Ivermectin decreases parasite load, testosterone, and potentially antler length in a group of captive red deer males (Cervus elaphus).

Secondary sex traits (SSTs) can favour males in intra-sexual competition, allowing females to reliably assess their quality. They can also be connected to other aspects of fitness, such as resistance to parasites and pathogens, as parasites have negative effects on the development of SSTs. Antlers are one of the most recognizable examples of SSTs whose development is regulated by testosterone and reflects the actual condition of the bearer. Elevated testosterone can exaggerate the size of SSTs while impairing the function of the immune system ("The Immunocompetence Handicap Hypothesis") posing a trade-off between antler development and immune function. In this study, we experimentally manipulated the parasite load in captive red deer (Cervus elaphus) males with Ivermectin during antler development for two consecutive years. Expecting an inverse proportionality between parasite load and antler size, we hypothesized the treated deer to have larger antlers than the untreated ones. Our results showed that, following the immunocompetence handicap hypothesis, parasite load was positively associated with testosterone levels. However, the application of Ivermectin suppressed the parasite load of the treated animals but did not lead to the development of larger antlers. Instead, it significantly suppressed the concentration of testosterone in the treated animals, whilst the animals that had higher testosterone also had the highest parasite load. Our findings show that Ivermectin can potentially decrease the levels of testosterone and, consequently, antler size. These findings have important implications for the management of captive populations, especially in contexts where the development of large trophies is desired.

The effects of challenge or social buffering on cortisol, testosterone, and antler growth in captive red deer (Cervus elaphus) males.

We equipped 17 captive red deer males (Cervus elaphus) with GPS collars to measure inter-individual distances throughout the 5-months of the antler growth period. We expected some individuals to associate regularly with others while others would not. We predicted that males aggregating with others within a socially stable environment (Associates) would benefit from a form of "social buffering" and would likely have lowered cortisol (C) and testosterone (T) concentrations. Males only irregularly joining social groupings would experience elevated levels of aggression; according to the "Challenge hypothesis", their T and C concentrations should increase. Interacting with a higher proportion of Associates did indeed reduce C concentrations. Conversely, avoiding Associates and challenging other males stimulated the T secretion. Admittedly, males avoiding regular proximity to others tended to develop the largest antlers. They probably benefited from frequent successful agonistic threats to conspecifics, resulting in elevated T concentrations. Regular association with tolerant, conspecifics and "social buffering" did not seem sufficient for producing larger antlers despite reducing C concentrations. Alternative social strategies were adopted within the same group of individuals and showed how the trade-off between these strategies could have an essential impact on C and T concentrations.

Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors.

Proteasomes are essential for protein homeostasis in mammalian cells1-4 and in protozoan parasites such as Trichomonas vaginalis (Tv).5 Tv and other protozoan 20S proteasomes have been validated as druggable targets.6-8 However, in the case of Tv 20S proteasome (Tv20S), biochemical and structural studies were impeded by low yields and purity of the native proteasome. We successfully made recombinant Tv20S by expressing all seven α and seven ß subunits together with the Ump-1 chaperone in insect cells. We isolated recombinant proteasome and showed that it was biochemically indistinguishable from the native enzyme. We confirmed that the recombinant Tv20S is inhibited by the natural product marizomib (MZB)9 and the recently developed peptide inhibitor carmaphycin-17 (CP-17)8,10. Specifically, MZB binds to the ß1, ß2 and ß5 subunits, while CP-17 binds the ß2 and ß5 subunits. Next, we obtained cryo-EM structures of Tv20S in complex with these covalent inhibitors at 2.8Å resolution. The structures revealed the overall fold of the Tv20S and the binding mode of MZB and CP-17. Our work explains the low specificity of MZB and higher specificity of CP-17 towards Tv20S as compared to human proteasome and provides the platform for the development of Tv20S inhibitors for treatment of trichomoniasis.

Efficacy and Safety of Deep Sclerectomy With the Esnoper Clip Implant for Uncontrolled Primary Open Angle Glaucoma: A 1 Year Prospective Study.

PRCIS: Deep sclerectomy (DS) with the Esnoper Clip drainage implant in patients with uncontrolled primary open angle glaucoma (POAG) achieved a complete success rate of 87.2% at the 1-year follow-up. PURPOSE: To investigate the efficacy and safety of DS followed by Esnoper Clip implantation in patients with uncontrolled POAG. MATERIALS AND METHODS: In a prospective, consecutive, interventional study, we investigated 39 eyes of 35 patients with uncontrolled POAG who underwent DS with Esnoper Clip implantation. Complete ophthalmologic examinations including corrected visual acuity and intraocular pressure (IOP), were performed preoperatively, and at 1 day, at 1 week as well as at 1, 3, 6, 9, and 12 months postoperatively. Moreover, any goniopunctures and glaucoma medications required postoperatively were noted. RESULTS: The mean preoperative IOP was 20.8±5.2 mm Hg and it decreased to 13.9±3.1 mm Hg at 1 year postoperatively ( P <0.001). The number of glaucoma medications decreased from 2.9±0.7 preoperatively to 0.3±0.8 after 1 year ( P <0.001). The complete success rate (IOP≤21 mm Hg without glaucoma medication) and the qualified success rate (IOP ≤21 mm Hg with or without glaucoma medication) were 87.2% and 94.9%, respectively. Goniopuncture was performed in 33.3% of cases. No significant corrected visual acuity changes were registered at the final follow-up. Perioperative complications consisted of 3 micro-perforations of the trabeculo-descemet membrane. Postoperative complications included: hyphema (6 eyes), hypotony (6 eyes), shallow anterior chamber (3 eyes), choroidal detachment (4 eyes)-all of which were resolved without surgical intervention during the first postoperative month-and conjunctival dehiscence, which required resuture (2 eyes). CONCLUSION: Deep sclerectomy with the Esnoper Clip implant was safe and effectively lowered IOP in patients with uncontrolled POAG.

Still beyond a chance: Distribution of faults in elite show-jumping horses.

This study aimed to identify factors that can influence show-jumping performance during top level competitions in the Western European League (2017/2018, CSI5*). The performance data of 144 riders and 222 horses were obtained from video records (FEI TV/ website). Riders with horses achieved a total of 9114 jumping-efforts over 320 obstacles including oxers (n = 142), oxers with water (n = 15), triple bars (n = 6), verticals (n = 136), verticals with water (n = 14) and walls (n = 7). Obstacles in the first round (FR) or in jump off (JO) were standing either as single (n = 6290) or as a combination of two or three fences in a row (n = 2824). The overall fault rate (dropping the pole or refusal/run-out to jump) was 7.85%. The probability of a fault increased with the rank of the fence in the course of FR (F (1, 7649) = 5.29, P < 0.0001, GzLMM; PROC GLIMMIX, SAS). The highest probability of a fault (F (5, 7649) = 2.51, P < 0.03) in FR was found on the vertical obstacle with water (0.125 ± 0.021, LSMEAN ± standard error) while the lowest was on the triple bar (0.037 ± 0.015) and wall (0.048 ± 0.020). Riders who completed more starts in previous competitions achieved a lower fault rate (F (1, 7649) = 6.17, P < 0.02) in FR as well as in JO (F (1, 931) = 7.05, P < 0.01). The probability of faults in JO decreased with a higher speed (F (1, 931) = 6.66, P < 0.01) but there was no significant correlation between the speed in JO and FR in individual horses (r = 0.26, P < 0.01). More faults were found on the fences within combinations in both rounds (FR, JO). The highest probability of faults was found on the first fence (FR 0.095 ± 0.016; JO 0.043 ± 0.008) or second fence (JO 0.055 ± 0.020) of the double combination compared to the least probability of faults on single obstacles (FR 0.057 ± 0.007, F (5, 7649) = 5.29, P < 0.0001; JO 0.100 ± 0.027, F (1, 931) = 3.39, P < 0.04). Other tested factors did not affect show-jumping performance. Some faults are still more likely and not random in a show-jumping course, therefore, the appropriate training focus can improve performance and safety in competitions.

Long-term trends in the body condition of parents and offspring of Tengmalm's owls under fluctuating food conditions and climate change.

Physical condition is important for the ability to resist various parasites and diseases as well as in escaping predators thus contributing to reproductive success, over-winter survival and possible declines in wildlife populations. However, in-depth research on trends in body condition is rare because decades-long datasets are not available for a majority of species. We analysed the long-term dataset of offspring covering 34 years, male parents (40 years) and female parents (42 years) to find out whether the decline of Tengmalm's owl population in western Finland is attributable to either decreased adult and/or juvenile body condition in interaction with changing weather conditions and density estimates of main foods. We found that body condition of parent owl males and females declined throughout the 40-year study period whereas the body condition of owlets at the fledging stage very slightly increased. The body condition of parent owls increased with augmenting depth of snow cover in late winter (January to March), and that of offspring improved with increasing precipitation in late spring (May to June). We conclude that the decreasing trend of body condition of parent owl males and females is important factor probably inducing reduced adult survival and reduced reproduction success thus contributing to the long-term decline of the Tengmalm's owl study population. The very slightly increasing trend of body condition of offspring is obviously not able to compensate the overall decline of Tengmalm's owl population, because the number of offspring in turn simultaneously decreased considerably in the long-term. The ongoing climate change appeared to work in opposite ways in this case because declining depth of snow cover will make the situation worse but increased precipitation will improve. We suggest that the main reasons for long-term decline of body condition of parent owls are interactive or additive effects of reduced food resources and increased overall predation risk due to habitat degradation (loss and fragmentation of mature and old-growth forests due to clear-felling) subsequently leading to decline of Tengmalm's owl study population.

Making semantic commitments can be delayed: Evidence from aspectual processing.

Semantic interpretation of aspectual verbs has been shown to cause a processing cost. The present study provides additional evidence that the semantic interpretation of events interacts with sentence processing. The study focused on telicity, an aspectual property that does not solely depend on lexical items but instead on the semantic composition of verb phrase (VP)-level events. Results from a working memory task showed that committing to a semantic interpretation incurs a processing cost and that some adverbials force the parser to commit to a particular aspectual interpretation. Specifically, in-X-time adverbials force the parser to commit to a telic (completed/terminated) interpretation before the VP has been processed. In contrast, for-X-time adverbials, which are compatible with an atelic (completed or incomplete) interpretation, do not force the parser to make an early commitment to a particular semantic interpretation. Instead, processing is always delayed until the VP has been completely parsed. Results support the partial interpretation hypothesis according to which the parser can delay making semantic commitments until it is necessary to do so, that is, in atelic but not telic sentences. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Interactive influences of fluctuations of main food resources and climate change on long-term population decline of Tengmalm's owls in the boreal forest.

Recent wildlife population declines are usually attributed to multiple sources such as global climate change and habitat loss and degradation inducing decreased food supply. However, interactive effects of fluctuations in abundance of main foods and weather conditions on population densities and reproductive success have been studied rarely. We analysed long-term (1973-2018) data on Tengmalm's owl (Aegolius funereus) and the influence of prey abundance and weather on breeding densities and reproductive success in western Finland. We found that fledgling production per breeding attempt declined and laying date of the owl population delayed during the period between 1973 and 2018. The breeding density of the owl population decreased with increasing temperature in winter (October-March), fledgling production increased with increasing temperature and precipitation in spring (April-June), whereas the initiation of egg-laying was delayed with increasing depth of snow cover in late winter (January-March). The decreasing trend of fledgling production, which was mainly due to starvation of offspring, was an important factor contributing to the long-term decline of the Tengmalm's owl study population. Milder and more humid spring and early summer temperatures due to global warming were not able to compensate for lowered offspring production of owls. The main reason for low productivity is probably loss and degradation of mature and old-growth forests due to clear-felling which results in loss of coverage of prime habitat for main (bank voles) and alternative foods (small birds) of owls inducing lack of food, and refuges against predators of Tengmalm's owls. This interpretation was also supported by the delayed start of egg-laying during the study period although ambient temperatures increased prior to and during the egg-laying period.

To beat or not to beat: Behavioral plasticity during the antler growth period affects cortisol but not testosterone concentrations in red deer (Cervus elaphus) males.

Out of rut, male red deer (Cervus elaphus) associate themselves in bachelor groups where animals compete for rank position via agonistic interactions. In a previous study on red deer, males were recognized either as "Non-Fighters" (NF, low frequency of attacks) or "Fighters" (F, high frequency of attacks). This study, therefore, aims to verify the consistency of the inter-individual differences in fighting attitude across different social contexts and investigate whether they could be considered an individual characteristic. Behavioral consistency was presumed across three different sampling seasons, assuming that NF would have lower cortisol (C) and testosterone (T) concentrations than the F males. In 2015 the males were kept in one large group and labelled NF and F. In 2016, the herd was divided into two subgroups ("NF" and "F") based on the frequency of attacks. Finally, in 2017, the males were divided into two randomly composed subgroups. Data about agonistic behavior and concentration of C and T were collected during each season. In 2015 the individuals differed only for the fighting attitude. After the division, the frequency of the attacks always increased, being consistently lower in NF than in F. Unexpectedly, a slight increase in the concentration of C was detected in the NF in 2016, compared to the F who experienced no difference neither in 2015 nor 2017. No significant differences were found in T. We concluded that, even though the males had shown behavioral plasticity, their diversified interaction-prone attitude had been maintained despite the modifications of the social environment.

A sociobiological origin of pregnancy failure in domestic dogs.

Among domestic dog breeders it is common practice to transfer a domestic dog bitch out of her home environment for mating, bringing her back after the mating. If the home environment contains a male, who is not the father of the foetuses, there is a potential risk of future infanticide. We collected 621 records on mating of 249 healthy bitches of 11 breed-types. The highest proportion of successful pregnancies following mating occurred in bitches mated within their home pack and remaining there. Bitches mated elsewhere and then returned to a home containing at least one male had substantially lower incidence of maintained pregnancy in comparison with bitches mated by a home male. After returning home, housing affected strongly the frequency of pregnancy success. Bitches mated elsewhere but released into a home pack containing a home male were four times more likely to maintain pregnancy than bitches which were housed individually after returning home. Suppression of pregnancy in situations where a bitch is unable to confuse a home male about parentage may be seen as an adaptation to avoid any seemingly unavoidable future loss of her progeny to infanticide after birth and thus to save energy.

Lateralized suckling in domestic horses (Equus caballus).

Brain lateralization enables preferential processing of certain stimuli and more effective utilization of these stimuli in either the left or the right cerebral hemisphere. Horses show both motor and sensory lateralization patterns. Our aim was to determine whether a lateralized response could be detected in foals during the naturally side-biased behaviour, suckling. The foals' preferred suckling side could be the effect of either visual or motor lateralization. In the case of a visual lateralized response, foals are expected to suck more often from the mother's right side, so potential danger can be detected by the better adapted right hemisphere (i.e. left eye). Motor lateralization can be identified when a foal will suck predominantly from one side, either left or right. We found no population trend in the preferred suckling side, but we detected significant differences amongst individual foals. One-third (35.4 %) of 79 foals showed a strong, either right or left side preference which increased with age. The mothers did not influence the foals' suckling side preferences either by side-biased rejection or termination of suckling. According to our findings, a general pattern of sucking with the left eye open for better danger detection and recognition is unlikely in foals up to 7 months old. Foals of this age are probably young or fully focused on suckling and rely on their mothers' vigilance. Individual side preferences amongst foals are suggested to be based on motor lateralization.

Laterality of suckling behaviour in three zebra species.

Although side preference while suckling is an easily characterised lateralised behaviour, few studies have been conducted. We observed laterality in suckling behaviour in three captive zebra species to test two hypotheses: laterality affected by the foal (motor laterality) and laterality affected by the mother. In total we observed 35 foals of Grevy's, plains, and mountain zebra in two zoos and recorded 5128 successful suckling bouts and 9095 unsuccessful suckling attempts. At the population level the only factor affecting side preference of suckling bouts and attempts was the identity of the individual foal. Ten foals showed individual preferences: seven foals preferred suckling from the left side of the mother, three preferred suckling from the right side of the mother. The individual preferences increased with increasing age of the foal. Only one foal was refused more often from the opposite side than the preferred side used for suckling whereas three other foals were refused from the preferred side. Foals that preferred suckling either from left or right side were refused by the mare more often than foals which showed non-preference. Thus lateral preferences in suckling behaviour of zebra foals seem to be in line with the motor laterality hypotheses.

Benefits for dominant red deer hinds under a competitive feeding system: food access behavior, diet and nutrient selection.

Social dominance is widely known to facilitate access to food resources in many animal species such as deer. However, research has paid little attention to dominance in ad libitum access to food because it was thought not to result in any benefit for dominant individuals. In this study we assessed if, even under ad libitum conditions, social rank may allow dominant hinds to consume the preferred components of food. Forty-four red deer hinds (Cervus elaphus) were allowed to consume ad libitum meal consisting of pellets of sunflower, lucerne and orange, and seeds of cereals, corn, cotton, and carob tree. The meal was placed only in one feeder, which reduced accessibility to a few individuals simultaneously. During seven days, feeding behavior (order of access, time to first feeding bout, total time spent feeding, and time per feeding bout) were assessed during the first hour. The relative abundance of each meal component was assessed at times 0, 1 and 5 h, as well as its nutritional composition. Social rank was positively related to the amount of time spent feeding during the 1(st) h (P = 0.048). Selection indices were positively correlated with energy (P = 0.018 during the 1(st) h and P = 0.047 from 1(st) to 5(th)) and fat (only during the 1(st) h; P = 0.036), but also negatively with certain minerals. Thus, dominant hinds could select high energy meal components for longer time under an ad libitum but restricted food access setting. Selection indices showed a higher selectivity when food availability was higher (1(st) hour respect to 1(st) to 5(th)). Finally, high and low ranking hinds had longer time per feeding bout than mid ones (P = 0.011), suggesting complex behavioral feeding tactics of low ranking social ungulates.

Concurrent lactation and pregnancy: pregnant domestic horse mares do not increase mother-offspring conflict during intensive lactation.

Lactation is the most energy demanding part of parental care in mammals, so parent-offspring conflict arises over milk provided by the mother. In some species females commonly become pregnant shortly after parturition of previous young. This further intensifies mother-offspring conflict due to concurrent pregnancy and lactation. In equids it has been well established that pregnant females wean their foals earlier than non-pregnant ones. Intensified mother-offspring conflict was presumed to associate with pregnancy also during the period of intensive lactation, i.e., before the weaning process starts. We investigated the effect of pregnancy on suckling behaviour characteristics as indicators of mother-offspring conflict in domestic horses. Contrary to expectation, here we provide evidence of a decreased mother-offspring conflict related to pregnancy in lactating females during first two trimesters of pregnancy. Pregnant mares provided longer suckling bouts and did not reject or terminate suckling of their foals more often than non-pregnant mares. Our results suggest that pregnant mares cope with parallel investment into a nursed foal and a foetus through enhancing nursing behaviour in early stages of pregnancy before the initially low requirements of the foetus increase. They compensate their suckling foal with the perspective of its early weaning due to ongoing pregnancy.

A case of adoption and allonursing in captive plains zebra (Equus burchellii).

Although allonursing (allowing non-filial offspring to suckle) can be a costly behaviour, it has been reported for many mammals including ungulate species. However, such behaviour is very rare in equids. This is the first report on adoption and allonursing in captive plains zebra (Equus burchellii), recorded in the Dvur Králové Zoo, Czech Republic. We observed a case of adoption of an orphaned foal by a lactating mare, who then regularly nursed two foals (filial and non-filial). The allonursing mare rejected more suckling attempts, terminated suckling bouts more often, and had a shorter suckling bout duration than other mares. When nursing both foals at the same time, the suckling bout lasted for less time than when nursing a single foal, regardless of whether it was filial or non-filial. The allonursing mare apparently did not discriminate between the filial and non-filial foal.

UVA-activated 8-methoxypsoralen (PUVA) causes G2/M cell cycle arrest in Karpas 299 T-lymphoma cells.

We investigated the effect of UVA-activated 8-methoxypsoralen (PUVA) on the cell line Karpas 299 derived from anaplastic large-cell lymphoma (ALCL) expressing chimeric fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM/ALK). NPM/ALK activates phosphatidylinositol 3 kinase (PI3K)/Akt pathway responsible for the cell protection from apoptosis. We found that PUVA treatment first induced G2/M cell cycle arrest resulting in a decrease in the cell proliferation rate. The mitochondrial apoptosis was triggered immediately following PUVA treatment, as we judged from the unmasking of mitochondrial membrane antigen 7A6. However, the mitochondrial membrane depolarization was not observed and caspase-3 was only slightly activated. The late apoptotic events were lacking: neither translocation of phosphatidylserine to the outer side of plasma membrane nor DNA fragmentation occurred. We revealed that PUVA enhanced the expression of peroxiredoxin, stress protein endoplasmin and galectin-3. Galectin-3 has been shown to protect mitochondrial membrane integrity and prevent cytochrome c release thereby blocking the effector stage of apoptosis. We suggest that the elevated level of this protein following PUVA treatment acts in synergy with the constitutively expressed chimeric kinase NPM/ALK to block the apoptosis.