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This work was undertaken at the University of California Davis Dairy Teaching and Research Facility from June to September 2018. All experimental protocols were approved by and carried out in accordance with the University of California Davis Institutional Animal Care and Use Committee (protocol # 20505).TreatmentsWe enrolled all female calves born between June 19 and September 1 2018, for a total of 28 Holsteins and 8 Jerseys. Our sample size was determined by the availability of calves being born in our herd of approximately 105 lactating cows during this period. Calves were blocked by birth order and randomly allocated to 1 of 3 treatments balanced for breed: disbudded the morning of (Day 0) or 21 days before (Day 21) the startle test, or sham-disbudded (Sham, n = 12/treatment). Among the control calves, half were sham-disbudded the morning of the test, whereas the other half underwent the procedure 21 days earlier. Birth weights were similar across treatments (mean ± SD; Day 0: 35 ± 5 kg; Day 21: 35 ± 6 kg; Sham: 36 ± 9 kg). The startle test occurred between 25 and 32 days of age for all calves. Thus, all Day 0 calves and half of the Sham calves were disbudded between 25 and 32 days of age, and all Day 21 calves and half of the Sham calves were disbudded between 4 and 11 days of age. This design meant all animals were at the same stage of cognitive and motor development during data collection. This was a priority for us because we expected age to strongly influence behavioural responses during the startle test. While it is also possible that disbudding at different ages may affect responses, previous research suggests disbudding has similar outcomes across this range13,15,20.Animal husbandry and housingImmediately after birth, calves were housed individually in outdoor enclosures consisting of a plastic hutch (2.0 m long × 1.5 m wide) and a wire-fenced pen (2.0 m long × 1.5 wide × 0.9 m high). The enclosures were spaced 0.5 m apart and bedded with sand approximately 15 to 20 cm deep.Calves were bottle-fed colostrum twice a day for 5 days. From 5 days of age, calves received milk replacer (26% CP and 16% fat, 15% total solids; Calva Products Inc., Acampo, CA) in bottles at 0645, 1245, and 1845 h. At each meal, Holsteins were fed 1.9 L from 1 to 13 days, 2.4 L from 14 to 23 days, and 2.8 L from 24 days. Jerseys received 1.4 L from 1 to 13 days, 1.9 L from 14 to 23 days, and 2.4 L from 24 days. Water and starter (18.3% CP, 2.8% fat, 4% crude fat; Associated Feed & Supply Co., Turlock, CA) were provided ad libitum in buckets. As part of a separate concurrent study, 11 calves (3 Sham, 3 Day 21, 5 Day 0) received chopped mountain grass hay (34% CP) ad libitum.DisbuddingDisbudding occurred between 730 and 1000 h. For the procedure, the calf was restrained in a head device in her home enclosure21. A 5 × 5 cm patch of hair was clipped with a size 40 electric razor blade on each side of the head to locate the horn bud. We used a 20 gauge × 25 mm needle to administer a cornual nerve block consisting of 5.5 mL buffered lidocaine (2% lidocaine hydrochloride diluted with 8.4% sodium bicarbonate in a 10:1 ratio). If the horn bud was not numb after 10 min, as assessed by pinprick, we gave an additional 2 mL of buffered lidocaine (13% of horn buds). An electric cautery iron (X50, Rhinehart Development Corp., Spencerville, IN) was fitted with a 1.3 cm tip and heated to 439 ± 15 °C (mean ± SD). It was applied to the horn bud for 17 ± 5 s (mean ± SD). Immediately before disbudding, the calf received approximately 1 mg/kg of meloxicam tablets in a gelatin capsule (3.5 g; Torpac Inc., Fairfield, NJ). For Day 0 calves, meloxicam was given after the startle test had occurred later that same day (maximum 12 h later) to ensure the calf was in a drug-free state during the test. Sham-disbudded calves received the same treatment, with the exception that the iron was ambient temperature and the gelatin capsule was empty. Sham calves did not receive meloxicam because the Animal Medicinal Drug Use Clarification Act limits nontherapeutic off-label use of this drug22. SJJA performed all disbudding procedures.ArenaWe tested calves individually in a single 10-min period in a shaded outdoor arena bedded with 10 to 15 cm of sand. The arena was divided into a waiting pen (2.0 × 1.5 m) and a test pen (3.0 × 5.5 m) constructed of 0.9 m high wire panels (MidWest Homes for Pets Foldable Metal Exercise pen, Muncie, IN). A rolling gate provided access between the pens (Fig. 1).Figure 1Aerial view of the arena used for startle tests, including the position of the milk bottle and speaker used to broadcast the startle noise. Figure is drawn to scale.Full size imageA bottle containing 500 mL of the calves’ regular milk replacer was secured to the panel opposite the entrance to the test pen. The bottle was fitted with a rubber teat positioned 80 cm above the ground. Between calves, a fresh bottle was placed in the arena and urine and feces were removed with a shovel.Testing procedureCalves were habituated to the arena for 15 min daily between 700 and 1100 h for 3 consecutive days before the startle test. Calves were brought to the arena in the same order each day, with order balanced across treatments. During habituation, no startle stimulus was delivered, but otherwise the same procedure followed on test days was applied.The startle test occurred between 1530 and 1800 h (Supplementary Video S1). The calf was transported from her home pen to the waiting pen in a cart (Caf-Cart, Raytec, Ephrata, PA). The test began when the gate providing access to the test pen was opened and ended after 10 min. The gate was closed behind the calf after she had entered so that the waiting pen was inaccessible during the test. Three observers were seated quietly 3.5 m away from the pen during the test, and were partially concealed behind a tree branch. One observer remotely controlled the speaker broadcasting the startle noise, while the other two observers were present to respond if a calf escaped from the arena (only one calf jumped out, on the first day of habituation, and was promptly escorted back into the pen). Calves showed no apparent responses to the observers and had no visual contact with other animals.As soon as the calf’s mouth was within a tongue’s reach of the teat, a 0.4 s, 105 ± 2 dB burst of white-noise was emitted through a wireless speaker (OT4200 Big Turtle Shell, Outdoor Tech, Laguna Hills, CA) mounted directly behind the bottle. The noise was created using an online signal generator23. We measured the sound level using a decibel meter (BAFX Products, Milwaukee, WI) held 30 cm in front of the bottle, approximating the distance of the calf’s ears to the source.Behavioural data collectionTests were recorded with a camcorder (HC-V180, Panasonic, Kadoma, Japan) positioned on a tripod approximately 3 m away from of the pen. One trained observer, blinded to the treatments, scored behaviours in all videos taken of the startle test and the third day of habituation (Table 1). Videos were analysed using BORIS (Behavioural Observation Research Interactive Software24). Intra-observer reliability was calculated using 12 randomly selected videos of the startle test (Intraclass correlation coeffcient ≥ 0.95).Table 1 Behavioural definitions used to evaluate calves’ responses in an arena test.Full size tableAccelerometers (Hobo Pendant G Acceleration Data Logger, Onset Computer Corporation, Bourne, MA) were used to assess the magnitude of the startle response. On habituation and test days, we fitted calves with a triaxial accelerometer set to record acceleration in the x-, y-, and z-axis every 0.05 s. The accelerometer was placed in a pouch, strapped around the right hind leg, and secured with Vet Wrap (Co-Flex, Andover Coated Products Inc., Salisbury, MA) while the calf was in the waiting pen of the arena, immediately before the gate to the test pen was opened. Data were downloaded using HOBOware Pro Software (Onset Computer Corporation, Bourne, MA). To calculate the magnitude of the startle response, we summed total acceleration in all 3 axes over the startle duration for that calf. Total acceleration was calculated as the square root of the sum of squared acceleration in each axis25. No startle response was recorded for one calf who did not approach the bottle on the test day.All calves were weighed the morning of the startle test (mean ± SD; Day 0: 56 ± 10 kg; Day 21: 55 ± 9 kg; Sham: 55 ± 11 kg).Wound healing and sensitivityWe measured sensitivity via mechanical nociceptive thresholds around the horn bud area 1 to 2 h after the startle test using a digital algometer fitted with a 4-mm-diameter round rubber tip (ProdPlus; TopCat Metrology Ltd., Little Downham, UK). The calf was restrained in the head device in her home pen and blindfolded to reduce responses to visual cues. We then applied an increasing amount of force to the edge of the disbudding wound, or intact horn bud for sham calves, as described previously13. The test ended when the calf moved her head or a maximum cut-off point of 10 N was reached. We repeated the test if a fly landed on the head, a loud noise occurred, or the calf urinated or defecated. If a test was interrupted 3 times, it was abandoned (0% of tests).Wound sensitivity was tested at the lateral and caudal edges of each wound or the equivalent location on sham calves. The order of test sites was: left lateral, left caudal, right caudal, and right lateral. To ensure force was applied at a consistent rate, personnel operating the algometer were trained and met a set of rigorous criteria before performing the tests13. We calculated the rate that force was applied in each test from video recordings (0.29 ± 0.10 N/s; 2% of videos missing). If force was increased at a rate  0.6 N/s or video was missing, the data were excluded (3% of tests). Due to the nature of the tests, the operator of the algometer was not blind to treatment.We took digital photographs of the wound with a DSLR camera (D5300; Nikon Corp., Tokyo, Japan) after sensitivity testing was completed. Photos were taken 15 cm from the wound. One person scored the photos for tissues present in the wound bed using a 0/1 scoring system13. Due to the clear differences in Day 0 and Day 21 wounds, the scorer was not blind to treatment.Statistical analysisDue to the presence of zeros in the data, we used zero-inflated beta regressions to assess the effect of treatment (Sham, Day 0, Day 21) on the proportion of time suckling on the third day of habituation and during the startle test. A zero-inflated beta regression is a mixture of two models: a beta model for estimating non-zero proportions and a logistic model for estimating the probability of zeroes26. This approach allowed us to infer treatment effects on both the occurrence and duration of suckling. General linear models were used to test the effect of treatment on the duration of the startle response and its magnitude as measured from the accelerometer data.We analyzed the effects of treatment on latency to approach the bottle and latency to return after startling using parametric survival regression models with a log-logistic distribution. Days on which the calf did not perform the behaviour within the allotted time (15 min for habituation, 10 min for startle test) were handled as right-censored data.We ran a general linear model to test the effect of treatment on wound sensitivity. A preliminary analysis indicated that there was no effect of side (left vs right) or location (caudal vs lateral) on wound sensitivity, so we averaged data for each calf into one score.Data were analysed in R, version 3.5.227. General linear models were fitted using the “lm” function in base R. We confirmed homogeneity of variance and normality using residuals vs fits plots and Q-Q plots, respectively. Beta and survival regressions were performed with the “glmmTMB” function in the glmmTMB package version 1.0.028, and the “survreg” function in the survival package version 2.3829, respectively. If treatment effects were identified in any of the models (P  More

This is the first study to evaluate the mercury content in the fur of Siberian tigers in the Far East of Russia. It is a commonly recognized fact that fish are the main source of mercury entering the organism of predators and the trophic network of the ecosystem. In some areas, the seasonal abundance of salmonids can provide tigers with protein: masu (Oncorhynchus masou) from April to early July, chum (O. keta) in late autumn and up to December and pink salmon (O. gorbuscha) in July–early October. However, our observations during 1976–2018 (15 (Poddubnaya, unpublished data)) and data on mercury content show that tigers do not eat salmon often. Tigers do not hunt the redfin dace (Tribolodon hakonensis) a cyprinid fish, moving up in huge swarms from April to June.Although tigers were never observed to consume fish in mass quantities, as is the case with bears, one would expect that the total concentration of mercury (THg) in the body of tigers from two sections of the Sikhote-Alin (basin drainage of the Sea of Japan and the catchment of the Amur River) would vary depending on the availability of anadromous fish. The rivers of the Sea of Japan basin are shorter and shallower than Amur’s tributaries. Therefore, the likelihood of a tiger catching fish here seems to be higher. However, Amur’s tributaries are richer in fish and the probability of catching fish has to be no less than that observed in the coast. Thus, it can be assumed that the proportion of fish in tiger’s diet on the coast and in the inland region should be similar. Apparently, the consumption of salmon by tigers can be neglected in this analysis.The minor role of fish in the Siberian tiger diet is further evidenced by comparing its average mercury content with other large felids known to consume fish and other aquatic animals. Thus, individuals of Florida panther (Puma concolor coryi), consuming aquatic and fish-eating animals have elevated levels of MMHg—1.62 ± 1.87 mg/kg or 1.84 mg/kg THg 20. The average mercury concentration in the jaguar (Panthera onca), mainly preying on fish and alligators, reaches even higher values of up to 4.27 mg/kg (from 2.13 to 7.26 mg/kg) 21. The average THg content in the Siberian tiger is 0.383 ± 0.062 mg/kg indicating that it eats little fish, if any.In the south of the Russian Far East, some ungulates caught by the tiger on the eastern macro slope of Sikhote-Alin periodically go to the sea to lick salt and eat algae. This can lead to some increase in the level of mercury in their tissues and in the tiger along the trophic chain. In addition, ungulates, especially deer, can eat various lichens, including Usnea in the temperate forests.As we found out, THg in lichens from the coast, where sea fog is observed, was 0.170 ± 0.017 mg kg−1 (n = 30), which is 2.6 times higher than the average value for inland areas (0.065 ± 0.004 mg kg−1 (n = 24) (Fig. 1A). The absolute values of THg in Usnea lichens from the coast in the south of the Russian Far East turned out to be higher than in the Ramalina menziesii lichens (from the same order Lecanorales and the same ecological form as Usnea) from the coast in California 3 (0.138 ± 0.012 mg kg−1). It is possible that such differences are related to species-specific features of their thalli. Different species of lichens from the same locality can accumulate different amounts of toxic substances in their thallus. Thus, Usnea contained 0.170 ± 0.017 mg kg−1, and the mesomorphic evernia (Evernia mesomorpha) collected on the same site—0.292 mg kg−1(n = 2).Figure 1Map of sampling sites and mean values of (A) THg concentrations in lichen (Usnea sp.) (site names correspond to data in Table 1), (B) THg in tiger fur. The blue triangles and circles represent the samples from coastal sub-region and the black—from inland sub-region. Lichen sampling was done in 2019 and tiger fur sampling was done in 2004–2014. The map was generated in Adobe Photoshop CS6, based on a map from the public domain on the site https://yandex.ru/legal/maps_termsofuse/?lang=en.Full size imageWeiss-Penzias et al. 3 do not give the average THg for inland lichens, but they show that the high MMHg content in lichens on the coast is obtained through coastal marine atmospheric fog. We compared our data with those for THg on Bathurst Island 22, where the spatial pattern in THg enrichment was very similar to that of MMHg, with enrichment highest at coastal sites and decreasing within 10 km, suggesting similar origins of atmospheric THg and MMHg to lichens. Potential sources of inorganic Hg and MMHg to lichens are diverse (e.g. 3,22). MMHg from THg can range from 4.4 to 23% 3, therefore special future studies are needed to understand the dynamics of Hg species in lichen.The average individual THg concentrations in tiger fur samples from the coast ranged from 0.115 to 0.918 mg kg−1 (n = 12), on average 0.434 ± 0.067 (Fig. 1B, Table 1), while tiger fur samples from the inland regions (n = 12) had lower concentrations of THg (range from 0.057 to 0.950 mg kg−1, average 0.239 ± 0.075); the differences between the means of the two sites were statistically significant (p = 0.01) (Fig. 1B, Table 1).Table 1 Statistics on the subsets of THg concentration data used in this paper.Full size tableThe average concentrations of THg in the tiger fur of two subregions were lower (0.434 ± 0.067 and 0.239 ± 0.075 mg kg−1) than similar values for pumas from California 3. In contrast to California, where the average THg content in pumas from the coastal area was three times higher than in animals from the inland areas, in the Russian Far East the average THg content in tiger fur sampled in the area influenced by the sea fog was two times higher than that in comparable samples from inland areas. Although, it is the inland area (the Amur River basin) that is subject to high levels of human activity, including the mining of coal and gold in the past and present, and we could expect higher levels of mercury in living components of ecosystems. The average concentrations of THg in the tiger fur were only from 0.056 to 0.232 mg kg−1 (n = 4) near coal and gold mining sites.Different age classes were sampled in both the coastal and inland areas, and THg concentrations increased with age (adult  > young) in both areas (Table 1). This pattern is typical for predatory animals in general and for pumas, in particular 3, which is natural due to the cumulative effect and increasing mercury content with age 22,23,24,25. Differences in the average individual mercury content in individual fur samples of young and adult tigers were significant (p = 0.04) (Table 1). Moreover, the differences between the average mercury content in young and adult tigers were insignificant in the inland site (p = 0.32), while being significant on the coast (p = 0.04) (Table 1).We did not observe any significant differences in THg concentrations between the sexes (p = 0.86) (Table 1) and between males from the coast and the inland (p = 0.25) (Table 1) as was noted earlier for puma 3,21. On the contrary, the average values of mercury in the fur of individuals from the coast were 3.1 times higher than from the inland sites within the group of females, this difference was statistically significant (p = 0.03) (Table 1). These data contradict to what was observed in puma by Weiss-Penzias et al. 3. Such feature of female tiger is apparently associated with their shorter migration routes and smaller individual territories compared to males 26,27. Unlike males, which can cross the main Sikhote-Alin ridge, females are usually located either on the territory in the zone of sea fog influence, or in the inland areas.In addition, young females often remain within the territory of their mothers during dispersal 15. Rather similar information was obtained for the wild European cat 28, where THg in females was about 1.4 times higher than in males, although the differences were not statistically significant. There were no significant differences in THg content between young tigers in coastal and inland areas, as well as in the samples of animals, which died in autumn–winter and spring-early summer (Table 1).Apparently, preying on land animals does not lead to the accumulation of high Hg levels in felids. The average Hg levels in the fur of a near-water species such as the ocelot (Felis pardalis) mainly preying on terrestrial animals, varied in the same range as the tiger: 0.5–1.25 mg kg−1 29. Tigers are mainly consumers of the second level and therefore the average content of mercury in their body (0.383 ± 0.062) (Table 1) is lower than in the fur of consumers of the third level such as the pine marten 1.80 ± 1.34 mg kg−1 30 or Daubenton’s bat 1.15 ± 0.27 mg kg−1 31.The only sample with a maximum mercury content of 1.402 mg kg−1 (age and gender unknown) was from the southwestern Primorye, which is located on the coast and where there are cinnabar deposits nearby. This sample was not used in the total analysis. Interestingly, the available sample of a young female Far Eastern leopard fur (Panthera pardus orientalis) from the same site had practically the same mercury content (1.456 mg kg−1). Local increased mercury content in the body of tigers can be associated with deposits of mercury-containing minerals. These data do not confuse our understanding of the sources of mercury in the ecosystem; they serve as a signal for a more profound study of natural processes.Our data on a higher mercury level (THg) in lichens and tigers of the sea coast compared to inland areas may be related to the effects of coastal sea atmospheric fog, a potential source of monomethylmercury (MMHg) produced in the ocean 3.The levels of mercury we found in Siberian tigers from the Russian Far East are about four times lower than the mercury content in the fur and vibrissa of puma from California 3. It seems that such differences are related to the position of these regions relative to the zones of deep faults of the mantle formation of the East Pacific platform 32. The maximum concentrations of Hg in the near-surface atmosphere are confined to such zones, and the concentrations decrease at a distance from them. California is located closer to such zones, while the south of the Russian Far East is further away.And the fact that different levels of mercury in ecosystems depend on the distance relative to the deep faults of the East Pacific platform is confirmed, for example, by pink salmon: fish from the Sea of Japan contain much less mercury than fish from the Kuril region closer to the fault zone (from 0.045 to 0.087 mg kg−1 wet weight 31. At the same time, we must not forget that California is the most populated and one of the most industrially developed states in the USA. However, it seems that natural processes currently play the main role in formation of heavy metal content in the discussed populations. Thus, lead concentrations in organs and tissues (liver, gonads, and muscle) of fish from Kuril oceanic waters was one and a half order of magnitude higher than that of pink salmon from the Sea of Japan 33.If the global anthropogenic mercury pollution of terrestrial and aquatic ecosystems continues, coastal food webs in the zone of influence of the East Pacific platform will be at most risk of toxicological effects. More

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