deficits in bats. Many echolocating bats exhibit exceptional longevity and rely on acoustic behaviors for survival to old age; however relatively little is known about the aging bat auditory system. In this study, we used DNA methylation to estimate the ages of wild-caught big brown bats (Eptesicus fuscus) and measured hearing sensitivity in young and aging bats using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We found no evidence for hearing deficits in bats up to 12.5 years of age, demonstrated by comparable thresholds and similar ABR and DPOAE amplitudes across age groups. We additionally found no significant histological evidence for cochlear aging, with similar hair cell counts, afferent, and efferent innervation patterns in young and aging bats. Here we demonstrate that big brown bats show minimal evidence for age-related hearing loss and therefore represent informative models for investigating mechanisms that may preserve hearing function over a long lifetime.
Project description:Bats are remarkably long-lived for their size with many species living more than 20-40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigated requirements for malignant transformation in primary bat fibroblasts in four bat species - little brown bat (Myotis lucifugus), big brown bat (Eptesicus fuscus), cave nectar bat (Eonycteris spelaea) and Jamaican fruit bat (Artibeus jamaicensis) – spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence and express active telomerase. Bat cells displayed attenuated stress induced premature senescence with a dampened secretory phenotype. Unexpectedly, we discovered that bat cells could be readily transformed by only two oncogenic perturbations or “hits”: inactivation of either p53 or pRb and activation of oncogenic RASV12. This was surprising because other long-lived mammalian species require up to five hits for malignant transformation. Additionally, bat fibroblasts exhibited increased p53 and MDM2 transcript levels, and elevated p53-dependent apoptosis. The little brown bat showed a genomic duplication of the p53 gene. We hypothesize that bats evolved enhanced p53 activity through gene duplications and transcriptional upregulation as an additional anti-cancer strategy, similar to elephants. In summary, active telomerase and the small number of oncogenic hits sufficient to malignantly transform bat cells suggest that in vivo bats rely heavily on non-cell autonomous mechanisms of tumor suppression.
Project description:Bats are the reservoir for a large number of zoonotic viruses, including members of Coronaviridae (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2), Paramyxoviridae (Hendra and Nipah viruses), Rhabdoviridae (rabies virus), and Filoviridae (Ebola virus) as exemplars. Many retroviruses, such as human immunodeficiency virus, are similarly zoonotic; however, only infectious exogenous gammaretroviruses have recently been identified in bats. Here, viral metagenomic sequencing of samples from bats submitted for rabies virus testing, largely due to human exposure, identified a novel, highly divergent exogenous Deltaretrovirus from a big brown bat (Eptesicus fuscus) in South Dakota. The virus sequence, corresponding to Eptesicus fuscus deltaretrovirus (EfDRV), comprised a nearly complete coding region comprised of canonical 5'-gag-pro-pol-env-3' genes with 37% to 51% identity to human T-lymphotropic virus (HTLV), an infectious retrovirus that causes T-cell lymphoma. A putative tax gene with 27% identity to HTLV was located downstream of the pol gene along with a gene harbored in an alternative reading frame which possessed a conserved domain for an Epstein-Barr virus nuclear antigen involved in gene transactivation, suggesting a regulatory function similar to that of the deltaretrovirus rex gene. A TaqMan reverse transcriptase PCR (RT-PCR) targeting the pol gene identified 4/60 (6.7%) bats as positive for EfDRV, which, combined with a search of the E. fuscus genome that failed to identify sequences with homology to EfDRV, suggests that EfDRV is an infectious exogenous virus. As all known members of Deltaretrovirus can cause malignancies and E. fuscus is widely distributed in the Americas, often with a colonial roosting behavior in human dwellings, further studies are needed to investigate potential zoonosis.IMPORTANCE Bats host a large numbers of viruses, many of which are zoonotic. In the United States, the big brown bat (Eptesicus fuscus) is widely distributed and lives in small colonies that roost in cavities, often in human dwellings, leading to frequent human interaction. Viral metagenomic sequencing of samples from an E. fuscus bat submitted for rabies testing identified the first exogenous bat Deltaretrovirus The E. fuscus deltaretrovirus (EfDRV) genome consists of the typical deltaretrovial 5'-gag-pro-pol-env-3' genes along with genes encoding two putative transcriptional transactivator proteins distantly related to the Tax protein of human T-cell lymphotrophic virus and nuclear antigen 3B of Epstein-Barr virus. Searches of the E. fuscus genome sequence failed to identify endogenous EfDRV. RT-PCR targeting the EfDRV pol gene identified 4/60 (6.7%) bats with positive results. Together, these results suggest that EfDRV is exogenous. As all members of Deltaretrovirus are associated with T- and B-cell malignancies or neurologic disease, further studies on possible zoonosis are warranted.
Project description:Big brown bats were trained in a two-choice task to locate a two-cylinder dipole object with a constant 5 cm spacing in the presence of either a one-cylinder monopole or another two-cylinder dipole with a shorter spacing. For the dipole versus monopole task, the objects were either stationary or in motion during each trial. The dipole and monopole objects varied from trial to trial in the left-right position while also roving in range (10-40 cm), cross range separation (15-40 cm), and dipole aspect angle (0 degrees -90 degrees ). These manipulations prevented any single feature of the acoustic stimuli from being a stable indicator of which object was the correct choice. After accounting for effects of masking between echoes from pairs of cylinders at similar distances, the bats discriminated the 5 cm dipole from both the monopole and dipole alternatives with performance independent of aspect angle, implying a distal, spatial object representation rather than a proximal, acoustic object representation.