Serum Prestin After Ototoxin Exposure Is Not Dependent on Outer Hair Cell Loss.

HYPOTHESIS: Cyclodextrin (CDX)-induced serum prestin burst is not dependent on outer hair cell (OHC) loss. BACKGROUND: Serum prestin has been proposed as a biomarker for ototoxicity. We recently used an automated Western approach to quantify serum prestin changes in a newly introduced model of CDX ototoxicity. To gain insights into prestin as a biomarker, here we further characterize serum prestin in the CDX model. METHODS: Guinea pigs were treated with 750, 3,000, or 4,000 mg/kg CDX, and serum samples were obtained through up to 15 weeks after exposure. Serum prestin levels were quantified using automated Western, and hair cell counts were obtained. RESULTS: All three doses induced an N -glycosylated ~134-kDa prestin burst; however, only the 3,000 and 4,000 mg/kg resulted in robust OHC loss. Prestin levels returned to baseline where they remained up to 15 weeks in the absence of OHCs. CONCLUSION: The ~134-kDa prestin burst induced after CDX administration is N -glycosylated, representing a posttranslational modification of prestin. Serum prestin seems to be a promising biomarker when using therapeutics with ototoxic properties because it is not dependent on OHC loss as a necessary event, thus affording the opportunity for early detection and intervention.

Automated Western Blot Analysis of Ototoxin-Induced Prestin Burst in the Blood after Cyclodextrin Exposure.

HYPOTHESIS: Ototoxin cyclodextrin (CDX) will induce a burst in serum prestin when quantified with automated Western blot analysis. BACKGROUND: In the clinical realm, we primarily rely on audiological measures for diagnosis and surveillance of sensorineural hearing loss (SNHL) and have limited therapeutic options. We have proposed a blood-based biomarker approach to overcome this challenge by measuring the outer hair cell's (OHC) electromotile protein, prestin, in the blood. Previously, we demonstrated a burst in serum prestin after cisplatin exposure using enzyme-linked immunosorbent assayELISA. METHODS: Guinea pigs were treated with either 3,000 or 4,000 mg/kg CDX, and serum samples were obtained through 3 days after exposure. Serum prestin levels were quantified using automated blot analysis, western and hair cell counts were obtained. RESULTS: Both 3,000 and 4,000 mg/kg resulted in robust OHC loss, although more variability was seen at the lower dose. Automated Western blot analysis demonstrated that the prestin profile after CDX exposure is different than baseline. Specifically, a new ~134- kDa band accounted for the prestin burst after ototoxin ablation of OHCs at both doses. CONCLUSIONS: We reproduced the prestin burst seen after cisplatin administration using CDX. Automated Western blot western analysis revealed that a ~a ~ 134- kDa species of prestin is responsible for the burst. We suggest that the induced band may be a prestin dimer, which could serve as a biomarker for early detection of ototoxicity in the clinical setting. These results add further promise to the potential of serum prestin to serve as an ototoxicity biomarker when using therapeutics with ototoxic properties.

Whooping crane use of riverine stopover sites.

Migratory birds like endangered whooping cranes (Grus americana) require suitable nocturnal roost sites during twice annual migrations. Whooping cranes primarily roost in shallow surface water wetlands, ponds, and rivers. All these features have been greatly impacted by human activities, which present threats to the continued recovery of the species. A portion of one such river, the central Platte River, has been identified as critical habitat for the survival of the endangered whooping crane. Management intervention is now underway to rehabilitate habitat form and function on the central Platte River to increase use and thereby contribute to the survival of whooping cranes. The goal of our analyses was to develop habitat selection models that could be used to direct riverine habitat management activities (i.e., channel widening, tree removal, flow augmentation, etc.) along the central Platte River and throughout the species' range. As such, we focused our analyses on two robust sets of whooping crane observations and habitat metrics the Platte River Recovery Implementation Program (Program or PRRIP) and other such organizations could influence. This included channel characteristics such as total channel width, the width of channel unobstructed by dense vegetation, and distance of forest from the edge of the channel and flow-related metrics like wetted width and unit discharge (flow volume per linear meter of wetted channel width) that could be influenced by flow augmentation or reductions during migration. We used 17 years of systematic monitoring data in a discrete-choice framework to evaluate the influence these various metrics have on the relative probability of whooping crane use and found the width of channel unobstructed by dense vegetation and distance to the nearest forest were the best predictors of whooping crane use. Secondly, we used telemetry data obtained from a sample of 38 birds of all ages over the course of seven years, 2010-2016, to evaluate whooping crane use of riverine habitat within the North-central Great Plains, USA. For this second analysis, we focused on the two metrics found to be important predictors of whooping crane use along the central Platte River, unobstructed channel width and distance to nearest forest or wooded area. Our findings indicate resource managers, such as the Program, have the potential to influence whooping crane use of the central Platte River through removal of in-channel vegetation to increase the unobstructed width of narrow channels and through removal of trees along the bank line to increase unforested corridor widths. Results of both analyses also indicated that increases in relative probability of use by whooping cranes did not appreciably increase with unobstructed views ≥200 m wide and unforested corridor widths that were ≥330 m. Therefore, managing riverine sites for channels widths >200 m and removing trees beyond 165 m from the channel's edge would increase costs associated with implementing management actions such as channel and bank-line disking, removing trees, augmenting flow, etc. without necessarily realizing an additional appreciable increase in use by migrating whooping cranes.

Investigating whooping crane habitat in relation to hydrology, channel morphology and a water-centric management strategy on the central Platte River, Nebraska.

The Flow-Sediment-Mechanical approach is one of two management strategies presented in the Platte River Recovery Implementation Program's (Program) Adaptive Management Plan to create and maintain suitable riverine habitat (≥200 m wide unobstructed channels) for whooping cranes (Grus americana). The Program's Flow-Sediment-Mechanical management strategy consists of sediment augmentation, mechanical vegetation clearing and channel widening, channel consolidation, and short duration high flow releases of 142-227 m3/s for three to five days in two out of three years in order to increase the unvegetated width of the main channel and, by extension, create and maintain suitable habitat for whooping crane use. We examined the influence of a range of hydrologic and physical metrics on total unvegetated channel width (TUCW) and maximum unobstructed channel width (MUOCW) during the period of 2007-2015 and applied those findings to assess the performance of the Flow-Sediment-Mechanical management strategy for creating and maintaining whooping crane roosting habitat. Our investigation highlights uncertainties that are introduced when exploring the relationship between physical process drivers and species habitat metrics. We identified a strong positive relationship between peak flows and TUCW and MUOCW within the Associated Habitat Reach of the central Platte River. However, the peak discharge magnitude and duration needed to create highly favorable whooping crane roosting habitat within our study area are much greater than short duration high flow releases, as currently envisioned. We also found disking in combination with herbicide application to vegetated portions of the channel are effective for creating and maintaining highly favorable unobstructed channel widths for whooping cranes in all but the very driest years. As such, resource managers could prioritize the treatment of mid-channel islands that are vegetated to increase the suitability of roosting habitat for whooping cranes.

Integrating species-centric and geomorphic-centric views of interior least tern and piping plover habitat selection.

The Federally endangered interior least tern (Sterna antillarum athalassos) and threatened piping plover (Charadrius melodus) nest on emergent sandbars in several braided rivers in the USA. Previous habitat selection and geomorphic investigations identified a relationship between channel width and nesting incidence. Species-centric analyses indicate selection for the widest available channels whereas geomorphic-centric analyses indicate the probability of species occurrence was higher in narrow channels that better supported suitable sandbar habitat. Given the disparate conclusions from each of these perspectives, we examined species use in relation to channel-width metrics across segments of the Platte, Niobrara, and Loup Rivers from both perspectives. We found the probability of nesting incidence increased with increased maximum unvegetated channel width in all river segments. However, maximum unvegetated width decreased with increased total channel width once total width exceeded 300 m in the central Platte River and 500 m in all other river segments as did the probability that the channel was free of permanently-vegetated islands. Channels within the Lower Platte, Loup and Niobrara River systems with total widths of 500-800 m appear to be both wide enough to have a high probability of nesting incidence and narrow enough to be free of vegetated islands. Actions that affect channels with total, bank-to-bank widths of <500 m and >800 m would likely have a small influence on species use while actions that change the width characteristics of 500-800 m channels could have a strong negative or positive influence on species use. Integrating species- and geomorphic-centric views into a single analysis provided a fuller picture of the relationship between species use and channel-width metrics.

Reproductive ecology of interior least tern and piping plover in relation to Platte river hydrology and sandbar dynamics: Response to the letter to the editor.

This is a response to the Alexander, Jorgensen, and Bomberger-Brown (Ecology and Evolution, XX, 2018, XX; hereafter, AJB) Letter to the Editor critiquing Farnsworth et al. (Ecology and Evolution, 7, 2017, 3579; hereafter, our study), which investigates the reproductive ecology of interior least terns and piping plover in relation to Platte River hydrology and sandbar dynamics. Herein, we address each of AJBs' technical arguments, demonstrating that our technical approach and model assumptions were reasonable and provide a conservatively high estimate of the potential for reproductive success when compared to observed nest inundation events. We conclude with a description of the realities faced by the Platte River Recovery Implementation Program (PRRIP) as we integrate learning to adjust management actions. Linked Article: https://doi.org/10.1002/ece3.4109.

Reproductive ecology of interior least tern and piping plover in relation to Platte River hydrology and sandbar dynamics.

Investigations of breeding ecology of interior least tern (Sternula antillarum athalassos) and piping plover (Charadrius melodus) in the Platte River basin in Nebraska, USA, have embraced the idea that these species are physiologically adapted to begin nesting concurrent with the cessation of spring floods. Low use and productivity on contemporary Platte River sandbars have been attributed to anthropomorphically driven changes in basin hydrology and channel morphology or to unusually late annual runoff events. We examined distributions of least tern and piping plover nest initiation dates in relation to the hydrology of the historical central Platte River (CPR) and contemporary CPR and lower Platte River (LPR). We also developed an emergent sandbar habitat model to evaluate the potential for reproductive success given observed hydrology, stage-discharge relationships, and sandbar height distributions. We found the timing of the late-spring rise to be spatially and temporally consistent, typically occurring in mid-June. However, piping plover nest initiation peaks in May and least tern nest initiation peaks in early June; both of which occur before the late spring rise. In neither case does there appear to be an adaptation to begin nesting concurrent with the cessation of spring floods. As a consequence, there are many years when no successful reproduction is possible because emergent sandbar habitat is inundated after most nests have been initiated, and there is little potential for successful renesting. The frequency of nest inundation, in turn, severely limits the potential for maintenance of stable species subpopulations on Platte River sandbars. Why then did these species expand into and persist in a basin where the hydrology is not ideally suited to their reproductive ecology? We hypothesize the availability and use of alternative off-channel nesting habitats, like sandpits, may allow for the maintenance of stable species subpopulations in the Platte River basin.